Tobacco Documents Online

~s:PE]IDERC::EON CTCJ3Z2TE S~G - A itEV'I1CW BEPOETE0. RD.1532 RESTL~C'J:ED 15.12.1977 ~E= A. Kay Comer ISSUED BY: Z.E. Thornton FROG. ]~F: 13.01.O5 DT~T1LTJK~ZON: Dr. S.J. G~ae~ D=. Z.W. H=$hes K.M. G:Lbb, Esq. K.S. Wade, l~q. E.G. NLchoZls, Ksq. Haz'r E. Kictarshs~uJ Dr. F. Seehofec Mr. ,A.J. lr.rusz3q~ki Dr. C..1.P. cLe Siqueira Dr. D.G. Felt.on Library Cop7 lio. 1, 2, 3, 4 Irt " " 6, 7 111 tl 8 " " 9, 10, 11 " " 12, 13 " " 14 " " 15 " " 16 " " 17 " " 18 " " 19, 20 (:OPT NO. ,mmm~ cr~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

CONTENTS ~e 2. t e e ,,. 7. 8. 9. 10. 11. 12. sumu~¥ INTRDDUCTEON DEFINITIONS OF ADDICTION, HABITUATION AND DEPENDEHCE EV%DENCE FOR THE ROLE OF NICOTINE AS A DETERMINANT OF CIGARETTE SHOKING 2.1 H/erotical 2.2 Evidence from ExperJ~nents UsinK Animal8 2.3 Evidence from ExperLmenrs on Humans: The Effects of Nicotine nnd of ~ed Delive~ of Smoke Constituents on Smoking Behaviour 2.4 Comparison of CiKarette, Pipe and ClEar Smoklns THE EFFECTS OF SMORIHG AND NICOTINE IN HUMAN SUBJECTS 3.1 Physiolosical Effects 3.2 PsycholoKical Effects 3.3 Effects on Performance DIFFERENCES BETWEEN SMOKERS AND NON-SMOKERS AND BETWEEN SMOKERS OF DIFFERING CIGAKETTE CONSUMPTZON PhysioloEical Differences 4.2 rsychoZoEical Differences Social Differences SMOKING MOT3~VJ~TON 5.1 PharmaeoEoKica~ Theories of Smoking Motlvanion 5.2 Behaviourel/Psychological Theories of SmokinS Mo~ivetiom 5.3 Mixed Theories of Smokinj Motivation ~NITIATION OF SMOKING BEHAVIOUR CESS&T$ON OF SMOKING BEHAVIOUR TOLERANCE TO NICOTINE &HD b'ITHDRAHAL SYMPTOMS THE CONNECTION OF SMOKIBG WITH THE USE OF DRUGS COMP&R~SON OF SMOKIHG WKTH THE USE OF DRUG8 USE OF THE TERMS "ADDICTIOH", '~ABZTUATIO~' AND "DEPENDENCE" IN THE COHTEXT OF TOBACCO S~K)K~lfG COHCLUSIOHS REFERENCES I 2 3 11 12 14 17 37 41 41 47 53 56 57 63 71 7~ 74 75 84 96 101 126 135 139 150 159 162 t.n CO CO BAT Co LTD - MINNESOTA TOBACCO LITIGATION __

AJ~ / CAL / 4 6J Group Research & Development Centre, Brlt~sh-Amer£can Tobacco Co. Ltd., SOUTHAMPTON. l$th December 1977 DEPENDE3gCE ON CT~ SMOKZNG - A REVIEW (Keport Ho. RD.1532 Keecricted) Dependence on c£Karette 8mokln8 is reviewed with reference to the definitions of "addictlon", "habltuatlon" and "dependence". Evidence for the importance of u~coc£ne in 8mokiz~ behavlour is dLscussed and a number of the affects of ~kinK and nicotine are considered. Differences betweeu 8moke~s and non-smokers are rev~eved and a Var£eCy of smoic~n4~ motlvmClon theoc~es ~re pressured tosether w~th information on the phanomenA of smoking initiation and cessation. The counection of mnolc~n4K with the use of druKs ks expZored and comparisons 8remde between the use of tobacco and druKs such as oplaces and marijusna. It is concluded thJt the majority of smokers are to some extent dependent on s~k~ but that behaviourel, 8oc£aI and psycholosical factors may be as important as those of a pharmacologlcal nature. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-2- ]~T~ODU~ION Since interest was first shown in the reasons for smok~ tobacco there has been conslderable confusion about the use of the terms "add£ctic~", "habituation" and "dependence". The purpose o£ this report is to try and cSar££y the position v~th reKatd to cigarette smoking and also to discuss some of the theories and experiment&l results obc~[ned on the effects of nicotine and smoking and on smoking motivation. The report is divided into a number of sections, ~ach representing • different aspect of factors Invo1~td in clsa~ttt• 8moklnS. An attempt has been made to structu=• the sections in such • may that they can be read independently. This involves • certain amount o£ unavoidable repetition and some publications are discussed 4, more than one section. Zt is hoped that • £L~rly r~presentat£ve selection of the work on smok£~ is presented here, although it is obvio~ly not possible to discuss •lZ the avaiZabZe publications. Some emphasis is placed on the work of Dr. H.A.B. ]bJsseL1 o£ the Addiction l~se~rch Unit, Znstitute o~ Psychiatry, at the Haudslay Bospt:al, London. Re has pubZished a Zarse nmsber of papers on i vide m~rie~y o£ aspects of smok/~S, sad his work is discussed in relation to that 0£ other authors. BAT Co LTD - MINNESOTA TOBACCO LITIGATION c~

-3- D~NITIONS OF ADDICTIONv H&BZTUATZON ld~D DF~PENDENCE The inCmnCion in ChUm emotion is Co present jose of the definitions chac have bmen published, as It~h£s ~11 form the basis for discussion of them and chair relevance co smoking, in subsequent sections. The de£iuiCions of the ceres addiccion mad habltuacion which are most often quoted wars SivRn by the World Health Orlanisacion in 1957 (224). Addiction is said co be "a scmcm of periodic oc chronic inco~4cac4ou produced by repeated consmnption o£ • drug". Xts char&cter£scics include: An overpowering desire or need (compuXs£on) Co continue Caking the drug and Co obtain iC by any moans. 2. A tendency Co £ncruse Cha dose. 3. A psychic (psycholos£cal) sad jmmrsIly • physical depeudmnce on the effaces of the drug. 4. kcrlmmntal effects co the ind£vidual mad Co sociecy. Hab£CuaCion is • "condition" reaulClng from repeated adm~nlscraCion of • drug. Its characteristics include: (a) A desire (but noC compulsion) co continue Caking the drug £or the s•nse og ~ell-being ic engenders. (b) Little or no tendency to incrmmse the dose. (c) Some deKrme of psychic dependence on the mf£ect 0£ the drug may be present buC physical dependence and hence am &bsCiwence syndrome are absent. (d) DecrLmmnc~/ e£f•ccs, if any, et pr/marily to the /Jldividual. The "official" 'de£inicion o£ addiction given by the Drug Addiction Co~iCCee o£ the National Rasemrch Cmmcll (U.S.A.) (21~) is similar to thaC o£ the World Health OrKmaisacion buC stresses ehAC the development C3~ BAT Co LTD - MINN~C~TA TOBACCO LITIGATION

-4- of the means to continue adminlstratlon of the drug becomes an importRnt motive for the addlctts ~st@nce. StunSo (201) suKKested in 1961, that the @rld Health Orsanlsatlon ddinition did not sufficiently elphasise the i~evitabiltty of abstinence symptoms ehen an addictive drug i8 withdrawn. ~e defined drus addiction as: "a physical and psych4c dependance on a drub and the need to ~ake it in proKressively Lncreasin~ doses or at shorter intervals because of the development of tolerance and because, othezwiee severe abstinence Symptoms Ere e~perie~ced". As Lateen and Silva•re (124) have iudlcated, there are at ~aast £our di£Eeranc v~s of usJ~=K the term "addiction". The phaz:~colosist defines it at s cellular level as involvlnS an altered physioloKical state, with tolerance development. This state is produced by repeated administration of a drug and administration must be continued to maintain the altered state and prevent the development og the abstinence s3mdr~n. Beha~ioural scientists define addictiou as a be~tvi0ural pattern of compulsive drus use. There is an ovarwhelm/~s ~avolvement vith aspects of use mad supply o£ the druK a~d a h~Kh tendency to relapse agter withdzmml. Set,el•Keats delineate addicCion on the bas£s of the ham Chat the usa of certa£n drujs does to society in Sen.•tel. To the layman an addict£on £s any poverful habit thmC is difficult to break, vhethar it applies to drugs or activities. Any deflation of addiction mast. thera£ore, if it is to be readily understandable, indicate Ln which sense ~ha word 48 bein8 used. In 1964 the World Health OTKa~Loaeion sussasted ~hat the word "dependence" be 8ubst£tuted For both addiction and habituation. The -mmm~ C~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-5- de, in, clans given here are taken from a report of the Expert Ccm~Ctee on Drug Dependence. which was published in 1974 (226). '~: Any substance Chat. when cak4m into the living or~mism, may modify one or more of ice functions." "Drug dependence: A scare, psychic or sometimes aXso phys£cal, result£nS from the interaction between • 1£~n8 orrju~em and • drug, cha~mcterised by behmvloural and ocher responses that always include 8 compulsion co cake the drug cm a continuous or periodic buls in order co avoid the dLscc~forc of its absence. Tolerance may or amy not be present. A l~erson may be dependent on more r.ban one drug." '?sychic depender•: A condiclon /:: which • d~'uK produces • feeling of szcisfacc£on and • psychic drive Chat requires • periodic or continuous admln~sCreCion of the drug co produce pZeasu=e or avoid d£scomforC." '~?hys£c&1 dependance: An adeptly• scare chaC man, rests Itself by LuceuJe physical dlscurbances whm~ the mdmiu~scrac£on of the drug is suspended. These disturbances i.e. ohm u~chdrawmZ or abstinence syndrome, are made up of specific arrays of symptoms and glens of • psychic or physical naL~re that are characteristic for each drug cype." "Dependence-producing drug: A dz~K having the capacity to interact with • living orKanlsa £o produce • mCm£e of psychic mr physical dependence or both. Such • d~ may be used medically or nou-modlcally v~Chout necessarily produc4~a~ much • sC&Ce. The chErmcterlsC4cm of the stare of drug dependance, once developed, will vary with the type of dru~ involved o" The Amaz~can Psychiac~c AnsocLaCion 1968 ad£cion of the Diagnostic and $cac£sCical Manual of Manta1 D~sordets (DS~Z) (4) subsCLcucad BAT Co LTD - MINNESOTA TOBACCO LITIGATION C.,,':, Cr'2~

~m "dcug dependence" for "drug addiction" ~th a s~n~lar de££nitlon to that used by the World Health Ocganisacion. Drug dependence gas catelor£sed under '~ersouallcy disorders Rnd certa£n other n~aTsych4atr£c mmntal disorders". Freedman (68), commmntinS on Chls, points out Chat drugs r which are med£cally prescribed mud the £nCmkm of which conforms to medlczl need, art not included. Yor s psychiatric d4s4nosis co be made, the therapist needs evidence of t~b£tuml use or a clear sum of need in the patient. The presence of an abstinence syndrome is noC t~e only evidence for dia4snos4s. Freedman also t~dicmCed chat aZchouKh the calm "drug dependence" is am £mprovmmnt c~ar "addiction", chert are s~ill mnb£guities. "Drug use is so £nextr£cmbly e part: of modern soc£ety that one £s o£cen re£e~£u8 Co social de£1nltion8, related to e parCiculax culture and slcuation". Russell (168) has also cc~enced on the de£inttions o£ dependence Kiven by the World Health O:gm~Lsec£ou. He states chac physical dependance is 8chorally held to involve the presence of phys4oloiic41 adaptive changes. These include: (i) tolerance to effects of the d~ primarily due to changes aC syc~pses and also in some casts Zo increased capacity to netabolise and excrete the drug, as a result of euzyum ~:duct4cm, mainly in the 1:1.vet; (ii) wichdr~l sympc~ resulting Jr'ore rebound overa~t4vi~7 at 8yu~pses when the ~mt~k8 o~ the drug ts reduced or discont4nuad. Psychic dmpendance is bal£eved Co have no mzch underlying physioloK~cAl mechanimns. Russell objects Co the a4scinct4on heCumm phys£caZ and psycholoK4ce1 dependence since stz~ng dependence may occur 4n the absence o£ t demozmCrmble Ir~Chdrmmel rTndrome m~l., u psychologiui p:ocessas are mediated by physiological mvemcs in the brL~u, them Ch£s BAT Co LTD - MINNESOTA TOBACCO LITIGATION "-O

-7- is alSO m £m~£rectly, a physical effect. .Accordlug to R~ssell it is scme~u~t 8~bStrax-y how hiKh a deKree o£ depe~dsnce is required before a dependance disorder is texmad an addiction. Pa~n (157) suggested Chat "drug dependence iwises when as a result of giv/~g up • dTug, forces - physiological, biochmn~c~l, social or 8nviromental - are set up which predispose to continued dru8 use". Russell (168) has criticlsed this daf~Ltion and has stated rJ~st: "dependence on a drug, object or activity requires the crucial featmre of negative a££act in the absence of that drug, object or ac~i~,Ity. The deKree o£ dependence is equated vir3h the smmant o£ neSative a~fect which may range fz~n mild discomfort to ~trm distress, or may be equated with the amount of di£ficulty or e££ort required to do w~thout the drug, object or acti~ty". Thls is =eiated to the P~m~ory o£ T~k/~s who listed the phenomenoLogicalIy oriented criterla £or psycholoKical addiction (206). He said chat the absence 0£ the addicting substance is always noted and awareness of absence ~eKuls~ly t~sttsaCes incense ~$ative a~ftct £or which there is also avatuss and this increases with the time o£ deprivatiou. The addict expects that only the add~ctin8 substance can reduce this neKative af£ect (or emotion) and produce positi~ L~£eCtS. and these expectat£on.s, s~e invariably con~iz=s~/. Both (94) distinguished be~woen "habit" which reflects ropetiti~e. behav~our with no a~fectima c~c~nt, and "dapsndonce" in ~hlch the~e is en increasing desire or need for the e~£ects produced. Runt and l~atarsu~o (96) also discussed hab4t, addiction and dependence. Their de~in£tion of "habit" is- "learned behsm~c~r - a fixed bed~viour pttcer~ cmerLaarned to the point of becoaJ:~ s~t~atic and ms~ked by dsc::easi~ awareness and increasing dependence on sacond8~7 rather than BAT Co LTD - MINNESOTA TOBACCO LITIGATION c'~

-S- prinary re~uforce~ent". They reserve "addiction" for situations in vhich tolerance occurs and dosase must be increased to avoid withdrawal symptoms, lephylioal dependence" is said to be related to 8dd£c~on w~th the body develop~ dependence on e drug, but little tolerance is developed, the dose is not incrused and wt~adrmwal sympcams are mTng~nal or m~ss~. Hunt and Hatarazzo ad~t that the tetm~noloKy is 8ommdamt confusing mad di££erentiatlon between habit, dependence and addiction is dif£icult. They also define a term s'awlre~tsJu; "consciousness of u4~c is Ko£ns on, or the ability .to a~ke verbal report on the precedgmK or attendant stylus situation. It i8 minimal or missing with the performane~ of repetitive, stereotyped behsvio~ and present with some intene£~y in the phenomenon of craving and with the v£thdrm~tl symptoms comou to edd~cfiive dz~Ks." They alms su&Kest that psychic and physical dependence as defined by the World Health O=Kan,~sav£on can be :elated to their own re=ms '~bAbit" sad "m~rm~ess". Co svold confuslon between pu:ely physical processes and psych4c processes vith a physiological b~sis (of. R~ss'ell 4168)). ¥~slly in this section it amy be useful to give smae of the de£~tions presented in varLous lay. and mndiul dicciona~ies. The Concise Oz~o:d Diccionm~ (~7) defines addict as= "(verb) Devote. apply habit~ally or cmepu~sively: hence add£ctLon (noun) (romp) condition of d~ ezcess£vely and beLuK unable to cease dot so without adverse effects; add4cC~ve (8djecCi~n), causing addiction and depem~ence. Addict (noun) ~ereon 8ddicCad to a habit, sap. one dependent on a (specified) druS". B1ak4stons Gould ~edlcal Dictloumry (26) defines "habit" as: "a beh~v~our pattern f~zmd by repettc£on". Heroines for '~mb~ttion" include: "1. A condition of Sole=trice to the effects of a dru4J or a poison acquired by its continued use; ~ by a cra~K £or BAT Co LTD - MINNESOTA TOBACCO LITIGATION c.,m Oo c.,r't

-9- the druK ~:en it is ~tbdrmm. 2. DuE tdd,'ction, tape:tally •sLld £oz~ in ~b~cb v~thdrm~sl does not result i• severe abetiJ~emce symptoms". "Addictim: is • marked psycholoKic add physiologic dependence upon a substance, such ss 81cobol or a d~K, whir.h has llmZe ~ voluntaz7 control". The BEL~ah Hed~cal Dictioua:7 (31), barney•r, records that h~b£tuatiou~8" : "in drug addiction, the psych~cLt p~L~lel tO acqtL{red physlcAZ tolerance". '~)ependence'e Ln thin d£ctionary, which us pub14-hed before the World HeLlth 0:Km~sat£o• mrLtcbed from the ms• o£ "addictiou" to "dependence", is de£1ned as: "Z~. • d~ addict, tJ:mt state o£ body mind vbich J.s ¢cmdittmmed by iniesti~ o£ • ~rtain q~tity of d~s or ~ t~reu~ qu~ti~ of £t. ~y dmcre~e 4n dose g£ve• r£s• to ~)St~e Jy~pt~eeo 0~e can see that there £s l£ttle 8Breast in the area of de££n~tlo=, but one o£ the sets of def£nJ.tious vhich enema to cove= met points of view and which is .£alrly cmscise, is rJ~t in Uhe Horck Han~sl (143). The £ollo~L~fi para&Taph is jives under the hea~Lnj e~)tu8 Dependence". '~q; ad~ction is • state of periodic o= chron£c ~[ntoz~catLon, detrimental to the t.nd4vl.du~l and Co society. Drub abuse 4s 8 beh~our pmttez~ cb~tmctettaed by the repetitive use o£ a drug or dzuzs d~e to m strong emotional or me~tLt •eed to obtain pleasure or to mid discomfort. Psychic dependonce or habituation i8 the repeated use of dz~Ks Ln order tO e~Jxleve • S~bjectlve nziOlr~eln state, l~n~s~c~l dspend~ r.bdt~cter~see name but not all tYl~S o£ dr~K dependence and i8 de£Lnod 88 a state of adapt~tlon co • dru~ as um~L£est by 1) the vLtbdrm~l or abst4ne~ce rTndt:me, the cha:~cterietic ph~sLolosic cheeses Chat occuz vhe~ the dt~S ks discontJ~ued ~bz~ptly, when the e~£ect o£ the drug in counte=~cted BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-10- by 8 specific --telouist, or under CtrtL~U phys£ologlc stresses (e.K. seve=e infections), and 2) tolerance, the need to progressively increase the dose £n orde: to p:oduce the e~£ect origlna1Iy achieved by smaller aaoun=s. Add£ct£on is a tez~ w£th many social as well as umdicaT msan£~s, but £8 usually 8ppl£ed to states ~ere boUh phTs£cal and psTchic dependeuce are present, characte:imed by ma:ked /~olvemsut wLth use of the drug sad the secuz-JJxK of its supply, and a b£sh rAmdency to resman use of the drug a~te: i¢I ~thdratml". Zu most cases an 8uCho: tends to choose the definltion which best su£ts h/s vievpoin:. Host arKumsntJ concez~Ln4 the use of the terms "addlction" and "habituaC£on" in connection ~l~h smoking tend to centre arouDd ~h@ ev£denct for: (a) the pbarmacolog4cal basis for the use of tobacco. (b) tolerance to ciKarette mmk~n8 and/mr n~cotine. (c) tendeacy to increase the dose of ~cot£ue. (d) ~tbd=awal symptom8 m~d vhevhe: these ~m be co~nide~ed to constitute • '~r~thdrawal syndramat'. Zn pracC£ce. ~ tez~ "dopenden=e°' is now used by mm~r wuthoz~ but • dlscussion of the £ssues involved ~n distin4ulsh~nj "sddLctLon" and '~abi~t~on" £s • u:e~ul way o£ :evi'~ s~ne of ~he e~£ects o~ n~cot£ne and smoking, some o~ the ~otivstio~ ~heorie8 proposed for smol~z~ and the processes of smoking initiation and :8ssat~on. BAT Co LTD - MINNESOTA TOBACCO LITIGATION c...m ",,O

-11- 2. EV1~mqCZ FOR THE ROLZ OF ~ICOT~gK AS A DETEi~qANT OF CIC~TTE Throu6houC chess discussions £C is 8ssumed chaC nicoC£ne is the major psycboph,,rmacotoKical!~, active principle in tobacco smoke. It sbouZd be remembe:ed, hol~ve:, ChmC ocher 8moko componmaCs could also be 0£ /~porcance. Most authors ktve disregarded this posstbi14Cy buC it has been mu4~emCed that compounds such as terpenoids could be /mporCmnc Co the smoker (74). The two authors who appear co be most convinced about the t~porcmnce of nlcot/~e in cigarette ~nll and hmve worked @xtmnsively c~ the subject, are Russell end Jarv£k. They have, however, different views &bout the extent to ~hich the central role of nicotin~ has been proved. Russell states Chat: "There Ls 14ccle doubt chac 4£ £t weren't for uicoc£ne in tobacco mnoke, people would be ZicCSe more incl£ned to smoke then they are Co bZow bubbles oz' lishC sparklers*' (171). Jmz~J.k however seems Co be less sure. He has said Chat he believes that peopXe hm~e stumbled on. the most e£££c£ent way to bring high concen~raClons o£ n~coc~ £uCo the brml.u (104). Re IIso ch~nks (105) that £t wouZd be • remarkable co£nc£denc~ /~ the ~ects o£ Ch£s powerful pharmacolo~c~l • Zent had noch/~K to do w~Ch the reasons for mmok4nK, but this does re~ai~ a poes~b£1i~y. IC is also amazlus chat ohm retn~orcinK properties of nicotine have not yet bean demonstrated unmqn4vocaZly. Authors di.cues~ mmkiq as an addiction tmually usa Chat smok~ns has • strou8 p~log£cal basis with n~coC4ne as the active • Kent. Some o£ the ev£dence for, and 8Keener, Ch£8 £8 rev£ewed in ¢hLe section. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-12- ~storlce.1 Tobacco see~s to have been used first by Jwnericmn Indians in the form of ciKars and in pipes. It is used in most societies in the world today. In some pr~u~tive societies other oral compulsive behaviour may predmninate such u bate1 nut charon8 or teeth clicklnB (160). In fact 8 umber of societies sen to use the betel nut is: a sd--41a: pux-pose co n£cotlne, and it "contains arecoline, a psychophaz:RcoLosica£1y active alkaloid. Russell points out that some form of elaborate non-nutritive hand-mouth activity associated with taking a stiamlatiz~ alkaloid has been part of the humRn bekuavlour repertoire for nearly 500 years (168). lqo population has been knowD to $ive up tobacco L~ter being introduced to it. The use of tobacco has survived various forms of official disfavour and penalties ranking from decapitation to uccmaanicatiou. Since ie was brousbt to Zurope in the 16~h Century, tobacco has been used £or chewin$, snug££nK and smok£ns. In 18tb Century Britain snt~£1n8 predated (171). C~Kerettes appear not to have been introduced into this country untll soldiers returned fro: the Crimean Waz (1854- 56). At first cigarette smokiuK gas • luxury confined to ~he upper classes but since that time it has spread to all social classes (115). Cilarette smokini has also tended to displace -11 other forms of tobacco use. The possible reasons for this are mentioned in section 2.&. The fact rJ~t tobacco mmklzt8 has continued in the £ane of so ma~y penalties and in recent years, health ~mrninKs and h~Kh taxation, is l~aken by itusstll to t=~dLcate that it produca8 • very stremK dependence (171). Jsrvik &leo mentions the fact that in Eu:ope in World Her IZ people would Ks to incredlble 1emErge to obtain ciKarettes, collect£nK e~um~ %O BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-13- butte from the gutter, resortlnS to prostitution and barterLnK meagre food supplies (104). The common factor in all forms of tobacco use is nicotine. Tobacco ingestion has never been vLdespread. Kussell believes that chls is because £nses~ion leads to metabolism o£ nicotine in the liver to form cotinine which is psy~opharmacologlcally inert. Tobacco is only used in rays allou,~aK nicotine to bypass .the llver a~d enter the brLin in its active £orm. This mens it mJst Senerally be absorbed throu~.h the buccal or nasal mucosa or in the lungs (171). Accordins to Jarvik, purely psycholoilcal theories og motivation £all to cake account of the use o£ tobacco 4n non-smoked forms such as snuff or chevlng tobacco. This is not entirely corcect, however, since these theories often meek only to explain cJ~cette smokLns as it is che most widespread £o~m of tobacco use at present, mad they do not consider the 8eneral came. e ~t should also be noted that herbal end other non-tobacco cigarettes and smokln8 mixtures for pipes, which contain no n£cotium, have never becoam ~dmly popular, although that have been available for many y~mrs. These non-tobacco blends, however ogten seem to have smoke which has a very unpIeuant taste and smell. Their lack of success in terms of sales :nay not be entirely accounted for by the absence of nlcotIJxe but this probably plays the da~Lnant role since even tobacco masks may be considered to be unpleasant by the novice mnoker. On balance the historical e~rLdence favours the interpretation that nicotine i8 of importance in tobacco use. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-14- Zvide~ce from F.xperiments Usluqi; ~im,,ls, Kussm11 often quotas the results of experIJnmnt• in which monkJys and rats learn to self-/~ject n~cotine, as e~dence for the /~portsmce of z~cotine as a dru8 of depend•nee. He has maid that mzL/Jnmls mast be either re~mrded vlth someth/~K pleasdmt or threatened with so•stALing u=pL•asant, bafore ~he7 can be t~a£ned to do anyth:[~g. Nonkey• •elf- inject nicotine for its oqm sake so it must be 4~¢z-~ssicall7 ~wazd~ni in some mty. The quality of actLn~ as s pt/matT, "unnatural', :eLu~orce: of behs~iou: is shazed with other dependence-producing drug• (171). The wRys in wh~c3~ the dependance potemtlal of druKs may be determined by an/aml expe=imentst£on are coy•red vez7 thoroushly in • recent World Kealth Orfju~sst£on publication (227). "Results o£ experJ~entj on animals are, however, not particularly easy to /~terpret. The study on self-lnjection of t~eotiut by monkeys which is most ~r~daly reftr:ad to, is that of Dmn~au m~d ~:oki (52). They used seven rhesus monkeys with /ndwell/~K catheta=s which ~ere connected to /~jecCors activated by • lever in the4= cases. The m~J~eys would press the lever out of cuz~osi~y and obt~n a dose of nlcot/J:e. ~f they did not self-admLulster the drug at • Kivon dose level, uicotlne was auc~stlcally injected once an hour for several weeks or unt41 self- administration started. I£ this was not sucessful the dose was raised. The authors mention that a raisin on the Imr was o£tan ~ee4e4 to ~nduce press/rig, so it appears that monkeys did not •1rays self-/niece nicotine readily. &t 25 ~q~/~4~ two mon~eys aalf-ad~Ln~stsrad spontaneously and the others did -Fte: two to ten days automatic injection. They ~ve=a~ed BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-15- £rom 0.7-1.7 mgfkg per day but the dosing patterns were very variable and sometimes changed by IOOZ on eonsecut£ve days. Days on which a large total dose yes taken were often £ollowed by reduced dosage the next day. Then, 8C one month £ntervals, she dose was raised (to $0, 100, 200, 500, 1000 and 2000 ug/kg per dose). Ac each dose the lever was pressed less £requenCly and ac 8 g£van dose the monkeys refused to self-admiz~scer nicotine. 0£ the six monkeys in this part of the experiment one refused at 50 ~g/kg, one •t 100, own at 500, one at 10OO and one still injected 7000 ug/ks aver•SlnS 9.6 mg/kK per day with • maximum of 14 u~/ka. The monkeys d~d not self-administer nicotine between midnight and eight a.m. (when the cages were in darkness). Jarvik has done m number o£ exper£mencs using monkeys Cra£ned co smoke (105). He maya, however, ChaC althouah they will smoke they don~t inhale. Honkeys trained co smoke cigarettes •1so show • hLgh day to day variac~on in 8~okiD~ ~ poor extL~ccion of r~e boh~r~our (104). Gl£ck, Jarvik and Nakmnura (76) persuaded :onkeys co puff smoke by makdng them take 30 puffs co get one drink of water. They then ~nsCed four rhesus monkeys ~ch drugs co see i~ cbJir smoke/air preference was altered. Smoke was usually pre£erred under noraal circumsr~ances. 14ecmayl~ne, which blocks peripheral and central actions of nicotine, depressed ~he smoke/air preference and produced • mll decrease in puffLu6. This may iud£caCe that smoke is avers£ve if not accompmLLod by rev&rdinS phTslolos£cal effsccs. KexasmChonlum, which blocks per£pheral actions of ~LcotLne, also reversed the smoke/air p=eference and decreased pu~£ rate, sulWeet£ng r~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-16- that peripheral actlous may act as an incentive. Pentobarbital, a Several sedative hypnotic, merely decreased pu~finK rave but did not reverse smoke/air preference. Nicot4~e tartrate in dri~k£n~ water could lover 8moke/a£r preference if a suitable dose level was chosen. These experiments have been covered in some dotaLZ as they serve to illustrate several points. F~stly monkeys do not leiL-n to smoke easily and do not smoke in the sa~e way as humans, Smok~ behav£our is vet7 vsrlable, as is sel£-injectlou when it is induced. Js~Tik has pointed out (IOA) thac this indicates that monkeys do not have a fine degree o£ control for n£cotlne. £nimals will, however, resulate the intake of addicti~ druKs such as opiates, alcohol, cocaine and mnphotamlne and keep the dose :ore or less constane once dependence is established. H~tch£~son and Emley (97) have stated that the d££ficulty in induc~nK s£&~L££cant tobacco or ~cotine usa6e in anlmals may be 4us to incomplete co~slderatlon of the dual ~scure of the reinforcement p:ocess. There are c~o classes of reinforcers: positive reinforcers which senerally involve /~take of, or contact with, substances which are =ntritive or essential £or life or health or ~Latc such agents; the other class cause reduction of noxiousness, avarslveness, pain, irritation or stress. Their results 8usgeet that nicotine sez~es to reduce reactions and a££ects caused by noxious aSents and it is not there£ore surpr£sinS that animal expsr/mants, in which stress £s m4ntmal, do not lemd to SiSZL~flCant tobacco usage. Yhe~e are savor81 points wh£ch should be considered in e~n~tction with the experiments on m~4~als. As with a human population it seems llkely r, hat indiv£dual monkeys prohably d££fer in their reactions to BAT Co LTD - MINNESOTA TOBACCO LITIGATION c~

-17- drugs ~ in their propl~i~y go~ se~-I~niitr•¢ion. ~hu,e .o~peri~nt• • sin•.11 n~er of monkeys may not be z'epresentat£ve of 'le.rser sRmp%eSo ~n the Den•an end ~nokl study, d£f£eremces beer•an indivldul8 a:e seen in the ~ nicotine doses that were tolerated. The monkey /nject~ £cse1£ w~ch 2000 t~/k~ dose• was Caking very Large amounts of nicotine, £•r more than the equivalent dosage taken dur£n8 swokins by human subjects. ¢c is also interesting Chat: monkeys cra£ned r.o puJE£ 8moke show e~£ects due to nicot£ne in their drinkinK ~uater. One would expect Chat nicot/.tun ingested in ~his way would have little eJ~£ect since it Would be metebolised in the liver. Considerable caution must almays be applied when results on animals ere extrapolated Co humans but there is ~ indication Chat nlcotine does provide some sort og "¢everd" ¢o monkeys. The posiclon, especially with regard to comparisons w~h dalHnxla~ce produciJ~i druss is not. however, as clear-cut as lussell su4~emts. 2.3 Evidence =ro~ E xpe=~ts on Humans: The E~£ects of Nicotine and o£ Changed Deliver7 o£ Smoke Constituents on Smokins Behaviour As Jerv'J~ has stated: "To prove that: n£cotine is the essential inKredienc in cigarettes it i8 necessary to show I:ha1: cigarettes £rom vhlch nlcocine has been rmnoved are not crooked and. conversely, that n~cotiwe alone can substitute for el•metes" (105). This has been extremely di££1cult to prove in practice. The £irst study published on the e£fects o~ n.'lLco¢:lLum ~t smoking seems to be that o£ Johnston in 19~2 (109). Re ~a~e intrmnous nicotine to smokers and non-smokers. The smokers thouKht that it was pleasent and were disincl£ned ¢o smoke £o: som~ ¢~ne a~ter ~he inject:ion if the BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢,...m,

-18- dose was adeqtmte. Non-smokers termed the sensation after injection "queer". This study lacked r~nCrols and no girm c~nclusim can be drawn fr~ it, but it prompted F~anejan, L~rson and HaaK, in 1945, to izr~estigate further (62). They obtained some low nicotine tobacco and, by 8ddlng u~cot£ne to sa~e of it, made up cigarettes dellverlnK O,3~ mK and 1.96 mK n£cot£ne per cijaretce. Their subjects were 24 mnokers who first kept records of nmnbers smoked lot their own brand, Chert the hiJ~h u~cocine ciKarettes (about two weeks), then the low nlcotine ciKarettes (about one month). The differences in the numbers smoked were small and some subjects were not concerned by the lack of ~4cot/Jae in the low delivez~y c£Karette8. Nine subjects, however, ~4ssed the ~Lcotine, and did not adapt, but they accepted the lov nicotine eiKarettss as better than norJ:Lu8. This e~per~Jnent showe~ that nicotlx~t may be o£ mportance for some mnokars but not for others. SurprisinKly the holt study which is ~u~orr~nt in th~s area ~s not publlshed until 1967 (133). This is the work of Lucchesi, Schuster and ~nley, who remlised the importunes of dolnK an expari~emt in which the subjects were unavare of the purpose of the tests. They ~arried out 8~-hour pqcholoiical tests on subjects who were fitted ~th an tnCra~Inou8 drip deliveri3z8 either SL~JJae o= nicotine (iJx doses ~Hlich produced no subject£ve e~£ect in ~be subjects used). The subjects were allem~d to moke d~£nK the tests If they v~mhed to, and the mmaber of c£sarettas smoked were recorded and the butts were collected. Subjects were infused vith 4 u~ u£cotine per bout as rJais was squtvalmat to the averaKe smokin8 dose at • rate of one to turn ctSarattes per hour. Four imbje~te ~Lven 2m$ n~eot~e in the first hour. than & ~ per hour for five hours BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-19- (tot&1 22 ms) :bowed • seal1 decreue (aver•is 2.7 c£sarettes) /n the nmmbe: smoke4 and • decrease in the amount of each ciKa:ette consumed, when compared with the sal/ne control. Bit•flee was also 4~fused in • way more closely resembl~ am•k/as. The eucpe:4mm~ters /nfumed 1 mB nicotine in 14 minutes at intervals of 32 miuutee (total 8 ms in mix hours) and fro.rod • s48~Lficant decrease in nmabe: of C~fJL:etteS smoked £o= three of £ou= subjects. One subject showed the memo decz~mse £oT 8 lJ periodic •de/hie•ration and 12 mK continuous admln~etrat/~m (over 84~ hours). The couclus£on siren in thls peps: is that u~cot~e plays • small but sLKnif4csnt role /:~ 8mokL~ and that putt of the ctav/~s £or cleAts•tee ie sail•fled by intravenous nlcotine. In fact, 4£ the subjects had been smokLus for nicotine on/y and intravenous nicotine had been • pod substitute, they couXd have reduced rJheir qisarette msol~Ln~ to :at•. This is an example of u~l~t Jarv~k tills "the ~portant role played by secondary condlt4ou~ and functional autonomy in the maintenance, o~ the smoklnS habit" (105). He believes Chat, in very much looser term studies, the hab£t of smo]~ns umuld be e:t/:q~u~sbed in the p=osence o~ :~Lcot:Lne from other sources or 4n the compZete ahsonce of ~coc~. Hucchbon and F~zley (97) mKree with this and s•y that since st~Jnuli previously associated with power£ul reinforcers me• known Co sustain :asput se~ces for lonS periods tndepemdent o£ primary re~n~or~mment, abort- term tests cannot be •:petted Co show much e~£ect. The study b~ L~cchaei .o et •~. £s vs:~ o~tem quoted b7 R~80•11 am co~l~84ve s~i~ that u~cocine is ch~ ptd.~, rein£orcer t: c~s~recte amoklns, but as with the other studies he mentions, the pos4tio~ is ~ot ~C£~ely cIeaz-cuc. BAT Co LTD - lVlINNFSOTA TOBACCO LITIC;AT1ON O%

-20- In subsequent studies the technique of butt anJlysis has often been employed to indicate the ~motmt of nicotine taken from a cigarette. ~t should be remembered that results of this technique can only give estLmaCes of the a~otnat of n£cot£ne which a subject has obtained. Inaccurac£es will be 8fastest when mll n~mbers of butts are analysed, unless subjects act as their own controls. The amotmt of nicotine taken , from a cisarette also sires no ingormatiou about the amount which remains . in the body to Kive m phaxamcoloKical effect, as this varies with the depth of inhalation. This, of course, will apply to all mathods of est£mation o£ nicotine delivery, 4-cludln$ pd£ duplication. A number of authors have tried to determine the import~nce of nicotine, by using cisarettes of di£ferent deliveries. One very well- known study is that o£ Asb~ou and Watson (13). In their exper£ments : drivins simulator task was used, and 36 subjects smoked either b£sh nicotine (2.1 m8) or low n£cotine (1.O ~) CiEarettes. It was fo,md that subjects took mote p,,f£s on the lower nicot£ne cigarette and obtained almost the same amount o£ nicotine (as dete~ned by butt at~Iysis), as did subjects mnok~ng tho b~gh n£cotlne cigarette. In fact slightly more n~cotLne was ~sken From the low delivery cigarette by the subjects tha~ by machine smok£nS, and slightly less £ro~ the high nicotine c~Karette. The authors susKested that the subjects were unconsciously modi£yins their smok4nS pattetz~ to obtain an opt/mum dose of nicotine for a ~van activity. This is shown by the fact that wre nicotine was taken par unit t~sa duz~as rest than duriq tasks mad slishtly more nicotiJaa va.s taken duties the more stressful task tbma the BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~

-21- less stressful one. The effects demonstrated are, however, 8:a11, end it seems possible that the results may have been conslder•bly di££erent if other ~ypes of ¢iKJrette had been chosen. The h£eh nicotine ciKarette was probably hiKher in n~cotlne than the subjects were accustomed to, and the low nlcot£ne c£8erecce was not particularly low in nicotine. This seems Co be, however, the first real demonstration thmt subjects would nor necessarily take the maximum available amount of nicotine from • hish nicotine ciKarette, but prefer to cake less. Frith (71) found chat subjects Kiven c£jarettes with three different nicotine deliveries, took longer to smoke higher nicotine cigarettes, and that they smoked £ever of them in an eiKht-hour period, aKui (2) did an e-,cper4menc usin8 a lettuce ciKareCca control and three tobacco cisarectes ~th different nicoclne deliveries. Re £ouBd that smokers whose normal consumption was above ten c£jarectes pc= day d~sLiked the lettuce c£jarette most, but l£shC smokers disliked the h£8h nlcoCine c£sarette most. He also found chat d~f£erences in nicotine content of c4gmrettes were related co differences in puff £requency and puff t4me. Turner, Sillett and Ball (209) conducted an experiment durinS wh/ch subjects smoked a medium delivery cijarette (1.4 mK nicotine) for • meek, than • lov delivery c£Karette (0.8 mK nicotine) for a further week, and • very low delivaz7 ciKarette (<0.3 mK nicotine) for the last week. They found that there was • sisni£1cant in~rkase in the nmsber of ciltrectes smoked when subjects chmn6ed frma mmdlum to low delivery, but no differmnce in numbers of low and very low nicotine ciKarsttes smoked. They d4d find, however, that the very low nicotine ciKerettes were smoked to a shorter butt lensCh. The ratio of observed BAT Co LTD - MINNESOTA TOBACCO LITIGATION OO

-22- (butt) to expected (machine) filter nicotine indicated that subjects took less n£cotine from medium and low deZivez7 cigarettes than expecteS, but more from the very lc~ nicotine c£sarette. In fact subjects took an averase of O. 89 mg n/cot~e from the medium dal£vez7 "cisarette. This may be consldermd to be a rather surprisinEly low figure which may suggest that thase subjects were not typical of the majority of U.K. smokers. As Russell has pointed out (172), one in three of e11 ca&ereCts smokers £n Britain smoke Embassy Pilfer or Players Ho. 6 Filter (delivery about 1.3 q nicotine), about 751 of smokers smoke u~dium nicotine cigarettes and only about 12Z smoke cigarettes deliver£ng less than 1.0 ms nicotine (from figures published in 1975). There is little evidence, however, on the nicotine deliveries chac the majority of smokers obtain from Chair cigarettes. Six of the 13 subjects used by Turner et el. did, however, report thac the medium cigarette was too strong. It was shown, therefore, that the subjects made some attempt to chansa their smoking patterns to compensate for reduced nicotine delivery, and that the number smoked par day was also changed, to s ssmll extent. One of the longest term experiments thac has been conducted is that of Freedman and Fletcher (69). They used 200 male subjects in two Kroups. Group Z smoked a cisLretce concein£ns 30Z WSM (1.01 ms nlcoClne) for nine months and the control cigarette (1.39 mE nicotine) for 12 months. Group ZI smoked the control first. There vgs no change, on average, in numbers smoked per day for either group when they switched from one c4jantte to another. Butt analysis was conducted for 35 subjects foe some months ouly. althou6h it is not clear £rmn the paper why all the results were not available for 811 subjects who saved butts BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~

-23- (40 subjects) and all months. The results quoted from butt aaxLlysls show that Group Z subjects took an average of 1.03 sag nlcotine from the NSM c£garmcte and 1.Z2 mg from the control. The f£Eure for the control is an avarase for 11 subjects who took close to the expected amount of n£cotine and six subjects who must have altered the way /n wh£ch they smoked after nine months on the lcnmlr n~cot£ne NSM cisareCte end avermzed only O.g ms n£cotine £rom the control. Group IT took an averase of 1.4 mS ~cotine from the control mud 1.O8 mS nicotine from she NSM cigarette. These figures a~e v~r7 close to those obtained by standard machine amok£uK and ind£cace chaC bosh c£sareCtes vere smoked in a s/hurler way, ~ch no compenmaC£on for chauKed delivery. There£oce it can be seen thac most subjects d£d not chmnge the numbers o£ cilaretces smoked or the wmy they wre smoked when n~coclne 4el£very was changed by 27Z. A £ew subjects however adapted pertly to the lower delivery ctlarmcte end ma4ntm4nmd lower n/coitus intakes when Chmy switched to the higher nicotine controZ. Hammond and Ga~inkel (88) conducted • survey on 98,622 male c£KareCte smokers (sled ~O-6g years) and compared the number end type o£ cLsarecte8 ehey wre 8mokin8 in 1959/60 u~ch those in 1961/62. 83Z of the man had not changed in terms of clse nicotine del£Terias of cam c£lmCtes rJsmy mmok~lo lZ had cluu~ed fraB ciKermttes de]Livar~K 1og-2.7 ms ~coCina co Chose deltver~ O.A-1.1 mS. Of ~ gg6 men shm~ tills l~rse decrease, 65.1Z sa£d there had been no clumse in mmber o£ c~8~ectes smoked, 16.3Z had dmcrma~ad coasu~pC~ou and 18.GX had ~cru~ed £C. Of the g.$~ who had ~ed co cila:ecCms of l~Sber delivery almost the sma~ oxmber ~cremsed coumazption Is decrease6. These results. Cbere£ore, for t ZL~Se mmber of men, ahoy no evidence for compensation £or thanked BAT Co LTD - MINNESOTA TOBACCO LITIGATION ',,o r,,o

-24- delivery in terms of numbers smoked per day. Xt must be ra~mmbered, however, that sel£-reporc data are noc always accurate end chae smok£ng patterns may have thawed. Z¢ is also probable that only those who could tolerate a reduced n£cotLne delivery wLthouc Breathy increaslnS numbers of c£garecces smoked would ewCcch co m lower nicoclne brand. Gu£Llerm and his colleagues also have some evidence that smokers tend ¢o cake more smoke £¢om m lower nicotine cisaratte (86). They compared the e£feccs of smokLuZ Gauloise (1.7 mE nicotine) and Gallia (0.7 ms nicotine) and found siln£ficanCly h£gher blood carboxyhammoslobin ~(COHb) levels e£ter smok£ns the Lower nicotine cisareCCe. Th£s was surpr£sin8 s£nce this cisareCCe'deZ£vers less carbon monoxide ~hen smoked by mach£ne. The increase in number o£ lower nicotine ciBarecCes smoked (6Z) was £nsufflcienc co explain the increase in COHb and the authors sussesced chac some subjects had taken larger puff volumes mud Inhaled more deeply. There are two studies conducted vichin the tobacco £nduscry wh£ch can be manc£oned here. In m recent study in Croup R. & D. Centre (50) subjects smoked a control clsarette excluslvely £or four weeks (1.4 ms n£coClne). Ra1~ the subjects then sw£tched Co a hlsher n£coClne (1.8 mS) and hm1£ co a lower aicoc£ne (l.O ms) c£garmCce £or four weeks. ALL subjects smoked the control cizarette for the last £our yanks of the experiment. Results £or the numbers of clza~ttas smoked ace somewl~z¢ d4f£icuLt to intez~pcec due ¢o the way in wh£ch the cLsarecces wire issued, hsu2Cs of bucc a~lysis and duplication o£ some of the smok£nE patterns may be taken to £ndicace chat subjects obtained sim41ar amounts o£ nicotine frum Cha h~sh n£cotine end control c£sarattes, buc rather less from the lc~er u£cotine c48aracta. C~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-25- The average delivery achieved ~ts 2 mg nicotine, l~eliverles taken from each cigarette were higher than machine-smoked deliveries. Subjects also appeared co adjust to the ch~aKel in c4Sarsccas very soon mfter they started to smoke thmm. Creighton (49) has reviewed some of the evidence for compensation for changed delivery including work from I.T.L. Montreal and Group E. & D. Centre, Southmmpton. He concludes Chat "many established s~okers do compensate for chaneed delivery in an attempt to equalise nicotine delivery, when this is possible." Adams of TJnper4al Tobacco Limited (1) has ecudled three separate panels of 16 heavy and 16 lisht smokers of each sex and one panel of 15 males and 13 females. Only one panel was of persons closely associated with the tobacco industry. Eight cigarette types were used giving a range of Car and nicotine delivery and of pressure drop. Eight Eroups of subjects each smoked different tTpes of ctgmttes in six, f~ek periods. As in oh8 study by Creishton it is not poss4ble to interpret results for numbers of cig~etta8 gmoked since some abuses of the system of £ssuiu6 cigarettes were observed. Results for changes in nicotine dellvsry ~nd£cated no chE~es for t3ro panels mad a 8mall in~reua in total puff volume for an increase 4. nicotine delivery £o~ the other panels. This 4s aSainat the hypothesis Chat comp~etlon co constant ntcotLne delivery occurs. If nicotine and tar deliveries of m cigarette were reduced simultaneously smokers increased the volume of smoke taken. Butt analysis results indicated chat an average of 0.9 m8 nicotine was obtained £rom the rm~je of c4g~rettas. A SLued7 by Warbu, rt~ ~ hJ~8 (218) On the e~ftc~ of ~k~a~ on v~£2ance task performance has yielded some results indicating chac BAT Co LTD - MINNESOTA TOBACCO LITIGATION c.~

-26- 8ub~ects in e:cperlamnts smoke 8o as to £ncreue the nicotine de1£very of low n£cocLne c£Karecces. Rmsulcs of butt anelys£s for a smzple of heavy and 14zht rankers show chat subjects g£ven cigarettes of 0.3 m8 and O. 7 ms nicoClue de1£very may obtain an average of up to 0.68 ms and 1.5 ms nicotine respectlvely. This my not, however be applicable to normaX ~ok£n$ comiitions since subjects also exceeded machine-smoked n£cot/~e deliveries for a hish nicotine clearette (1.7 me) and wmre muokinS during a los~ test which may have cmumed bormdc~ in some subjects and stress £n others. Sch=chtez and his colleaB~es have also studied smokin~ behaviou: US~ madLum (1.3 mS) and Lov (0.3 mS) ,,~;cotiJ~e cigarettes (186). Seven heavy smokers (over 20 c£SarecCes per day, mok~8 the same number each day and flndin$ it dlff£cult to stop smoking) and f4ve l£ghc smokers (under 15 c~i~rettel per d~y, numbers of ciKaretCes 8rooked varyinK widely accordins to circumstances and f£nd£n8 it easy to stop smok/ag) were used. Unfortunately the only index of 8mok/~g behaviour used was number of c£Ka:ecces smoked per day. bsults Lndicaced that heaeTy 8rankers smoked more 1or than medium n£cotine ciKaretce-, even ChouKh the 1or dmXivery c£garettes were disliked. The average increase was 2SZ. L~ht smokers, however, d£d not alter the numbers 8rooked. Further mxpe~-lmsnts in ekts aeries (187, 188, 189, 196) concerned the e£fects of chmnEinS uz'iumz'y pH on cigarette consumption. The propo:Cion of un,~ed ~coClna excreted in the urine ~s sa4d CO be 35I i£ urine is acid, 7I ~f it is neut=al and less ~han 1: if it is 81kal/~e. Schachter states the the proporticm of n:l.coClne rlmain/.n8 41= the body, to Kive an effect; which Uh8 smoker may desire, rill therefore be lowest when the urine pW te low. It was found BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-27- that urine pH could be manipulated by $ivins vitamin C or Acidulin tablets (which form hydrochloric acid in the stomach) by mouth. This caused small buc slS~£icanc decreases in urine pH and iacreesms £n number of cigarettes smoked. Cilazecte coum~tlon was m~so increusd by stress and 8o£n8 to parties. ~oth of these conditions caused a drop in urine pH. If urine yes ualntaiued at neutral or alkallne pH, however, the expected increase in smokluK d~d DeC occur in a stzess£ul situmcion. Xt was also found chat all smokers smoked more in the morning when blood nicotine Zevels are low after the niKht's abstinence. Schachcer concludes that his results indicate that smokers smoke for nicotine but that liKht smokers have "tiKhc co~tive control" of their ciKarette cousumptLon. He also sussests that the urinary pH mechanism is the mediator for the s cress--smoklns relaclon. Un£orCunacely the conclusions of Chess stud£es by Schmchcer mumc be questioned, especially /~ relat£on to the use o£ ciKa=ette consumption as the win iudex of the chause £u smok~ behav£our. Differences tn urinary pH and ciKarette consumptlou are mi~£icant but teed. to bm rather a~al1. Zc seams Chac urinary pH may rill have an effect on smoking behavlouz but the relevance of this is not ties= if most smvke=s are smoking (as has been sugKested by Kussell (173) add ~y others) for the im0mdiate effects of nicotine which would be m~affected by the rate o£ nicotine excretion. Several authors have used yec another way of ehan~£nS the delivery o£ c£sareCte8. This entails either mmrk/:~ cigarettes or curtius them, so Chat only a fLzed proportion of the c£Ssrette is smoked. Jarvlk was the £1rst to use this approach and his work on full- and belf-leusth BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-28- cijarettes is co~idered tovards the end of thls sect£on. Stepuey (198) has studied 14 subjects 8mok~nK their own brands of cisarette to full lenK~h or Cuo-th£rds lenKth (as indicated by a mark on the ciKarettes). CiKazettes were smoked both inside and outside the laboratory. When observed ~n the labor&torT, most subjects were seen to take 1onSet puffs or more frequent puffs from the "shorter" eiKarette. Butt analysis indicated that subjects J~oked the ciKarettes to obtain more nicot£ne vhen they were in the 18b~atory than durlnK the rest o£ the dayo Some subjects smoked the "shorter" ciKarette so as to obr~a~n more than the expected nlooc~e delivery (calculated on the basis of the chanKe in tobacco rod lenKth). Deliverles from this ciKazette were between 66 and 95Z of those obtained from the full-len~h c£jarette and blood nicotine levels indicated that on averaKe 71.7X of the full ciKarette dose yes obta£ned from the t~m-third8 ciKsrette. There therefore seems to be some £ud£catiou tkaC subjects smoked to obtmin ~cot£ne £~om m shorter ciSarette but the ef£ect is a fairly small one. It is also interestlnS that in this study subjects took, on evera4e, only 66-89X o£ the nicotine del£vez7 obtained by standard machine mmk/ng. Ft=Lally in this section the work of R~ssell mad of Jar~Lk must be mantion~d. Russell has done experiments ustnS cis~rettes of dif£ereut deliveries and usins nicotine chewtnrS~m. ~n one emperimmac Kusmell and his colleasues looked at plasma nicotine (181) and carbozyhsamoslobin levels (180) after ten subjects rooked their own brand, mad h~h and low nicotine ciKaztttts. On the ~e two drays of two weeks gub~ects 8moked rJ~ir own brand in the Dorn~. For five bouts in the afternoon, on days one and three they msoked their own brand an4 on days .two and ~ouro hiKh or low n£cotine ciKarettes (Capstan Full $tranKth, 3.2 m~ ~4cot4~e, BAT Co LTD - MINNESOTA TOBACCO LITIGATION c~

-29- end Silk Cut Zxtra PL~ld, 0.14 ms nicotine). Each smoker was cone~scent from day to day in terms of mid-morning blood ~cotine level and th~S was unrelated to number of cigarettes smoked prev£ousLy. When subjects chansed to the high n~cotine cigarette there was a significant decrease of 381 in ntmber smoked in five hou=s and plasma w4cotint levels ~ere similar to those for their usual brand. When they smoked lo~ u£cotium cigarettes there was no significant increase in number smoked and plasma nicotine levels were lower than under other conditions. Carbo~yham~oglobin levels were hover £or both high and low n~cot/zw clgarettes than £or the subjects' usua~ brand. This study shows that subjects can regulate their cigarette consumption and amokinK patterns to obtain their usual blood Levels of nicotine from a high nicotine clgarette. When given the low delivery c~armtce, however, they were uzlable to obtain h4gh blood nicotine levels and all subjects rated these c4garettes very un~mvourably. It may be siL~L~f£cmnt that they nevertheless smoked more low nicotine than high n£cotin~ cigarmttes althouSh the Latter ~mre rated only modmrately 0% BAT Co LTD - MINNESO__TA TOBAC_CQ.LITIG_ATION

-30- Kussell and his coZleaKues have £nyesCiKated the effect of nicotine che~K-Kum as an a£d co smoking wlthdraval. They found (176) Chat • 4 mS n~cot£ne gum could SiTe blood levels approachi~ Chose o£ smoking, buC it had a number of undeslrable side effects and a 2 ms gun was used for initial experJJnenCs (179). This gum releases u'4coCina over 20-~O minutes at a race daCtrm~d by the vigour of chmwlq, m~d the nicotine is absorbed thzoueh Zhe buccal unseosa. 43 subjects who wished co stop smokes we=e asked to smoke and they ~ (~Lcocine &nan ~c placebo £o~ two days each) re= a week. They were then asked Co chew the Kum and try Co stop mnok£ng for C~o weeks. The Sum was chmwed for 20 m£nuCes at the race of one piece per hoim~ for saves hours mud thezl one piece mY•z7 two % hou:s for six hours. The co~cribuCion of ~coClne in the sum co the outcome of treatment was said, £n the conclusions to the paper, to be 7Z o£ the total reduction in c£$aracte consumption and LSZ of the reduction in blood carboxykemmoglob/n. From the rtaults section of cbo paper, houmver the £ieuzes appear to be nearer 6: and 11:. It seems likely chat cha decrease in sS~r Of ctg~LTtttSS Bked may be due /~ pmzt to the length of time spent phTsically chawia~j the 8urn. Kussall eC el. Jay chaC Chair f~MSs show • clea:, though modest /~h£bitory e££ecC o£ nLcoC£we on smokJ~s (when subjects smoked at ~ill durin8 the £izet week). They eul~esC Chat the 2 mS sum may not contain en~J~h nicotine to induce • lazier ef£ecc, since it produces blood nlcoCine levels which aze less chart tm~f Chose see= deer smoking. The results for blood nicotine levels show r~at they a~a the emma for smokLnK only or smok£u~ + u£eot£nt gum, so chanass in smoking patten must have occurred co keep • emcant ~4cotine level. However blood n/cotlne was BAT Co LTD - MINNESOTA TOBACCO LITIGATION ©

-31- q hLi~bar for smok£uK only than for smolc£n8 ÷ placebo gum, £nd£cac~nS no reK~Latiou, and ~t is suKeesced that relpzIation dotage:de may be becter than compensat4on upwa=ds. Th£s is a conclusion which seems to be fairly g~eral from ohm work on the role of nicoCine in cigarette smoking. The teaseD• for the z~lacive~y meal1 e£fecC of ~icotiue are not adequately discussed in this paper. Brant~a=k, Ohliu and 9esclin~ (29) for £nsCance, reported over 50Z lover cigar•tee consumption ~hmu uicoe£ne chevinS-Kum yes compm:ed So • placebo. Th£s was, however, • 4 ms nlcoCine Sum sad subjects were C~ Co sCop smoktuS. Jotmstou (110) has co~mnced thac chew~nS-eum would not be expected to h~ve much e~fect a: ohm e~£ects o£ ulcot~:e obtained by buccal absorption my be di££erent ~rom clear•tee smokieS. This ~11 be discussed iu a later section. T~ a more recent study, RusseT1 and his colleagues have investigated blood nicotine after chewink am /zproved Tersion o£ the 4 ms n£coc£nm sum (L78). Sub~ecCs smoked ~ocmally on one d~7 and blood was oaken ewe m~nuces afcer• c4$~cecce (peak level) and 25 ~4nuces aft•: a cigarette (cz~ush level). On another dmy subjects che~d one piece of 4 ms e4coCtne K~m eve:7 ho~r, chew~a~ £o= 30 m~uCes. ~lood ~8 ~al~u be£ore • (Crouch level) and 25 m~nuces aloe: 8CazC~nS a sum (peak level). bsulcs shoved Chat, on mr•st, there ~as no d~£erence between chmrLu~ sum and 8moki~g £oc ei~her peak or crough plasma nicotine leveIs. Some subjects, ho~eve:, achieved blood ~Lcot~ne lmls ~h4ch were ewe o: ch=ee C/rams h4sher a~er the Sum than a~cmr mmok4n~. Zn ccmclus40u ic was seated that, slthoul0s the chewix~-&~m produced au~tci~c ~4cot£ne co subsc£Cuce fo~ ~wk~aj. ~t was noc clem: ~ha~her the n~coti~e contributes Co ~he cmpac£cy o£ the I~m :o smt4s~y m deprived smoker or reduce his sense of m~ss~s ciKa=eCces. Yev subjects d~d noc f~nd the Sum unpZeuanC BAT Co LTD - MINNESOTA TOBACCO LITIGATION ,8 ~o

-32- but all buc £our obtained some satisfaction from it. This ~as not, however, related to the plasma nicotine concentrations achieved and may have been due to peycholoKical factors. Prel~nary resulcs have been given by lussell (173, 40) for an experiment usins intravenous nicotine. The procedure used was very 8J~Lilar to that o£ Lucchesi, Schuster and ~IeT (133) but ~cotine was adnLin~stmrmd co mimic cigarette smoking vAtb ten rapid, 100 ~S n/coclnm pulses delivered at the rate-of one per minute. The e£fect on gmoki~ was said to be uL~n/~al end some subjects even eked while nicotine was being adminLstered. Russell has stated that the analysis is incomplete buc the results seem co seriously challense the role of nicotine as the main reinforcer of smokinK. Another very recent study by Russell was deelped to Lnvestlsate the e££scts of cuttins subjects' owu cigarettes to three-q~artars- and ha~£-length (175). Prel/~nary results 0£ butt analysis £or this study show that subjects, on average, smoked the £u11- and three-q,,=rter-lenKCh ciKarettee in a similar way, taklnK sliKhtly less than the machine- smoked delivery o£ nicoclne £or each ciKare~te. There was soma attmnpt to increase the delivery of the half-leneth ciKarstte, but the averase £igures suSKest that only 67% o£ the nicotine delivery obtained from the full ciKarette was taken. Thus subjects ware either not interested in increas£nK thaLr nicotine intake to maintain In equal dose or ware unable to do so when JiVeD a half-length ciprette. Jarvlk has done a large number of experiments to try ~ad elucidate th~ role of nicotine in ciearatte smoking, workin~ with a ntmber of different collea~ues, r~slowskl, Jarv~k and Gritz (119) looked at the e£fect of "preloading" subjects with n~cotlne, on subsequent smoking. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-33- The subjects who we=e unavare of the purpose of the experimeuc were deprived from smoking dur/~8 a tuk, Chert Slven 0 el, I m8 or & ms nicotine ~m. They vere chert 8ivan hish (1.3 ms) nicotine, low (0.3 ms) uicoCJ~e or zero tL~COCiUe (lettuce le8~) cijarettee Co smoke. After this time the7 could smoke as the7 ~ehed. H~Kh n~eotine prelomds were follo~ed by lees amok~n8 chart lore nlcotine prelomds. Nicotine in m ciKarette 88 the preloed affected the latency to the next ¢~K~rette but not the ember o£ puffs taken from this cisarette. Nicotine preloede in Sum did noc delay the nmc'c cislctt.Ce but decrused t/m time spent puffing on ic. This suuescs tbac ~coci~e is play~ an iaporcauc role buc Chat nlcoclue ~u cisareCtes and in chevi~S-zum has di£fereuc e~feccs on mBokins behaviour. Jarvlk, Gllck mud Nmkamura (106) save 17 smokers five capsules per day - each conCalninS lO ms nicoclne or a placebo. The oral nicotine induced a ell (8Z) but si~ficmst decrease in uumber of cigarettes smoked. IC did uoc affect subjective e~t4~-ces of "screnKch" and "quality" of cisarettas. The subjects who showed the l~rsest chmuees due Co oral uicoc4~e were Chose who hebitully smoked to the shortest butt le=ZCbs. &SaWn uicotine is seen co be ba~iu8 an ~f£ecC, buc oul~ a sm~11 one. Goldfa~b, Jarvik and Glick (80) also looked at the effects of lettuce lam~ ctS~rettes ~Ch mud ~itbout added n~cot4ne (0, 1.26, 2.2.5 ms nicotine), lath type of c~s~retCe was ~moked £or one week b7 15 subjects. K11 the cisa~et~ee ~m~e mrstve co rim subjects mud, J~sdape~demt o£ ~Lcot~ cO~tam~, lees of r.hmm ma~a m.'.kmd the subjects' o~ brand. De.epiCs this the msbjects co~t4m~d to smoke a fs~rly lmrse n~mb~r o~ rJ~ latl~ce lea~ c~$8:etCes eve~ :L£ they coucaJ~d no added ~¢ot~u. This could mean Chat z~cotlue is not BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-34- important, or that the subject coutlnues to smoke in the hope o£ obta£nluK the nicotlue he des£res. Ooldfarb and Jarvlk (79) then looked at the effect on 18 subjects of either cuttini cigarettes in half or only a11ov£n~ smoking down to a red llne half ray aLouK the length o£ the ciKarette. Subjects speut a week smoking their us,,-I brand (vhole) theu a week of each of the cut and marked cigarettes (also Chair usual brand), followed by e final week on Che£r normal ciKereCtms mKJ£u. The subjmcCe did u~t llke the shorter cizarette8 but there mere no si~.ficmut differences between weeks, for number smoked or rmt£nSm of "etr~th" or "quality". Host subjects ~herefore reduced chair tobacco consumption by almost half. This result is difficult to reconcile with the proposed importance of nicotine and requirement for optimum levels. &lthoush it is a possibility Chat alterations in s~oklng patterns were made, theme mere unlikely to lead to gull compensation for reduced nicotine intake. One point, however, ks that in the paper there is an 4,mplicatlon t/~at at least some of the subjects mere pleased to have bean able to cut Chelr tobacco consumption and the results am7 not be applicable to anothe= Stoup of smokers. In a more recent ezperiaent, Gricz, Bear-Weiss and 3srvik (84) have studied a fu=Cher 12 smoke:s. The cisaretCes used were the subject's ova bra~d and mere stands:d, full-lensth tilL:acres; "prosimal" ciiarettas, cut to one-half lemKth; o~ "distal" cismrettes, urir.md md.th a red line half-w~V dam. The number of ciKarette8 8~ven vae the am number the subject usually smoked. Subjects abstained from smoking for the first day and then on alternate days. Ou each "8mmkiul" day they were K~n 8 dlfferent ciia~ette L"ype. Subjective evaluations of r~LSazette "screnKth" and "sStiSfsLctiOn" wrt positively related to the mount of ~4cotint obtained from each citrates type. A compeisou of "expected" ~cottne BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-35- (eat/mated ~cot~t presented to the Joker) -rod "exit•octal" nicotine (actual n£cot£ns recovered in the urine) was made. This shovl'd that subjects extracted proporClo~uately more nicot£ne from ~he half-lenBth ciBazettes ~ham f~om the ~bole ciSaretCes. Fi&~l:es for "extract•dee • ,;cotine ind£cate, however, that subjects d£4 not take the same amount of n£cot/~e from the shorter ¢~arettes •s £tcm the whole ¢~Kerettes. Subjects extracted 87= of ~ whole-elK•reSts ~coc4~e dellve~-y from the "ptox~ml" tiE,teStes and 62Z from the "d£mt•Z" clEar•teem. Scolex~a~, Gol&farb, Fi~k and Jar~Lk (200) have ~avestis•ted the effect o£ two drugs on clWecte consumpticm, NecmmylamL~ne 4s • drug vh£ch blocks the central actions of nlcotine and It caused an increase in the number of cigarettes s~0~ed and number of puJ~fe taken. The increase in ntmber was 30Z but this is cmly over a period of two hours. IC is thouEhC that smok~ l~-~eas~ as subjects r~ried to overcome the blockiz~ e£fec¢. Petroleum, • drug £nhlblt~ per£pheral actions o£ ~cot/ne, had very l£ttle effect ou cigarette consumption m~l number of puffs talmn. ~he ~uthots ¢o~clu~e chat ¢hLs study supports the b~poU~es~s that the demised effect~ of ~4¢ot~e awe an the central ~e~ou~ system. They say Chat ~here ~s m mall but: clearly demonstrable role for n£cot/~e as a primary reinforcer of the msokLug habit. Goldfacb, G~tz, Jm_-"v~k amd Scole~mm (78) have •leo studied ~he effects of tar and nicotine deliveries on subjective reactions and eommmption of e£garettes. In t~i~" f~st exper/a~mt: 20 subjects ~ere asked to 8mo~ the£r own b~:and (0.7-1.7 mE n£cot4ws) foc one week. Subjects then smoked low nicotine cig~ett:as (0.26 m~ n£coCine) and • co~t:roZ c£1r~recCe (1.3A ms u£cot:ine) for a week each. ~hese ~a~e ~c~all~ available c~Sarecc•s. Low BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-36- delivery cigarettes were rated lower £or "strength" and "satisfaction" than the control or usual brand. There was no siKni£icant difference in number smoked between control and low nicotine cigarettes. Tn a second experiment, on 15 subjects, six experimental ciKarettes were used. These had rJaree nicottJae levels (0.39, 0.77 and 1.36 mK) and ~ tar levels (8.8 and 15.9 mK). The f£rst week the usual brand was smoked. For the next three weeks ctKarettes oF either tL{Sh or low ta~ ~ere msoked, one ~¢otine level each week. The mean number o£ ciKazettes smoked fell el ~he n~cotine delivery increased, independent of taw levels. "Str~nsth" wee related only to nicotine level and "satls£act/~na" ret~8 ware not re~ated to tar or ~'Lcotine. Urinary nicotine concentrations were determined, and these wre proportional ~o nicotine content of the c4Karettes. Complete compensation was not, therefore, demonstrated. Urinary nicotine concenr~atlons were not, ~er, as hish as wuld have been expected from machine-smoked deliveries. This Kive8 some evidence for the role of nicotine but it i8 interestin8 that low nicotine ciKarettes were only rated as less "8atis~y~mK" in experiment l, when the brand was kncm~. Brand ~aKe may therefore play • p~t ~n detewn~edun8 subjective rea~tion. Taken •8 • whole the results sivan in this section, from m number o£ authors, seem to indLaate ~kst n~cotlne doe plsy • past ~n deten~ninK mokln8 behaviour, but £t is by no means the only factor involved. In most o£ the ~riwents mlnt~u~ned it sum possible that the cho4ce o£ both subjects mad cisarette8 has influenced the results to a larSe extent. It seems reasonable to assume that m people will be more 8fretted by uum£pulat~a8 in~ol~ nicotine than others and this is discussed fu~th8~ in the section on motivation. T~ most eases the u~e o£ c~Sazettes deIiver~ne lee8 than 1.O m8 nicot~Jae (machine skinS) BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢:~ ",,o

-37- does not £nduce the "expected" reaction f~om mab~ects in terms o£ increase in nmmber of eiKazettes smoked. One expXanat~on is that, if the n£coc£ne availabZe in • clsare~ze drops below a certain critical level, chert 8ubjece8 Ce~d ~o "sire up" and Obey ra~e the cIKarecte8, in ~7 CueS: U u~p1eUJmt or u~sacis£~tory. Am • ~zel ZUlS 8ubjeecS are more senl*c£ve to, ~acrmes in n£cotlne coucamC of ciSaraCCes than co decreases, in cez~m o£ mdj~tmmat o£ mmok~ l~act~ and consumption of cigarectu. This me7 indicate that the "nlcotinm adjustment smchmn£am" is more auicad to reducin4 u£cocinm intake (~tt the nicoCine is takmu from a c£garecCe), than increaztng ic. Some of the reasons why ohm adm/~isCracion of: nicot~-,e by incravmnoum injecclon or by" capsules and che~nK-Eum is noc "succmms£ul" in decreuin8 smok~ to amy $~eat extent, are coverm~ in the ~ section. It ca- be ma~d at Chi8 point ~/~eZ rJae available ewidence does not support ~he conclusion that smokin~ is specifically ass m~dicCiozl to nicotine and that ell or even most smokers will regulate Chelr intake of the druK to provide constant amounts. 2.4 Comparison of Cigarette, Fipe and Cisar ~mokin~ There seem Co be • number o£ d~ffermnces betw~e~ ciKarette, pipe and c~$8r amoki~8 ~n tezm~ of phye4oloKical effect, the people who smoke one type of tobacco product or another, and the motivmt£on for each type of mmok~az. People vho smoke cis~rs and pipes and ~ho ~ave never smoked cisarectes reKu~arly, rarely inhale the smoke, yet cigm~actt smokers who chan~e to ciSa~s or • pipe often ~out~Luue to inhale (171). Cigarette smokers ~e ~at~ly as satisfied ~Lth non-/nhaled e£8~r 8mokin~ u vith ~nhaled cij~ette 8mok~. Yet~ ~ J~v~k has poLnted out (105), BAT Co LTD - MINNESOTA TOBACCO LITIGATION ",O

-38- tim•tetra rmokers who w~'k for IonS periods of time /~ an environ:out where ramekin8 is forbidden (like a lumber mill or coal mine) may Cake Co che~K tobacco as m mubet£tute. There mzm no dace siren, hovever, on the exteuC to ~ich this becomes a hablt in its own =iSht or hey much it is used because it ks tbou~t to be better t~m nothing at all. Armlta&e (7) ham said that, although a c£Kar smoker does obtain a dome of nicotine even if he does not 4nhale. it is open co doubt whether enoush nicotine is absorbed 4~to the bloodsCresa quickly 4mough to ~ve the pluLYmacoloiical effects which an inhaling cigarette smoker would experience, lusmell has said (171. 173) that he believes Juch of the dependamce-producin8 potency of nicotine in ciSarattes to be due to the extremely rapid "intravenous-like" effect folloqrius inhalation. The slower e~fecC after buccal absorption may be less depende=ce-produc~K and more l~ke that of alcohol or b~rb£Cur&te8 taken by mouth. Russell believes that smoke from all ciKazs and a~z~cured cisarmttem (both ~th sl~s1£ne smoke which enables buccal absorption of ~4cott~e co take place) is ~h81ed more •iCon than that f:om pipes m3d 18~Ke c~Ka~s. This be explains by me~ t~tt mll c.tK~m contain too little nit•clue to i~du~e an appreciable effect by slo~ butts1 absorption. He believes that inhalation of cigarette smoke produces • bolus of blood conta/:L~n8 a ~4cotine concent~ation ~ tins bier than ~4cot/na ad~stez~d by ocher routes, this re~chem the brain quickly after each puff (173). This may have special ef£ecCs and once the ~4cott~e bolus has been experienced the effeCts of u~cotlne 4n any other form are not sufficient. Hult£ple intermittent douse probably leads to hi,her nicotine concentr•tlo~m in the brain and ham a 8~neter pktnncolo$ical effect (at lea~t in anise1 e=~perlzmncs) than continuous administration of the ma~e dose over the m~m~ perio~ (9). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-39- Ctr~tinly the ,~o:t of nicotine (--d carbon monoxide) absorbed during cISare~e mnoklns depends to a large extent on inhalation. &zlnicags e: el. (8) studied smokers sad non--smokers who smoked ciKarettes spiked with 14C nlcot/J1e. They found chat smokers who inhaled retained 82-92X of the n~cotine in the mainstream smoke. Non-smokers (who pnsmnably v~re less 1/Jmly to 4shale deeply) exhaled from 34 to ?OZ of ~h~ =~£ustr@sm n~Lcot£~, rjL~p ~asted in 1965 (59) that the lo~al concentrations of n~cotiue 4n the ~espiretory rystem m~y produce the e~Iscts soughs by smokers. It has not yet, however, been proved that tJ~ere are clear cut differences ~ local n~cotine coucentretlon ~n r~he brain £z~m c£8~ettes and c~Kars. Zt dons seem lo~Lcel to assume these differences 8x£st, but, as yet, no experiments have been publ£shed in wh£ch s£multaneous arter£al and venous blood nicotine eoncentratlon has been detern~ned, at sufficiently short inte~rvatm to detect any ~Lcotlne "boll" wh4ch my be present. It is also sommd~c d£ffleult to e~plaln the results of e~perJJNmt8 dssiped to study the t£~eets of /J~trm~mou~ -4cotine on smoking. ~n the study by Lueehesl et al (133) inte~ttent adba~a~stratlon of n~eoti~e yes sl~h~l~ more eff£eient in reduciq c~mtette consumption than continuous aAm~n~strat£c~. The effect van not lat~e ~er. :,,sssll's expsz~Jmnt us~ iute:m~ttent 8dm~u£st~stio~ shows4 l£ttle e£fect on 8mok~n~, Kussell ha8 8aid (40) that the lack o£ e££ect on smokin~ may have beam due to d4~u~Lon o£ the '~oolu8u. Blood from the lu:t~S JOSS d:L~tct to the b~&4~ (in about 7.5 stcouds) w]hez~taa blood ~l~m an trisection in the arm ~ld trml £u=~her mad take loujer be£ore reach~ the brain (13.5 seconds) (170). Expez~.,---nt8 in gh4ch -4eot4ne chet~nSoK~m is used a~e probably more representative o£ ciKat or pipe BAT Co LTD - MINNESOTA TOBACCO LITIGATION c..,,.

-40- 8mok~ than c£K~ette emo~uK, since the nlcot~ne is absorbed slowly through the buccal mucosa. It seam= that inhaled tobacco mmoko probably produces dL~£fmrmnc ef£eccs from smoke held only Ln the mouth but more work is Qecessmry before the exact di££erencem are defined. Some of the publicac£ons on mot£vacion ~ce relavAnt to chls point, particularly that o£ Marcovitz C3.35), and eh4s is discussed 4. • lata~ section. BAT Co LTD - MINNESOTA TOBACCO LITIGATION O'7 C~

-41- o THE EFFECTS OF SNOKINC AND NICOTINE IN HUMAN SUBJECTS These effects can be dlvided into three Keueral csteEorles : PhysioloKic81 effects e.K. on blochem~stzT, heart rate, e lectroencepha losram. 2. PsycholoKical effects e.8. subjective reduction of tension udder seres#. 3. Effects on perfoz~an¢e e.K. in simulated dri~v~nE tasks. There are obvious overlaps in amy system of cateKoz~sation. the basis for a£1 effects mediated by nicotiJae 18 physLoloKical. Pr88ustbly After a number of experiences with emok/nK, however, the effe=ts may ~pear to be larKely psycholoKical. If the smoker learns then smoki~K calms him down in certain circumstances it may, therefore, do so independently of nicotine effects, by • =ondltloned r~ponse reaction. Here factors such as merely handli~ a eijue~te and~nat~ tb 81Bok~Jay k ~ol~smt. Effects on performance see p:obably rJae :esult of both physioleg£~tl and psTcholoKical effects. Zt is obviously not poss£bIe to consider ali the studies on the effects of n~cotine and smoiu~nK mad a ~&:Ks number of ~8mhave bean reviewed by Larson, ~ ~ Silvecte (123, 124, 125, 126). Soma are covered bare as an introduction to amn8 of ~ ideas which will be included in nhe section on 8mokinS motivat£on. 3.1 Phys£olos£csl Effects CiKmrette 8~okin8 mad nlcotine c~alse physiolosieal effects on both cencr.l and pe=iphera1'structu:es ~n the body. For the purposes of s~mpltfica:ion the ef£ects are d£scussed here under ~vo haadtnSs: (a) The effects on brain activi~7. (b) Order effects, including peripheral effects. BAT Co LTD - MINNESOTA TOBACCO LITIGATION c~ c~

-42- (s) E£~ecC on brain activLt7 A number of stud£es have been publlshed in which the acute effects of mnol~uK on the h~ eleccroencephaloKTmm (~G) have been investigated. Many of these cradles on the "resting" EEC have been ~eviewed in a prav£ous ~mpo~t (44). A summary of much of the work on the KEC and 8mokin8 mad n~cotin8 is ~go Slvem by N~rphree (148). The ~facts of 8mokinK on the back~ wwC and s/~p1e evoked ~esponses (to sounds and liKht £1&shes) are usu~ly interpreted as beinK st~J~lent in zusture. The results oE two studies, ozze ¢m buau~J8 (61) and one on 8qu4rtel monkeys (38) sussest that smoking induces a=ousal wh£cb £s slm~lar to chec seen under normal alertLuS conditions. Zt has been 8uKKested, there£ore, that ~¢otlne may stimulate the normal arousal pechvays by act£nK on the midobrLi~ reticulaz formation (38). ~%70 JtlldleJ on the effeCtS Of 8mO1C~ mYter deprivation have a18o shown st/mulntlon of brain activ4t-y. Ulett, Ztil end tbe4r colleaKues (210, 102) found that the 81ow~ o~ th~ ][~G activ~t~ a~ter d~p~vation was reversid by smoking. The results of • recent 8tud~ by Knott and Ven~ble8 (117) also showed that dep~ 8~okers bad llOlg~ mlphe K~G frequencies than :-smokers o3 :deprived smokers and that their alpha £requency was ~cre~so4 by smog. Th~s effect 18•ted at ~east fifteen ~Lnutes. ~on-depz~ved smokers, hoverer, 8hmmd uo change in alpha act£v~t-y 8~tet ~ and it was thoueht that this may /~d£c~te • depee of toZerance to the st~umlant effects o£ 8mok~nK. Seam empmrtments on amo~tz~ and th~ ~G hate 8hou~ tibet the -f£eet8 seen ~ce Dot al~mys those of st/mu~ation. A m~tll study ~ondu~ted 4~ Group IL. & D. Centre on the alpha z~ythm (8 component of the no:me1 EEG)(&&), BAT Co LTD - MINNESOTA TOBACCO LITIGATION c~ c.,,,, ',,o

-43- did not show stimulant effects in all sub, acts. The results could be interpreted •s indicsttnS that cigarette ~kinK emabLe~d "sub~ects ~ho art jives informatlon about their own alpha rhytb production, to attar their braln activity in • way wh£ch they cousidered to be des~rsbXs. Friedman et el. (70) have also studied the aZpha rhy~b ms am indl.tion of the abillty to ignoke distracclug noises. (The alpha rhythm disappears wheu •ttnt£on 4s pa£d to d£stract£on but returns when habltuat~on to the st/~ulus has occurred.) They found that nlcot£ne-con£~n/~K ciKarettes decreased the time taken by subjects to habituate to (or ignore) distracting stimuli. Experlmmnts on one part£cular aspect of the EFt. the eont~nsmnt nmptive vaz£mtion (CNV), have £~d~cated that some subjects appear to be stimulated and some sedated by smoking. The authors of one of the studies, /~hton, ~ompson and their collamSuas (IO, 11) believe that u~cotlne acts u a stJ~uZant ~n small doses but that £t is • depressant in larse doses. There is e3rLd~nce that this is the case 4~ ~ls (9). Ashton st •1. related • depx~sssnt e~fecc on the C~7 to • hish rate of nicotine intake per unit time in introverts and 8 st/mutant effect to 1ov rite of Cut•ks in axtravmrts. Several authors, however, he1£eve that the doses of nicotine taken du=~ smokta~ would be in the stLmulmnt rqe (e.g. 207). The other study on smokinl and CHV w=- conducted at G=oup R. & D. Centz~ (39, 45), and ~elded results s4m4~ar to Chose published by Ashton et el. lq:e mpparamt e~fect on the C~V (4epz~ssant in some subjects and stimulant in ochers) was uot related ~u ~h~s study to total smoke vol, m~ takmn from the c~lp~ettes, llowmve: subjmcts showin~ as~ siSa/~4cant chanl~s in CNV (stimulant or depressant) took BAT Co LTD - MINNESOTA TOBACCO LITIGATION C.m, ¢"~ o

-Ad- larger volumes of smoke than those showing no chartS•. This suggests that the ~TPe of e~ect i• indtpedent of ndcotine dose. The hypothesLs which is favoured to explain both set• of results i• that nicotine almays act• as • stimulant but the •greets seen depend on the inlt£al arousal state of the subject. Other smoke components could also have an affect but n£coclne is. the most 1Lkaly •Sent which would cause a stdm, lant effect on the brain. Carbon monoxide has, for instance, been shown to have a depress~st effect on the C~V (85), but the effect of levels found a~ter smok~ ¢iKarettes wo~ld be small. Eysenck. (60) has su~estad ht the ~fects of nicotine depend on the deKzee of cortical aurousal which Ls a £~mction og (a) personality (especlally extruersion--lnt~overslo~) and (b) exte:~l conditions at the t~ (for instance presence o£ stimulation). The effects of nicotine could be positive or neSative and ~dcotine would therefore be uz~quely reinforcins as it would tend in all ecmditions (in suitable doses) to lead to a •hilt in arousal towards the optimum for a Slvm activity. The evldence doej indeed su6Kest that althoush nicotine is predomAnantly 'a st/JZUlant it may lead, under some circumstances, to effects which are apparently those o£ a sedative. 1~hl• is borne out by subjective impressions o£ smokers (see peycholoSlcal dfects). It is not known Lf the effects of nicotine o~ the brain are direct or indirect, but they may be a combination. Hicotine :ead£17 passes the blood-brain barrier and reach•• the brain very quickly ff samke is in]~]Led. Zt is b~oli~ ~lhat n:LcotiDe L-el•us• ece~leholL:Lne in the b~ain mad ¢h£• is a tranm~tr~r substance, lh~sell believes (170) that this may ¢ause effects ~n the cereb:al cortex for up to ~m hours which may BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-~5- be i~portaut for light 8~okars. The 8hort-livtd e£feet due to a~etyehol£z~e release is, hoverer, likmly to be Lmportaut to moat smokers and probably 8f£ects the hypothalamu8 and retlcular 8ctivatinK system of the brain. Hicotinm also ~ansss or £sc£1i~ates ralaass of noradre~l£ne in the brain mad It is this which Jarv/k (lOS) believes is i~portant to smokers. (b) Other effects The basis for the peripheral tf£t:~8 of amokiJ~ mad nicotine is primarily b4ochmn£cal. Nicotine causes release o£ adra~li~ and noradrenaline from the adrenal glands. The effect of this is predominmatly stimalant. Blood suK~ is incrused as 81u~ost is rtltased from Klyuogen stores, blood £ree £atty acid ltvell art raised, mad hydrocartisone is released. Hickey and Harne~ (93) h~ve suKsasted that nicotine may be used by some people to co~rect an JJaherent b£oenerKet£c de££c£ency, via the release o~ SLucose. 8mok£nK one to two c~garettes increases rest J~K heart rate by 15-25 beats per minute, blood pressure by 10-20 mm mercury systolic m~d $-15 mm mercury diutolic, m~d c~rdlsc output by about 0.5 lltre/mlnute/square cm (185). At the same time as this stimulant reaction to nicotine, stomach contract:£ons are inhibited and the patellar re£1ex (knae-jerk reflex) and electtomyeloKraph~e (unxscle) actlvity are depressed, • relmtion type o£ reS1~/tJle. Frankenhseuser, N~rsten m~ Post have done a number o£ e~perJJNnts relaCJ~K catecholmnLne release ~-d increase in real to c£sarette smoking. In one study (67) they invelc£jated the e£ftctl of amokJ~K two, £o~r and six ciKarettes in two hours. They found that blood pressure, m~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION c.,-., x~

-~6- skin temperature (which decreases due to vasoconstriction), were most affected by the first cigarette (after overniKht deprivetlon). The second to sixth ciKarettes ~aused proKressively 8~aller chanSe8. Urinary adrenaline rose continually as the nmnber of cijartttts Lncrommed but noradrenaline increased only for the first two ciKarettes and was unaffected by further smoking. Reart rate increased unt¢l the fourth cisaretce. In another experiment (66) m control condition (nonoamoking) was compared with smoking tither two hiKh nicotine (2.3. ~) ciSa~attes or two medium nicotine (1.3 rag) ciKarette8. The hiKher doses of n~cotine which were presumed to have been taken from the h~gh nicotine ciKarettes produced ~arKer and more persistent ch~nKe8 than those from the lower nicotine ciKarettes, althouKh these also had • pronounced effect. In later studies these chan68s were related to meokinE under different conditions and to performance (see later). The effects of 0~oki~E on heart rate as related to the rsmctionm of subjects to stress are also mentioned later. The effects of smokin6 on patellar reflex have been studied by Isaac and RAnd (100). They found the depression in the reflex was more pronounced in non-smokers (after 8~oklnK) and liKht smokers than heavy smokers. & biKh nicotine c~arette caused the depression in more subjects than a low nicotine cisarette. Doa~no end van KaumKartmn (54) also studied smokers (d~vided into r~ree cmtelor~es depending ou ciKerette consumption) and non--gmokers. The7 umed a lettuce ~mmf cisarette mad two different tobacco ciZerettms (0.8 u~ and 1.69 ms n£cot£ne). They found no dlfferen~e| beCu84~ 8mohars and nou-mmoker8 in depression of petellar reflex afar smok£ns. The depression was not BAT Co LTD - MINNESOTA TOBACCO LITIGATION &.,-, c¢, C.v

-47- seen with lettuce cisatettes or shin smoking and theh~Shar ~cotine cigarette had more effect than the lower nicotine c£sarette (67Z vs 45Z depression of reflex). Nicotine in am aerosol also caused depression of the :eflex. These results ~:d£cate that the effects seen are almost certalnly due to the nicotine in cigarette smoke. 3.2 Psycholozlcal Effects This is a difficult are8 to define but the work discussed in thls section may be said to fat1- broadly Lnto the "psychological" category. Much o£ this work concerns the reactions o£ smokers and non--smokers to stress and the way in which smoking behav4our can be textured to external stress and Internal azousal. Eysenck has hypothesized (60) Chat since extraverCs are cortically under-aroused they vould smoke pr/mar£Iy for st/Jnulacion, vhile ~nCroverts, being corclcaiZy over-aroused vould smoke mostly for sedation. There have been several studies in which this hyporJhesis, and the more Seneral one that different people w~11 smoke more or less clsarettes undm: different conditions, have been tested. FrlCh (72) constructed a quest£onnai=e in which subjects are asked to imagine themselves Lu various high- and Ion--arousal situations. They ere then asked to indicate their desire to smoke in these situations. If nicotine is mostly a st/mulmnt then people should £eel the maed ~o smoke in low-arousal sLtuac£ons. If ~eotine can act as a depz~assent there should be a desire I:o smoke 4n h4sh-arouaaI s£cuationus, b~bsn the quest£ouna~re was ~stered it was found, on ~veraKe, chat r.he low- arousal situations induced more 4msire £or ciKarettes than did hish- arousal conditions. This is consistent with stLmulent action of nicotine. BAT Co LTD - MINNESOTA TOBACCO LITIGATION C..m.

-48- Heavy smokers, hoverer, shoved a desire for ciseretcem on all occasions. Hen wanted to smoke more often in situations of boredom and tiredness (low arousal), whereas women ind£caeed their Sreaeese desire Co smoke when under stress (h£sh arousal). This is d££££cult to axplaln in terms of the orlsinal hypothesls that saokins behav£our is detained by the smokers characterls~£c Level of arousal, since women ere not chronlcally more aroused than men. Frith concluded that woman may inhale less and noc be influenced by the pharmacologlcal effects of n1~otlne but they my use the ritual of l£ghtins and puf££ng on niKarettes to caln thyselves £n stressful situations. )~y~stan and hat colleasues (150) selected two gz~ups of lale sBokers £rom a questlo~a£rs based on Frith (72) and HeF~onell (140) (see later). The h£gh- and 1or-arousal smoker groups were then studied smokins and not sRokLn8 in h~gh- and Lov-erousal exper/a~ta~ situations. The results support the assumpt£on that different amok~ habits are related to spec£flc di££erences in the /~medie:e effects of smokln$. There were no differences £n performance o£ the blab- amt low-arousal smokers, in either a=ousal situat£on, when not smokins, but dif£erences in performance ef£iciency and subjective a:ousal were seen during smoklz~. These dif£erences re£1ected the smokers' usunl smokins k-bits in terms of the situations in which they would no~lly have smoked. Bartol (16) has also used the Frith questiom~si:e when st~yi~ a panel of 40 feamle subjects who were $Touped as neu:oCl: extraverts, neurotic int:overts, stable extraverts and stable Introverts. ~ere was no s£snlficant d£~fez~nce in e~sarezze consu~pt£on bet-~een Stoups and, contrary to Eysenck's h~pocbesls, extraverzs showed a desire to smoke in BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-49- stressful sit~stious and introverts in non-stressful situations. Non- prescription drug and cof£ea co~mnpcion were •1so investigated. 1re was found Chac extr~rmrts often took co££ee and drugs together with cigarettes, iLntroverts smoked or drank coffee in non-stress situations and tended to take tranquillizers when under stress. The author concluded tha~ the situation vlth regard to 8moklnK was very complex and may be confounded by the use of other drugs. Fuller and Fort•st (73) hypothes£sed that it should be possible to manipul•te smoking by mantpul•t/~lg level of •rouse1 by external umans. Tt was expected that ulcot£~e would be self-admlnLstered •t • higher rate by smoking £n low-arousal conditions. 40 male and ~0 female smokers smoked or s~nuleted smok~ in high- and 1o~-az~usaZ conditions. Zn the high-arousal situation heavy smokers (over I$ ciearettes per day) smoked at a 1o~er rate than in the low-arousaL situation, but obta£wed the sum dose of nico~/:e. There was no difference in simulated smoking. All subjects tended co smoke and sLmu/ete puffins less during high arousal (watching a s~ressful fib) and may just therefore tend to smokm more when there is nothing to do (the low-arousal condition involved relaxing alone on a couch). Zn • rather di£ferent type of mqpar/smnt, Clad and Adesso (7.5) at~mnpted to determine ~he relative contributions of tension reduction ,em, d "behaviour81 contagion" to the instigation of stooling behaviour. The subjects were 72 males and 72 females divided into heavy smoker (over I] cigar~ttes per by) and Zight maoker (under ten cig~ettes per day) groups. They ware placed in high- or low-a:ousal conditions with other JJxd£v£duals who either all smoked or ali did not ss~ke. The BAT Co LTD - MINNESOTA TOBACCO LITIGATION c.,-r @

-50- conditions were different from those in other studies in that they vere social in context and more relevant to real-life sltuat~ous. TensLon was induced by •skinK subjects niC £or evaluation of theiz ansnwmr8 to • di£f£cult questionnaire. The low-arousal condition was one wLth • relaxed, £rimsdly social 8~mosphere. The results cast doubt on the ~mportauce of tiBer•tee smok~n8 in tenslon reduction. There was no di££ereuce in the mmouaC of mmok~ in h~sh- and lo~-aroumml 81tumtlons, or in self-reported anxiety in the tmnss slcuac~on I~ those who did and did not smoke. The results do, however, support the observaclon Chst people tend to mn0ke ~inly because those around them do. This is especially true for light smokers, but sven heavy smokers, who tend to smoke in most 81tuatlons anyway, Incr~eaed their n~uber o£ cigarettes and of puffs taken, wh•n others ~tre 8mokinK. Another approach has been to look for mood cbas~es after mmo~Lus. AEu~ (3) gave 24 male subjects • mood adjective check list (M.A.C.L.) (155) and &ct£vatlon scale questiomsaire. Di£ferent nicotine contmut ciKarette8 were then smoked. For all thm H.A.C,L. factors o~ly "pltumnCnms8" was correlated with ~Lcot~ne delivecy. For the activation scale (on vh~ch a subject estimated his position b@~geen the extremes o£ deep dr•mules• sleep and extra~e fear) it ns found that a decrease in inner tension was relmted to n~coC/~e content. This supports the role of ~cotine as m tranquilliziug agent, bimstra (90) administered the M.A.C.L. to smokers who were aXlowed to smoke on oDly some occamlous durins complex psychomotor o~ perceptual ~k8 or a h/shly stressful £i]~. ~k~ tended to reduce mood £Zuctuattot~ dur/~K the ~cpet~ummts and smokers who 8mobd showed loss mood chaqe (£ncZu~ins a88tems£on) BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-51- duriD4~ the ta~ka than uon-amoki~8 smokers or non-~lcers. This was not, hc~mver relatod to performance 4~ the tasks. Several workers have tried to relate smok£nS to m4LK~ess£on. Hutchinson and ~ey (97) have studied bitiu8 movements and jlw-za~cle contraction •s mn /~dex of 8K4~cessiou. They presented results for man and for squirrel monkeys £ndlc~tln[ Chat intake of small qusnc~ties of nicotine produce • dlfferemtlal reduction in beha~rLoural patterns associated ~r~th aSKressive~tss, hostiliL~7 mud i~c4tab411ty. These same doses •leo elevate the orienting end anticipatory reactions. Thus the impact o£ •varsive events can be reduced and responses enabling escape from or avoidance of aversive events are 8£8o facilitated, thus prov£ding s powerful reinforcer due to nicotine. Duns (204) has recently reported some uork umlnS • machine which "the•is" the subjects of their rewards for per£otm/~B well in tasks. Re found chac smokmrs and non-smokers did not differ £n their displays of aggression when frustrated, but that smokinS smokers showed less dmcramsut in performance, due to 8Kress£on, than deprived smokers or non-smokers. This sussssts that 8mok~nK does not control aK~ress4on 8s such but m/~/Jz~zes its effect. Russell (173) has, however, quoted the ~0rk of Schachtsr end Rind (190) which indicates that smokers hp~ived of cizarettes are more m~slvs in cmrmm of qummti~re mrs mnd bel~vlour in 8dm~u~ste=i~qB electt/~ shocks to other people. Smokers, especially those with ~ e/~aretts cN~mumption, ~Lmo tend Co have h~sh chr0~£c "anSer" scores on qu~st£mma~es (203). NesbiCC (1.52) h~ conducted • study w~ch 30 smokers and 30 non- smokers to measure their "mmtio~aln responses to electric shock. BAT Co LTD - MINNESOTA TOBACCO LITIGATION m O C~ %.0 C~O

-52- He recorded Absolute threshold (whe, the shock is ££=st detected), p~u threshold (when the shock first becomes paln£ul) and endur~ce threshold (vhen the shock is too p~ul to bear). The measure of "~t£~" was the number of shock= of increas~J~g m~8=itu~le that a subject could recei~ :before the endurance threshold. It was thought that 4£ smol~nE was stimulating then, as troussl increased, this threshold mat decrease, or that if amok/ni vls tranqu£1iz£nE then slok£ni Imokers should be able to take more shock than non-smok~8 smokers. Both smoker8 and non-s~okers ~moktd & high (1.6 q) ~eotine or low (0.3 q) ~¢otlne ciKarette or puffed ou an tmllt ¢iKareCte. Zt yes fottnd that: smokers who smoked couXd ~ake more shock ttum they could I£ they dld not smoke. ~'nis ef£ect was Sreatast I£ hish uicotlne c£sarette8 were maoked. Thls was not fotmd for smoki~ stud non-smokJ~ non-smokers. This Indicates am interaction o£ habitual smokini and the acute affects of nicotine. results are difficult to e~pl~ since ~ker8 and non-smokers differ in their reaction yet ~cotine level appears to be /•portent £o~ smokers. One plausible expl~tion is that since smokins increased arousal in • s~lar way to the shock (as ~asur~ by haa~t rate), the smoker attrlbutas his ~81 to the c~K~ette alone and is not alarmed by the shock. ~or the ~-smoke= who smokes, hoverer, the increase in ~co~•1 due to nicotine ks unv~u81 and may be attributed to the shock, thus lover|J~K the thre~held (there was a tendency £or threshold to decrease vlth u~cotine conte~c for mk~nK non-smokers). Thus the physiolosical e~fect8 of 8mo~.~nK do appear to be Lmp<~tant £or the u~notiou~l" (peyd~oloK~cal) ¢aJ~uq~ e~£ect8 of 8mo~ in e~periem~ad smokers but in the opposite direction to that exlm~te~[ on the bam£8 o£ ~rou~al due to ~cot£~. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-53- Finally in this section Ctm studies can be mentioned which indicate that smoking is used to decrease stress. Pincherle and Willlmmsou (161) found, that in a large sample of medical i~atients, hasty ci~jarette smoking (over 20 c£garettes per day) ross more cc~u in those patients judged to be under excemslve stress than in non--stressed patiemts. L£ndenthal, Hyers and Pepper (13I) found • direct relatio~sh£p between llfe stress and "psychologlcal impairment". They also found • positive relationship bergen smoking and "psycholoKical Impairment". Tncreases fm ~k/~g varied dltectly vlth psyehologlcal status and r.he nature and quantity of 1££e stress. Thus smokers of • ~ven psychological status have smoking rates associated ~rith particular numbers and kinds of life crises. These data lend support to the role of smoking as an aid to copinS with crisis. 3.3 Effects on Performance Some studies in which pc=ferments ham been mmmured brave aZ=eady been ~C£oned b=iefly. The studies considered bare only const4cute • mall proportion o£ those in which s~ upmct of performance in • task has been recorded before and after smoking. Heimstra and his coilea&~_es (91) have found thaC meek/hE can prevent deterioration in • reekers' performance in a simulated driving task. Ashtcm add her colleafums (12) have a/so looked st simula~.ed driving mad found chat smokers had shorter reaction tiers in some tests than non- smokers, only if smoklnS m permitted (non-smokers did not smoke). No differences were seen when the effect• o~ ~ (2.1 mK) and low (1.0 n6) nicotine cigarettes were competed. This mld be ezpectmi since the wTerage n~cotine taken f~ each of these ctl|aratte ~7pes was noa=ly the same (from results of butt analysis). Terriers and Eartamann (202) BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-54- investiseted the performance of smokers, deprived smokers and non-smokers in s visual viKil~ce task. Smokinj was found to prevent performance decrement. SmokinK smokers per£o~med better chart non-smokers and introverts better chart extraverCs. Thus, introvert smokers performed best, shc~Lng l£Ctle decrement in performance durinK the ewe-hour test and extravert non-smokers sho~ed the lax~est decrement. Frankeu~aeuser and her colleaKues (66) have found that • higher level of mental s£ficLency can be um£nte~ned in some parts o£ v~gilance teaks if smok~s is allowed. Some recent experiments conducted by Warburton and Wesnes (218) have else shown that smoking and nicotine affect performance in visitants tasks. Nicotine given on tablets which were dissolved in the mouth improved performance of both smokers and non-smokers ~-~th • long viK£1ance task end an intensive visual search task. Further experiments showed that per£orman~e was less e~ficiane in non-smokers follou~nS the first o£ three nicotine doses in the vigilance task. Equal improvements in per£ormance were seen £or liKht and heavy smokers Kites i or 2 ms u~cot£ne tablets. Heavy smokers ~so improved their per£ormance when Slven• hash nicoE£no (1.65 ms) c£saret~e, relative to performance after a low nlcotlne (0.3 ms) c£sarette. There are some ~ndicattons that neurotlc subjects show smaller performance decrements and are more sensitive to the ef£ect8 of nicotine m~d smoking. Tong and his colleagues (207) have found that re~ction times in Casks are decreas6d by noise d48traction only If mnokars do not smoke. This is in accord ~th ~ ~tsnlts of FrlJdman at el. (70) on br~Ln activity mad distraction which have been mentlon~d earlier. &ndsreson end Poet (6) have tried to ascertain whether emok~ns affects lurn~ in human subjects since it 8e~m8 to impa£r short-term BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-55- m~mo~-y and fac:Llitato Lonl-te~m memory in rats. First they looked at 12 male subjects and found that ~king lu~ an 4~t£al detr£meutal e££ect on ieaz~iug of nonsense sylZables. The number of correct responses decreased after tbe first nicotine containi~ CiKL~ette (compared v~th • n£cotine-£ree ciKa~ette) but the second cigarette reversed this trend. Ldman~£nK vu ~h.•lz ,,-,",re improved by • n~cotitm ~ non-sxicotLne ciKaz~ntt•. The differences in recall may be related to the level of arousal dur~n8 the experimen:. The £mpalz3nent of lesrnlnK luted for about 30 minutes durLnS which arousal due to mmok4~s was hishast (as mauu=ed by heart rate). The second ciKs=ette p=oduce8 • u~sller chm:se in hess• r•te than the first. T~ • further expet/amnt on ten subjects, similar resuZts were obtained by Andersson (5). The:e was • temporary impairment of learning after • cigarette. This was probably due to increased arousal dur~ learnin8 since long-term recall (after 45 u~nutes) was improved If smoking was alloyed. At this tatar time the incrtutd arousal due to 8mok~8 v88 no 1onSet p:esemt. Tt iS thouSht that the cigarette a~fects learn~n~ and recall only by altering arousal level which has d£ffermnt e££ects on the different aspects of in~ormatlon process/JaB. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-56- DIFFERENCES BE~J~ SHOKZRS AND N0~-SH0~ZRS AND 3ETW.EN SHO~RS OF DLWrElt]NG CZ~ C0~SUHPTZON As wlCh other sections in this report =hls topic cannot be considered in isolation and it may be related to both effects of mnokinK and activation. The differences between m~nkers and non-smokers can be broadly divided into three cstelorlesz (a) Physioloslca! dlg£erences (b) Psycho ioSical differences (c) Social differences Once asain the literatttre is ext~ive but an ettl~pt has been made Co refer to some of the most inCerestln8 studies and Chose not sdequetely covered in reviews of the subject. The papers will mostly be considered J.n ¢hronolosicel order. One problem in discuss/J2K differences between smokers and non-smokers and smokers with dlf£erinK cilarette consumption is to decide whether the differences are intrinsic and present before mmok/~K started (the "constitutional" hypothesis), or are "caused" by 8mokinK. Some phys£oloK£cal differences between smokers mad non-smokers are included under the section on tolerance to nicotine if they seem most likely Co be "caused" b? amokinK. Other differences which are leas easy to de£1ne 8~e included in this section and some ind£cstlons are 8£ven if these differences are considered to support the "constitutional" hypotheein. Where there are indications that one or other case may be true the picture is often considerably confused .by di~£erences in the use of other drugs by smokers and non-smokers. This is discussed further in the section ccmparin8 mnokinK and other druK use but 4c may be acted here chat several studies have shown that smokers sad aon-mnokere'often d4££er 4~ consunqption of tee, coffee and alcotmZ me well as othe= d~uss (108, 1A2, 203). BAT C_o LTD - M!N_N_E:-~)__TA__TO_BACC_O_ LITI_C;ATION C~

-57- A. 1 PhTs£olos£cal Diff6r@zkces l~n 1963 Seltzer ($93) published a paper s4~r£u4| results obtained from a study of college studencs which suggested chat there vere differences ~u • number of descripcm:8 of physique bellmen smokers and noD-smokers and also smokers with d£f£e~4,tg tobacco cousumpC4on. Peters mid Faz~cis (159), however, foundno relationship becvasm smoklnK and height -rid ve£$hc in a Iarger ssmpLe of students. Russell (168) has stated ~hac the associat£ons found beL'veen body-build and mnvir~ Im=e probab$y due to sampling at:ors. There are, however, some /ztdlcat£ons Chat adult smokers tend co veigh less chart non-sloke~s and chac ex-smokers are of an intermediate veiKhc between these two. Russell (173) refers co the work of Linco$n (130) who found Chac smokers awe, on avarqe, 6.5 Ib lighter than non-smokers, although they cake in about 350 ca$ories per day more than non-smokers. The dLfferences 4n mmighc rend Co /~crease wlCh age and men over 40 years of age who have near smoked are, on ave=age, ~3 Ib heavier than smokers (lussell refez~nS co Comscock and Stone (46) and Ehoela sad Loam (ll&)). lussell suggests cl~ac rim lain in weight cosmonly seeu dee= giving up smokJJ~ is. in one sense. • return Co noxmallCy, rather Chart a mmnlfestaCion of oral substitution, sLnce non-smokers rend Co expend calories lees efficiently Chart smokers. Jenkins, Zyzamski and Rose~mn (107) have mlao noted t/use smokers scudlad &C ages from 39 Co 49 years had shoun less wm~ghC ~ s£uce the age o£ 25 yea:s &1though taktzq; loss ToluaCaz-y emorc£se than uon-sm0kmrs. These d£f£erences in ~ghc may be due, sc le~sc in pa=t, co the e££tccs of 8molc/~g on glucose mmCaboltmm (93). Dl~£ermmcme in • vat/cry of body bu41d parameters may be due co cm~ctcuc~o~al differences buc, for weight, no f£rm conCSusions can be dram. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-58- A number of studies have been publ£shed vhieh ahoy differences in concentrations of various components of serum. AmonK these sCudles is that: of Jenkins and colXeaKtms (107). They found chats ~hen compared with non-smokers, heavy 8moluBrs had h~4~her serum cholesterol Zevels, h£Khe: content:sCions of t:iglycerldes after fastJ~K 8rid higher hemstoc:it readings (percents~e Of blood volume occupied by red cells ~Ce: centri£~zgation), ben further determinations were obt-4ned four pars after initial masurmmmnt, syscmmac£c serum l£p4d d£fferamces were found between um~-smokers who rained n-smokers and those who res,mmd smoking during the fou= years. These differences were seen in the read£ng8 taken initially and the overall pattern of differences did not appear to be rJ:e result of elevavad serum lip£ds £~luencinK smoking patterns. The data ~ce consistent ~Lth the hypothesis that comnma prior factors increase trJ~lycmrides and cause smoktn8 or the hypothesis that smok~J=8 raises tr£Slycerldas. Data £o= serum cholesterol and lipalbum~n could noC be readily interpreted. Thomas (203) also found cbac smokers tended co have h~b~r serum r.holescerol l~vele rJ~sn Don-smokers. She found, in addition, chat maokars had hi~:er resting heart rates and blood pressuxes. Russell (173), however, has stated that smokers u a group do not have h/~imr hmErt rates or htSher blood pressures than non-smokers, a/though he j~ves no references for ~s. As far as other differences of the t~notsbol£c type" are concerned there is ev~demce chat smoksrm metabolise ~ ~pee of compounds dltferently from non-smokers (89, 126). BeckeCc, Gorrod and Jenner (19) have iuvestiKated the mtabolism of nicotine by male and female ~kars and non-s=okere. ~y gave an injection of nicotine (equlvalent to I BAT Co LTD - MINNESOTA TOBACCO LITIGATION On: %O

-59- nicotine base~ a.d collected urine 8mnples £or 24 hours stud analysed these for n£coC~ and coC4nine. There ~re no s4K~Lficmnt d£~ferences between subjects for the Cite to eliminate half the n£cot£ne dose. Female s~okers excreted less nicotine mud more coC£ni~e thin female uon-- Jokers and save a k£Khmr combined recovery. This 8uK&~sCs an incrtause in mr&belle to cocin3J~t which may be due to mazym~ 4~duction. Male smokers could be divided into ewe groups. The "low recovery" group excreted less nicotine and cotintnm than male non-smokers, suggestinK thac mecabollsm of nicotine is occutT£uS by an 8ZCernaC4ve patbvay. The '~n£gh cecovetT" group excreted the stone a~ou~t of nicotine but more coc£n£ne than non-smokers. This suggests either i~bib£tion of £urther cotin~ne mecabol£sm or increased metabolism of nlcotine to cotlnine due to mnok4~g. It can be concluded from this study that than are sex dif£erences in n£cot£ne matabol£sm and t~utt stokers and non-smokers macm~oLise ~LcoCine differently. The tethers of the paper btliave that smokins alters u£coc~ne mstsbol£mn and this £s also che view wh£ch Russell has expressed (173). The possibility, however, still re.tins chat the di£ferences 8men are constitut£onal end only those persons who mrs able to nmtabol4ze nicotine in e "desirable" way beret smokers. Lateen and SilvatCe (126) re£e~ ~o • study (208) which shoved rJ~t resular smokers matabolise certain endogenous JELnas dif£erantly from non--seekers. It was 8uKsestmd that Chest clumSts were due to ch~ou~c mzpomun to ~4coCine but they were not reversed tamsdiacely on sCoppin8 smokta8. Russell (173) has quoted rtpo~Cs whlch show chst smokers tend to here marKinally more tolerance to ~ar4out psychoactive drubs. Th£s could be due to enzyme BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~ O,,,

-60- i~duetion caused by smoke constituents or to ~he tenden~ Sow ~mokers to use more alcohol and d~s in leneral, thus acquiring some £ox~ o~ tolermace to drug effects. Another aspect of 8moker/non-muoker differences has been invemtiKated by Johns (108). Be looked at the relationship betwuaen sleep habits and ciiarette imok£nf~ and also obtained 4~fozlnation on alcohol, tee mad coffee consumption. The subjects were hospital patients but the data eol£ected tenet to their sleepinK habits at home. Amos8 the males, the bea~ mlokews tended to 8o to bed on averager 30 ~nutes liter th~rt nolo- smokers dur~ the week and 40 m~nutes later at ~ekend8. Thls was considered to be consletent v~th evidence £rom personality data on stokers and non-smokers. SmokinK was not related to "poor" sleep. The author suSSeSts that there is a complex inte=act~on between a subject's "li£estyle" end use of coffee and cigarettes. The tendency to stay up later at night may be enhanced by n£cotlne ~d ca££elne consumption, but "late" nlghts allow more alms for, and mry therefore encourase, more smoking and cof£ee drinkLnK. ~his study does not therefore point to specific dif£erences in sleep habits between smokers and non-smokers vhicb are directly related to smokings as once qaln there are confound/n8 £actors. The f/~al approach to detectLnK differences between smokers end non-smokers which will be mentLo~d hez~t is that LzLttieted by B=auu (32). She looked at the electroencepbAloKrmns (XKG) of a number of subjects. She then analy~ed her resales and showed differences in brain activity becueen smokers and non-makers mad smokers with d/J~e~ e:LKarette consumption. Her first 8t~-,dy indicated r.bJt be.m~ smokers end non- smokers di£fe:ed :Ln their :espouses co coloulred fllckerins mzd FlAtmhinK BATCo~ LTD - MINNESOTA_TQBACCQ LITIGATION

-61- l£&hcs (but not in 8 colour-epeci~£c manner) end Brown rusKS•seed Chat the differences could be related co fundemenCml differences in the mechanisms underlying brain a.cClvicy. "RescinK" EZG was also recorded and qain differences mere seen. which coKether with the visual evoked response :egulCs mu~escmd chac the brain mcCiv£ty of hear7 smokers was related Co diffuse aCCmnC£on. The wRG's of heavy 8reekers ~reof • generally hieher frequent7 chin Chose of non-smokers (~ frequent7 C~ds Co rise end FJ~e ~ becomes m~re dei~hroz~Lzed as n•fiC~tiOn" iS increased). The frequency dietrlbutlon of the KEG for smokers of "mvermse" ciKareCte consumption "and £omr heavy smokers was intermedlmte between ChaC for non-moker8 and heavy smokers. The visual evoked response results however euKSesC ChaC fob-mar heavy smokers resembZe hea~y smokers and thac "averase" smokers are more like non-smokers. Brown (33) later published more results for • 1•reef sample of subjects buC consider/J:K only the "restin8" EEG. The results were similar to those in the previous study. Non-smokers aKaLn showed we-C patterns "~Tpical" o£ rest but maokers showed patterns more 4~4cative of &tie,ratio•x. ehis beinK most marked in vary heavy 8reekers and 4nterP,.dl&te in average 8moi~ars. B~m believes that: her results ~e ~nelsCiut with evidence Chic smokers read ~o be mo=e extrm=t than non-smokers. She s~etes thaC her find£n~s euKeesc the fo11~ hypo~s: (a) Yhece in • cl~aracter4s~£c fma~ly of brain wave patterns repceienCin8 • constitutional characteristic of heiehtenad bra£n electrical excitability uhlch may be aseoclmCed with a fund~t~l phys~oloK4c predisposition to the 8mokis~ habit or soma equivalent acciv~c~. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢,-m %0 O'/

-62- (b) There £s a positLTe relationship between mmunt of smoklns and degree of brain ezc~tab£1£ty. (c) Smok~g rate is reKu]Lmted to wmlnt~ effective balance between behsvioural 4ccompan/ments of EXG 8ynchron4zation and desynchron£zat£on. Some work done i~ Group R. & D. Centre (42) 818o /:zd£cates that there are EEG differences between amoke=s and non-smokers. Zn a s~le of 30 smokers end 30 non--smokers matched for see, sex and persanality, smokers vere found to have less power in the KF~ U:an non-smokers, at all frequencies considered. The differences seen are /:~lependent of eke and length of smoking h£scory vh£ch either sugseste that the d£fferences ',-,~y be constitutional or that changes due to mmldxxK occur soon after smokius starts. Smoi~n8 does not appear to have a ~lattve effect. When smokers we=e subd4v~ded accordlnK to c£lsrette ¢o~sumpt£on Ic was found ~hat both um~4um and heavy smokers shoumd less ID[G pmmr than non- smokers but l£ght smokers were tndist~shable from non-smokers. These 14she smokers may therefore have a different z~uJon for smokbs, since reduced power of the h£sher EEG fL~queucie8 :Ln other smokers £s cons£stent ~ith the effect of a st£mnlamt ad:LLnLste=ed over • per4od of time. This stimu]Lant couTd ob~Louely be ~tLcot~ and its eJ~£ect uould probably be to "noraallse" the ]D[G's of mookers and make tblm more s4m41a~ to those of non-smokers. J~a/= tt ~s possible that the tendency re: mnokers to drink more tea and coffee, which both cour~/n the stJJmlant • caffeine, may be • couJ~oundin4 factor. Zt m also found that extrmvert8 showed reduced EEG pc~er vben compared u~th int~vez~8. Th~ our results are :onsistemt with the idea that smokers tory tend to be more :rave:ted BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~

-63- aithoush the Jnokers and uon-ssoktts in this study could not be distinguished on this di.mensicm by quast£onna.ire (156). The results of Ch4m study are diifarent from those obCL~ned bY Brown. Her z~t]~ocl8 o£ reco~£n8 m~d ~17818 can be crlt~cimsd £or • number of reasons and her results were mainly detez3.~ned by 8ubject£ve 8•Jess•sue of the ~G- When hat results are recalculated 8,0 that they are s~n£1az in form to those obtained 8t Southampton it Eppeare that Brown £ound increased power in the EZG'8 o£ smokers over non-msokerm. The studies quoted here are therefore 4n conflict about the exact nmture of the smoke,/non-smoker differences in bra4n act4~ty. Brown suKsemts that smokers hays "8ctiytted" brain patterns whilst ~n 8uSKest that they tend to be 'sloBs activated" than non-smohars. Zt does, hou~ver, nee: £airly certain that dif£erences in brain actlv~t~y do exist mad that theme d£££ere~ces seem to be inherent .and are, therefore, likely to be counected with the reasons £or smokieS. Xt i8 hoped t~st future work £n the Group R. & D. Centre on • ~arser sample o£ subjects vLll enable the u~tuxe o£ the d~£erences to be e~u~£dmced. P.sycholoKLcal D~££erences In 1970 Smith published a review o£ :he enpirlcal studies o£ relations between 8mok~ and personality (197). He considered • larks number o£ studies vhich used many di££ere~t questiouna4res on vtdaly vazT/n8 populatiome. He dre~ e4~ conclusions about the literature ~£~h ~re sumnar£ sod below'. I. Suo~ers are more extraverted than ~~m. Zn 22 out o2 25 analyses, smokers wez~ m~fl~L£~cmntly more emcnryertod than non-smokers and no s~ud~eg showed the opposite ~/z~l~ng. 0% BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-64- o o e e Smokers have nor• anti-socfal tendencies than non-smokers. 27 o£ 32 anal78•8 nhow mmokers to be 8iKn£f£cantly more antg- ijoeial than nou.--~ker8, none f~d ~he oppontte. As ~ri~h the extrmvernic~ studies • trade =ariSe of tenth w:e used and populacious studied. More information in needed to support rJ~at which Is now available on intez~al-excernal o~entat£on but smokers appear to be mo:e externally oriented Chart non-nmokm:8. The five studies co•sidereal nhow smokers are more extez~nlly oriented and they th/nk chance, gate and luck, rather than their skill and e££o~, account for what happens to chem. Four of the results are 8iKni£~cmnt, the fifth nmarl7 so. It appears tl~t smokers a:e more impuls£ve Chart non-smokers, but aiLtn more tn£o~mat£on kn needed Co ve:t~7 th4n. Seven out o£ ten studies 8how smokers Co be s/4~n~flc:mcly more Impulsive th~ n~-~kers, none are si&~Lfle~nc in the opposite direction. There is suppoTt for the hypothesis that 8rankers have ntrcmner oral needs than non-smokers, but more av~Ld~t in needed. Of £~r mtudien on ~kins and "orali~y", three s~m misn££icent positive associations. One o£ tJae thee was, however, bmd on • very muZl ha•pie add one mcJ~eveK1 niKslJ~icamce only for the comparison of heavy smokers and non-smokers. l~vidence suJ4mentn that 8mokm~8 have poorer mtL1L health than non--smokers but more infomtion i8 needed to empire thin a~d era work in needed to de£4~e the 8peet£1c ••poets of mental health =e~ez~ed co. A number o£ stud£en hsve shown BAT Co LTD - MINNESOTA TOBACCO LITIGATION C..,~ ..d~. k,m %,0 Ox

-65- poorer "mental health" in meek,re but several well-designed studies have not found a relationsb£p. He studies have fotmd smokers to have significantly better mental health than non- mnoker s • The author considers that only the f~rst two conclusion6 should be reKerded as positive. In a 1969 study which Smith appears not to have considered, Veldman and Bowu (215) studied university students. £won6 the "psycholojical" results which they present, smokers ware not found to be more neurotic than non-smokers. Non-•wok.re were sa£d to respond more positively to self-report attitude measures and they had more pride in their own moral character. The "stimulus hunker" theory got smokers was supported as was the concept of greater "orality" in smokers. Russell, in 1971 (168). 8~q~KeJted that aLtheuKh siKnifie~nt personality differences are found, they are small and t~are ks mu~h overlap between smokers and non-smokers. "Smokers t~n~! to he impuls£ve, arousal seek£ns, danser-lovlnK risk-takers who are belliKeremt towards authority. They drink more tea, coffee, alcohol: are more pz~n8 to car accidents, divorce and job chang~K. Smokers almo tend to be more sexy: not only do they start at an earlier age, but they i~dulKe with gre~ter frequency, variation and enjoyment. &ll tbese character••else cluster with • degree of extraversion." Claims that smokers are mort tans•, azm~ou8, emotional and umurotlc are usually not substantiated. Russell also says that amok£ns t8 related (especially after its withdrawal) with oral act£1rLty l£ke na£1 b£t£nS, gum che~ng, meet eating and normal eating and drinking. Eastwood and Trevelyan, also in 1971 (56) imvestijated 8tq;gestions that meek•re tend BAT Co LTD - MINNESOTA TOBACCO LITIGATION k.m C~ r,~

-66- to be sore restless, less dependable and sere ~urotlc than non-smokers. In a study of IA71 subjects they compared the smoV~nq~ habits of 124 subjects with con£1z=sad psychiatric disorders, v~th matched eoutrols. I~o differences were found in proportion of maskers, amount smoked or duration of smoking. The authors co~clude that there is no support for the hypothesis that "smoking is related to neurotic illness. They also note that the prevalence of smoklng is much higher than the prevalence o£ psychiatric disorder (IO-20Z o£ the populat£on). Also, toddle-aBed flmales have an excess o£ psyeh£atric disorders over males but fewer of th-- Are smokers. ¥oss (aS) in 1973 published results o£ • study in which a questionnaire sTas given to deteru~ne the degree of inter~al or external orientation. It was hypothes£sed that smoking beheviour would be feinted to percelved salience of the dsnKer of smoking. Smokers ~uld be more £atalistlc and bel£eve less strongly than non-smokers that 8mok~u~ is danse=ous. There was some support £or this hypothesis buC no strong reZat£onsh£p was seen. The author concluded that psychological factors may not underlie much 0£ smoking behavtou= and that sock1 psycholoK4caL or sociolog4cal factors may be mo=e /~pOr~LUt in understandLn~ smoks:/non-smoker differences. N£1sson and T£bblLng (153) conducted a study which may be considered to be at least paz~ly physlolosical As weU as psychological. They consider that the e~arette as a phys£cal object and s~oklag as • 8oc£al factor both constitute "extez~al world factors", 1~Lilst cigarette smo~ as a central sc/~u.l~nC coati,uses an "late=hal ~orld factor". Yhey measured ~ndi~Ldual dif~eren~es in dtez--ef£ect perception using an oculoSyral £11us£on and ser£al colon: word test. T~Ls is said to give BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-67- £nlor~st/~n on the iadiT£duals' relat£ve 4eSree of investment in Lnternal and external world contents. The results showed that, as prtdictd by authors, subjects who shoved a high dependence ou extenual world or envlroumenr~sl factors tended to be heavy smokers (over 20 c£Karetteslday) add vet ~tra~eT~d. Xt was sulr~e~ted thac Ir~h~se subjects m,sy Deed the p~lolical effects of ••skinK to increase their mwar~ness of internal vo=ld contents. For other Stoups of sub~ects the recorded ciKaz~tte c~smsptlon was correlated with ext:avers£on/iutz~verslon and aftor- e££ec: perception, as predicted. In 1972. in • study on smoking and s/an=laced driv~nK performance, Ashton and her coil••sues (12) used the CatCall 16 Personality Factor Questionnaire. They found t~at mask•to were more extrmrt stud self- reliant thin non-smohers but there ~are no other s~Kn,4f4cant d~fforan~as. Both ~okers and nou-smol~rs scored 8Lmilarly £0: anxiety and neuroticism. ~:~ • paper by BItti41 (18) reference is made to • study of 400 students. C£$aretCo smok~ w~s ~oun4. b7 qusst£onnalre, to be 1Lnked with rofo~a/social/cr£tic=1 attitudes and, by the Cartel1 Husic Preference Test, with sober/ma=~er o£ ~act/soc£el make-up behaviour. ~L'nis is s ra~her d~f~erant fin4in~ £rom others ~b£ch tend to indicate that ~kars are more rebellious and "fun--Zovin$" than non--amo~trs. Fisher and Fisher, also in 1975 (63). ra£e~d to s~ud£es shom~ns that smokers describe the~eZves as usinS more o=al outlets than nou- smokers (e.g. na~l bit~nK). Smokers ~r• sa~d to be charscter~sed by • cluster of tra~ts (o.K. da~Jer--seek/~K, c~mpulsiv~7, cmace~: wL~h self- stLumlat£on) mlKKestins de£enc• aSsJ~nt oral passive /J~cl/~ation. ~antly M~ott m~l Mlott (146) have i~vestiKate~ msok~K and ~antmmy. They hypothas4sed that :Lnd4v~duals who smoke Fantms~se more than those BAT Co LTD - MINNF_~OTA TOBACCO LITIGATION O oo ",o

-68- who have stopped mmok~.q or have .never mBoked. They used the Z~aKinal Frocesses I~vmncory. Th4s shows the ~enC co which £ancasy is used in Ohm areas of problaR 8olvin8, £ea: o£ £a£1ure, achlmvmnenc, hoscillcy, sex, haro£am and ~lt. Us/~l 90 subjects of each sex, the hypothesis yes supported for males only. They £amCamised moaC for all c&CeKories considered, sad spec/~icaIly, male greek•c8 used 8chievemeut fantasy more Chmn n~a-smokars o~ ex-sn~kmrm. Female me•kate, hcrpsver, £amcamise lease, especi&lly w~Ch reiard Co mchLevzC fanS•y, which female non- mnokers use memo. The author muKgesc chac dt££arenC approaches may be needed in understanding male mud £mnale smokers, and in helpinK them co seep smokies. "- Pad•teen and Le£coe (158) have recmncZy looked ac as-re•kern vho have abstained from mmok/J~ for aC Isaac one yemz and found no si~£1camt personality di£ferance8 be~on smokers and ex-smokers. Reynolds and Nichols (163) have studied 8S5 students and £ou~d smokers Co be leas well adjusted and more likely to anKase in anc4- social activities, althoush thls was more C~u@ got £emales Cham £or males. They also ~ound chat female smokers were more exit•vetted than non-smokers. Subjects vho showed behavlOU:LT md~ivL1.ence Co amok/:q~ (either startles or 8toppins duties a one year period) were intermediate in characcmr£scic8 between smokers mad non-ewokar8. ChaFf7 mad F~ernan (37) have published • paper on the £ollow-up dace for a 8mnple o£ 5,362 subjects, all born in ohm £irsc weak o£ March 19h6, :spresmnClng a large mud 8moSraphically •careered ample 0£ normal males and females. Parson~ltey daea were cellos•am me 16 yet8 0£ qe and dace on smok~ babies me 88as 20 and 25. This is one o£ the fay BAT Co LTD - MINNESOTA TOBACCO LITIGATION O ¢...j'1 O'~

-69- studies in vhich 8unokers have been found to be more neurotic then non- smokers. As has been £ound before, smokers were mote extravert than non-smokers. The rtlationshlp between smok£nK and personality was not only seen for those ~r~th e:~reme scores but very stable or introvert subjects did smoke Ies8 than those vlth moderate scores, and the hLKhest mean extravsrsion scores were for malt heavy ~kers. The persoDml£ty effects seen were independent and additive. It ts 81so very inters•tinS to see that personality scores at one qe are related to • chanle in mnokin$ behaviour in follovlnK years in the period coveted; neurotic extrwTerts were most likely to 8tart 8~oktn8 and stable msle extravert8 most 14~ely to siva 4t up by the age of 23 yea~•. Finally in this section, seeTeral authors have questioned the validity of some of the psychololic•l work concez~uK mnoklnK. Lsbovlts and Ostfeld, in 1971 (127) aw4m/~ed the 1£tereture and concluded that few studies mat the mJ3~Jm standards of adequacy. They 8peci£1cally pointed out the follmrlnK ina4equacles: I. Little attemtiou paid to dfffaremcee /~ 8moklnK bebaviour as a £unctlon of eke, socio-economlc status, fms41y smok4nS habits, occupation and relljlon. 2. D£ffermt studies use different ~___d stoneS/rues i11Ol;£C81 ct~teris [or classif?~ ~d '~ssuriu8" smoklnJ behavlour. 3. Scores on personal~L'y tests are o£tan used oJJ indepemdent vazlables aug little or no attention is paid to: (a) defenslveness; (b) umsvatlabil£ty o£ controls adequate for vLr£ous ~je, sex and 8oc/o-economlc froups; (c) effects of diJ~ferant administrators msd settiuss on r~sts; (d) va14d£t~ and reliabi14L7 of tests used. BAT Co LTD - MINNESOTA TOBACCO LITIGATION O',,

P -70- Statiatlcal analysis 18 o£teu used ~-thout couslderlnK the .8 fact that e number of independent varlables are inter-correlated ¢ and may be, in effect, meaaurins the same variable. Some studies also quote only the SiKnificant renlts and if • larks number of g£Knificance test8 are cazTied out a £ev must ~'u~e~l.tably show s ~rnif£cance. 5. Hypotheses are not derived from theories and little attention is paid to related subjects. The maasuz'.Lq of independent variables studied An retrospect £8 doubtful and reports of parents' smokJJZS habits may often be /~accurate. Obviously some of the more recant studies are an improvmnant on those which have gone before, but a uund~r of them cJm be crdticised on at leut some o£ the preced/nK points. To desiKn the ideal experiment ks obviously •1nest an /mpossibilit7 as the mmunt of data vhich needs to be collected from a larK• sample ks £orbiddinS. Nany authors therefore choose to study only part of the relationship bet3man person•lit7 and 8mokinK behaviour. ~uener and Plates ~iting in 1971 (136)• stated that the £ailu~t to find consistently me~ul difference8 in parson•Ida7 between mnokers and non-smokers as 8~oup8 confiz~8 the ides that smokerst t~ts and psycholos£cal d~uai~s are not unique. What is unique ~s the way in which mnoksra choose to £ulf£L1 their needs. Zn conclusion it can be said that, in Ken•re1, there do se~n to be a few fairly eoasistant differences between •mob•re and non-smoker8 and, ks to be expected, the l mrjest ~4ffer~s ate oftn seen when smokers o£ heavy c/sarette consumption are c©mst4ated. ~ther amy of these BAT Co LTD - MINNESOTA TOBACCO LITIGATION O~ "',.4

-71- d£fferances are part of a constltutional make-up which predisposes to smoklng cmmot be decided on the present evlde~ce. Zt is also not poaslble to Lndlcate, in m~ny cases, exactly how these d4~fere~ces relate to smokln8 motivatlon. In jeneral, persOmLt£ty and othtr psychologic~1 differences tend to be small and £or a gi~m mmokar o~ a particular personA1i~ type there my well be a s4~41s~ non-smoker or ex-amok~r. 4.3 Social Differences TJ~ • study of 6,820 school children, publ£shad in 1964, 8alber and Rochmm~ (183) inv•st£g•ted.60, 16-17 year old8 of each sex. They found nude smokar8, especlally heavy smokers, to ha~8 a I•s8 satisfacto~-y rel•tic~shlp with •uthorlty and parents than non-smokers. The £e~ale smokers were 8~ULilar to the males but were mot• cheerful and 8el£- cou~£dent then the nou-smok~ girls. ~.Ram~ell (141)"in In att~pt to "tlrpify" the smoker has found that paoplm who are Jot~tLy~ mddle-cl•lo, ~mIt~ous m~t t~mtotL1, uadar • third 0moke ~i]Lst £or people vim h~ve ~ o£ tlb~a• r.b~t~r~ot~ca, surve~ data se~s the hypothati~s~ archetype of the KnKI48h smoker as • lo~er ~ork~ng class male of 25-30 years of 8~a ~ch a sac~b~y modern education, hav~ loft school at 15, his f'm41y are smob~s ~ho do little to dissuade smoking and he ptdtr8 chas/~g 8tr18 and reKular dtia~kJ.u~ ~th 8mok~ £r~end8 to I;o£=g to ehu~lb. • pmon lf~ke ebbs has a 95Z chance of be/~8 a smoker while the con~a-L~pe has only about • 10Z chance o£ bein~ a z~sula~ mnoker. BAT Co LTD - MINNESOTA TOBACCO LITIGATION C..m, C~

-72- Z: 1969 Walker and collaal~es (216) Lava•elK•ted 55 uou-mokJ=g 22 smo]~n8 female students. Smokers ~re fc~d to ]:ave more problems a~d be =ore anz£c~s, to be as J:ztel1£1~e=t as no~-smoksrs 1~t mess Lnterested in science and nmslc. The stooling studemts also d£sl£ked more foods, ~ere more fraz~ in response to papeT and pen personality tests, csme from the same size fm~.lies u non-~kers .rod yore more clon~nant r.l~n non-smokers. The •mount of smoking was positively :e~atad to smxieCy and negatively related to musleal and liter•z7 interests. VeZd~um and Bc~ (215) also sly=died students. They had • total sample of 2,321 subjects £rc~ vhich they picked matched samples of 601 smoke:s and non-smokers and they then compazed 70 depemdent varlables. Among the results we:e • number o£ "social" d£££erences. Smoi~a8 was more common iJ: makes and the d£££srences be~en.smokers and non-smokers were Kreatesc for maze students. There ~re £ev £nteract£ons with soc£al class and no d£fferences in £amily s£se but stole smokers were mot ~ikeIy to be first born or only child=on. Smokers sho~sd lobar academic performanQe and raze smokers had less iuvoZvemant in high school social act£vities than make non- smokers. Fesuale non--smokers were, however, less social than the smokers. The:e was no indication of nagmtive attitudes towards paz~mts and authority amot~ smokers. Another study of interest was published in 1973 by Js~klns, Zysanski and Rose, an (107). Unl~kt •my authors ~hay had not £nvest£saced students but 2,319 males a~ed be~nmn 39 sad ~9 y~ars. When he~ smokers (20 or s~te c/~arettes per day) ~ ccmpa=ed with non-s~okars, r~be smokers more oJ~:sm •hound "coronary prone beha~Lomr pst~ez~s", ware mess educated, had lobar lee•see and dif£erent L~pas of jobs. For those BAT Co LTD - MINNESOTA TOBACCO LITIGATION M O"., "%0

-73- subjects who ve:e non--smokers when £4rst seen but had remd 8uokt~ at 8 £ou~ year £olLow-up, there were hi•her test scores on "coronary p:ona behl~our" especlal%y haste and impatloz~ce. The £tJ~sl study to be me~tioned here is ~1~st of Goldbou=t and NL~LaL£e (77) on 10,000 adult males in Zsrael. This study, althouKh it may not be d£rectly ~licable to smokers in Britain or the U.S.&o t is of /J:terest partlculm:ly because of ~he very larks sample s/J•. There was • h£jher percentage of mnokars mnonK :hose born outmldm ~sreel, Smokers tended to have crowded hous/JzK cond4ticms, lo~n¢ oducat4onal levels, little leisure-t/me physical activ£ty and also tended to be non-- :e14Kious. The smokers a18o had more children, umee mart phys£ca117 active at work and were more frequemt17 e~assd in manual and technical work. From the £em studles ¢ons£derad hare £t becomes £elrly clear t~at • l~housh smokers and non-smokers are 4£££erem¢ in some o£ the "soc£al" aspects, these d£f£erencas may be area11 and depend larKely on the sample of subjects chosen. Some of £he soclal auspec£8 o£ scar¢ins r.o smok8 will be cons£dered later buC it does seem tJ~tt • Irres¢ deal more uurk v£11 Bed ¢o be done beJ~ore £¢zln conclusions are poms4b%s •hour dif£erences /~ social charactsr~stirs. Z¢ uuet also he remembered ¢M¢ there £s some evidence that the social pattern o£ smok4ns is eAumj~ua8 and it is beemL~nK less accepcable £or people in ~ h~4~he~ social •lasses I:o be mhers. This will be d~scussed br£efly when 8~vin~ up smokin8 £m em:si4ezed. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-74- 5. SHOKING HOTIVATZON 14uch of this area has aZread7 been covered in a reviev by Wood (221). When the ruiev yes written, bogeyer, Rx~melZ's theories had not been fully developed. Zt is the intention here to include ~mmseZl's modal of 8mokin8 motivation and to discuss r~his in relation to other models and theories which have been proposed. Smokin8 notivac£o= theories can be divided into three cJteKorles, buC any divisfon is co some extent arbLtrary. The divimlon made here is ~inly onl of convenience. 1. Pharmacological (usually based on the affects of nicotine). 2. Behavioural/PsTeholosical (baaed on am extrmly wide rqe of theoretical pre~pts). 3. Y~ed. 5.1 PbamcOlOl;ical ~L~eor£es of. Smic~ ~ioCivat£~ ~ese t~eo~tos are usually based on the l~emise t~t~t 8mokez~ f~d one or more of the phTsLolol;£cal effects of smok~q~ and ~ually of nicotine to be pleasurable and revarding in some way. It £8 not yet knmm which of the many phazmacoloKical actions or combinations of actions of mn0~ is rewazd~ to the smokar8. Xf u~cotf~e provlde8 the basis for amok£n8 behavlour ~m= it is euler to suralJe that sk~q may tJrwolve dependence or addiction. T~ dependence develops gumklnK is usually seen as continut~K in order to avoid witbdrmml effects. J~ny of the actious of ~¢ot~ue have already b~en discussed 4,, a prev~ou~ sactiou m~d will not be ~ad further hare. There is one papar which can be me~ttoumd in pne8:~8, which 8uKaasts a faLrly novel way 4~ ~l~Lch Giwst;ta ~Ok~l~ ~ ]~4) np]bl4LIL1~lCO~,O~i~8~,]LT" r~8~dilla. ~L~'go~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION C...r" CX~ "-,-0

-75- Silvet~e C126) ce£er to a papec by Cahoon (35), who hTpothes~sed that carbon dioxide may be the :eix~orciq qent in c£8~rette smoke, e~pecially since the brea~hins patte~'~s of heavy smoke~8 may lead to c~rbon dicac~de depletion. Znhalation of ca:bon dioxide ~ch smoka vouZd z~store the balance. Since the ~bl£cat~ o£ th£a paper (in 1971) ~m~re has been l£ttle d£seusslcm of this hTpotA~ais in the lLte~a~e and Lt may be co~s£dered by sum7 authors to be inconzeqmmtLal. Cahoon 4id homier :~sl£se ~hst, in many csses, ca:bon d£~de re/:z~orcemant amy oRly plsy a small p~t 4~ nmok/~qB motivatt~. rroB • rwr~ of the evidence for the rolLe of nicotine in smoking behav£ou: CSection 2) it has been seen that .ny theories reZyins solely on the phaz~acolosica~ a~l~Cts of mack/aS ~11 be ~mable to explain all the expe:/~antal results obtaln~d. 5.2 _a~h=v~ou~al~¥s~cho~osicL1 ~heo:ies o£ b~ Hot!ration 1"n~se thaorie8 are leas "p~olo~1" in co.rant than o~A:er8 but £t is not usually /~plied ~st the action o~ nicotine is not l~volved. OnZy s~lies with some :eZevance to d£scuss~on o£ ~usse11'8 ~:~ sre included here. 3.966, To~k~n~ published a psycholos~cal ~o4el £~= s~o~/~ b~our (206). This was proposed on ~heoret~cLl Founds bued a~ his work an a~fect (h~m ~8eXin~s and ~C£o~). ~£ects amy be posit£~a (e.g. ezcLte:ent, smjoyma~ and surprise) or nesat£ve (e.8, dt=cres8, ~e:, £ea:, shoe or contempt). A~cord3~ to T~, ~ a=a iana~ely motivated to ~se positive and sd~L~Lze ~p~ve af£e~8. Smok/zq~ can rsduce neSat£ve a~£ect and evoke pos£t£ve a~£ect both Lanal~ly and u • =esuZt o£ 1~ processes. Tamk~ua v~sual~sed £ou: types o£ smolr~us • BAT Co LTD - MINNESOTA TOBACCO LITIGATION r',,o

-76- 1. Habitual mlokinS: Thi• may orislnall7 hay• been amoklnS for positive or to reduce ~|ative aff•ct b~t nov the emok•t snobs as if it feels Kood but tffecc4valy ~Chout ~ff•ct. 2. Positive ~fect ~: (•) st~sml~ac smokinS for ezcices~nc (b) relm~mt s~oking (undue pleasant eircmnsr~mcu) for sue oymmat. 3. NeK•tive ~f•cC ~~. ~nis is s~dativa ~ to rRducm neKmtive affect and the mmokmr may smoke ou17 q~aon thinks are not going yell. (•) partial sedative 8mokinK -- helps to w•du~t n~Kative affect so that problems can be solv•d. (b) complete sedative smog. kre smok~q is 8ton u the only way to reduce ne~sttTm aff•ct but p~bZmss arm not solved. 4. &ddlccive smoking. reduce uasstive sff•ct. The smoker smokes for positive and to b is mrs of not masking which inducts nt$•tiv• s/fact which only a ciK&rette c~m raduc•, b also ferule that ou~y • c~4~rmtc• ~11 8yoke positive a~fect and these failings are confirmed each time he smokes. In 1969, ]3u~d. G~eeu and Horn (98) published • paper giving results of a study on 2094 smokers. The ~Ul~LxLa~w scale lm8 admin~ete~od (a questlonmstre based on Tomk~ns' theory) sad the authors obtained broad support for Tomkius" modal, bn has developed J f-4rly shot• qummtionnairo (21t) which has 18 quemt~ Kiv~a~ s4~ factors repmsmntins Kratifications dmrivmd from mmok/~K. "St~umlation". "8ensorimotor manipulation" and "pleasurable relaxation" all re~lmct positive reu~ls (positive s~fact BA_T Go LTD - MINNESOTA TOBACCO LITIGATION -..,j

-77- smoking), -,',d "reducc£on of uegstlve feelings" /,ndicates that sao~ is used u • trsnqui111zar to allay unpleasRnt feeli~e (nee•tire ~ffect smolr..~ng), The remain£n8 Cvo factors race "ph78iolog£cal addA.ct£on", applying Co smokers who a~e avawe more of not amok/~S than of smoking, (addictive sBok~), and "habittmtlou" re~e~-r/z~ to ~e smokers ~oo smoke mxtcmmt~cal~y, not m~ss~ elK•reSt88 4y they awe ~mmvL~labLe (smokins without aZ£ect). A £u:cher paper, by ~ and Tm~kina (99) claz£f£ed :he position-somewhat. As a result o~ sere:el experiments it was shown chat neK&cive a~£ecc smokm:s smoke only where e~periencin8 he•Solve a~£sct stud Ohm: pos4c4ve a~fect imo~4n8 4s of low /ncidmace. Hixed posiclve and negative a4:£ect smoke:s y~11 smoke unde: both af£ectlve cond£C£ous :,f they are male. The females £n r, hi8 gcoup, hotm~er, mm~ke only when experiencing negative a~fscc. The cravin8 due Co deprivaC£on £rom smokinK t8 related co the type of 8~okiu~, addictive 8mokm:s ~avinK c£garettes moat and pos4tive and nmKat4ve affec: mmokm~s - leut. &ddict~ve smokers smoked mo:e and had more d~££iculCy in len~~ the e/me be~ c£Karettes. Russell (168) where d~scuss/~S the Horn-Tomki~ epp::oach suggested thac the corrslac£on b~L'~eess ~SaCive ,,,~£ec..t ~k.i.D4~ stud add~cc:Lve smoke.n• ~cltcaCes ChaC much nmSac/,vs a~fecc ~.s due co wicl=d='a~al symptoms. This us in fact impl£ed in the orts~=a~ Tom, n• model alChoush there was uo d4scuss£ou o£ the uaCu=e of the nesative affect caused by ~LtJ~lrawal. ~,ssell has also cz~c£c~sed Born and ~omk/n~ for omitc/n~ the 4mporCant oral and social aspects o~ smoking and fcr~ i4Pso~ua~ thus conscious and u~co~cious symbol£c =re•u/aSs of •rook/a4. NcKenneZl has c18ss£~£ed smokers ~cco=d~ns co the occa~ions on 'which they smoke (140). H~s seven £actors £ali into ~ broed cattS~nc~ts, BAT Co LTD- MINNESOTA TOBACCO LITIGATION %,O "--..I

-78- ":Lsmer need" ~b~.cb £s~c:lu~clem uez'vous iz-rJ.tat£ou suok£~, reI~t£on Snokiuj, Iloki~l -lout, ,e~v.'r.i.v'It:y •v.eoop,lm..iulnt atokin~ lad food substitution smokin8, mud • "soc£&2 £mccor" includinK •o¢~al smok£u8 and 8o¢£&1 con~ideuce mnok~K. "Znne~ ~ted" can be ¢mssldered to be a =e£1ection of the need £05 pbAcmmcoloKical ef£ecC8 o£ 8mokLn8 (and ms much ~ould make •:be c~tse for ~ne11'• work to be ~cZuded in the nmzc 8ecc4on). Tt ~JL8 beezl h~por~leSiled tllmc "~JoKte~ 1~4mldt' would be related Co preferred nicotine da2[vez~7 (222, 223). Za Proje=t k~BKJLT which ms set up to investiBat• this bTpothme4~, partial codirmmtion was obtm~amd but cb, d£st4nction between =1~8=e~8 o£ smokar8 v~tb d4f£e=e~t Ltme~ need respect of pre£erred n~¢o=~ dt14vez? wmm uot ms Feat as aacpecCtd. Zt could be couclude~, ~pmveqcs t~mC h~8~ iJ~mSr need ¢lustez8 t~•fer cisa~ettee with • h~R~er n~cot:J~e delivery than do low inner need clusters, NcJ[ennell (138) ham compared his cypoloK? ~Lcb that of Tmnk~ns (see TabZe 1). B~ did not £ind ev~dm~ce for Tomk~nsv lmbit~al omo~ . but: did con£tz'm that, as gmok,:i.nK is most: pleasant for positive affect 8rook,•r•, that they have 1888 ,risJh to fray• up smoir, ln$ and 8re Le88 likely to try to do so. 'I'A.BLI[ 1 | McEm~•12 e, ,~ T~ins i Addictive Helr~t::i.v• /t~£ect iii ~osLClveJ2£ocC e ÷ No Clusificncion by Tomk:in8 BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-79- Later, in ccmparinE his factors with rheas of the Born-Tomkins typoLoF7, McKnnell found siailarities beEveen the factors (139). McKsnnell used "addiction" as ma /rid•pendent variable not • motive. Tomkins addictive smokers in contrast, wre motivated to satisfy their or•vinE. UsinK Horn factors, addicted smokers were found in the tension raduccion and habitual 0•akin8 ~roupa. McKennell's "addiction" was made up from nervous £zTi~atlon mad reluctant mokiz~. Tension reduction (Ro~n) and nervous itTitstlou ~11) measure the same varieble~ as do habitual and reluctant smok£nS. ~icted a~ok~rs have the characteristics Of "dissonant" 8~okeEs who ~k4 to redt~e the ~5•t4ve affects ~ki~S automatically with no e~joyment. This contradicts T~' ortKinal idea of the addictive smokers •leo experfenc/~K positive affect and the nnatual exclusivity of addictive and habitual 8~ok~K. Russell (177) has crlticlsed McKennell for c~Ltt~ the son••rim•tar aspects of smoking and ilnor/~E the symbollc mess/hE of suok~. A completely differut "psycholojicsl" ty]~ of theory hal been proposed by Marc•ritz (135). Ha has stated that pharmacolosieal and social factors are relatively unimportant for em~kin8 no~ivat4on. He believes that smokers awe psycholosically addicted to /nhalation. The inhalat£on-exhalac/on--visualisetion ~Lad Is soon 88 an •tt~t to fulfil uumy unnonscious purposes z (i) d~lineation of /-net boundaries and fill/J~ of the emptiness of the chase. (£i) r~i~ of f~ar of ou££oeation. (lli) ~ratiflcatlon of respiratory erotieln or pleasure drive. (iv) respiratory introjectiou of • symbolic object with maSic powers for t~be purpose of identification ~r mastazT. BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~ --.I

--80- (v) projectic~ by way of exhaled moke or onto it, of unconscious fRntasy of self. This theory Ls often dismissed ms it sem to be uncmmected to other theories of mnok~ motivation and to have llttle Kemeral relevance to understandlng smok~K. Zt is included bert, houqvtr a it is own of the few theories which seeks to explain why ciKa:ette smokers are often . unsatisfied by other fonts of nicotine intake much as pipe and clpr amokin8 (non-~led amoke). Also in this section there is another type of a~proech which can be considered. This involves flndin8 out when people smoke in relation to external cues. Zn the cue of JLsuener amd Plate (136) the experiments were completed £n order to study e model of sBok/nS motivation. They believe that behaviou= is umuall7 a respo:se to intrinsic forces intersctlq with external ~zfluemces. Env£rom~ntal factors m~y affect beha~Lou: when they are potentiated by spproprlate umdlatlnS systems in the /ndlvldual. Thus they reasoned that smokers v~th a hlgh need for a~fillatlon should smoke pr~wLrily when others are mnokin$ and find it rmmu~LtnE u smokinE emsanders a feel/JzK of closeness and warmth. S4~41arly anxlous smokers should smoke mhen umder stress and report that mmokin8 is an effective source of relief fret am~ety. People who are uncert~n of their idmntlty should rely on mki~ to provide self-concept to a ~eater extent than those with • strouB sense of identi~y. Hausne: and Plate also felt that slo]d~l; could play 8 role in supportt~K feeltJ~gS of social cohesion, reduc/~S tension, or beLu~ involved in eelf-de~in~n~ behaviour, for people without acute psycholosical problems. The mochaniams far malntainins 8mok~n8 were not unztually exclusive and could occur tosethar in amy one BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-81- pt=Jon. The studies wh£ch vm:e pe=£orme4 co~£rmed the observation that smok£n8 is very often stimulated by other people smoklns. C£Ka:ette smok£nB mid noC appea: to £ucrease cohms£vaness of ~roups and enhance the sense of identification ~Lth fellow smoke=s, for • iro=p of female students. The studies did not confirm Tomk£ns' concept of types of smokers having pitte~s of ~Jii~b~t1~j ~:l~J~tIVi i~fi~.t~ l~l~ItlVi 'iL~/:iIP-~ tddictivt llmok'{~. T~D.{I h'td /Jplliid ~ h~l OriJiDIl I~l that each imoicmr was limited to me CFpe of mffect£ve supporC but in the scud£es of Mausnsr and Plate nearly all smokers showed m~xcuces of a££ecC~ve support. Zt was "d££f£cult Co :econcile the results with the concept of i£~ecclvely neutral kab~Cuml soiling (Horn. Tomklns). The results supported the idea chic rooking is used for teRs£ou =eduction. There was l£Ctle ev£dence for psychoLosical addicC£on but there was some iudlcstion tl~at crsvi~ for cisirettls could ]be ,mrelated to exterual tens£ou. There va8 mv4deuce cbac swol~Lu8 was used by some amokmrs as pa:t of role-def/~n6 behav~ou:. The authors ~est ~c smokers may no¢ have ~u=£que traits and psTcholoB~cml d~v~ma~cs (compared v~Ch ssou- smokers) but whaC is unique is the ws~ ~u which smokers choose to £ulf£~ their ntods, vhettvt: these my be. • rith (72) has rmason~d CI~C smokars who smok8 for st:J~ulat~ou (ph~mcoloKicaZ and psycholozical) sbouZd smoke most /n low-arousal s£tuac~ons. Smokmrs ~ smoke in hish-a=ousal situations-mould be II~D~ trmssqu£114utiOD- b hvi$op~d • qtu~SCiOOS~L~rl ~Or q~h~h I~j~tl had to ri~e Che~: dem4re co ~mmk~ in • ntmbe= o~ h3qPOChmt4cal "h4Kh- and ~ow- a~ous~1" s£cu~C4m. He found chit me~ wa~Cmd to smoke most in lc~- &cousal and vome~ in h~zh-arous8~ 81cuacions. ~Lu Seu~ral there was more BAT Co LTD - MINNESOTA TOBACCO LITIGATION (-m Oo -,,,,,j

-82- desire to smoke in lay-arousal situations (ptrkaps using nicotine as a stimulate) although hLsvy smokers tended Co v~nt to smoke in shy situation. YriCh presented the hypoChas£s thaC zkiuK behavtour ~s daetrs,4~d by the smokers characteristic ZesTs1 of arousal. He points out, however, Chat, on this ~asim, the results obCai~d ~uld muSSesc Ckat mmu are wrs a~=oused Chin ~. Th~s camzoC be mubsr2mc£aced. Frith therefore muKKests that ~ ~y smoke for p~colosic~sl st~lttlou w~LLe ~, who are less likely co Luluzle the ~ke, use the r4t~l of ~kJJZK to cabs themselves vhen they suet under stress, brmm~ (92) ~ted scene expert,s on mwk~ng which ~rt bued ~ 5cJzachCmr's studies of eat4,a8 behaviou~. SchachCer (I84) fo'md ChaC normal wiZhC people relied on internal cues (hunger and thirst) fo~ eaci~ but obese people ral£ed on extez~al cues for uciuj (Eva£1abilicy and appearance of food). Hmrm~ £ound ~C ZighC smokers smoked ~ra and soone~ /s~ the cast under h~sh sm£itncy condicions(c£Ks~actis 4n the room ~ra illuminated by a spoC-IighC) than under Low saliency co~d4t£ons (ciSartccts less conspicuous). Rear7 ~kers we:t umch less te~8~tive Co 8aLieszcy sad Cht£r antitank hab;ts vauc£ad most 8ccordJJa4 co leusth of depr£vaClon from smoking prior Co she cast. L£Khc ~kers ~z'e. hommvar, &1so m££mcctd by dmprivmclou, especi&lly under high saliancy coud£cions. The last emmnple of Ch£s tTpe of wrk which will be msntionsd here is the recant work of Glad and ~asso (75). They hooked at the ~nc4dance of 8moktu4 behavior under sevar&l arC~£c£ally eoustrucCad s~uat£ons ~o decermta~ the relative con~r£but4ou8 of tems£on reduct~ou and behs~Loursl cohesion co t:sciSsC£on o~ amoktmS. Tbay used two c:=dlC£~ end in each one the subject ~s wL~h ocher ~ndiwlduals who were tither 811 BAT Co LTD - MINNE.SOTA TOBACCO LITIGATION

-83- smoking or e11 noc smoking. One coud~c£on was set up ~n an attempt to provide socially i~duced tens£on, vh£1e subjects ~ere wa£t£ng to be evaluated by others. The oCher cond£tiou was cruced to provide • friendly social a~nosphere. 72 maze and 72 female students acted u subjects and were classi££ed as heavy (over 15 c£Km~ettes per dsy) or 1/Bhc (less than Can c£8azettes per day) smokers. The results cast doubt on the ~potCmnce of the ciKerette u • veh£cle to reduce tenm~ou, et least for these subjects. There was no dtf£ers~ce in the amount of smok£nK in the tense and the relaxed s£t~aticms. There Ira• also no difference in sel£~reported anxlecy in the tense sttuat£on becveen those who did and d4d not smoke. The mnx£ety man4puLat~on was, however, considered to have been successful and waiting to be evaluated does represent • more nozlnal situation than, for /nstunee, waitinlr, £or an electric shock. The results did prov£de elm•rout mvld~nce for beha~ourel cent•Keen in mnokiu&. Only ~£sht smokers were induced Co smoke when others ~ then qmre 8mokLu~ but both heavy m~l liKht smokers inetsmssd the •saber of c~swettos, p~f~s, fliclcs on the cisawette, and m'Lmztes spume smok£nK uncle: these conditions. Zn this section, ve have seen thmt soclallpsycholoKical/behavloutal factors my be /•portent in datez~[~ mud msinte/z~ng smoking behaviour. There is however, one study which casts some doubt on the role of social f&c~8, e¢ lSauSt iD car~ia preZiterate (priaicive) societies. Damon (51) invest/sated mnokd~s behav~our in fou~ Solomon Zslmnds add th~eu~ sub-~sm A~-~c~n societies. Zn S~Sr OUt Of tb 8e~@sl Societies t:he~ was no evldemce £or ritual o¢ myths invol~z~ tobacco, and sociaX £actors mere not reported or recessed as st/smli or supports for smok~. The ~t motive appeared to the personal sat~sfactlcm. Yet the only BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~ %,.0 Co

-84- society using tobacco in ritual and social contexts, it vu used pbarmacoloi£cally not wymbol£ca117. These Tesult8 are similar to those iudicat~ that of 22 out of 26 Oceanic societies vhich used tobacco. only two used it £u r£tua18. TI~I co, crests with the use of tobacco by Znd£aus in North and South Ame=£ca. How far this mort of result can be applied 4~ e IrLder context is open to couaiderzble doubt. Zt does lmever i~dicaCe quite claazly that althouKh tobacco is used very wlde£y around the umrld conclusions cam probably only be drawn for the partlcular type of soc£e~ studied. Thus, most of the work p~biished and rev£aved hers ~LII apply only to United States or United K~nsdon smokers. 5.3 H~xed Theor£e8 o£ Smok~n6 Motivation re.small is often co~side:ed to have been the £4rmC author to provide a modal for 8mokinS moc£vaCton which cecofp~4sas Cite ~port~ce of both 8octal/psycholos£cal/bel,~v4oural and pharmacological factors. Ha ks probabZy the first pmrsou to have preaouted a coherent model £n wb£ch the 4~tar-ralat£ouah4pa of the factors ~a co~lidered in dmC~l. To create this model he has bozTomed heavily frm a lares number of 8otwcas, mad he freely admits this. Zt is worth mutim~D4~, however, that mn in 1963 there were some authors who were ~hLnkLng ~ons the s~me lines althoqh they did not p~esent a speci££c modal. ~napp. Blls8 mzd ~tlls (~16) publ£shed a paper on methods of KivtnS up 8m~k/ns. The7 state that= "Smolu~u$ ~ppeJurs to represent m Zamrued psychosomatic pette~. Primary plemre £z~n Cl~ lwbit occsscs but becomes ambord~u~ta to jocoad~:7 u~e to v~rd o£f pa~u~, espec4811~ run'at7 o: • masse of 1088." BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-85- They mentioned the £ollo~r~n~ aspects wh£ch can contribute to the urKe to smoke: {•) symbolic and personal me•nine of smoking to the smoker (b) the nm~arous sensations accompanying smok/~s (8usr~atcry. pulmonary, ~sct£1e, visual and kinisrA~tlc). (c) the J~pulse to take ~n and elJ~LLmate, interwoven but Qot identic•l u~th alLment•ry urSes. (d) seeking by the hemvy smoker of • state of chronic low-grade arousal. They hypothesised that the motor act of smoklng contributes to the relaxing •spects of smok~ns b~t that sT•path•tic nervous syatam a~ousal is mediated pharmacolog£cally by n~cot£ne. This view of 8mok/z~ covets • large number of points made late: by gussell in the lash: of further s~ud£es by •urgers such as Tomk£ns and t~Annell. Kussell himsel£ £~rst published deta£1s of his cluslf£cat£on of smok~ns in 1971 (166). The £irst scheme ~nvolved five types o£ smoking and is represented in Figu=e 1. The types of smoki~ ire not rout•ally exclusive and smokers would be expected to have mixed motives for 8moU~j, The tTpe8 o£ 8mokLnK s~e: 1. Psychosocial. This was seen as be£nK laz~ely c~y~ftned to adolescent smokers wh~ ts~s in •Zmost ~ ~c~tins. Th~s type o£ smok~nK would be 4~term~ttent and usu~11y o~I~ take pXsme 4~ social s£tu~t£ons, with l~ttle desire ~o smoke outside those stCuat£ons. Th~s type o£ non-~nhaled nmokin~ could persist or may evolve into smoking for sensory rmmrds. BAT Co LTD - MINNESOTA TOBACCO LITIGATION c~ r',,o

-85n- FIGURE 1 s~m~ Fox cx~sn~z~G sMoxzsc ..accom)mc To x-ae x,x~xxx~,rc .PA~ERN OF REINFO~. (Frc.n reference 166) ? Types of smoking shogn in c4rcles. Types of pos£tlve ~8£nfo~ament 8houri in bozes. Arrows £nd£eate inte~reLltionship8. Low Nicotine Intake SENSORY REWARDS ~cotine Hizh Nicotine Int~8 PHARMACOLOGICAL REWARDS Oral | i Senmo=~moco~ f I' ! I $enaocy- pharmacological Continuum / \ \ \ \ \ Eupho'rJ.mnc Sedmt£ve 181 StLu~l~t W£ r~drm~l Rel4et m / / // BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-86- 2. Indulgent smok£us" This ~as conce£ved of as smok£ng for pleasure and occurr£us in many sicu~cions (such as watching telev£slou, read£ug and relaz£ng). The pleasure may be mainly from oral revards (oral indulgent), sensorimoCor rewards (sensorLmotor indulsent) or a m£xture of these (mixed £ndulseut). The oral £ndulseuc smoker would smoke mostly trlCh other, or instead of other, oral acclvities (e.g. satins or drink£nz) and would resort to oral compensaC£ous if he save up smok/~K. InduiKeuC smokers may So for Cvo to three hours viChouc smoking especially if they are 'busy, but may smoke heavily on induLSent occasions. 3. Tra~quillizatiou mmok£ns. Use uould be made of the sedative efface of nicot~ mud the cA~ e£fect of oral Scarification and otcupaclon of the hands, Co relieve a~iety and tenslom. The freqzcy o£ mmokiu[ would v&ry KreaCly with emotional scare. 4. Stimulatlou s~okins. Use wuld be made of the stimulant effects of nicotine Co mainta4n performance and allay fat£lue when perfocmins borins tasks, or to enhance performance and alertness in deIAnd£nK 81cuacions requlrins creacivlCy. The frequency of smokiuK would £ucruse in these situations. 5. Add£cCive smok~ns. The smoker mould Set w~thdrmval symptoms when Soius for 20-30 mLnucas without smokies. Re would smoke Co avoid or relieve the symptoms and amok~u4 £:equmncy vould vary little ~th chausin6 external situations. This type of ~ir.i'ng ceases only duzi~g sleep msd is regulated Co ma4ntalu brain levels of nicotine. In a paper publlshed in 197A (170) Russell aXso reEer8 Co She ~ay ~: which smoklnK can be related co classic leerninS cheozT. This had BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-87- prevf.o~Jly bten discussed by ]h~t: and Ktttrttzo (96) but ~sell has produced & £alrly conc~.se way of consldsriug smoking in this context. Hab£c £s a leLcued connection between a stlamlus-cesponse sequence and a re~aforceme~c. A negaC£ve ~e~J~orcement (~.e. punislwent) dlscourmKes behaviour. A posic£ve reiufo=c~ent is • reva=d, or escape from, or avoidance of, • .pun£shmmn~ and it promotes behaviou=. The 8v~mnsth of • habit depends on various pr~uc£ples and Russell has explained hot chase rolate co smoic~nS. 1. The number of reln~orcod trLaZs. SmokLuj pz~v~des • larja nmnber of tr£aLs or stimulus--tesponse-te4n~orcemant sequauces. This my be seem ~ a smoker o£ 20 clKmceCtes • d~y, each puf£ed on average seven to ten Clmes, perhaps over • period of 20 years. 2. Strength of re~j~otcemsnt. As strenKth increases so strength and rate o£ leaz~:S inc:ease. Thus an ~1 learns • cask more rapidly if ie is hzm~zT. Smoking 48 learnt more quickly in the presence o~ st=on~ 8pproval. S~m~lazly cutt4u4 down ~mok~ ~s • bad way Co stop 8mok~q~ s~.u~t the =ema~d of each ~.g~ette to the deprived smoker ~s en]umcod. 3. T~zLn4 of reLu~orcmnenC. The strensCh and raco of 1~uum~nS J~cre~se £~ thin ¢e4-forcament £ollmm c~osely. Thus Ln~ta~t peer approval by mmk£ng sr~h fTi~mds 4s s~ougot rJum d~lay~d spprovs~ i~ one smokes sAonm and Cells thmm laver. The z~oce haalch risk ~s a veak 4£s~ncm=~ve when compared with Ch~ sCron8 pos~t£ve re:Ls~o~cmmm~t o£ th@ ~t~mt ~£ect o£ gmokLus. The umKat~ve re4~otceme~t o£ mxpense of cila~ottes 4s ~so ~t remote £rom clue act o£ msok~S. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-88- 4. Schedule o£ reinforcement. This is the propo:tiou of responses follcmed by reinforcement. Learning occurs most rapidly if it is alvays followed by a positive re~orcemont. ~:ters~ttent reinforcement leads to slower lea~D~K but once leaz:u~ baJ occurred it is more di~flcult to extiJ~lsh. For many 8mo~rs Dot every cisazetto ~s revacd£us and reLu2orcement is Lutez14ttenc. /'his C~pe of :eiz~orcemeuc also occurs £f slokers try, paz~ially or unsuccessfully, to stop m0okiug and yield to the temptation to smoke pertxxltcally. By 197& u,,ssell had also eomsgtmt rev~Lsed k4s u~lel of smoking mocivacic~ and had publLmhmd a proper cemcm~ • questiou~mire des£~ed to ver~y the model (177). Seven factors or types of 8mokiu4 vmre nov recognised and their ~tez-~teLaciouilhipe are shown in Fi&~.re 2. l~ae seven factors rill be described before the results from the quest4ouzus4re mce discussed. 1. Psychosocial. There amy be almost no ~Lcot~e 4~Cake and the s~nbolic v&lue of smokJ~J is used co produce an tease of toushness, precocity, sextames and 8opbisticatiom. Bmok~ increases social considerate and helps the smoker to con$oz~ and Pin ~ceptance from peer Stoups. ZC is mostly found durin8 adolescence when smokies occurs IB,Ilil~ly in SOCial 8i~t£O=US. FOr lost Skirl b ablorptioD of nicotine is thought co umre evolutJ.om to amok~ £or phmnmcolol~cal revards but £o: those who do uot iahmle th~s type of smoki=g may persist £o: yeas. 2. Sensor~moto:. This involves enJo2qmmt o£ the uou--pbazmscolo~Lcsl sensations of smo~ and the use of ore/, smmusl and resp£~atoz7 man~pul&tiou~ £~c pleasu=e mud to red~ce cm~sloa. The pack appos~ence, BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-88a- FIGURE 2 ~From reference 177~ J~rov8 show r.he proirts,tion from one type of smokin~ co another. N denotas nico¢~e reward,,. SH denotes semmo=iumtor re.urals. / Zndullent Add£ct4ve m r~ BAT Co LTD - MINNF_5OTA TOBACCO LITIGATION

-89- fee~ of ~be c£Karette in hand and ~uth, tl~ p~ocess of lightins, dra~rlns in, puffLng out end watch£ng the smoke, the snell, taste and sound, all contribute to the rewards. Kepetltlon of the act itself is more important than pharmacolojLcal effects. This aspect of smokinK is said to be considered ~s~porcant by llZ of smokars. 3. InduLgent. The most cc~on fo~m of smok/~8 which Ls characteristic of most smokers of less than 20 cisaretr~s per day. Th£s is 8mok£nK for pleasure and occurs ma£nly in pls&sant s4tuatio~s. It occurs particularly in social situations and when drlnkln8 tea, coffee or alcohol. Unllke pe.ychosoc£al smokers, /~du~Kemt smokers also smoke alone. They can usually go for L~o to r.hree bouts w£thout smoking if they are busy but smoklns may be frequent on £ndulgent occasions. 0uCside these occasions there is little craving although cigarettes are missed if not available on indulgent occasions. This type of smoking is usually associated ~th /~halation and much of the pleasure of smoking comas from one or more of the pharmacological effects of nicotine. 4. gedatlve. Smoking is used as • trdmquilliser to relieve unplmant anxiety or tension. 8mok~q frequency varlas v~th emotional state. Zc is not clear to what extent n~cotina effects are Lmportnnt. This type of smoking is more cos•on 4n women and tense, nervous people. Zt is associated ~th 8ddictivt Jsokiq and it sty be Chit the tension and anxiety to be ~elievsd are v~thdra~l symptoms. 5. Stimu~aCion. 2~Ls kind of mok~ns £s pursued when the smoker is busy and .active and uses the stimulant ~tions of n£cot4na to • £d think£n~ and concentrst£on, to allay fatigue and mainta£u BAT Co LTD - MINNESOTA TOBACCO LITIGATION Co Co Co

-90- per£o:mance. Unlike sedative ruskin8 vhic~ is used Co avoid stress, st/mulation mk/.nll is used to help overcome stress. ZC ~nvolves hiKh n£coC~e intake, especially in demandins slc~tt4ons. It ks associated ~Lch both addictive and automatic amoki~S. 6. Add£ccive. The smoker sets w/Chdrmwml symptoms a~Cer 20 Co 30 minutes w£thout • cisarette and smokes ouc of the necessity to •vo£d or reZieve the s3~npcoms. SmokJ.nl ks no lesser pomitlvel~ enjoyed and consumption ks larsely independent of extez~tl circumstances. 7. &utomaC~c. This CYI~ of smokin8 is found only in very heavy mnokers who are stimulation or addlcCive smokers or both. A second c£sarecCe may often be lic whale the first ks still burninK. SmokinK has become automatic and ~he act o£ Lilhtin8 up is o£ten unconscious. Positive rareness of mJcJ:~ has been replaced by an acute ave=chess when c£Ka:ettes are m£1mble. When R~ssell, FaCe and Yetel (177) met out to devlse e quest£onna~re ~hey wsnted to combine the better feustu,x-es of tJ~e morn-Tmsk£ns and 14cr~nnell-Thomas c~poloKies and to /J~clude some aspects not hitherto covered by these questtouzuL~res. The mo~lel proposed had 4~corporlted £ive of tke six Horn £actors tolether rich the psychosoc~ml aspects suuested by P~=Kmunell mad by Bynner (34). Russell attempted Co incorporate HclCmanell type £cmns into • Horn type qumst£onnaire. The :msult/n~ questionnaire heed on RuasellSs model was publ4shed toje~he: vLth :smelts from s sample o£ 175 subjecC8 uork~sK ~:1 m hosp~sl and 103 subjects • CCend~uS a 8mokiuS clinic. SLz o£ the seven £acto:s proposed in the model vere found 8~ter StSt£StiCLl m~Iys4s Of :he dan. The~ mere ms £o~1o~: BAT Co LTD - MINNESOTA TOBACCO LITIGATION Oo

-91- 1. St~nulation masking, iJlcludins aspects o£ Homes s~JsulaC£on £acCo: and Ncr~nnell's activity accompanY•eric facto=. 2. /odulsenC smok~J~;, combln~ng Horn's and HcF~=Jze11's smoking for pleasure in relaxed sirumtlons. 3. Psychosoci&l smoking. Sat aspects £ram ~11. This factor represents soclal mnok~ug and the use of the symbolic value of smoking to create an image and improve social co~fidemc8. 4. Sensoz~mocor emok.~ng. SimLlar co that found by Ho=n. 5. Addictive smoking. J~ain 8~JELIar to ~on. 6. Automatic smoking. Similar co Horn's habitual smoking. Sedative smoking did not mrge as • £ac~J:r although Horn found evidence for :uagetive LffeCC or elision reduction I~okin8 and Hcgennell found a nervous irr£tation £&cto:. Sedative smoking am•rEed as e factor from the analys£s only 1£ Hcganz~ll =ype qulsC£o~s vsre om~cced. Russell explains the absence o~ the factor in the aULt~ analys£s by indicating that tension may be desirable for some people rather than unpleasant. these people would score on the eel•relation smoking factor. For ochers negative aggect would be due ¢o srlthdrtwal symptoms and they would sco=e go: addictive amoking. The items and £actors separated Co suggest • factor ind~ca.ting degree of dependence or addiction and another £tcCor represemttJSg • phazwaco~os~cal versus non-phezwacolog£cal ~iou. IndulsenC, psycbosocia~ and son•sties•or gacCors were Unou-~pbansacologtcal". St£mulec£on, autommtlc and addicclve £accors vere Wpharmscological". Although the non-phmrmacoIogtcal lCmu ware spread along the dependence dimension, the pharmacological items all scored hCgher £or dependence. C ¢j.- ',,C ',,0 0 BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-92- The pharmacological d~usion resembles the X~Kennell's concept of inner need but HcF.nnnellVs relaxation smoking came in this cateKory. PmssellWs tadulient mmoki~ was, bowe~r, "~o=-phar:acoloKical"- For some of the mlys£s se<Lacive smoking was included on the bss£s of scores for ice.s intended to reveal this lector. There tr&s e correlation helen cilarette consumption 8zzd st/Jnulatlon, addictive, su:maatic, sedat£ve and 4ndulsent smoking. These factors were also scored hdsher £or tho smokies cliL~c sample and appear to be pk-rmacolosical ly rmla~ed. There w&s a small negative correlation between age and psychosoclal smoking, as expected. Woman tended to score lover for stimulat£on and addictive smoking and significantly lover for sensorJJnotor smokink than men. Women also scored hLsher than man for sedative smoking. Th£s does mot support ¥r4~hes theory (72) Chat woman It7 use sensoz~Luotor aspects of maoking L= hiKh-~rousal situations while men use ~coti~ for st~nulstion Lu 1ov-arousel situatloud. The proposed model was fl¢ted £airly well by ~ h., but indulKent smokLn4 was not found to be more "pbarmacoloS£cAl" than sensoriJnotor and psychosoclal smoking as w0uld have been expected, and the oral rewards did not separate from orJ~r sensorimotor aspects. The postt£on o£ the sedative smoking concept was not resolved but it did not appear to be associated with sensor/notor smoking as postulated. :tams intended to provide tim sedative smok/~J £actor tended to appear in the phaz~nacoLoKical The resu11~s sullest a prolression frot psychosoe~al to immlUlllant and/or sensorlmomr smok~nK and £inatly Co mmok.J.ng for phamcololicel BAT Co LTD - MINNESOTA TOBACCO LITIGATION m m

-93- effects. Since o~ly paycholocitl snaking yes related to eke, Rnasell m~KSested that proK:essiou to 8ddlctlve 0mo~aJ is not ~e~table; it only occurs ~n i proportion of 8makers. T~, hey•yew, the p:osression to 8dd~ctiye 8mok~n8 does occur £t is rapid. Since the paper on th~s qu~stionnaire was published, B~saell has continued to use the queationna~ro. Be has said (17A) hownver, that he is not ent£re17 satisfied v~th the £oz~st of the ques~onna~re and • St•at deal more work ~11 be needed before 4t can be used with conf4dence. There seen to have bee~ no published attempts to ~mprove it by my other • uth~rs° Pe~.sps th£s model, since it includes the majori~ of aspects o£ smokin8 motivation suggested in the past by • varleCy of imthors, is the closest approx/~atic~ to a composite represe~taclon o£ the reasons why people 8make and the way in which these :eAsels may be tel•ted. ¥£nAlly in this section urea•ion must be made o£ the ~eoriel ezpe:Ludme•l vo:k o£ Schachte: and his colleaKue8 (186, 187, 188, 189, 196). Re believes that 8mol~nq~ ~s phaz3nacologlc~117 and ph~s£oloKic~11y dete=m~ned and that hea~ 8mo~e:s, at least, smoke £or n~cot~ne. H~s ~:eo:~es do, hou~ver, belon~ in th~a section on ud~ed umtivat£on since he ~1L~3~8 the ef£ects o£ p~TcholoK~csl events such is stress, J~d~c~t~K that these e~£ec:s may ~t mediated physiolos£ca117. Be has conducted a aeries o£ so:pert:lots ~tletinK u:~ pH to c~Ka:ettt consumption under ~•rious c~etw'ttan~es. F4rat17 Schachter (187) £ound that omokera ~hose urine was ~zti~tc~lly sc~d~ie4 smoked more than those ~L~h alY~l~ne urine. Be emp~sJJ~ this ~u te=ns o£ ez~ret£on o£ un~haaaed u~eott~e into che ur~:e u ~h£a Is • pH dependent process. He quotes the results BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~

-94- of Beckect and Tr£sss (20) who found that smokers with acid urine excrete about 35Z of adncLnistered nicotine in the unchansed form. Sci~chter estimated that "normal" pH urine contm~ 7X unchansed nicotine and elkal£~e urine, less ~han 1Z. Therefore, if changes in urine pH are assumed to be reflected in c4rculatlnK nlcotinm in the blood, and amounts smobd depend on blood nicotine concentrations then urine pH should af£ecc the remount smoked. When this v88 found to be so, Schachter looked for a correlation between urine pH and number of cigarettes smoked per day on days when urine pH was not controlled and found that the lower the pH. the more a parson 8mokod. It m then found that subjects smoked mote and had more acid turin8 on days on which they had been to a party. A f~r experiment ~mxl£cated that part~-go~ d£d tend to cause acidification of the urine in smokers Rnd non-skers. Stress was a18o found to £ncres4e smokinK and to decrease uri~ pH. In order to try and test the hypothesis Chat some of the psycholoKical determ4nants of emok£n6 rate are mediated by the e~fects of these on urinary pH, subjects ~sre subjected to stress vh£1e chair ~e pH was ~ndependently controlled. Stress was found to affect mmokiJ~ rats (in terms of nmnber of puffs and cisarectes) only when urine pH was uncont=olled. It was also hypothes4sed that if blood nicotJ:~t l~vels ere below a certain optimum level for the smoker then k will smoke ~esardless of urinary pH. An ezperis~nt wls chafers:re conducted in the moL~::Lu4| when urine tends to be aLka~/~n and blood u£cot4ne levels are law. Subjects were found to smoke at a rate whlch m ~lependent of stress and u=i:axy pH manipui&c4cms. Schmchtar believes that it is tnntectseez7 to propose cypolosLe8 to explL~n smoking. He proposes as a working hypothesis that virtually all BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-gS- lou4~tima smokers, heavy mud light, are addicted and that many m~d perhaps aZZ mpparmnc exeepc£ons to the add£eciou model can be understood in terms of notions such as self-control and concern for health. ~Ist these phArmaaOlOliCll/phys[OlOliCal axplanmtlons for Che psychological effects on mmok£u@ bmhavlour have some attract£on, a certain amount of doubt must be cast on the content of the papers in which the theories are presented. The papers include a fa£rly h~lh proportion of anecdotal detail and • number of sweep/~qB statements. Tt iS, for instance, po£nted out that studies conceruin4 the effect of mam~pulatlng ~cotLne intake indicate nicotine resulacion only for EnSl£sh smokers. This is explained by stat£n8 that since cigarettes are likely to account for • hi$he¢ proportion of the take-home salary in En81and than in the United States, then most English smokers vho can Kive up 8mokinK have done so and the remalnJJ~ smokers are more addicted than the 8vereKe U.S. smoker. Schachter else makes only scant reference to the ~sys in which n~cot£ne intake can be regulated apart from the nmnber of c4lsrettos smoked each day. It is the £ee1~ o£ the author o~ this report chat the "mixed" theorles of mmokin~ motivation stiZ1 serve a useful purpose add that to entirely disr~lard any concr£bution from non-pharmacolosically determined ~actors ks not Justified on the basis of the available evidence. The bulk o£ publlshmd work to dace would seem to ind4cate Chef psycholosical theor£es must have a place /~ undtrstand/J~ mno~4nK moCivatio~ and qu~te possibly non-pharmscolos£cal factors have some importance for most of the amok/J~ populatlon. BAT Co LTD - MINNESOTA TOBACCO LITIGATION /

-96- v 6. INITIATION OF SMOKING" KEHAVIOUR_ The reasons why people 8t~t to 8mole have not yec been clearly dete~sined, h this section a number of cutTent views on the factors which may-be of ~port~mce 4n the early stages of gmokln8 are presemced. Most of the views concern sociolo~y and.psychology since phaxzmacological effects can oxd.y assume importance once smoking has etarne~. McKeunell (137) has examined data £or British smokers end concluded that the onset of regular smoking is an adolescent phenomenon. The "age of onset" graph looks like a grouch =urve for other pubertal or maturation phenomena, starting in the early teens, aceeleratlnJ in the ,-4d-taenJ and levelling off by the late teens. The largest increment in stoking occurs at 15 to 16 years when most people leave school. By the eke of 20 most people have already starred co smoke if by are eves pine to do so at all. The masking behaviour of one's parents appears to be important. Among boch adults and adolescents the percentage of smokers is highest if both parents smoke. Am may perhaps be expected boys are more influenced by their far~ar's amoki~B habits than are girls. The attitude of the parents is also important as far ~hildren smoke if cheLr parents are sCronsly opposed no mnoklnK than if their parents tee indifferent to smoking. Bynner (34) studied ten to 15 year old boys and found thaC there were four main influences leading then to smoking. These ~rm: (1) (il) (ill) (iv) the uumber of friends who mmokm anticlpatiou of aduZthood panmts panu~eslvsnees cowards smoktzs whether they ~re put off mnokin8 by "the dam4Ser of lunS c'~cer'', BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~

-97- Zf all four favoured laoking 70X of boys laoksd but if all four were negative influences then none of the boys smoked. The first in~lumnce was the most important. Anticipation of adulf:hood was linked with rebelZ£ousness and delinquency and includes dr£~kinS, So/uS to coffee bars and dances, steylz~ out late and Kenerally pa~ticipmtin8 in the activities of older boys. Bewley. Bland and ~:is (25) s~la:ly found that boys of ten and 11 years old were most 1/~sly to smoim if both p&re~ts, their father or any brothers smoked. 1"ns7 sufjBested that this £ndicated that £f c£Karetteo were 8vs~18ble in the household and smokLns was obvlously acceptable this could be very important in shapln8 early smoki~S behav£ou:. ~ttl£n (144) has also =utsested that smoking beh:viour may be largely i~lueuced by persons other than the iJ~dividuaL smoker. The sources of ~uaBct to which the imsoker has ~eattst Ixposure have tim 8reatest effects but all sources of £~luenee have some effect, lkttlin defines "Hodels" as those whom the individual takes to be examples of various upects of ciKarette smok~, as4 "Definers" u persons to whom the iz~liv~du~l has spoken shout ciSa:ette smoki~. Xf the ind£~dual is cont£n~slly exposed to both Hodels and De££ners who th~sselves smoke CiSL~ettes and expect ~he i~divldual in question to do the same, th~n he Is m:st llimly to smoke and hLs s=oki~ may ha very dlff~cult to chan~e. Since the individual has llttle control ove~ the behav~o~r of those around him, t~elr att~L~des sad expectations of him, than ha ~Lll have difficult7 in controll/n~ his mm beh~viour. Hc~m~:ell (137) has /~l£cated that patallelinK the a4olesce~t eu:~e fo~ the onset 0£ =efp~:La~ gmok~=K but three to fou~ yes=s before this ~e the ~ £or the a~e o£ the £~rst c~Karette. ~ussell (168) lists the L~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-98- reasous for the first cJ4~ettt 8s curiosity, co~orai~y, bravado or to appear Krc~n-up. He states that the first few cigarettes are invariably unpleasant and w~th curiosity satisfied by the first c£Karette, s~ok~ng is only repeated if physical disco~ort is ou~we£ghed by psycholoK~cal or social rewards. Barley, Bland end Harris (25) found thJt m~nS children of t~n and I1 years old who had slre4uiy tried their £irst ciKarette 32Z were sick mad 21Z enjoyed it. Of non--smokers at tilts ass 67X expected to be sick add only 3Z to e~joy :Lt. lbzssell Juts stated that of r.bone teenagers 8uac&/:aK more than one ciearette oulT ].SX mid becom£nK reKular dependent smokers (170). The der£vation of these £1Kures has already been discussed (41). ZC appears ~hat Russell has used the results of 8 survey by NcX~m~lL a~d Thomas (142) end presamts these in rat.he= a d~ferent £otm. The sssuspt4ou, £rca his statmsant, ~at only ISZ of non-smokers have ever smoked ts not valid and the f£L~Lte iS nearer 62Z £or adolescents who are 8t present non-smokers. HcRennell (137) :slews to the result~s o£ a survey for the MLu£stry o£ ltealth c~ boys of 11-1_5 7ears old who were already "resular" smokers (cme ¢iKaurette per 1reek oz more). ThQse boys ~ated £ouz e~Acepts, ~hetr idea o~ themselves U t~ty aura, their 4dLsl selves and the4r ~dea= o£ mmkinS and non-smokes boys. l~:e ware ~h:ee main 4/meaJ£ons Sove~ the boys' percept£on - the notion of educational success (success ~n school terms), toushness and precoc£ousness or maturity. The gesture o£ smokes ~hich attracts boys is toughness as not seeking is also associated ~tb ~matut~ty. The at~:act£ons to mk.t~ a:e, however to m extent £o,~tered by the 1~ o£ edu~stio=al 8~=cas8 associated ~rLth 8mo~inK. The boys ~o m~ke velu~d convent£oa~l school standards snd £a1~ ~e:£o: BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~

-99- in failin8 to achieve them, aeeiDg noD--smokers am wore muccess£ul. Nou- smok£n8 boys also saw themselves as more success£ul buC were attracted by the toushness sssoc£ated with smoking. Both 14cKeune11 and Russell suzSest chsc boys who feel £msdequte in school terms may be those who ere most l£kely co be attracted to the toughness, mmscu£1nlCy and mmcur£ty associated with smoking and therefore smoke to compensate. This also follovs L£ boys compensate for lack of success at school by jo4n£n~ the out of school culture of older boys, many of whom are smokers, thus being exposed co important soclal pressures Co smoke. Russell (170) has published • diagrm s-mmmriSi~K the positive and negative reinforcers controlling early smokinK (FiSurs 3). He points out also that sensory 4iscomfort will only apply Co the first few cLsarettes and the unpLs&sanC s£de-effects of a.LcoCJ.ne soon disappear as tolerance develops. Farent•l mtCltude School attitude itealch risks Sensory discom~orc l~ico cina affeccs Nou-~ksr FZGUIUE 3 BAT Co LTD - MINNESOTA TOBACCO LITIGATION 4- Availability of cLgarecces Cu~£osicy l~balliousnmss TOqb|~tSl d~C4cipmt£om of aduL,~hood Social coaSL~ca P~ceuCaZ example 014er sibs mid.aS lrriea4s ~ir.tLns ,) Smoker C

-IO0- Fi~lly, it ~8 been et"Id th~ peteonaLity c~tributte llttle to t~e acquisition of 1~o~8 (168). C~erW aud ]r.{et~lm (37) have, however, rocencly sbmm tt~t pers~lity data ~ollacted at the aSe of 16 i8 ~elated Co =il;o=rette amok~ at the qes of 20 and 25 ye4ts. ]~ a 8t~7 of more tba~ 5,000 ¢h£1dten they found that of those not smoking at L6 years, ch£1dreu ocot~$ hi4;best on =~mtot£c£m 8~t extr~ers£ou (E?senck Petsm-sl£ty ]r~entozT) were nmte l~kely to start amol~4n$ than those sco:~=li b~i;best on stsb£1£t7 ot J~t:m~:s~. Stsble exttmtt males were found to be most 1lilly to stop omoi~n4 b7 the aKe of 25 years. BAT Co LTD - MINNESOTA TOBACCO LITIGATION Co

-I01- 7. CZSS,TZO. SMOr a Xn order co understand the nature of c£garetCe smoking and the degree to wh4ch people may become dependent on ¢4|a~etta8, it is necessary to cous£der the diff£culties of Slvi~$ up mnokLn$. There are ~vo ways of 1ookins at the phenomenon of smokiul ~smat£o~. Y£rstly one can look ac ~he LTpe of people who can give up and che£r reasons for doing so. Secondly one can consider the various types of mthod wblch have been advocated to help people stop mmk/ng m~i to see which of these are successful and to what degree, both in the short term and the IonK term. Here the L~rpe of people who $£ve up smoking ~11 be considered first, Ln roughly chronolog4¢al order of the papers refaced to. A survey of the uethod8 used and their effectiveness will then be presented. Wear~erle7 (219) has &sEed whet forces would operate to ¢suse a person to persist in his resolve to stop smoking in the face of personal discomfort involved. Be assumed that althouWh external forces .my be important, inte~l forces must ~8o operate. Ha rJhtrtfore SU~LKtScod that there mat be dijt4nct personality characteristics usociattd ~rlth persons who successful17 stop smoking. Be sL~died four groups of students. Group A - 70 non-smokers who had never mnoked. Group B - 42 cu~rmmt cigarette smokers who bad never made 8 serious effort co stop 8mok£nS. Group C - 48 c~rremt cigarette smokers who had made at l~ast one serious effort tO atop 8~oJ~L~. Group D -- 22 formsr ~herm who had ~ot ~ for at 2eut mix ~tbm. Al~J~ugh students are a rather 8pecial ~7pe of population and on2y uales were /nvestigaCed, ge~atherley did f£nd some differences bet3men C~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-102- Kroups usinE the Edwards PersonAl Preference Schedule. Ha found no evidence foe differences between smokers and ~mn-~kers (A and B) but both these sroups diffe=ed from the ex-smokers (D). Ex-smo~rs scored hisher on achievement mad a~sress~on and lower on deference, affiliation and cheese. Those who had tried umsuccessfully to stop (C) scored sla~l~tly to ex-~rs but sc~red hiSher on achis~lment and cheese. The author speculated that if a pc:son tends to make decisions for himself (toy deference) and to express af~ress~on openly (hiEh asEresslon) he trill be predisposed to iniC£stlng an attempt to stop smo~ng. Success, however, depends on hev;ng a weak ~ed for close ties with peers (lc~ aff£1iation) together ~th s, inclination cowards behav£ou:al stability (low chaz~e) and a sCronK Eeneralised drive to successfully master difficult tasks (h~h achievement). An alternative hypothesis was that, since the e=t-smokers had started ~kinI e~Elier than the 8moV~rs, persons who start Imokin8 earlier have different personality chsracteristlce. However the perscmalt~y differences were still seen when see of startle8 to smoke was taken into account. When asked why they had tried l;o stop smo~nl, concern for health was meucioned by 62X of u:succeesful students (C) but only 36Z of ex-smo~rs (D) and amy not therefore be a stroni enough motive for success. Rnssell (168) believes that the ~ey to the differences may lle in McKem~ell and Thomas' consonant sad dissonant maokers (I~2). Consonant smo~rs are outwardly bapp~ about their mkln~ although they ~s7 have attempted to stop in tJ~ put. E~ssell has said, however, that t~Ls may be an attempt, In soma cases, to ratlo~sl£se their smoking behmvlour without mdm~ttinE that they cannot ~ive it up. D4ssonanc ~moi~rs ha~e BAT Co LTD - MINN~TA TOBACCO LITIGATION k.r't

-I03- neE•tire atClCudes Co mmok~us and say thac they smuZd like to or have tried Co give up mud are dependent on smokla~. F~r-mmokers resemble the consonant smokers ms they race Xow on dependence s~ales, but they have negative attitudes to msokin~. Russell surest• rJ~a: in consonant smokers a charade in actltude s~.11 be ~011owed by • ahanse in behmviour whereas dissonant smokers are too dependent on smokinK for this to occur. This does not, however seem to be entirely compatible vlth his idea that most people ~d:o say they are happy with heir lmok~18 are in £8ct to some extent raincoat and dependent smokers. He does however point ouc Chac the AOX of consonant smokers who have in the past triad to •cop score higher on dependence and inner need (like dissonant smokers) than Chose who have never tried to stop. Eisi~Ser (58) has cried to discover predictors of amokins bmhaviour thanK• by LuCervim~nB lp~opla C~-~ca, with Cvo years between Lnte~ewm. He states Chat previous studies had shown Chat those vho stop 8mokLnS tend Co be older and to smoke lass. These studies also found Chat men were more successful in stopp~ than wuman, Chat hiahly educated smokers were not better at stopping and that subjects who have prevlously tried mud failed have more success than those tryin4~ for the first t/me. Eis£nssr classified his subjmccm as: quit, reduced, no thanks sad increased. Hales ~ere mo:e likely to quit or reduce than females as were all subjects with children in the house. KLsht variables tare sham to be associated vlth behaviour chanae: (i) number of ~Lsarectes pc: day (ii) perceived di££icul~y of quiCtind~ (iii) adremz~mt or disagreement sr~th • scat•nat concarnlns tmaZch risks ~rT BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-104- (iv) (v) (vi) (vii) (viii) acquaintance with someone whose health is or has been adversely affected by smoking presence of children in the subjects' household sex score on Ton&ins' psychologically addictive type score on Tomkins' habitual smoking type. Habitual score made no difference to quitting rate but the score was correlated with reducing race (probably due co the correlmfiion with number smoked per day). Addictive score was correlated with reducing rate buc also with quitting .rate (subjects scoring low addictive were more likely to quit). Over the period of ~ years studied. 15Z of the sample had stopped mok£n6 a~d 20Z had reduced their cigarette consumption. These figures for the United Scares (1966-1968) are similar to those for the United Kingdom which Russell (168) has derived from Todd's data from Ig58-1968 (205). Male ex-smohars make up IBZ of the population who smoke or have smoked. Pot women the percentage is nearer 17. Russell calls this the natural discontinuance rate and points out that iC occurs mostly after the age of 30 and increases with age. He also scares that the ex-smokar status is unstable and relapse rate ks related co the duration of ex--smoker s~atus. Of those persons who have been a~- smokers for less than one year there is a 37Z relapse over the next years, compared with a 19Z relapse for ex--smokars for one to two yurs and 5Z relapse for those Dot nmsokin8 for ~uo ya~s. KttssaTl St~SeStS that, in view of this dynamic turnover it is ~mlikely Chat more than 15X of ~eKular smokers unde~o natural dlscontlnumnce to permanent ex- smokin8 status before the ass of 60 years. BAT Co LTD - MINNESOTA TOBACCO LITIGATION C

-105- Thomas (203) investil~•ted various char•cteristics of fomer ciKarette smokers, continuins smokers and non-smokers. She found that of the personality scores and psychob£oloKic=L1 mLssu:es obtained, anz~etT, coffee and • lcohol conJumpcion d£st£~£shed former smokers who were intermadi•te between the other two Stoups. Former smokers dad not da££e: £rom couci•ulnK smokers in terms of qe of sCmrCinK to mmoke but had smoked less before the •Ks of 30. Kyen (182) looked •t the characteristics o£ those who successfully stopped smok£nK in 8 cozmunlty ef£ort in the United St•tes. The Kroup method only appeared to work for Kroup-orlanted persons. Those who stopped smoking were more willing to undertake new projects, had strong self--control and freedom from azucie~y and were more likely to be of hiKher social class than those who did noc stop. Meyer, Friedman and l~:arsfeld (l&5) studied the re•ponies of 200 Ame=icans to Cha ¢ampaip •saiust amok/~8. Only 23Z cont/~u~ smokers had no reKrets and tended to reject cautioumry st•Cements about health and discount their ~j~porcance. Other smokers had conflict about chelr smoking and may, perhaps, be compared trAch HcZennell's "dlssoDaszt" smokers. The fOX of smokers with Kreat conflict belle~e that health hazards exist and apply to them but some weIKh the costs and ben•tiCs of smokinS •Kaiust those o£ stopping and decide Co continue. OChers compensate for the conflict by v~umly prcm.4sing co stop 4n the future. The costs o£ stoppiq and bene£1ts of continuing ere often masn~fied. The authors have tdenc4£ied • self-PezlPeCUAting cycle of delayed Sra~L£icmtiou: (1) (ii) (i£i) • fulinJ of b~Lus out of control aud de~denc $uilt or shmme over be~ Coo we~k Co act delaying • ciKarette C BAT Co LTD. - MINNESOTA TOBACCQ LITIGATION

-~06- C£T) (v) (v£) (v££) (viii) (ix) a ftelins e:~ some control and pride iJacreas:~q; tension or d4stres8 from denial og imaedlate f~ratlfi~tlon relapse into smokJ:~ enjoyment because of knowledKe of new d~lays ahead reamed re~lariCy of smokins recurrence of (i). Oscillators aze defined u those who have rather lonKer abstinence and relapse cycles and have been throusb st least th:ee cycles. There are t~o patterns, firstly, symptomatic oscilletlon when scopplnS mad resumin8 smokins occur at onset and ramlssion of symptoms such as chest p,.~ns and coulhLnK. These people have no difficulty in stoppin8 but resume when clem: of symptoms. Secondly there are eel£-snanaSemlnt osc£11mtors who stop for VmlPSe reasons of i~slth o: desk.re for sel~- control, find it difficult to stop, abstain for several reeks or months and then return to smok/ns unhappily, because of external stimuli.. 0£ the cuL-cent abstmissmrs (o£ at 1sue 6 mouths) studied. 4£ rJaey have stopped :ore Cha~ once chs~ ire more like the sel£-maBaKmmnC osc411ators than chose who have stopped for the first time. The results of thls study serve to indicate, once qLin, the ~scab£1tCy of non-smoker status and underline the umcessiCy of quo¢in8 relulte £o3 lozq~term follow-up f::mm experiments des/4~ed to help people s~p 8mok~. C~plan, Cobb and French (36) divided persons aCtempC£nS to stop smoking into two types. Type A persons awe hard dr4vtns, persistent, competitive, involved 4- chmlr jobs and ovmrlomdmd ~Lth work, type B persons are the opposite. They hyporAtesiee Chat L'Tpe B will find it BAT Co LTD - MINNESOTA TOBACCO LITIGATION t...r-1 ,,,.to c...r-1

-107- tu~a: to stop Imokin| ~J they have less occupational stress but rear r~ose who perceive tbe/~ jobs as stressful and receive little social support ~11 fL~l tO stop. The authors 8uKKest that since Type & persons ace most ILkmly to be at risk due co hea:t disme they should be persuaded to stop and evaluation of mtop-Imok~g methods should be based on the parcentqe of t3~e A who stop. Pedsrson and Le£coe (158) compared 46 ex-mmoker8 (at Xeast one yeats abstLuance) most of whom stopped on Chair own, ~JLth 24 sen and 24 women who wanted to stop amokinli and had tried at least sacs on ~J:sa£r ms, unsuccessfully. There lace Do lis:~dficaDt pergosxaXtty d££ftrmuces betvaen the Ircoups (unllke some previous £indtnss). Successful ex- smoke:s had, howeve:, tried to stop at least once before. Eanzle:, Jaffa and Ze£denbecK (111) hive looked st the characteristics of persons who stopped masking succmms£ully ~ter taking part in a proprietary tteat~ont course (Smokandars). They £ound that men 8ave up more successfully tlum u~mmn and that the succeas£ul men wre mote likely, co be married. • Succsss£ul women were mote 14kely co have a non- smok~ husband. CLfr~rette cousmnpt£ou was not related to success in stopp£ndt smok~8 £ot men but success£ul women had smoked lass. At follow-up ££ve years later the only d~L££arenct blouses smokers (talljpsad ex-smokers am/ chose who did not stop d~rtflK treatment) and ex-mokmrs maJ sex, women heine less succass£ul. The authors sulLsaet that results of experiment8 to help people to stop amokinli should be reZated to the see o£ the pa=tic£pants. As £ar as the actual methods used 4n assistt~l| lpeople to stop 8mok~4; are cones=ned the literature 4s vez7 extmsslve. There bays been mmmu~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-108- several good review8 on the subject and these ,,~11 be s~r£sed here, together ~th papers Kiving results which have not been included in the reviews. The main problmns in revim~ng this type of work are chac almost every type of method imaginable has been tried, the quali~y of the work varies considerably, ss~ple 8£see ere variable and often £nadequate, follow-up f/~ures are often not reported and results may be expressed in such a way as to be m£slead£ng about success rates. The • standard of experimental work in thls area has not risem appreclabl7 in recent years and caution must be applied when cons£derlu~ papers which claim h~Kh success for new methods but which Kive Lnsu~f£c£ent deta~is about the methods and subjects used. & rev£ev by Schwa=tz in 1969 (192) l£sted initial and £ollo~-up results for 62 scud£es on smoking cessa¢¢on program us£n4 100 methods. sulmary the author concluded that few o£ Cha methods have h4gh success rates but the combined effect of the p~oKrams considered may be to aid an "anti-smoking" climate. He suggests that success races may be d£sappo£ntinS because of the lay acceptability o£ the methods used which causes h~sh drop-out races. The results indicate that at least some smokers can stop mnoktn~ but chat druss (o.K. nicotine substitutes and tranquilllsers) are not am effec¢/.ve L~d. Cond4¢i~ merho4s are ineffective and impractical as they can only be applied to small numbers o£ subjects. Schmtrtz su~Kested Chat cl4n~cs had r~hed tha point of diminishing zecurns and nay and mass media approaches umst be explored. He cautions investllators not ¢o expect ¢oo much froR any ono approach as leaK-term results must be £nducsd by sociotal and enviroumantal influences. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-109- Hcl~nne11 also suKsested (137) that tbe general level o£ acceptability o£ smoking must be Ic~ered, especielly in social groups which, at present, ccmta£n a lares proportion of smokers. He also suKseste that it may be easy to stop miult lisht smokers from smok£nS and that if this £s done the resulti~K la=se Stoup o£ ex-mnoktrs ~ould have eufficient influence to cause heavy 8moke=s to t~-y to Siva up too. He suKKasts that the main focus o£ health education should be the "consonant" smokers who are able to stop smoking i£ they are persuaded co. NcF~mme11 does, however, real£ee that considerable research must be done before • campL~i~ ettackluq~ the social acceptability of smok/~K can be launched m:d be effective for a11 socloeconouL~C groups- imss811 :ev~ewed the issue o£ smoking cessation ~n 1971 (167). He mentions the results o£ ~11 and Yhomas (142) indicatlns that 66Z of adult 8x-smokars had not found 8£vin8 up smoking d~i~flcult at all and 56Z of ex-smokers who had relapsed said that stopp~u8 had not been difficult. Russe~l also 1lets the reasons £oI: d£scontinuluK ImokinK: (£) hLslth - the most i:Kportant Not£ve. Lesser sit:ants such as coush and sore throat have more tnflmmce than the z~sk of more serious illness such as luns cancer. The smoker is usully experioncLuS a minor a~L~t when he stops smoking. (1£) mqNmse; this is the pr/amry motive in adoles'cents. (£££) social pz~s su=e (iT) example o£ doctors, pa~ont8 m~d |r~nachers ~bo do ~ot vlsh orAxers to 8~oke. (~) the w~_sh to master a test of w~ll-pos~r o~ self-control. (v£) the feellns that smoking 4s u~sL~y or dirty. BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~ CO

-110- The last three are of minor importance. Russell 8uKKests thst, in view of the predmn/nmace of the health motlve, doctors should be in • good position to influence smokers mad persuade those who stop mnoklns during a brief illness not to stsrt skein. Of successful ex-smokers S£vLuS illness as the reason for stopp~ns, 54~ sa~d they did so c~ doctors advlce but only 20Z of smokers recall advice of this sort. An Amsrlcan study showed that advice from a physician on one visit caused 33Z o£ patients to cut down 8mokinK for at least six months. One U.K. study also showed that routine advlce caused 47Z of chest clinic patients to stop 8mokinK for at least three months and 4n smother study 23Z stopped for six months. It is pointed out that these results are at least as good as those from spmcialismd clinics with many methods on nemerou8 visits. Thus Russell concludes that simple, f£rm, unequivocal advice to stop saok~g, gi~m by • doctor to a patient ou one ~rLstt ha as good a chance o£ being e~fective as any other cutTent method. Doctors should, however, be aware of the doKree of dependence £nvolvad and the motivation to stop. If motivation is Kood than supportive councill£nS should aid proKress throuKh the withdrawal prc~ess. The smoker should be encourasad to see the process as mac of learn/nK, that is, learnins to £umct£on e££1clantly and contentedly without smog. The potential e~-smoker must stop 8moklnK completely and thereby remove any rslnlorcessnt of the old behavlour and allow new behavlour to be learned. The recent ex-smokar nteds support so that be does not relapse and should avoid difficult led tempt/ng situat£o~s. Russell also 8u4wests. that lobaliJae can be given for its placebo e££ect, that patients could be told to smoke excessively for several days before stoppiu~ (twice or three times BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-111- the normal rate), or that c~ga:attes should ouly be smoked under unpleutnt coud£t£ous before the ~:hdrmwal accuzpc. &11 this seems to be £L~rly Soc~ advice but uo fLSures 8:e presented co ~dicate the actual success that thls approach has had. Hunt and Mac~trazzo (96) have also stressed that smok:i.ns is an overlaaz~ed beh~v~ou~ and that it has a response potential ~ich can linker on 1oak L~Cer the behaviour has d4sappea~o4 f:c~ the perfozm£nS repertoire. Most mnok~ "therapies" a~e merely concerned with the disappearance of mnok~ndS behav£our at the end of treatment mud folios-up data resemble an "ext£nctlon" or "£orKett£nS" curve ~d£cat£nS that the uon-smok~ behaviour has not bean learwsd suff£cleutly. Brsdstmv rev£md the methods used to stop people from saok~ up Co 1973 (28). He d£vtded the attempts to control smok~us into proacr£ptlve and prmscr£pt£vm. Proscriptive approaches are priamrily pol£tical ~md inclu~le increases in tobacco tax, restr~ct£on of mmok~ iJz publlc plies mzi rescrict£ou of edvertisi~. Prescript£ve techn£ques arm cost:oiLed by pro£eas£onals concacned ~th prevemCLve medicine. Ylrstly Sradshaw has revir~ad the effects o£ doctors advice In which" Russell had faith. Zt is concluded that many doctors are not interested in the problem. Green and Horn (81) found this to be t:ue in the United States mnd McEmnBell mud Thomas (142) 4wd4cate that ~hree-qumrters of adult mm0ktrs denied h~v~ bee~ advised not to smoke. Bradsba~ points out, however, that :aces of complLance u~th mmd£c~l advice are 1or. A :~v£ev on th£s subject o£ 58 studies in 8 ~de range of s£tumt£ou8 shoumd that failure to follov doctors tnstruct~on: occuzTed 4, ~1-50Z of cases. Another study in America had shown that 97Z of 93 patients ~re st~ll BAT Co LTD - MINN~TA TOBACCO LITIGATION

-112- smoking six mon~'hs after being advised co scop. This may be attributed co the failure of patients £o remember the doctors /~structions and may not, thmrefore, reflect medical £nd£fference. Educat£onal campaigns are than discussed. The health educator is sa£d ~ rely merely on making inforaat£on available and results are d£sappoint£na. & survey og 14 caspaigns in 1960-1970 in local cmmun£tLes, schools and un£verslcle8 An the U.S.A. and U,K, .indlcaCas ChaC none bad more Chart a minor e£fect and some had no effect aC all. 14osC csmpalgns have had little or no £ollow- up and only six of the 14 listed had control groups mad An only two of Chase was a reduction in smoki:~ found. Bradshaw states thac It £s d£ffLculC to avoid the conclusion Chat the only merit of health education ca~paiKns has been the enthusiasm of the orKauiser8. Re next considered anti-smok£nS clients. Those S£v£n8 medicat£on usually Save n£coC£ne substitutes, t=maqu£11isars, smFhsr~m£nes and an~£chol£nerS£c druss or anaesthetic lo=enKss or mouSht~shas. Few msudies of th~a nmSure have hiKh success rates. Noxr-madlcat~on procedures have been very varied, most being conducted in groups, the most popular being She '~ive day plan" of the Seventh Day Adventists. This includes group d£scussion and support and avoidance of situations conducive Co msokin~. Behaviour therapy techniques are usually based on the sheory thac maok~ns is a learned behaviour which can be suppressed, replaced, or disenaased from em~roumenSal sti:nuli co which i~ is cond£Cloned. Sredshaw refers to she earlier revim~ by KeuSzer, Lichtemstein and Haas (113) and Bernste£n (21), and £ndicates chaC comparisons between stud£es are very dlfficult especially if results are e~rprassed in Cezzes o£ reduction and not cessec£on o£ smoking. Tables ere presented showing studies which give BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-I13- abstinence rates. RiKh drop-out rains are common and for 24 studies Kiv£ng numbers for this there was an average o£ 30Z of subjects fa£11ng to complete treatment. Success rates o£te~ ilnore those vho drop out and may thus Kive unrealistlc £1Kures. Of ~A lroups considered, using ~our different cllnic4L approaches the median success Fate vss 37Z for persons abstinent from smok~nK. At one to three months after cr~a~nt this had dropped to 30X (results 'From IA pups), 8t four to six months the median was 16X (£05 eiKht Kro~ps). The f/~u~n8 suggest that rapid relapse occurs, estimated at about 47Z at £ou~ ¢o eL: months. Kmmnond and Gar£inkel (88) found only a 37Z relapse in sue year for those who stopped smokiuK on their own. Kelepse therefore appears to be hilher £or treated than untreated e~-smokers. This is ~atis£actory £or those who r~m antl-smok/.nK clinics but may be explained ~n terms o£ ~ type of people vho can Kive up 8making on their cram and those who seek help to do 8o. In s,~m=z7 Bradsbaw sussests thee most effort should be a/mad at: dsvelopi~18 a practice1 method of c~unic~ttion to decor young people £rom starting to smoke and Co persuade compLacaztt adults to atteanpt to stop 8mok~nK on their o~m. Clinical methods are applicable to much small numbers of people that they may n~ver make a si~ficaZlt coutr4bution. In 1973, R~ssell (169) £wTest£gated the effect of price on ciKarette consumption by men and £ound nn inverse lln~ar ralaclonsh~p between price and consumption. He looked at elastici~7 of demand which is the percontqe cba=se in conslnption resultinK £rom a 1: cban4e in price. Unit elastic£tF is a 1Z change in cons~tlon £or IZ thanks in price. Z£ the chaise 4~ co~sm|ption Is over 1Z the utarket is elastic, an increase ~n price clap:eases sales and a drop in price inc:sases torsi BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-ll&- expend£ture - thls applies to luzuries and easily substituted lisle. Zf / :he change is under IZ, the sucker is /~elast£c end the drop £n consumption is proportionately less them the price £ncrease so total expenditure increases - :his applies for food and necessities and also cigarettes. R~ssell's analysis 8ho~d that successive annual pries (or t~x) /~creases of over SZ vouI.d depress cons~tion. Be suggests that the '~blstc" price of cigarettes should be increased by IOX per year and la~ge tiers and pipe tebecco should be pu~ /::co the class o£ ~ll luxuries. Then c£gszette smokL~K would decrease at an acceleratOrS rate and acceptably safe conerolZed smok/:K o£ eige=s and p£pes could be achieved. Russell has o£ten suggested that the present inelasticity o£ ~he ciga:ecte ~=rket £s an /adication chat smokers are dependent. He also believes that: not: ell smokers cam be persuaded to stop altogether and Chat they should be directed t:owards smoking 1•=Be cigars and pipes as loeb as t:hey do not inhale (171). Hunt and Bespalec were next to revlev the evailable methods £or modi£ying smoking behe~r~ou: (95). They studied the relapse rates L~ter tre&t:nent £or smokinB, alcohollsm and heroin addiction start:inS with persons who were abstinent at t:ha end of treat=Int. Their results are represen~d in • now very wall known gr•ph Indlc•tln8 r~st many persons relapse quickly and Char the residue is about 25Z of long tern abstainers aft;st about: ni~3dt mmlths to one yeut.z', regardless of the behav£our being considered. The aut3:ors suggested that: th~s ~:8ph, wh£ch is a c0mposite of wmy d££ferant studies sad treatments, should be used as a basis £or compar'~a8 new t:~eat:memts and it: has since bee,', used by other woz-lr~r8 on 8mokin8 cessation. H:mt end Beepelec ~ound 122 studies in ~he litersture BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-115- from 1968 to 1973 and considered 89 of them. They rejected studies with no follow-up, treatment or follou-up periods of unspecified length and very meal1 samples. They first looked at abstention from ramekinS. &versive conditiozzlnS save six months abstention rates of 22-67Z but results are often subject specific due to selection, and dropoout rates are h~gh. Drug therapy save one year abeteDt£on of 8-17Z (lower rates than for other methods). Education and group support save results which compacted £mvourably wlth other methods, abstention of IA-78Z over various periods. One study yes mentioned particularly (Bozzetc£, 1972 (27)) u hav/J~ 79Z abstinent at one year. RypnosLs save 15-88Z abstention which was seen to be encouraging but treatment groups are small, it ks a costly procedure and is subject specific. For base rate reduction, avers4ve coud4tion/~8 Save f£Sures of O--IOOZ reduction, Education end group support gave l~-81Z reduction but again used presmlected sub~ects, aehavlour mod££1catiou studies tie/sad 17-70X reduction but none wore exceptional. Combinations of methods Save 0-80Z reductions but £t is not possible to analyse the contribution of each component o£ the treatment. Hunt and BespaZec conclude that while the range of reported results is wide it does seem posslble t0 modify mnokinz behav~our with some success. They point out that subject preselsction attenuates reported success rates and that on.17 subjects who went to stop 8mokin8 enter treatment and even thou many drop out. Xt is tbousht that once a smoker is motivated to change his smokes8 beha~ou: then the cTpe o£ therapy used may be irrelevant. This is add to be supported by the conc~usic~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION <-.r"l

-116- z th=t mmoklu~ mod£££cation ks • complex multivariate problem in vhich an invescilator ks conceFnad with some elements of the proble~ but no one encompasses all of them. The most recent re~rla~ is by Benste/~ and NcAll£ster in 1976 (23) which upd•Css Bernstelu's previous review (21). The paper tries to su~arise the status 'of controlled experiJne~t•l research o~ the modifLcatlon of smokLng behsvlour, to po~zst out approaches which do or do noC seem promis~nK and to make suEs•salons for £uCure work. The authors surest that •]JnosC •ny intervention can be ef£act£vm in eliminating or drastically reduc£nK me•king behaviour but these cleanses tend to be relatively short- Zived. Most dace show an ~Jm~diate and drmnat£c reduction in riser•tee consumption by most subjects, followed by relapse to pc•treatment rates in 75-80Z o£ cases within one year. RmZspsa is hiKhemt in the £irst three mouths buc still occurs du, r:i.n& the uext ~ months. Zn the paper, investiKat~ons considered are clinics, drubs, hypnosis, sensory depr£vmt£on, soclaZ learninS approaches (systematic dssansiclzacion, punis~m~tut and •versivt cossdlt4on~nK), stimulus Coutz~L, re4n£orcemenc o£ non-smoking and multi-component Luterventious. The authors conclude that there are nov two treatment packs•as which are •ble to ral£sbly • lim/~ate c£sarette 8mok~Lns for the vast mm~orit7 o£ subjects treated and which K£ve ions--term abst/neuce rates (up to six mouths) which ere clearly superior to previously 8v&£1mble £ntmrvmntlons. Both treatments are complex. Firstly rap£d mnok~nK within • positive social ttaacmeut context (mainly based on work published by I~chtenmtaln and colZaaKues). Secondly muZti-cmaponent Lutmrvent£onm proSrmnn/n8 the teaching/reinforcement of non-smok~ behaviouz8 with am•kinK suppression tactics (e.g. Yla~san, BAT Co LTD - MINNESOTA TOBACCO LITIGATION c..m

-117- £974 (64)~. Sensory dmpr£vecion procedures were sald to have effects which are similar but less durable. There have been • number of papers on rapid smoking techn~qumsp hypnosis and more complex methods which were noC included in DernmCe/~'8 last review (23) or which have been published more recently. These will now be considered in order to brink the subject up co date. A nmnber of these papers compare the effects of several different CreacmmnCl which have in the past proved successful, often with results ~Lch mqKemt that exact experimental procedure maT be cr£t£eal. This ha8 disturbins consequences for the wlder appllcabilit7 of some methods of smok~nk control. When considerlnk the rapid 8moklnk aversion techniques it 18 helpful to consider the basis for these. In a study by LichtanSte£n. ~a~c£s, Birchler, Wahl and Schmahl (129), an attempt was made Co compare the effects of rapid smokins and blowink warm smoky air at subjects. These techniques ware chosen because Resnick (162) hid achieved a 63Z abstinence amens students four months after • treatment /srvolvinK 8molc~n8 at two or three times the normal rate for a w~ek before etcmmpt~nk co stop. Lubl~ and JosZTn (132) achieved abstinence or reduction ~n emokink in 40Z of subjects one Tear after trea~t of subjects ezpoaed Co warm stale cisaretce smoke wh~le they ~ked at an ~acre~sed rate. There were methodoloK£cal ££aws in both studies so 8c~nmhl. Lichtmnatein and Harris (£gl) developed a acandardlsed procedure mud found Chat blou~nK warm mwky e£r at subjects vbo mere required to puff mad i~ha~e ciaarette smoke every mix seconds us effective. IncZud/nK subjects who dzopped out of treatlent they achieved 93Z mbmt£nmncs mt the end of treatment and $3Z abstinence at six mouths. Lichtenstelu et el. (129) found sLmilar BAT Co LTD - MINNESOTA TOBACCO LITIGATION <..m, O": o'x

-118- results for warm smoky =4r, rapid a~ok~ or both tosether, the total of abst£nmnc subjects at slx months was 60Z resardless of the method usd. The attention placebo, InvolvlnS Bantron pills (contalnlq iobeline sulphate) and visits to the laborator7 to smoke two clsarattes for four m~nuces each, was far less effective although some of thls ~roup did stop. The authors conclude that warm smoky air end rapid 8mokJ~K procedures did not have additive affects and 1mrs equally e£fmctiva. Best (24) sulgested chat smoking behav~our modification may be • two stage process and that achieving abstinence may be relatively u~relaced to malntalnlnl abstinence. He also believed that tailorlng the treatment to the subjects' characteristics could anlms~nt mainte~mce of behaviour chmnSe. Re Created subjects vLth warm smoky air while they smoked rapidly. Several 8ddiCionmX procedures were also introduced. The focus of the C~eaCment was varied £or subjects 4~ di£fereut ~oups accordins co chelr score on the Zncernml-ExCernal Locus of Control Scale. Subjects were told that they wuld be punished by havins to smoke at double chair pretraacmmnt rate £or a day if they resumed 8mokinK a~tmr trma~t. Timin8 o£ attitude thanks was also invmstiKated, the author bypotheslm/~g Chat anti-mmok/~g attitudes could be more readily induced after skinS abstinence bad bees achieved. Of the total sample of 80 subjecc~ 68.6X were abstinent at six months. IC was found that treatment du~abillty was, t.hez~fore, inc~sssed over that £ound in some ocher stud4es and chat cai~orinS the procedures used to indivldual characteristics could be 0£ value. The remzlCs ~ce not, however, particularly superior to those cbtalnod by ochers uslns elm/far technlquas and ~ indtvidual£cy of Ix~t~nsctions had not drmmatlc~ly a~fected success rate. BAT Co LTD - MINNESOTA TOBACCO LITIGATION --.,,.o

-119- Krei~ler, Shah~ and Kre£tler (120) classi£ied smokers as positive and .negative af£ect 8mokmrs from Tomkins' t3rpology (s@e motivation section). They hypochesised that negative affect smokers would benefit more from desenslt~zatlon therapy than £rom tre&Cment by saturation, and vice versa £oz positive d£ect mmokers. Desensitlsatlon was mel£- control and zelmtiOn t3asrapy while mstu~atlon ~.nvol~ subjects smoking three c~arettes in succession, pu~£~ every ten seconds and breathing in smoky air Chert clean air. The authors also hypothesimed that subjects in whom antl-mokin8 attitudes ~re present would benefit more from the therapy provided. The results indicated that this second hypothesis wu correct but thJt there warn no effect o£ m~Eect 8corm. ZC appears, however that the subjects only reduced their eiKarette consumption rather than absta~LuK completely. Levenbe=i and Wa~ez (128) also divided their subjects accordinS to their personal characte=£stics and used :ap£d smokinK am one of the cond£=~ons. They ad:tu~d r.h~c £or "~nxiety smokers" the best tree,meet would involve neutralisinS the am~e~y responsible for 8mokinK while n~--~iety ~ZS" would be bast treated by ~wersion therapy. The subjects were classified as anxiety mad non-anziety smokers by beth8 observed s~oklns before and after bein8 8£ven • (sham) /~terpersonal stability questimmaire on which ~hey were told they had scored badly. Croups of both types of mmokezs were used foz rapid 8mokin8 (similar procedure to Lichtenstein et al.), syst~natic desensit~sation (relaxation in the presence of anxlety pzovoklnK thoughts) mad z~Imtion control. After treatmeut 36Z of the total sample had stopped smok~n8 (5~Z o£ the rapid mmoklnK ~roup and 25Z o£ each of the ~w other L~oups). At folLow-up four months later there were no differences becwemn treatments BAT Co LTD - MINNESOTA TOBACCO LITIGATION ",O C.o

BAT Co LTD - MINNESOTA TOBACCO LITIGATION ',o

-120- or for "appropriateness" of Kroups. The authors believe chat the couclus£on by Lichtenstein at •I. (129) that rapid smoking had bema shown to be an "•ffmctive cYaLi~m@nt'' is pYre•maitre. Lands and Davlson (122) had found that over • th4rd of subjects who self-paced the£r mmok/nK in the laboratory after bein8 told that it would be unpleasant, were absc£nmnt mix months later. Lends (121) Chare£ore 8tcempcmd co compare a self-paced Broup with mrsive conditton£q and a non-my•rely• control. The mversive cond£tion~ Kroup ere told co smoke got three, thr~a-m4nute periods, pt~Efing e~w'er'y mh seconds. Self- paced subjects were £rae to mnoke at ~rLll but ware told it would be unpleasant and were asked not Co engage in diatractlns actlvitie8 while mmok£nK. Six months later about a third of •11 subjects were abstinent. and 43Z of the mvers£ve conditionlng Kroup were not smokinK. Sel£-paced mmokin~ was no better than the control and reductioaa in conotm~ption were not long-lasting for any Kroup. 0£ pEp•re published on mmok~ns cessation in 1977 several describe work on rapid 8mok£nl. Barkley, Kaetins8 and Jackson (15) noticed that individual therapy had proved to be more successful than Stoup rJhermpy. They tried • KrOUp rapid mk~n8 procedulre ~Lth subjects pufflnK evez7 ten seconds, l~v£ns thelr lishCed butts in the ashtray, liKhtt~ another ciKarette and rejoining tba group, pu£fLuS until rAmy gelt very unwell. & number o£ subjects vou~tod du~£nK this ~eatmsnt but none dropped out. kesults 8how that the8 group procedure is prom~siq, with 75Z abstlnent st and of trust and 41.7Z still abstinent dter ~ months. The 8uther• bml£eve that Cheer procedure ks more mr•iv• than Chat used BAT Co LTD - MINNESOTA TOBACCO LITIGATION ".,,O

-121- by ochers, •s indicated by subjects' vom£t£ns. They also suggest Chat, in the group situation, seeing oth•rs re•ling unwell must enhance •versive effect. In this experiment, however, only 12 subjects were included in the •version Stoup, too small • number for firm conclusions to be drawn. Norton and Bar•ks (154) •Is• looked at rapid 8mok.Lng in iroups us£ng two d££gerent procedures. One group of 46 subjects was treated with mild aversion, putting on c£Karettes every six seconds until they couldn't tolerate another c/~mrette. The h£sh aversion Stoup of 30 subjects had to ,|moha until they vomited or wnre feeling too sick to continue. After tr~sasent 90Z in both ~roups were abstinent and members of the high aversion Jr•up tended to relapse more slowly than the mild aversion group. By six months after treatment, however, only 30% of each Stoup were abstinent. The authors conclude that rapid smoking can work in the group situation but that there is no luting advantage in making the therapy eztremely •versive. The other main catesory og treatment can only be described as multi-component or m~:ed. There m:e several recent studies not included ~n published reviews. Zuterestln8 results have been obtained by Breusels~ann (30). He used • sample o£ 256 men and 99 women and elsht dlf£erent types of ire•went (control, loheline, placebo, psych•therapy and group conversation, electric aversion, smoking to a natron•me best, am•king while imLKinin8 lumg cancer, and self-control). &1though gull procedural der~ails are not given, the self-control group d~d best in terms of numbers o£ subjects abstaining or reducing their cigarette cons~tlon. This prompted a £urther experiment BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-122- in which 40 subjects who had never been treated and A1 subjects who failed to give up smoking /.n the first experiment were seudied. They practised sel£-coutrol of 8mok£n8 eccord£z~ to e set of rules and enKased in a form of be~tinK, contrsct£nK to smoke ~o self-daf£nad r~az~et levels and forfe£clng money if the ~rgec reduction fux coneumpt£on was not: reached. Two--thirds o~ the subjects managed Co sr~p 8mokins mad there was no d£fferemee in results bar, dean the ~ Eroups. 249 subjects were than sent £nformat£on about tills method, by post. Over 60Z of these subjects stopped smokinK and 15 months later A7Z of the coz1:eepoudence subjects were contacted. Of these, 44Z were still abstinsue. These ferules are the only on~s which appear to have been reported in the literature, at least in recent years, for a method of stopp£q Kk4nS by correspondence course and they 4o seem to present an optim£st£c view of the method used on a 18=88 sample. This assumes of course that subjects were truthful about be/~S abstinent. F, an:ler, Ja£fe and Zeldsnbar8 (111) have presented results for the proprier~ary crent~Inc offered by Smoksnders in the United Sr~r~s. In reviewing the literature they Dots only ~o studles gives results at four Fears follow-up, buC doubt was expressed as to the reasons for the abstinent subjects having llven up (these may have been unrelated to • treatment). Two stud£es had Kiven follow-up at five years. ]ii, s~lr (87) h-d t:eated 3861 subjects who had vaslous physical d£sotders, at a German health spa, usin8 • mmbet of me,beds. F£ve years later ~Z were not smokinK but females bad found sr~ppinK more diff£cult. /:a borJh the long- and the short-term. Zban males. Wettewq3rlsC (220) /Ja Scmadanav~e had also found that males were more successful in Kiviz~ up mmok:LnK BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-123- nhan females. In/tia/ cessation after treatzmnt was $OX for males and 33Z for females, five years later the corresponding fisurss wera only 9Z end 5X. Kanzler, Jaffe and ZeldenberE theEefoEe dec/ded to conduct • study with long tez~ follow-up of about four years on Ss~kanders. Subjecns pay for trestment which involves b~v/~u: modIE£cation, decond£tlon£nK, group support and • "buddy system". SmokJ~g ~s stopped a~ter five weeks of treatment and 8ubjec~ then cont£nu~d co uuat £or • fuzther four weeks. The /~nsdlate success rate after ~ weeks was about 70Z • bst4Qent. Of the 385 successful abstainers at this time, 165 were contacted about four years later and results extrapolated to the original sample Indic•red a long term abstinence rate of 39Z - tb/s could be subdivided by sex givlnE 57Z ~tripol&ted success for mn and 30Z foe women. Zn dLscusstns ~hess results the authors point out that ~he success rate for percent~s6t absta£urs at the end of tTsatzlnt £s much better than many other stodi•s. Zn the absence o£ other reliable Long term follow up results they compared theirs with the curves publ£shed by Runt and Besp•lec (95). These show asymptotes after 18 months at 2SZ and 30Z for two curves - pre 1968 and later studies respectively. Few previously published s~udies have given results for ~ and woman separately. Kisinger's results (57) are quoted show/rig that of l~ople 8£~n$ up suecess~lly (sppar~tly on t~air ram) in a t~o year l~rLod, 70.4Z were ~m and.29.6X ~re ~ma~. Bosset~i (27) end Moses (147) had also found ~hat s~n ~ars most successful in ~v~ng up but m~y used small s~les. Zt is t~erefc:e dt£f£cult to compare stud£ss by overall success rate If male/f~le ratios are not S~ven. and it appears in the BAT Co LTD - MINNESOTA TOBACCO LITIGATION ',,o r,,c

-12+- Snokenders study chat results for women approximate to the overall averages given by Hunt end Kespalec and ocher revlasmnrs, while success rates for men are higher. T~ summary to Chi8 section there ~e several points ~£ch can be made. Firstly it is possible to say that there are a few methods of smok/~g behavlour control vh£ch do seem to be useful in 8~d£ns people wenting to stop musk/rig and that chest may have 8 long te~m effect. RepllcaCion o£ these methods may, hoverer, prove to be d~fficult. Generally Long term success rates are low, especlally if one considers Chat most people who put themselves fo~vard for 8peeialioed CresCent huave probably already Cried and failed Co give up mnokLng on Che£r own. These awe people who went to give up smok~u4 and should here eu£ficieuC motivation to do so. Most c14~c~1 methods to hmlp. people stop 8mok4z~j are labour intensive and expensive, especlally so when only 30% of subjects may give up mmoklnK permanently. About L5% of smokers in E.g. and U.S. (58, 168) are g£viDg up sponCaously mY add success races should perhaps be quoted in relar~ou co this figure co give a real 4des of the efficacy of the methods used. It is also interast£nS Co note the results of a study by I8&cmson and Jm (101). They invest£latsd pulmonAt7 function in m rmndcu, ly selected populaC4on of 55 year old men in Hmlmo, Sweden. 58 heavy 8~okers were asked, £our years after the In~t£al study, co cake pare in research requiring abstinence fram smoking for eight co nine reeks. 881 sKi-sad Co parClcipaCt and attended sk. a-houm mmeciqs co discus health aspects of smok/~j and problm in sCopp/J~, 60% of those parClc£paciug stopped amokiuK for nine web and deer eight to nlne mouths 33% of the subjects rare s~ill ex--smokers (2g% of Chose or~gCually coucscced). BAT Co LTD - MINNESOTA TOBACCO LITIGATION <.,'1 r'x.a

-125- These results sugKest that, at least in the population considered. most randomly selected heavy 8reeker8 are w~llinK to 8~op smoking and. although only asked to stop for t~o month, a r~Lrd of rJaim art able to achieve long--term abst/Jzenee. The llck of success o£ methods using pharmacological substitutes for 0mokln8 is strlk4~K. ~ omok~n8 is considered to be an ~Idiction to n£coC~ ~ ic would follow that use of uicot~ tmblaCs or e.hesri~- Kum or a substitute such as lobel~we should replace n~eotlne £rom smokLnK and enable people to stop mnokiJaj. The methods whLch ire successful in aid£nl the laOkLD~ CellatiOD prOCISl ire COndittOD~De, psycholoslcal and behaviomral emthods which must indicate Ehat smoking has a stronK habitual component. BAT Co LTD - MINNESOTA TOBACCO LITIGATION r'~

-126- 8. TOLERANCE TO NTCOTTNE AHD 14TTHDRAWAL SYMPTOHS Tolerance refers to the aZtered physioloK£cal state produced by repeated druz mhn£uistraClcm. Th£s orate can only be mm£nta/~ed by continued ~Imln£stration of the drug concernRd or one that is very closely pharmacologically related to it. TY use of the drug is term/hated then withdrml symptoms occur as the body returns to the orifinal pre-drus phys£olozical state. Tolerance is responsible for tim need fc~ Increased doses of dru4p8 in order to produce a constant effect when the dru8 is admin£ecerod reK~larly. There i8 semi evidence that limited tolerance to nicotine occurs. ~n rats, tolerance to the depressant effects of uicotlne on spontaneous activity and re~r£ug activity have been de~onstrated (112, 199). In man tolerance can be demonstrated by Slvlng ~4cotlne injecClons to smokers and nonsmokers. Johnsten found that smokers reported pleasant effoctl from the injection ~h£1e non-smokers ~erm the effect "queer" (109). KeckeCC. GozTod and Jezme~ (lg) /J~dicaCed Chmc no smokers r@poz~ed feelings o£ nausea after u/cot£ne £njecC£on ~bile alZ non-mnokers felt this to ~ extent. The t~o ~oupe ~re &Zso found to differ in thslr rates of n~coti~e metabo14sm co cotinine. Th£s ind£cates chat ~c adaptatLon may have occurred in reKular smokers. R11sIe11 (168) pOJ.ll:ttS OUt r.hat scan tolerance to the side-~ffects of u~cot£ne must develop since the first elKs=mete ever smoked often prod~el umpleasent @ffectl. Later on, this moz~ of aide e££ect 4s mot e.l:peri~, iuasall {~Nlbl ~O1: po4mt OUlF., ~MWlrl~'er. I:hmt ~t ~LI fa£rl~ combos ~o~ reviler a~k~rJ 1=o tad/care rJ~c ch~ ~£ret cL~areCce each mornlnK may cause dizziness and stiJht nausea. This .m.,y Lndicate chat BAT Co LTD - MINNESOTA TOBACCO LITIGATION r,,,.., o-,,

-127- the deKzee of tolerance 4sveloped £s not hiBb, oz that nicotine is not the only factor izrvolved in slde-e~£ect8 from smok~. Larson and S£1veCCe (126) ~ndicate, in t~nir ZaCest renew, that toleramce c"m also be seen by observing the nyst~m~s (eye tremor) pattern dur~ smoking and by ekLn se=s£tlv£ty testlng in tobacco £ermencation p3.~nC w~kerJ. RnoCt and Variables (117) Interpret results on the brain activity of non--smokers, deprived smokers end non-deprived smokers u ind£cAtinK toler~e to ~Lcot/J~. Non-deprtmsd smokers shoved no change in the alpha frequemcy of the XEG deer 8mo]kJJIg u~hile such e change yes observed in smokers smoking alter 13-15 hours depr£vetion. This sort of tolerance is obv£ously of fairly short duration sad r~e authors point out that it only eppl£as to the central nez-7ous system. As far as increasln8 the dose o£ nicotine is concerned such depends on the starting point chosen in the smokinS histozT. Taete is no doubt that mhe number of cIKartttas smoked per day increases, for most people, £rom the ti~e of the first smoking experience unt*l resular smok~ is established. Once smoking becomes reKular it appears to be £eirly stable over long time periods vith unbeat £1uctuations due to ezternal cireusstences. This does not rule out the possibility that the amount o£ nicotine obtained fram each ciKarette 4s increased. This could be achieved by incraasin$ /nhalation, mmber o£ pu~£s per cisa~ette, volume o£ smoke pet pull mid amy other o~ b utJuxls 8v~Llable for c~i~ delivery. Ovs~ at least the last ten years the ~cot:ine delive~-jr of ciKerette8 has been 8radually decz~ssJJq~. There is no evldacw.e that smokers are nov smoking far uwre c~aaretr~s to compensate fat this and little evidence BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-128- that r~ch;n-ciKaretcm compensation would be expected to be m~££cient to make up the deficit. Zt may also be noted that smoke~s do not part£cularly prefer the higher nicot~J~e ciiarettes at present available since the bulk of sales are in the ~i,m nicotine cateeory. This aspect may, hemever, be influenced by health and f4~anci81 o~ms4derations. Any tolerance which develops is not su~£icient to permit the ~z~ous system to be exposed to eve~-~ncreas~ nlcotlne conceat=a¢ioz~ without t~c effects vhich would automatically l~Ja~t dose levels. Withdrawal |3repress follmrlns mmok~ csssatlon t~-ve been st,,~led speci££cally by surpris/x~ly few workers. The Lmfo~aticm presented Lu reports of experiments during which subjects stop 8~ok/~g or smoke very Zow nicotine cigarettes is often anecdotal. A selection of reported symptoms often ~mcludes jastric disorders, dry mouth, irritability, sleeplessness, headaches, Risht Seth, smxtety, tremors, uusea, r~ell~ of hands and feet, drogs~ss, impaired c~aceutration and restlessness Ce.K. ~e~nste/n (22)). A larKe number o£ "pgycholoslcal type" w~thdrmml rymptoms have bean reported. F~zmeK~m, Larm end ~as (62) studied 24 subjects ~.ven hish and low nicotine ctSarett~8 (1.96 and 0.34 m8 n~eot/~a). ~nen chan~tnK to low n~cotine c~Karettes for • month, s/~ subjects showed no chanKe, six reported an i~Ltial vague lack o£ satit~actiou from smoking, three missed the n~cot/~a bat adapted and ~e ~4ssed th~ ~Leottn@ for the ~ho~e month. The latter 12 .m~bjects cc~pla/~ad of wj~ptmss o£ h~i~ht~n@d irr~tab£1ity, bcreased ability to c~ncentrate on ~ental tasks and £eel~.n~s of inner humor or emptiness. These are very 8/~ler to the s~ptc~s described by p~sons S~vinS up ~k/~ ~ ]~ssell has su~ested (173) that the subjects report~ns s~pt~ are those who made l£ttle or no attempt to compensate for the reduced nicotine delivery. BAT Co LTD - MINNESOTA TOBACCO LITIGATION %O /,o oo

-129- UZetc and Ztil raporCed (102, 210) that subjects in mn experiment zequir£~ 2h hours smoking deprivation complained of drowsiness, restlessness and dyspbor£a. Many 8tud£es on mChods Co aid seek/rig cessation tend Co d£sresard poss£ble ~r~chdrm~al symptoms or merely sta~ thaC patlmsts or subjects couZd discuss Chess 1riCh a Oh@rapist. Pedarson mud Lmfcoe (158) holmve=, ~n a study of 46 ex-smokars found chac 43X of subjects had no iaanmdlate w~thdrmwal s~n~ptoms except czavlz~ for ctfj~ettes mnd Z2X had no symptoms or cravins. Vsacssou and Jm~zon (101) in r~e£r study of 58 heavy smokers who ~mre asked Co Siva up amokins for eisht to nine weeks found that of 51 who save up 50Z suffered rastZassumsa at some time in the eight weeks, 20Z ~re restless the whole alms, 301 rare £rricable m~d 20Z found difficulty in concmntraC£on and felt tired. Jacobs ~nd his colleaSues (103) suKsestmd chat amokinS ~thdrawal may produce affects slmila: to depression in /~d£vldumls who seem vulnerabZe in oCher ways to hprassive d£sturbanca. Zn the U.$. SurSeon General's keporc (212) iv is scared chat there has been no dmsonstratlo~ Chat the w~thdrawal symptoms due to smoking abstlnence differ in my significant way from symptoms seen in any stloaml disturbance secondary Co dmprlvation of any hsired object or habitual experience. Physlolosical withdrawal symptoms have been studied in rather more detail but the n~mbez of studies is remarkably low. Enapp, Bliss and Wells (116) scudled h3 heavy smokers. 11 subjects smoked at will for ££ve days mmi 15 subjects wee uk~l Co stop smoktz~ for the last ~m days. These subjects ware unmmploy~ mr hospttal/-,md for uaurotic dis&bility. A further 17 unp-4d volunteers smoked at ~r~11 for five days, soma of them switched from normal n~cottne (1.75 m~) to lo~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION r,~ %O

-130- n£cot£ne (O.& inK) eJ4J~etta8. Results should that the m~t~.h to low nicotine c£s~ettes had effects sLmil~ to abstinence (~ltboush abst£nence was not complete ~n most cases as subjects tended to smoke at niKht). The physiological effects seen were a drop in heart rate and in diastolic blood pressure. Ulett, Ztll mad their collaaK~uts (102, 210) kutve 8tudLed the e£fects of 24 hours smoking deprivation on brain sctivIL-y. In ~be~r first study (210) on ten subjects they found deprivation produced a drop in peak alpha frequency (EEG in the 8-13 EL: rqe) with m~ i~ease in pou~r of slower and faster ZZG frequsnc£es, toKether with a drop in pulse rate and increased systolic blood pressure. These ehan~es were reversed by smoking. The bra4n activity chanse8 tire described as being in the direction usually classified as EKG abnormality, showing sips ~yplcal of decreased vigilance. ~x a further study of 32 male hoary smokers (102) similar resu1~s were obtained, again shou~ng a decrease in pock alpha frequency, drop in alpha pmmr and increase in slower ~requencles, They quote the results of Hurphree and Schnlts (l&9) who found increases in ~pha activity after six hours deprivation which ~ere reverend by smoklu~ and ware 4nterpretod as shourLn8 the depressant e~£eet of withd~al. Enott and Variables (117) have recently studied a 81"sup of 17 smokers deprived for 13 to 15 hours. Nine of these subjects smoked ~ the test, in which alpha EZG 8ctlvi~y was recorded. Zt was found :hat deprived smokers had a lower alpha frequency than non-smokers or smokers had been partied to smoke. This d£ffarance d~LulFI~a~od after smok£nS 4~ the subjects who smoked dur£ng the expettsmnt. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-1.31- Two s~diem have been reported in t~hich the e~fects of abstinence have been studled in some detail. Shi£f:nan and Jarv/k (195) studied 12 l£KhC m~kers (under 20 c£Saretces pa= day) and 23 baa~7 smokers (over 20 cisa:e~es pe: drT), du:~8 12 d~ys of abst£~ct. TheT used • questionnaice which had been devised to provide ~:~ormstion on cra1~nK for cisarettes: psTcholoslcal and physloloSic81 mymptaas and 8t/amlmcion. The results suKKested chat r.he symptoms msasured are not ~mi£ozzLly severe over 12 dsys o£ 8bsc~emce. FhTs£cal ~rJ~:m~1 symptoms dec:eaned In seve=ity in the early days but ~nc:eased asian later. PsTcholoKical symptoms and c:a~Ln~ decreased l~n~arly with time. No ore:all dlffe:ences were fouud between light and heavy smokers but r~he:e were dif£ereuces in stimulation scores over the tJJne period. Some subjects achieved only p~al abstinence but r3~ere were no dtfferm~ces be~mnen part£ally and totally abstinent subjects e:cept £or crm~=K. TOtL~Zy 8bs~Luant subjects had less crEv~:K ~o: cila=e~tts, and this d~crta~ed with t~Jne; ps~t~ally 8bst£nant 8~bjec~8 reported that crsv~z~ ra~a~ed ~8~:1y c~ms~ant over ~ns. Udortums=ely the de~Lls o£ questions used in this experimant are not li3~n tu the paper and it umst be assumed that vhe withdrawal s3npt~no investigated are those which had been described prwT£ously. ~n their liCera~u:e survey. Sh~an and Jaz~ point out that thee ~8 a K~eat deal o~ d£saKrea~ent about the real maa~LuK o£ any ~1~=drav81 s~mpt~ms repoz~ed. The~ :e£er to • number of ~hors who believe that 4Lscom~o~t a~te~ withd~m~al o£ mnok4nS £s ~despread and to orJ~a~ ~uchors who h~vu emphss£eod the poss£blity o£ 88~mptomatic wlth4rm~al £z~u mok~nS. ~ste:, KZserot and KdKren (15~) compared 12 subjects who smo~nd st w~11 £o: three weeks, v~th 14 subjects who abstained ~o: the mlddle BAT Co LTD - MINNESOTA TOBACCO LITIGATION .......................

-132- week o£ the three week axperiawJzt. All subjects wure po1£ce~en and women at a rea£dential t~Lin£nB school. Heasu~es o£ phys£oloK£cal a~-ousal. 8ubjective'e£fects ~md mental per£oz~ance umre made. Durins abstinence most subjects had m stz~n8 cra~q~ £or tobacco and many reported sympCm such u irritation, depression, restlessness, mzx£oty, aKKreas£on, tlrednss8 and drowsiness. Some subjects, .however, azpez~emced no symptoms, and there was no relationship between previous tobacco consumption and £requsncy or severity of abstinence symptoms. Ad~~ and norsdre~aline excrtt£on decreased dur~J~ abst/J~nnce, skin temperature increased and hand steadiness inprwed. Heart rate was determLned during a standard physical fitntl8 ttSt m55d vaJ8 fov~ld tO be lower iu the abstainers but chanBe in hmart rate due to mrclst was not af£acted by abstention. There was no evidence r~ac absca/J~n4 smohrs were fester or, surprls£nSty, that abstLuance /mp~Lrad mental ability or a££1clency. The results wee taken to indicate • dec:ease in s:ous81 durlnK abst/J~nuce. The authors did not, however make any ~are:ce to tolerance to u~cot/~e a~d £t is unclear whether the decrease in arousal is du to ~thdraal effects or just the absence of st4'aulatiou frma ~Lcotine- The 1964 SurKeon C~meral of the U.S. Public P-alch Saz~ice kport (212) describes • numbmr o£ symptoms but concludes that no cha:actez-lstic abscina~ce s3n~rmm occu=s on ~thdrmral of msok~. The abst/nence syndrome is not spontaneous, tne~icable or uncoaL~rolled b~ the sub~ect a~4 wLr~drawal is nave= l££e-tJ~estm:ia~. ~ez~ste~,: (22) also sr~stes ~hac ~he:e is no mrlde~ce of a co~sista~t cha=acter£sClc w~t~drmml syndrome in all or mvam moat individuals who stop ~mok~nK. Byes whsm symptoms appear to be 8/~LZar thmre my be widespread differences in terms o£ paine of onset and duration o£ discomfort. BAT Co LTD - MINNESOTA TOBACCO LITIGATION / 05,45

-133- Larson atld Silvatte (124) have commented that it is di~££culC to understand vhy "cisaretta vithdrawal irrltab£1£cy" in heavy smokers who are abst/~xent is not as v&l~d an indication of physical dependence as the "cat£a£ne wichdraval headache" in heavy coffee drinkers vhlch has been recoi~isad as a ales of physical dependence. ~.~ssa11 (16B, 173) states that the evidence For the tobacco vlthdrawal syndrome is clear cut, quot£nK a s~la~ list of sTmptom8 to those described in the Su='geon GeneraL's Report and more recent evidence for phTmlolosical ef£ect8 of abstinence. He considers that mince m~ psycholoKical ef£ects have a phys£oloKical basis ~hey must not be dLsreKarded £n tezTss of the abstinence syndrome. R~ssa~l notes that ~chd~awal e~£ects have been demonstrated £ot amphecmu;~a vhich yes prevlou~17 thouKht to produce only peycholoe~cal dependence. &Iso, the opium vithdrm~l syndrome has been produced as a classlcally conditioned response and induced by hypnosis. The previously held d£etinction: be~aen physical and p~cboloEical symptoms a:e the~e£ore not £~rm ones. Soam ce:e must be taken in reechJ.zzg couclue£ous about the e~ieteu~e of a tobacco u~thdrmmtl rTndrome. There is l£ttle doubt that ps~choloK£cal and physioloK£cal symptoms do occur in at least some persons who ~Lve up smoking or switch to very low -4cotine cigarettes. Whether theme rTmptom8 are sufficient to cha:acte=ise an actual syndrome ~u~t remt£n in doubt. It should ~Lao be remmbetad that, whets pbysiolos;iesl msamarem~ts ~e concs'cnlm/, the run~781 of the a~£ects o£ ~ u~r7 pees£bly be uncoverS,:8 const£~ut~l d~fferences bet3meu mu~kers and now-smokers which were i~volved in mmok4n~ £u~tiat£on. Thus persons who start to BAT Co LTD - MINNESOTA TOBACCO LITIGATION m C

-134- smoke may have ~tttrrtlly lovez pulse =ares amd eXmmr fzequency b~ain pmt::t:ez'us s,s,b~r.ls mrs 1revealed in ~ absence of mD~. ~tmC would be need.e¢t £8 8 study 1:o 4Follov the phyoioloilc81 effects of lonK'-te~c'm abstinence 1:o det:ez'mine rift:her the mmamsremsuce reL'u~n Co "UOZl~ln u Cole~snce e££ecCs dec14ne. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢...r'!

-135- 9. ~ CO~CZION OF SMO~NG ~I~ THE USE OF DPJ~gS X number of studies have been p~bllshed which indicate tbst tbere is a hisher proportion of smokers amonssc drug aAd£cCs and alcoholics than in the gmseral popuLatic~, A selectlon of these papers ~11 be considered here, HcKmunell and Thomas (142) are among authors who have found that smokers are more 1£kely to consume alcohol and co££ee than non-smokers. The coonection with alcohol has usually been studied in derail by considerins alcoholics. Dcaher and Fraser (55) studied the smokin~ habits o£ alcoholic outpatlents and found then to be "excessive" cisarette smokers, when compared to the general popuZation, w~th 8 larse p:oportion of heavy smokers (79.1Z of the sample wire 8mDking over 20 c£sareccas per day). The proportions of smokers and hear7 smokers were also higher than those previously determined for non-alcoholic psychi~trlc patients (50Z and 37Z smokin4 over 20 par day in separate studies). & sampZe of 100 •lcohoL4c outpatients was compared dLtrsctly ~rLth a control group of 98 ~on-•leohoZic p~chiatric outpatients. Tt wee found that there were no dif£mrances in t:ypa of smok/z~ (ciSarettes. ~LSLTe or pipes) but the results sufd~asted thac there were more smokers in the • lcohollc population, trLth a hiKhar daily cona~t£on, tend£ns to inhale more, ha~i.ng been smoking longer and sCartlz~ at an earlier abe. The authors stress that as sub-stoups were small the findlngs are sul~estive rather than eonclus£v•. Russell (168) quotes results from • study reporting that 92Z of alcobollcs arm smokers compared with 58X o£ "nee:or:ice" aC the same BAT Co LTD - MINNESOTA TOBACCO LITIGATION ",O

-~36- hosp£caZ. Re also notes that, of non-~kers. ~ly 19Z have been foumd to be reKulaz dr~ukers and 6Z use drugs, the coz-respond£ng parcencaKes for heavy smokers being 40 and 21 respectively. Valton (217) compared 130 hospitalistd alcohollcs lrith 100 nou-- alcoholic psychiatric patients. H~ found that 96.9Z of the alcoholics were smokers (94.6X Of th~ ssmple wlre ~k/~g over 20 c/4~aroecas Per day) and 62Z of the control ~oup smoked (A6Z over 20 per day). w~letsky sad Elotter (134) investieated the emok~n8 habits of 57 non-hospLt&l£sed alcoholics and of controls matched for see and sex. The alcoholics smoked more than the cont:ols and 8 higher proportion were smokers. A larKe positive correlat£on was seen between the mnount of alcohol consumed and the number of ciKarettes smoked. No increase in smoking was seen wh~ the alcohol£cs stopped drinklng and the authors therefore conclude that oral psychologlcal factors csm~ot be responsible for smokinK and alcoholima. They conclude tJ~at once the addict4ons are established t.]~7 operate i~dependently 81r.houKh they may be connected to e t.ar t w;_.th. Ayers, Ruff and Templar (IA) have also ~est~Sated this topic. They ukld questions on smoklng and coffee drink~ns and 8da~n~stered the Eysenck Personality Xnvem¢oz~7 ¢o 94 male alcoholics and 43 male non- alcoholic psych/~trtc patients and also ten female alcoholics. They £ound radar male alcoholics smoked sore ciEarettes and drank more coffee than the ecmtz~ls, e~m £f the greats: extrsvers4on of the alcoholic Stoup was taken into ameount. The proportion o£ smokers was uot s£enificently d£ffez~nt £n tills case (93.6~ of alcohol£es smoked and 83.7Z of cont=ols smoked). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-137- An /~terestlnK study which is related to rJ~ mnokins habits of alcohollcs has been conducted by Cri££iths, aiKelov and L£ebson (82). They ~vestiKated the relatlo~shlp beL3men cigarette amd aIcohol consumpclon :in five resident aZcobolics. The number o£ ciKarettes 8mokod increased on days when alcohollc drinks mere given m~i it was shown r~at the total number o£ pulis and wtiKht o£ tobacco ~ked were also greater on a per day basis. The assume of masking was related to the dose of alcohol consumed in ~hat day. This study, on a very mll sample, can only be taken Co be i~dicmtlve of e£fects £or the alcoholics concerned but u~ay st~Jnulate further research on the short-term interaction o£ smoklnK and alcohol dr/~kinS. Kussell has stated that 99Z o£ a sample o£ registered heroin addicts were smokers (168). Re has also quoted results from a study o£ 278 opiate users at addiction clinics who rated ciKarette 8mokinK ms the most "needed" d~ above hero/Jz, methadoum, mnphetsmdnes, ba:biturates, LSD, cannabis, alcohol, tea and coffee (170). iatteSay, )~lhlemann and Zehnder (17) £om~ that i~dividuale who smoke over 24 ¢iKarsttes per day mere si~ai££csnCly over represented t= a 8rroup rich hish narcotic drub intake in a survey of S~lss u~l£ca.-~ schools. Seltzer, Friedman and SieKelaub (194) looked at mmoki~q~ habits and umdic/nal druK use in 70,289 white, black and Oriental men and women. ilasults for Oriental subjects mere not clear-cut but ~hite and black, sale and £mla smobrs wets more Zilwly to use any oLr a ~de rqe of medical preparations, the only axcaptto~s bei~sB dues £or alle::Ktc couditlons which were more widely used I~ non--smokers. 1t was hypocheslsed that the use o£ tranquillizers mad stomach mmdicinea my be related to alcohol cousumption but no relmtlonmhLp vmm £ound. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ",,.O

-138- Katie1 (16) studied Stoups of female neurotic extraverts, neurotic introverts, stable extraverts and stable introverts (Eysenck Personality Inventory). Beery non-prescz-Lption drug use was found in all groups and no person&lit7 differences vere found becveen smears and non-smokers. Extraverts reported that they drank coffee and took druKs (especial17 sheerest.has) in ¢omblnaticm ~r~Lt:h ¢:LKarette smokiDK, especi&lly JLn stressful situations. Introverts ienerally smoked or drank coffee ~n non-scress£ul situations and took tranquill£sers in stressful situations. The author suKKests that the results indicate that smokers m.a,y employ additional pharmacological moans co man~pulate cortical arousal and that this may confound results of research on nicotine. Tl~omas (203) £ound thac Kroups of smokers, non-smokers and former smokers could be dist~q;uished on the basks of coffee and alcohol consumption. Smokers ware found to drink coffee and alcohoI more £requently tha~ non-smokar8 and h~avy smokers drank more £requontly than liKht smokers. Johns' (108) study on 219 hospital patients else indicated an association between heavy 8usok/J~8, heavy ¢ons~umptlon o£ tea or co££ee and usa o£ &lcohol. • t therefore appears that smokers are more likely to be users of almost all classes o£ druss than are non--smokers. Tt 4S di£ficult to ezplain why such a larse proportion of persons with alcohol and drug dependence problems are smokers, but it is probable that in 8eels1 circles tdwre drub exper/Jnmltat:ion first occurs there w4_11 be a h~sh proportion of mnoJutre. There ran be no /mp14cAtlon that mnokiq causes add4ct:ion to dz~qSs, only that those who become addicted tend to be smokers before they start to use or abuse 4ruSs or alcohol. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-139- 10. CO~A~XSON OF SHOKII~G ~T~ THE USE OF DRUGS In this section some t~smples of comparisons of smoking with the use of drugs are considered. Some aspects of the use of opiates and marijuana ere also discussed to facilitate these comparisons. Since drug users ere oEtan smokers as tel]. ic is necessary to remember that any dz~ effects may be seen in conjunct4on with those of n£cotine. Several authors have compared nicotine with druss of addiction. Johnston, and Dock ere among those ment£oued by Lateen and S£lvette (124) who have considered tobacco smoking to be equivalent ~n some ways to non-prescripcioa opi-m or morphine adm~nlstrattou. Hunt and Hacarazzo (96) drew attention to the fact that reZmpse curves for 8ivins up smokins, alcohol and heroin are very similar. Starting with subjects who complete treatment successfully and are abstemious at the end of treatment it is found that many relapse quickly co their previous pattern and only about 25g are able to abstain in the long- term. Denson ($3) compares tobacco and opium, stat4ng that they were both OriKinmlly smoked in p£pes. Since than technolos~ has been used to produce heroin from opium to enable intravenous injection to be made and also to ma~e c£Sarettes from which smoke can he inhaled to produce an effect similar to that o£ £ncravenous injecCiun. Kussell (168) believes that ~t is easier Co become dependent on nicotine than on alcohol or barbiturates mince mat users of the latter two drubs 14--4t t~msmlvmm Co intmrmlttsnt use and dependence only usually occurs in a settiuS of psycholos£cal or eoc~aZ dlf££culCy. Only 2Z of smokers, however, smoke £ntermictantly or occasionally (from HcEmnnell and Thomas (142)) and even the most stable, well adjusted person will sooner or later become a BAT Co LTD - MINNESOTA TOBACCO LITIGATION c~o

-140- regula= dependent use=. Russell also points Co the ~act thac monkeys can be trained to self-4~jact nicoclne and the q~allcy of actlnz as e primacy buc unnatural reinforcer is shazed by other dependence producing dross. JmrvLk (lOA) also refers to this aspect of nicotine which 4s based mainly on the work of Denmau and Inok£ (52). These L~o wrhrs used rhesus monkeys ~Ch ind~elliuK catheters uhdch /~jecCed n£eo~/ne when • lever was pressed. T~. a~cer beln$ persuaded Co prism the lever • few times the monkeys did not se1£-LnjecC, n~cot/~m was Injected aucomat~cally every hour for ssvecal weeks or ~Cil se1£-Injeccion occucred. Z£ there was no self-edm£nlscre~ion the dome was raised and injecced automatically. Seven monkeys were used end did noC sel£-adm£n£sCer at 10 ~g/icB nlcocine. AC 25 ps/kg •11 melg-~kalnis~ermd nicotine but some did so only after auto••tic injection. The averse daily dose Oaken was between 0.7 mad L7 ~/kg but this could chmnge b7 I00X on consecutive days. L~rge total doses on ohm day were umumlly gollc~ed by small total doses on the nezC day. Znjecclon was noc ~3sere£ore amcirely re•olaf and no sel£-~straCion occurred between 12 mddndsht amd 8.00 •.:. vhile ~hs 14ghCs were out. AC c~e month 4~csz~ml• the available dose was raised and eke monkeys cook fewer 4~Jeccions ac each level. At any given level soma -~dm~ls would refuse ~o ~jeec. One monkey, however, ~jec~d domes og 2,000 ~ks caking an mveraq~e o£ 9.6 m~kd~dm~. It was repo=ted Chec s~c~le doses o£ 200 ~/k~ mud ore: pz~ducm~ symptoms o£ ~dcoc~e Cox~c£cy £or up co 20 :~msCes buc no date ~ce &~veu £mc reactions co withdrawal o£ ~Lco~ne tnjscc£ons. i~:ssell has moz~ receucly commuted (173) Chat Ct~s s~udy ~-s been reported 4n ~su~£cdmuc decmdl amd descends Co be£~ a~mos~ amecdoc~1. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-l&l- Opiate dependence has been reviewed by Freedman (68) and Chim review is taken as a basis for the discussion. Opium has been used for as long as history has been recorded, psrcicularl7 in China. Xt was first imported co Amaric~ in the m4d-17Ch CentutT. Factors which lead members of present-day society Co experisae~t with opiates are part of a complex and ill-understood pattern. Opiates are known to produce tolerance mud physical depmnde~ce and the development of abstiamnce syndrome leads many who experiment into addiction. However, not all, or even most, persons who experimnt with them become addicted. Robins, Davis and Goodwi~ (164) have studied U.S. Amy enlisted men leaving Vietnam. Almost half had tried heroin or opium or both and one fifth had used narcotics amd had developed signs of physical or psychological dependence. Most of those who had used narcotics bmav£1y in VimcnRm had stopped doiuS so when they lm£C and had not restarted elzbc Co 12 months later. This show that narcotic use is possible wlthout the development of 8ddicclom and narcotics can be discontinued relaClvely easily in many CABS • • There are a number of dlf£ereut drugs £n the opiate class. Opium is prepared from poppy plants (Papmver som~£ferum) and contains about 1.0% morphine. It is morph£na qghich Kives opium is phermacoloKical characteristics. Reroin, the most widely abused opiate, is a derivative of morp1:~,..~ and has similar ef£eccs, phez~acolosically, methadone is also slmilar miChouzh £C is dissincilar in structure and is synCbasised chemically. Methadone can be substituted for heroin in addicts and will allay withdrawal symptoms. The clinlcal e~£ects of morphlmm depend on the sect/~8 of mdmtz~Lstrmcion, previous opiate use, personality of Ch~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-142- user end prestuce or absence of pti~. To the salve subject wlthout ptln morphine generally induces dysphorla due co nausea, glddlness and a subjecc£ve sm, se of meutaZ clouding. Psychomotor per£ormance £s unimpa£red except under stress. Morphine acts as a powerful analgesic for chose in pain. For the narcotic 8ddict who has noc d@veZc~md tolerance m 8~a~le £njecc£ou usuaZly produces a pleasant scare of pos£C/vm euphoria but some persons may vomit m~ter injection and a state of eas41y-rousod semi somno lence may be observed. Znject£ous may produce a senaat4on similar Co orKasm which may provide the in, tim1 mDtlvmt£on for further drug exper/~mntmtlon. A~ter an injoctlou the skin may hoccme flushed itchy, pupils constrict, respiratoTy race is depressed, cardiac race slows, and smooth muscZe sphincter spasms may occur. The effects reach • peak about 20 ~4nutes after intravenous 4njecc£on and decline over the folloud.n8 four to six hours lemrJ.n8 • "Zet down" £oel:i.ng. Tolerance to the drug develops f~Lrly rapidly End am increasi~K dose is needed by the addict to restore the e~fects of the drug. After lons-tez~n use. hc~mver, the origi~al euphoria cannot be ~pcurod end many add£ecs continue to use the drug mainly to avo~.d Cl~ absC£n~ce 8~nd:ome. The eys~drc~8 4= • coustellat£on o£ symlPtOm8 ~4ch reach a peak intensity on Ch~ second or third day ~ter the Tut dose of op£ate. The~e symptoms subs4d8 in the following seven days but t stable •tats ~my not be ~pproachod for six months. Duties absti~ce a single dose of ~m opiate will abolish the v£thdraval symptoms. Yawning, =h/no=rhea, lacr4~'c4on, pupilla~7 d£1ation, piloeraecion and rastXasmnmss start 12 to 16 hours attar the Last dose. Lar~sr mumculmr aches mad twitcher abdom~mal cramps, vcm~t~J~, 4£ar=hoem, hypertension, insomnia, mnora~c£a, agitation. C~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-1~3- pr0f.st .eati.t, ~iih~ loss, hyperglycaem/a and output of 17-ketosteroids usually occur. There are, however, zm=ked :tndiTidual differences in symptoms. Witbdrmmal symptoms are both physlolosical mud psTcholoK£cal in ~mture and incense cravlnK for the druK is usually presenCo Morphine and morphiJ~e-ltke a~Llgesics ',~y be rested 8o r.bat ,m evaluation of dependence ltab£1ity ,rod depend,race pot•racial can be made. The W.H.O. (227) state that rJxa~acterisC£c profiles of rate phmcmmcoloKtcsl prope=cie8 cam be described. The profiles include: (a) psyrJ~omoCoc m~d autonomic effects L~pical for Cbe 8pecles studied (b) effects mucmSonised by spec~ic mnCaSon£sCs (c) tolerance mad cross-tolera=ce (d) capaclCy Co iJL~C£aCe and sustain morpblum-liXe pbyslcal dependence (t) c&pacicy to suppress most si~ of lorph£~e mbsc4~m~ce, 4. contrast to druss that modify mLty some --pect8 of the s].udrome in • nouapec4~£c msm~r (f) re~orcanmnt of se~Lf-sdm£u£ecrat£on bad.turnout. Morphine is often used ms an exmzple of r~e classically mddictins drus to ~hich ochers can be compared. ~ m~kIict:Lon /~ well advmnced, tolerance has developed and the user becomes trapped in m spiral of hmviu8 to incr~• the dose to avoid the abstinence rjs~LTome but uot belnK able to recreate the in4tlal euphoric effects vh4ch first e~Jzourqed use Of ~ dX'tll~. TJMI~ use of ~I~Ep~L12e (~E:N~E ~tj b~l~verj autommtically lead to this situation and occmsiouml use ts poeeible ~iChout mdd~cClou, although the percentase of users who are not e~mpellmd to take reEUlm: closes is not known. r~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-l~h- The p~aolof;icsl effects of cis~ette smoki~K are in contrast far less drm~ic, u are my ~r~thdra~al symptoms eocperien~e~t. Tolerance to niter/he, if it develops in the user at all, is far less marl~d. Both drugs can be used c~cas~ally by some persons. It may be felt by some rJhat the parallel be~en morphine and related addictions is seen in the XonK-t:e=m user. ~n@ morphine addLc~ must keep tsk~ the drug, the lens-term smoker must keep 8mokLns (althouKh hls nlcot~ inr~d~e may rmln fs4rly constant). Attempts co give up are unsuccessful in many cases mad ~he smoker or morphine user feels that he is better off conCinui~8 to use ~ drug concerned ra~har than face ~ relearning process which is necessary fox" lon£-tent abet:in•nee. ]In both eases the parsons may be part o£ a eoc£ety or culture whlch as a whole d~eapproves of the£r drug use but part of • social ~roup tJa which druK use is the accepted norm. In order to stop smokes8 or morph/~ae use the person ~ust Itaz~ which •Itern~ive bed~a~rLou~s must be ~betitutod, and to come to ~e::s v~th the l&ck of druK e~fect and ~th ~i: oyez--lead,e4 hab£~8. The main differences b~en morphine mad nlcotLne are, hows~r, large. While both morphine addict and smoker amy say that they are unhappy with their drug use, the masker £8 potenti•lly able to live up on his own without the inev~Lrabiliry of the appearance of ~e~-y unpleasant phyaioloKic•l w~thdra~al symptoms. The mu~ph4ne add£et eontiw~ms takin~ the dru~ ~o avoid thee 8~ptoms and may ~rive little pleasure or benefit from his in~oz~ca~ed sta~e. The smoker may derive l£ttle centimes pleasure or benefit from his mnokin~ but ha is gully a~are og his own ~ctlons and smoking • c£1~ratte will not disrupt his l~fe st71• and may be tmprc~/z~ his perforaance under cerr~L~n circuastsnces due to the physiolol~ical e~fects of ~cot~ne. BAT Co LTD - MINNE,-C~TA TOBACCO LITIGATION

-14S- Another druK which is often compared to ~icotlne is mar£jum~ (or the active princlple tetrahydrocannabl=ol). Use of marijuana has been reviewed by ~rinspomn (83) and his article is taken as a convenient re£er~_~_cs point since the literature on some aspects of marijuana use is extensive and often difficult to interpret. The earliest descriptions of marijuana use ~re found in Chinese writings about 2000 B.C. It is prepared from the Indian hemp plm~t (Caunabis satire). The least potent fore is bhang, obtained gram cut tops of uncultivated plants mad this £s low in resin. Ganja Is of higher resin content end is obtained from the flowerinK tops and leaves of cultivated plants. The hlsh@st Krede of the drug is made from the resin frma the tops of mature plants and is called charu or hashish. The active constituents of the resin are isomers of tetrahydrocmnnab£nol. Marijuana may be smoked, often mixed with tobacco, causing a fairly rapid affect lastin8 for two to four ho~rs or it may be insested to g~ve a slc~mr e~£ect lasting from five to 12 hours. The effects of the drug are dependent on a large number of variables tneludi~ the drug type used, route of administration, previous experience of ~ha drug. settlnK in which it is taken and the other persons present when It is taken. On first taking matlJuana, the user may feel an In~tlal period of anziet7 sad restlessness. This is usually £ollmmd by £eel~.q~s o£ euphoria and intoxication and semse distortion. Users may empet-iemce heightened semsiti~Lt7 to eztez~sl stimuli and many claim it ~n::esse8 their sensitivit7 to sounds and products • sense of thinking maz~ clearly and havi~8 a deeper awareness of the ~ of thinks. Time sense if often distorted. Harijuana increases pulse rate but Ln most BAT Co LTD - MINNESOTA TOBACCO LITIGATION k..m.

-146- subjects it does uot cause pupil dilation or chsuJee 4. blood pressure. Marijuana is nov thought not to produce physical dependence as cassmCLo~ of use often produces no ~thdraval symptoms. There is no need for the user to increase the dose used and he amy ev-~ be able to reduce the dose when he is e:cperiemcsd at coutrolld~g the rate of ~utske of the drug. S~timmm use of the dz~g may uncover pr~mtt~8 psyehiatTic problems and in suseept£ble persons it my precipitate mt~L dys~ti~. A recent W.H.0. Raport C227) provides ~otmmticm about cAnnabLs and delta-9-trsn~-tetrahydrocaanab~ol (TBC). Zt is stated that self- m~hninlstratlon of THC in a~ud~eys is established cmly fleer forced e=qposure or priming with other dues or food. Zn animals, bebavlour is depressed by the dug in a dose related fashlon. Zn man the level of self- ad~Lnistracion by mmok~ is related to properties of the drug and uon- phazmacological factors such u the appe~cance mud size of the cigarette. The report of the W.H.O. Sciamti£ic Group on tb~ Usa of Canzu~is states that "~my reip~la: (almost da£1y) users of ~is e:~ibtt psychic dependence, as do many less £requJnt but relatively "heavy" users, ~bereas the great majority o£ people ud~o use it on an exper~Jneutal basis, or CuuLUy Oa a few :satire occasions • 7eaz, could not be said to exhibit psychic or .,my other deqpemdmmce on ~is" (225). The name report concludes that: n~re is no ev~dmsce to sudS•st that vitbdzml of cannab£s eveu from an extremely "heavy" user produces an absttJun~:e syudr~ that bests to Ipproach in severity those produced by drugs of tbe alcohol, barbll~wat• and morphi~m t'yl~S", fkmm w/.thdrmml symptoms have bees reported (83) such 88 insomnia, t.z'z'4tmbt14ty, restlosms8, mmat~, rhlaor=hea, decreased a~pmt~te: iucredmed salivatlou and zuddeu BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-147- ~e£ght loss by diures~8. These effects start s£z to eiKht hours after cessation o£ ~C adm£nlmtration ~d last wp to 96 hou:m. HAuy mtud£em, however, have found no obvious withdra~l syndr~. Tolerance to the effects of marljuana is not seen unless there is hem~y, regular use of the drug when tolerance to heart--rate eff~:tm and subjective effects (level of perceived intox£cmtion and mood changes) may be seen. Harijuana use therefore seems to be similar in several ways to tobacco masking in that tolerance and a tr~thdrawal syndrome and hence phym£cA1 dependence are very difficult to demonstrate. It must be remembered, however, that amrijuana is often smoked in eomb£nation ~r~th tobacco a~d the relative effects may be difficult to dies•ranKle. The main difference between marijuana and tobacco is t~at the foxier is normally smoked on • far more intermlttent basis and the effect of mar£~uaxus is to produce a £ozl of into~ution. This is ths effect of the drug which ts probably sought but it is such that it would inter£ore with many no~maL dsy-to-4ay activities. The only drug which is really comparable to n£cotine in many ways ts ca£fe£ne. This amy be obtained from either tea or coffee and is another socially acceptable, lesal, st4~ulant drug- It must aSain be rmaamhered that most smokers also drink coffee, add often smoke wb~]Le doing sot euid the effects of n~cotJJ:te and cef£e:Lne are often seen together. The use of ca£fe/~ae ~uses bralu sti~lati~ although this may be of lmss "natural" type ~ ~hat ~aused by nicotine (38). Zt is one of the very few alternatives to u~cotLuJ which does not alter the tb~u~ or behav4our of the user or produce i~aebr~sti~ or Intozlcat£on. BAT Co LTD - MINNESOTA TOBACCO LITIGATION c.rr O",,

-148- Van ProoJdij (2].3) has been quoted by Lacson and S£lvecCe (124) erich re£er~nce to this subject. He compared tobacco ~th alcohol, betel nut, cocaine, cmffeima, hashish, op£~m, sopori£1cs mud amphaCmmlues, with respect to Chelr value as a memos of escape, enjoyment value, as soclallsers, risk of addiction, injury Co health, social drawbacks mad attitude of authorities Co non-medical use. Van Froosdlj concluded ChaC only bevatades concainLu~ o.af£aine are superior in mrit to tobacco buc i:~ar£or Co ic as a mane of escape. DruBs capartn8 favou=ab17 with tobacco in this respect such as alcohol a~d mmphmtmm~nm are no less dangerous than tobacco i£ abused. It was also moated Chac u~pleasmac sensations become m~ced mad pleasurable sensacloas acceuCu~Ced by mmoklns, the pharmacodynmmic properties of u,~coClue help mmlucain an equable mood and even sCron8 ~fecCs like rmse mad fear can immedLaCely be toned do~ma. With all chic the personality rsmains inviolace, an advantage shared only q~th caffeine. One of the UULia differences between ca£feiue mad nlco~nm is the =outs and moan8 of admizsistration. The smoker may set an izmmdi~aCe sensation ~:om JJ0hallns smoke mad ~dcocinm ~aches the bra/~ very soon after each pu~£. Tha:e £s exact control o£ the ammmc o£ n~coCine delivered (assua~nK thac clam ci~mretca is noc o£ the very low n~cottJxe delivery type). 0£c8n psycbolosical factors involved in, for instance, handling the cisaratca, uay be benef£clal to the uBer. • CiSa~eCt~s are also easy to usa, needinl only to be removed from the packet and lit. Ca~£a~ne on ~ other hand is mdm~s~sterod o=mlly in tea or c~££aa mud may uoc produce its maxiamm a£fect for over 30 m/~utas. The merest o£ ca~£eiue cam be varied only by incrsasin~ ~ 8crenKch o£ the beveraKe BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-149- and relative cm££eine contents of different brands ~e extremely di££icult to discover. Psychological factors mmy be involved, such is the comfort of a warm drink, buc there ~v~ll ulually be a delay between t:~ &esire for sCt~malaeion ~ ~hJ e~gaett while ~he e~gfee or t:ma is prepared, and miter drink~ 4t wh£La the eg£act: on the brain dmvtlops. More work is ~eedod begore any real assessment of the ability of caf£e~ne Co subscLcute for n£coCine can be made. l~sIowuk~ (118) him found tl~sc smokers take in more nlcocine £rmn cig~ceCces when they ingest almost no ca££e4~e than when they insesc ammmCs of c~feine ranSlnS from 75 ms Co 300 mS. ~emvler users of c~E£eine showed Chls egfect less strongly chart did lishcer users of ~£iine. The anchor su~esc8 t:hat: ~he advice co sive up coffee drinkins while Crying co s~op amokins should be reconsidered, lc is uoC known, however, whac effect restriction of t:obaceo ~ou~umpt£on ham on c~l~feina 4~caka. BAT Co LTD - MINNESOTA TOBACCO LITIGATION Qo

-150- • i. USE OF ~ TZ~S ".,i~DZCrI.O~",p.."ImLiZ'~ATIO~" ~ ,'m~,Em)z~c~" .x~ CON'/:EXI "OF '"EOB&CCO ' SNOKING In this section some of the ways in which the different tern luave been u~ed in the l£teratn~re w~ll be illustrated. Larson and Silvette (224, 125, 126) have rwr4e~d the ue of ~he ~rns in quesclon by l larse =mnber of authors and Kive lumy references ¢o publlcacions Which iu¢lude all three reams. Rere • select£on of papeEs ~rLL2 be consldsred, mai~ly in chronoloEical order. Be~teln has discussed the def~ultions ~n ~vo pRpers (21, 22) and considers the topic minly from the point of view of |~okinl behavlour modification. He beZieves that if smokinl is proved to be am @diction • coo:dinE to the rIKid phazmtcoloEical defln£~fon (g.H.O.) r~en this would have iztpoz~ant consequences in ~ee&eing smokers. The best way co treat add£ctlon is to use pharnacoloslcaT moans ¢o counter it. He points out =hat al~houKh smoksrs, especially heavy mnokers, experience an "overpover~J~K desire or need (compulsion)" ¢o concinum 8mokt~K it ts open Co serious doubt whether ~ey w~ll obtain clSarettes '~y any m~ans". Tolerence develops but •his is not in itself evidence for addiction and there is no sickle eharmr.tmriscic ~r~bd=mml 8ynd=o~ occu~ctui spontaneously and inevitably. He suisescs ~C it is undeniable Chat cilarects ~moking hal som~ decz~Jmnt&l effect on the iod~qr~duLl (in ¢e~m8 of increms~d blood pressure and heaz¢ EaSt, reduced ozysen supply ¢o the bEL~n o: othe:, Ions-ten•, effect) but que|ttons ~he effect on society ~h~ch may be beneficial in view of the s~se and importance of ~he ~obanco industry. ~tz~stiin concludes thrall: c~K~etCe 8moktJtK satisfies the W.R.O. defiu~Ltiou of habituation far bel:Cmr Chart it does that of addict4on. He also su88•sts thaC the u~e of ~he term "addlcClon" even ~ben less ri~z'ou81y BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢..m ",.O

-151- defined should be d£scouraSed in che hope that nnch o£ the confuslon and m~sunderstandiug eur'rmmml!nl~ ~ issue can be el/m~naced. ~:eovtCz (135) seem c£Karette 8mokinK as • z'esp£rmcory add£ccion ~th pharmacopsychosochl i1~ts, b snlKKsstJ ~butt addiction 4j dependent on the tnhalmtLon-exhalmtion-visualizmtian tt~ad sad stresses that n£eot4~ absorbed ocher than by inhalation does not satisfy c£8atecte snokera. He dls~insu4shea bitumen "add£c~£on" and "compu18£on'. Add£ct£ve behaviour 18 usually coaci~td. IrLth • pleasurable act 4~ an attempt to tell•re anxiety msd Kuilt. Campuls£ve behavlour is 81so dr£van by azm£ety and suilt but is usually not pleasurable and may be used to avo£d soma £orm of l~nlsbm8~C. Zn tJ~e case of hsmvy c4Karette 8mokin~ thL~covttz st&tea chat £t is not really necessary to dec£de whether it £s cowpulsion or addiction. Van Froosdlj 18 quoted by Larson and 8ilvette (226) as saTLu8 that tobacco or n~cott~e cannot be couJidered to be mdd£ct~ on the bas£J of • Urestr£cted" pharmacological def£nition. The Ever•Be habitual •reeker v111 no¢ attempt to obta4- ~obanco •t my cost and tobacco consL~ption elm be 8toppod m,tddem.ly lr~Jlc~t the appiarJm~t of 8evtce or dm~K8~ somst:£c v£thdrmml s~mpeoms. He 8ul~ests, hcnmrvmr, that in some cases prscl:~c~l ezper~emce shows that the bold o£ tobacco on man mY be 8o f£rn as Co dLf£er ~au add£c~£on to druss such as morph£ne snd mo=e quant£tat4vely than qual4tatLvely. Ulett and It£1 and the£~ collesKmss (102, 210) have sul~ested that the deuoustration of neu~oph~s£oloKica/ citruses Luducsd b~ mwklnK depz~vat£on Cosether v~th the observation that bra~u aet43r~t~ return8 to the pre-q~hd~81 pattern on reaumpt£on of 8mok£uK lends mupport to the view that mnok~s £s m~XmKouo to druK ddicClon. BAT Co LTD - M1NN~TA TOBACCO LITIGATION

-152- The role of habitual beha~iour in drug uS.~e has been 4~Lscussed by Hunt and Matarazzo (96) who stress £ts relatlve /mport~cs in connection with "milder" drugs and de-emphaslse its /mport~e with "severe" ones. Thus, they scale druK usage from "mild" practises such u coffee driDkins and 8mok~, up throuKh alcohol End marijuana use to the use of haXiuclnoL~nJ, psychedellcs told opiates. A1onl ~hi8 seals hmbltuJ~ behavlour would # decrease, that is, the more the repetitive behaviour involves a pronounced physioloKicaI reaction and the possible development of physical dependance, the less viii it resemble habit. On this schema 8mokin8 is tJae~fore larjely habitual. McKennell has used the teem "a~diction" but has been careful to point out that theoretical assumptions about its nature have been avoided and it is defined 4n terms of questionnaire answers (138). He also states that his use of "addiction" is net 4~tended to cmmote sty damp- seated chazactar£stlc (139). In some ways the use of "addiction" by ~kard and TomkLuJ is s4~418r (99). They describe the addictive smoker as someone who experiences nqative affect as soon as he is w~are of not smoking, independent of feeling good or bad at that moment. uae Of the vaEJ~us ~e~m8 ban 818o b~ O.ODJ~eEad 4~ a plq~ by Jarvik (I04). He defines "dzus addiction" u 8 bedun~ouz pattern characterlsed by a tendenc7 to obtain and tntToduce into she body quantities of a drug to achieve pleasurable effects and neither physical dependence nor tolerance ts a necessary sequel, 81thoush they may occur. This means that amokins can be included. The use of "addiction" Ls said to be better M "druj ab~se" and possibly better than "p~yehie dependence" which has spiritualistic connotations. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-].53- Denson Ls nn m:tJ~r who stz~mKly advoc4~es the use of the term "~iction" ind c©eplre8 clilrette Imo~i to '~mttJ~l~Lnl" of opiates (53). He states that 8mok~ £s penlstently and et-toQeously desc=ibed am e "habit" when it is in fact e form of drus addlctiou. Calling it • • *habit" jives ch~ldrem th~ impresmlon that mno~ng =am be brouKht under VOlitLOD&l cOQtE01 m~4 easily modified. Denson 4eplorestbe a:t£on of the W.E.O. in dro~pJJI8 the word t'add£et4oD" 4~ £mrot~ of eed~eace,t vh£ch he c~118 • veKue concept with no else: ms~ for anyone. Bradshav (28) quotes the g.H.O, defiJ~4t£on of dependem~e and states that the ef£ects of tobacco are cemsLste~t ~rith this, especitlly as two types of dependence are desc:ibed (cam~nbls type and ¢oc~L~ne type), in the absence of acquisition of role=ante and ptodw:tion of • chazecter~stic w£thdrawal syndrome. Costa (48) sidesteps the issue somewhat by saying thst smoking is addictive but that --diction to nicotine occurs 4, far than one per cent of cues. What is see= is an addiction to tb~ habit of smoking. Schtchter (186) has ind4catad that the e~ldence that tobs:co and nicotine aze a~dict4ve £s inconclusive and inconsistent. Re concludes that heav~ stash•re aze addicted 8~e they will z~gulate the~r n~cotine intake but £0 not certain 8bout l£Kht mnokers who ~p~ea: to smoke independently of nLcoti~ content of c£Kazettes. He hal£~ves that these people may be addicts who me to keep their habit under "tLSht cognitive cone=•l". Schachter also sul~gests that t~gulat£on of n/cotine intake £s seen only ~n st•dies on U.K. ~mkers m£nce c£earettes are :elet4vely more e~pens£~e here than 4~ the Unitad States. Thus most non-addicted U.K. mmka~s have 8iven up amok/n~ for f£nanciel z'essm. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ~.:'t

-154- No real evidence is presented in support of this hypothesis. 8chachter, SilversteLn and Perlick (189) propose that even light smokers mre addicted to nicot£ne because they ~11 8uoke as many ciKarettes as hsa~ smokers if restraints mrs removed An certa£n situatlou:. They also found in their studies that a mall sample of liKht smokers tended to veilh less, taka more puffs on each cigarette and amoke cigarettes of h£Khe: n£coti~e deZi~et-y tham heart smokers, thus opt4~nis4ul their nicoClne intake. LiKht smokers ~ty therefore tabulate their nicotine intake (a prerequisite for addiction), independontly of ntunber of ciKarettes smoked. Russell has ~itCen a Irreat hal about addiction and dependence in connection wlth smokinK. He rarely, however, uses any definitions to clar£fy h£s poslt£on. In his e~rliest papers on 8moklu8 (165, 166, 168) he re~ets to emok~ Js a dependence diIo~der. He states that depee of depeudeuce should be @~phaslsed rather than type (physical or psycholoKical) and says that most smokers ~e dependent alchonsh not mremaly dependsnt. Ettssell is apparently fond of sayinK that= Wctsarstte mnok~aK is probably the most addictive and depandence-pruducinK form of object-speci£ic salf-adm£nistered ~cati£icaCion known to man" (170). Here he uses the two tez~s toleCher and An other papers they are used interchanKeably. Often. in revi~ of the evidence for ~4coti~e reKulatlou, tolerance mid withdtmmsl effects. 8 somewhat one-sided view is preseuted. The emphasls is usually on the importance o£ nicotine in 8mokins motivation. The evldence is presented end taken to indicate that ~4cot~um is e~tre~aly izrportanc and is the reason why people smoke. Russell has, however, included other reasons for 8mokins in h~s model for 8mok£n8 motivation (166, 177). When cons~derin8 the reported effects of smok£n8 withdrawal BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-155- these are taken to c~sti~ute a vlthdraval ryndrome. The evidence is always used to show that smokers, especially cigarette smokers, are dependent on nicotine and different interpretations of this sm evidence are not presented. In Russell's w~el for smoking motivation, addictive smoking is described (166, 177). The smokers Bets v£tbdrmwal symptoms i£ he goes v~thout cisarettes for 20-30 m~nutee and 8makes to avoid or relieve this d£atressiq 8tats. Smokies is no lesser positively enjoyed but hms became • nsce~sltT. Frequency of smoking varies little vlth chanKinK external 8it~mt£ons, it beKins soon after wak/~g, ceases only duriu~ sleep and Is reKulated to maintain • h£Kh level o£ nlcot£ne in the bra~n. Originally it was SUfLSested that most ~aokers would proKress from mnok£n$ got psychosoc£al and other non-phazlna~oloK£cal reasons to smokin$ for n£cot/~n (includin8 addictive mnokinK). In practice £t was found (177) that there is no associatiou of addictive smokes8 (or other pharmacoloK£cal £actors) ~r~th ass 80 the prosression is not /~evitable and occurs in only • proportion of smokers 1~t when it occurs it does so quick17. Zn his most recent review on "Cisarette 8mokinK and u~cotine dependence" (173), bsell cooaidera a £airly large amount of t~e evidence for the role of ~i¢ot:L~e in imiok/~q~ behaviour and for the dtvelOl~4mt of dependence. He stets by 8ttt~ that: nThr~t history no other Sinl~le bioloKically unnecessary object has m~nt 80 much to so many people who, ag~er so £ev inlt£atinB experiences have needed to have it 80 siren, 8o reEularly, mad £or 80 ms~y 7oars, despite t~ so hard to do vithout it; mad for which there is no orA~r adequate BAT Co LTD - MINNESOTA TOBACCO LITIGATION L.,-7

-IS6- subst£tute. Tobacco see ".k~n8 is • foz~ o£ drus dependence dlffe=ent but no less strong than that 0£ other addict£ve dzuKs." Th£s may be seen, perhaps, as marely a way of Imsmdlately p~ the reader's attention. Russell uMmtions two form8 of psycholoKical dependence. The first is • purely psycholoKical need for an object without the /nvolvmnent of pharmacoloK£~al effect such as the dependence of an 4~ant on its mother or dependence on bettinS by the compulsive Kambler. The second type is a psycholoKical need for or dependence on, the phaz~acoloslcal effects of e druS such as the tranqu~lliz~=8 e~fect of alcohol or the pleasu=able effects of inhal~:~ clsa:e~te smoke. When these objects or effects are unavailable, intense dlstress or crav~ may occur but the symptoms ere simiLaz in both cas~s. It is pointed out that although these w~thdraval effects are psyeholoKical they are also physical in the sense that they are mediated by chases• in b=aL~ acti~rLty. Russet1 states that many c/4pu:etts smokers also fulfil the criteria for physics1 depem4ace, showlns tolerance and physlcal vLthdravaZ effects. Zn conclusion it is musK•seed that: "c/Sat•tee smokers are not 8~ply dependent on nLcotine so much as the inha/ation-bolus form of intake, wh£ch sakes cisa:ette smokins one of the most addictive of the addictive behav~ours". It is dlfficult, hc~wer, to see how such a conclusion can be justified £r~m the evidence which is presented sine@ much of the Im~rk he mentions is open to other intez~retat£ons. It muat be accepted, therefore, that this is a state~t of KusselZ's persouA1 vim (43). At the end of this section 4t see~ approp=iate to consider the vim expressed by the CosmLttees of the World Health Ozlpmisation 8iuce Lt is ~e their de~inie£on8 that much of the ~fpJnant revnlv~8. In BAT Co LTD - MINNESOTA TOBACCO LITIGATION t..r-:,

-157- 8~me rays one o~ the p:obliBs is &1read7 :olve~:! in Close the W.H.O. have adopted the use of ~he term "dependence" in place of "mddict4on". It has also been stated Chat physical depe~d-mce is nm4chmr a necessary nor • muf£icie~ condi~4on £o: p::odu~tio~ o£ cclpulstve druS-~a/c/z~ behavlou~. Thus nmZorph~a~ and cycl4:ocine produce physlcal dmpe:damcm but noC druS-seek£ns behaviou: tn animals and man. The m~lges£cs p:ofadoZ and pmsxr.szoc:tne :eadily p::oduce self-a4mta~scracion behmvlou: in monkeys buc noc sisns of physical dependence (227). J~cordins co one W.H.O. report (226) • 4ruS-relmcad problm exists when some aSenc or ,s41ency judies ChaC • jim, presumably dru4r-relaCed, phenomenon is produc/z~ o: is capable of p:oducin8 haz~ Co or di££iculcies for an /~d£vlduaI or mocietT, even thoush it may later be £otmd Chat the phenomenon £s uot ha:mful or that £t is not related to use of the druK in question. The hun problem :elstmd to uma-madlcal use o£ d:uss my seam prjJZar41y £:om: (a) man-druB lnceracC4on (e.K. ~raf£ic mad ocher acc4denCs duz~ug iucozicacLou, dmlolmmUt of r~Lssue pacholo87 or demob due to ovl:dose) (b) man-society lute=action (e.$. sC£EmacizaCion or impr~soc~ant fo: 4rus use) (c) a combinaC£on of these and other £accor8 (e.S. uulm~ul or asoc£al behav~c~c such as ~hmft or deserC4ou or tn~ecC~on ~rom use o£ conCm~ced dz'up or LnjectLou equipment). Certain c~pe8 o£ d .z~, £nclu4/~ t~hose present in Cu or co££ee a:e said Co be capible o£ producJ~q~ ~ dependence 4~ s vez7 broad 8erase but ex£s~ence o£ such • state £s noc umcessar£1y harm~uZ ~u ~cself. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-158- A n~nber of tYl~S .of dru6, however, produce substantial central nervous system st~lmtlon or depression or disturbances of percepClon, rod, th£nk£ng, b@havioar or motor function, and such druss are recosn£sed as hav~J~ the ¢~pmclCy, under some clr~toncms of use, to produce /ndividual and public health end social problm. The W.H.0. te~ such druEs as "dependence-producing" mad they are IioCed as follo~: 1. alcohol-barbiturate type ~pheta~Lue type cannabis type cocaine type 5. hallucinosen type 6. khat type 7. op£ar~ (morphine) type 8. volatile solvent (i~alRnt) type. Tobacco is noC llstod althoush it is said to be "clearly a dependonce-- producing substance with a capacity to cause physical ham to the user and its use is so widespread as to constitute a public health hazard. Uulike the drugs listed, however, it produces relatively little sti~Jlation and depression of the central nervous systm or disturbances in perception, mood, th/nkinS, heh~v~our or motor function. Any such psychoto~Lc effects of tobacco, even when used in lsurKe smotmts, ~e slisht compared v£th those of the types of drus listed. Thsrafoz~ dsptndonco on tobacco, which is perhaps the most w~lasptead form of dLrus dependence, Ls not siren splc~f~ic attention since this is restz~cted to the use of dependence- producLu4~ drubs cspabls of 8xerttng major psychotc~Lc effects". The W.H.O. therefore admits that tobacco mnokiu8 produces dependence but the effects awe of a completely d£fferent nature to those of other drus8. BAT Co I~TD - MINNF~TA TOBACCO I.ITIGATION

-159- Z2. COHCLUS~ONS & number of dlfferenC aspect:s of dependence on cisarecce smoklns have been reviewed. The history of tobacco use suggests thac nicotine is an important factor but experiments on monkeys which are ~ven nicotine or trained to smoke c£gawet:tes provide lit:tle evidence of this. Evidence fzom ezper~nent:s on hmmm 8ubjoct:s liven uicot:tJse bY a variety of rout:as, includ~ 8mokiuK. may be t:mksn to indicate t:bmt: s~Lcotine plays a role but th~t ocher factors are also /Important in deCe~min~ mmok~ bmhmv~our. The cole played by ~4cot:4um also seems t:o differ in c£Karette, ciKaz and pipe smoking. A number of physiological effects of smoking can be recognized but it is noc known which of these. £f any. mould be involved in smoking motivation, sit:hough it: seems reasonabXs co deduce t:hat the effects on brain acCivlCy may be suitably re4v~orclng. Smok/~g also has varied psychological affact:s amd affect:s on t:ask performance, sow of which may be perceived u be~ bmfic£al t:o the smoker. At: present, however, it ks not possible to define the 4~tent to which Chest types of effect are pbaz~a¢o logically det:erm~sed. Yhysiolog£cal, psychological and social differences can be found beCveen smokers and non-smohers. Those differences are clean small and thair significance is debatable although some of them my be const:it:ut:icmal. iudicat:ing that: chose persons who cake up smoi~Lns are iah&rantly 'different fzom those who rmmain non-mnokars. Further mork is needed to r_~n~£rm this. A number of 8mo .k~g smt:4vat£on Chaoziss hays b4mn considermd but: only those vhich include both pharnmco!os£cml and bebArviour~/psycbo!o~Lc81 m~pmcts appear Co be able to explau~n t~m mot:ivmClon of the mmjorlty of mmoke=e. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-160- • t is probable that some smokers will smoke for ~3olly psychological reasons wh£1e others will be completely motlvaced by pharmacologlcsl factors, The majority of the gmokinK population rill be bo~eu these two extrmnss. The process of initlatlon of mnoking behaviour is obviously detained by non-pharmacological factors. Nose smokers started before the eke o£ 20 years and were influenced by relatives, friends and acquaintances. Cessation oE mnokinK is probably more complex and a ~r~da variety of methodm hmve been used to assist people tr~sh/u8 to stop 8mokinK. Attempts to Lid the 8mokinK ~thdraval process by the use of pharmacoloKically active preparations have been larsely unsuccessful. Host mmok£ns cllnics can only claim that 30Z o£ their patients are' stiI1 abstinent after one year. The most effectlve methods are based .on psycholojical and behvioural theory, but even mnong these techniques, am averese of 50X o£ subjects relapse after tree~nent. Smokers who stop 8mokins may experience wlthdrewal symptoms but there is insufficient evidence that a specific ~Lthdrawal syndrome exists. ALthough some tolerance to the pharmacoloKical effects of nicotine appears to occur there is no evidence that this leads to a proKresslve increase in nicotine dose. Smokers are more likely than non-smokers to be users of almost a11 classes of drug but it cannot be /Japlled that gmol~ns leads to the use of, or addiction to druKs. Smoklns can be compared to the use of opiates, marijuana or caEfe4n@. A1t~ouKh there are comuon aspects ,in the use of these druss, e..af.f~Lno use is most s~n~lar to smoking. Zn overall ¢oncluslon it can be stated that smokin8 does not appear to involve addiction to n~cotine for the majority of smokers. Host smokers can be considered to be dependent on mnokinS but the deKree of dependence BAT Co LTD - tvlINNF_.SOTA TOBACCO LITIGATION

-161- uny vary considerably fros one s~kar to the next. They will also vary in the extent to vhich the£r dependence is pharmacoloK£cally basad (on nicot£ne). Smoking is am ~r~r~-ly complex phe~m~non which can only be d~scribed by :eso~t to a number of ,d4£~eent diseipl~es, to acaoumt for ph~z~seololtcL1, psycholos£cal, beh~r~our&l and soda1 Lspects of cisa:ette 0mokiJ~ behav~ou:. BAT Co LTD - MINNESOTA TOBACCO LITIGATION C.r7

-162- BZTEREHCES 1. Adams, P.I. ~e o o e e o e o Chanses in personal smoking bab£ts broulht about by chamleJ in cillzctte smoke TisId. Prec. 6th T~t. Tob. Sci. ConKTess, Tokyo. 102-108 (1976). J AK~8, C. Smokiz~ pattez~s, uieotiue ~ntlke at d~ffete~t t~ses of day lad cha=Kls ~ L~O c4urdlovaJcull~r vmc~lbles ~4~ile Imok~ag tile:ceres. Psychop~cololia. 30, 135-144 (1973). &gu~, C. HicotiDe mad ~: Effects ~ 8m~Jsctive ¢haD881 ~Jl meal. Psycbopbarmscolol£a. 30, 323-328, (1973). Ame=lcan Psychiat:tc Associet£on. Dia4psostlc and 8tatlst£cal Hanuel of Hantal Disorde:s, ed. 2. American P87chiatTic &ssociat£on, Wash£~ton (1968). Andersson, E. Effects of ¢iKarette smoking on IIaru~J~B and retention. Ps3~=bophaz~scolos£e, 4L, 1-$, (1975). Andersnon, E. and Post, B. E££ects of c~8arette 8mokinl on verbal rote learninS and phys£olo8i~sl arousal. Stand. J. Psycho1., 1__55, 263-267, (1974). &rmita&~, A.E. Same recent observations rela¢in6 to the absorption of nicotine fram tobacco. 83-91 Ln Dunn, W.L. Jr. (ed). 8mokins Behavior. Hot£Tes and ZncenCives. Winston and Sons, WuhtnKton, D.C., (1973). &z~Lts~e, &.E., DoLlezT, C.T., Geoz~e, C.F., Hou4emam, T.H., Lewis. P.J. and Tuu:s:, D.H. £bsorption end metaboltmn o£ u£cot£ne fz~m c~llrettes. Bt. mad. J., 4, 313-316, (1975). Azu~Ltsse, A.E., H811, G.H. and 8ellete, C.H. Effects of u~cot~ne on electrocort~ca/ acti~ty and ace~71chol~me release from ~he tat cerebr&l cortex. Br. J. Phsz~8col., 35, 152-160, (1969). BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢,..m

-163- 10. Ashton, H., l~Ll]Jnan, J.E., Telford, R. and Thompson, J.W. Stimulant and depressant dfects of c£Karette 8mo~4nK on brain activity 4n man." Br. J. Pharmacol., 48, 715-717, (1973). 11. Ashton, H., N~llma=, J.E., Tel£ord, K. and Thompson, 3.W. The e£fect of Ca~£eiJ~e, n~trauBepam add ¢iKaJrett@ mki.lz8 cm tll~ ¢ont~nSant ~esa~Ive v~ria~ion in man. Electroenc~h. clln. Heurophyslol., 37, 59-71, (197A). 12. Ashton, H., Savage, K.D., Telford, R., Thou~8on, J.W.amd Watson, D.W. The effects of c4gs~ette 8mo~K on the respot~e to stress 4n • drivJ~S slmulator. Br. 3. Fhaz~col., 4_~5, 546-556, (1972). 13. Ashton, H. and Watson, D.W. Puff£ug frequency and nicotine intske in cigarette mmokers. Br. reed. J., 3, 679--681, (1970). 14. ATers, J., Ruff, C.F. and Templet, D.X. A1eoholi~, eiK&rette rookie, coffee drf~kin$ and eztraversion. J. Stud. Alcohol., 37, 983-985, (1976) • 1.5. Ba~k]Ley, g.A., Ksst£nSs, J.Eo and Jackson, T.L., Jr. The effects of rapid meokLn~ and lx3~mosis b the treatment of smoking bshmvlor. Int. J. clln. exp. H~osls. XXV, 7-17, (1977). 16. Kartol, C.K. ILx~ravers£on and neuroticisu m~l n~cotine, caffeine and drug intake. Psychol. Rap., 36, 1OO7-1010, (1975). 17. Ksttegay, g., J~fhlemann, K. and Zehndar, U. Camparat4ve tnvestL81t4m of the abuse of aleohol, dz~gs and uA~otin~ for a reprtsutative group of 4082 man of sSe 20. Compreh. Psy~t., 16, 2A7-254, (1975). 18. IUtt~lS, i:. I/otivatio~ of mwkins. Tabak. J. Xnte:nat., 5_, 299-302, (1975). BAT Co LTD - MINNESOTA TOBACCO LITIGATION O',,

-164- 19. Beci~tt, A.H., Gorrod, J.W. and Jenner. ?. The affect o£ JmokLug on nlcot:ine metabolism in vivo in num. 3. Phmrm. ~c., 23, Supplement, 625-678, (1971). 20. Beckett:, A.R. and Tri888, Z.G. F~zymn induction in man caused by smoking. Eat~re, Loud., 216, 587, (1967). 21. Bewnstein, D.&. )Jodi£ic&tio~ of 8mok£ng b~: A~ evmltmtive rev£ev. Payohol. BuZ1., 71, &lS--~O, (1969). 22. Bernst:e£n, D.A. The mc~lt~icaeioa of 81ok:LnK b~iottr. An ennalu~tive revLew. 3-41. in Hunt:, w.a. (ed). ldm~ Meelumimu in Smokies. Ald£ne Publlshlng Co., ChicaKo, (1970). 23. Bernscelnj D.A. and lqcA11st:er, A. The modification 0£ smoking behavior. Progress and problems. Addict. Behmv., 1, 89-92, (1976). Best:, J.A. Tailoring smoking wit:hdrawal procedures to personality and mo~ivat:ional differences. 3. consult: mad olin. Psycho1., 43, 1-8, (1975). 25. Bewloy, B.R., Blmul, J.H. and Rs.t'r';s, R. Factors associat:ed with the 8tart:ing o£ ciK~rette jmok~nS in prkry school children. Br. J. prey. moc. Hed., 28, 37-44, (197&). 26. Blak£eton8 Gould Nodtcal DiceionazT. 3rd edn., HcGrsv Hill, (~972). 27. Bozzmtti, L.P. Group pmychotherEpy with 8ddLcted mnoker8. Ymychother. Paychos~C., 20, 172-175, (1972) • 28. Bredshav, P.W. The problon o£ c£Saret:te smoking mini it:s control. Int:. J. Addict., 8, 353-371, (1973). 29. Brantmark, B., 0hl~Ja, P. mad Hest:lin8, R. Nicot/~zs-conta£ning c~ 8um am on amti-amokinK 8~d. Psyehop~lojia, 31, 191-200, (1973). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-16.5- 30. Brengel~snn, 3.C. La th~rapie c cmportmmmtele des etats de d~eudance. Psycholo$ie Ne~dicale, 8, 41-60, (1976). British )kndic81 Dicttonm17. )LIcHal~ (ed), Caxtcm Pub. Co. Ltd., (1963). 32. Brown, B.B. Some chs~acter£sC£c meg diffe~mces helen ham~ retake= and non-smoker subjects. Heuropfycholog£a, 6, 381-388, (1968). Brmm, B.B. Add£tional characteristic DG di£ferences bellmen mnok~:s and non-smokers. 67-81 in Dunn, W.L., Jr. (ed). 8mok~ug 3elurvlo:: Hot'.yes and ][ncemtives. W:JjlsCon ~ Sons, Was~ton, D.C., (1973). 3A. Byuner, J.M. The YounK ~nokez. Govermsent Soci&l S~-vey. H.M.S.O. London, (1969). 35. Cahoon, D.D. C£garette addiction stud carbon dioxide tnhalatiou: 8 hypothesis. PsycboL. let., 21, 247-2&9, (1971). 36. Caplan, R.D., Cobb, S. and French, J.K.P., Jr. Roletionsh£pa o£ (~es,tton Of mk4"n$ Idr~t~h job stress, p4t~Jonilit:y k lOCii1 lul~)olrt:. J. eppl. Fsychol., 60, 211-219, (1975). 37. Che~ry, H. and lr.tLernan, E. Personel£ty scores and smoid~8 behsv£ou~. K lons£tudinal stud:y. Br. 3. prey. soc. Had., 30, L23-131, (1976). 38. :39. Cheshire, P.J., Kellett, D.N. and Wtlley, G.L. and arousal c,~ the mook.a7 electroencephaloersm. 71--73, (1973). Kffects o£ nicetY;he ~We=lent~a, Zg, C~mer, A.E., B~e, C.D., Bu~nett, L., D~rk~V. C.l. and Tho~ton, R.E. The effect o£ e£eare~ee smok~LnK on the con~Ke~t neeae£ve va~Lation (CHV) and eye s~vement. Klecttoeuceph. cL£n. leuropby8£ol., 39, 222, (1975). BAT Co LTD - MINNF_..SOTA TOBACCO LITIGATION O",,

-166- 40. C~r, A.K. Co~e=ts on a ~Ik Slvea by Dr. KoA.L ~aseZ1. File ~. 14tJ~ July 1975. Comer. A.L Commmsts on £igu=es quoted by Dr. H.A.II. ltumme11. F£1e 463. 18Zh &u&~uH: 1975. 42. Comerp A.K. XuCeractioss of smoke and the rocker, Pazt 6. KZG studies. EAT Keport Ho. RD.1374 Rmstricte4, 27.5.76. A3. Comer, &.E. Tobacco ~lc/nK and w4coC4nm dependence. 1~1e &6J. 218c December 1976. Comer, A.K. and Thornton, R.E. Alpha waves and ~k~: the effect of ciKaretce xmok~K on the alpha denslCy of subjects provided vLth audlcory feedback. BAT Lepo=C No. ED.1173-R, 6.12.7A. AS. Corn=, A.K,. aucl Thornton, ]LZ. Zuce=acc4on o£ amoka and the smoke::. Pa=t 3. The e~£ect o£ cIEarette ~ki~ on rJ~e continent nesatlve varLat£on. BAT ~poz~ No. 1164-I, Z2.12.74. 46. Comstock, G.W. and Stone, R.W. ChaaSes is2 body wmiKht and subcutaneous (1976). BAT Co LTD - MINNE--C~TA TOBACCO LITIGATION Ox

-167- 52. Deneau, G.A. mad Inoki, R. Nicotlne self-adm~nistra~£on in mozskeys. Ann. ~.Y. Acad. Sci., 14_~2, 277--279, (1967). 53. Denson, 1. Cisarette smok.~nK. A ch£1d°s Kinds to addiction. Can. J. publ. Hlch., 6~4, Supplement el-S4, (1973). Domino, E.P. and you Bmumq~arcen, a.H. Tobacco cilarette 8mok.tJag and pacellar reflex depress£on. Clin. lrnmzmsc. Thor., 10, 72-79, (1969). 55. Dreher, R.F. and Fraser, J.G. Smoking babies of alcoholic out-patients I1. Int. J. Addict., 3, 65-80, (1968). 56. F~uc3~od, M.lt. mad Trevelymss, H.H. Smok£ug and neurotic £11umss. Lancet, 1, 107-108, (1971). 57. Eisinger, R.A. Psycbosocial predictors of ~ki~ recidiv~mz. J. lealCb and 8oc. ~d~v., 1_~2, 355-362, (1971). 58. E£singec, R.A. Psycbosoc£al pred£cCors of smok£us behav~our change. Soc. Sci. amd Had., 6, 137-144, (1972). 59. Ejrup, B. The role of nicotine in mok~Ls~ pleasure, nicoCin~mm, treatment. Zn Von Euler, U.S. Tobacco Alkaloids and 1elated Compounds. Pergamon Press, New Fork, (1965). 60. Eysenck, H.J. Personality and the mmincenmz~e of the mnoicln8 habit. 113-146 in Duns, W.L., Jr. (ed). Smoking Behavior: Motives mad Inceucivem. WineCou mad Sous, Wa~k4uStou D.C., (1973). 61. e ysenck, E.J., Frith, C.D. and d4~e, C. ~iecC8 o£ mok£n8 on human per£ormmzct, 54-55. Tobacco hsearch Council bviev of Acclv£ciem, 1967-69. London (~970). 62. YiumeKan, J. ]~., Lemon, P.S. and BasK, H.B. The role of nicotine in the cigarette habit. Sc£emco, H.Y.t 1~02, 9&-96, (1945). BAT Co LTD - MINNESOTA TOBACCO LITIGATION o,,,

-168- 63. Fisher, J.M. ~ Fisher, S. RJsponse no ciKarette d~l=rlvetlon as a function of owel fantasy. J. Pets. Assess., 39, 381-385, (1975). 64. F1axmsn, F. SmoEinl; cessation: Gradual v8 abrupt quitting. Paper presented an the meeting of the Asec~iation for nhe Advancement of Behsvlour Therapy, Chic.ago, Novmshez' 1974. 65. Foes, E. Persona liLT, soclJl influence and cieszette smok/ug. J. Health and Soc. Behav., i_.44, 279-286, (1973). 66. Frmlenhaeuser, M., Myrste~, A-L. and Post, B. Fsyr2aophysiolol;icel reactions to ci4;szette smok/ng. Stand. J. Psycho1., 11, 237-245, (1970). 67. Fraud£enhaeuser, M., Myrst:en, A-L., Waezeck, M., Beri, A. and Post:, B. Dosage and time effects of cigarette smok~,'g. Psychopharmacologla, 13, 311-319, (1968). 68. Freedman, &.M. Opiate Dependence. 1298-1317 in Freedman, A.M., Kaplan, H.I. ms~ Smdock, B.J. (eds). Cmsprehensive Textbook of Psychia~/IX. We1, ZI, 2rid ode. Will£sms and Wilk/ns Co., Balt:Imore (1975). 69. Freedman, S. and Fletcher, C.M. Chmnees in smoking habits and cou4~ in man smoking c4jareCteJ ~lth ~3(Y~ H~ t:obecco substitute. B~. med. J. • I, 1427-1430, (1976). 70. PT£edmmz• J.• Borvmch, T. mud M~LTan, R. Tobacco msoki:~ and • ' sclmulus bmrrier'. Nature, Loud., 248, 455-456, (197&) • 71 Frith• C.D. The effect of vaz~FlnK the sLtcoCine ~nteut of cigarettes on human smokies behaviou:. FeychopharmacoloKt8, 1-9, 188-192, (1971). 72. Frith• C.D. Smokia8 behsv4our mui its relation to the ~ker°e imnadlat~ exper/Amcm. BE. J. sot. :1in. Fs~bol. • 10, 73-78, (1971). BAT Co LTD - MINNESOTA TOBACCO LITIGATION ",e

-169- 73. 7uller, E.G.C. stud Foz~est, D.W. Behaviou:al aspects of c4ga~etce ~king in relation to arousal level. Pr~chol. R~., 33, 115-121, C1973). 74. G£11, Z.W. Persoul comRmlcat£on, (1977). 75. Glad, W. and Adssso, V.J. The relative ;,nportance of socially induced tension and behavioral contagion for 8mok:LnS behavior. J. abnorm. Psychol., 85, 119-121, (1976). 76. Gllckp S.D. • Jarv~k, H.E. and Eakammra• R.K. ZX~L{bltion by drugs of smoking beh~rlour in monkeys. Nature, Lond., 227, 969-971, (1970). 77. Goldbourt, U. and Medalie, J.H. Characteristics of smokers, non-smokers and ex-smokers ~ong 10,000 adult sales in Zsrael. 1. Distribution og selected soclodemoFaphic and behavioral variables end the prevalence of disease. Israel J. lted. Sc£., 11, 1079-1101, (1975). 78. Goldfarb, T., Grits, E.R., Jaz~rlk, H.E. and Seole~man, T.p. Reactions to c:Lsauc'etl~es as • £uncl;::Lon o£ ,F,4colr.::Lns ~ ~t;az"~. C]L;,',. Pha~mc. 'l"hez'., 19, 767-772, (1976). 79. Goldfarb• T.L. and Jarvik, H.E. Accomsodation to restricted tobacco smoke intake in cigarette smokers. Int. J. Addict., 7, $$9-$65, (1972). 80. GoLd~arb, T.L., Jaz~rik, H.E. sad GlicJ:, S.D. Cigarette ~4cotine coBtent as a determLnant of human smo~ behsviou:. Psyclmphamcolosia. 17, 89--93, (1970). 81. Gretn, D.I. and Born, D. ~nys~ci~~ atttt~les toward thelr /nvolvmnt in smoki~g problems of patients. DLs. Chest., .~, 180-185, (1968). 82. Griffir.hs, LL, BiKe.low, O.l. and Llebson, I. Facilitation o£ htman tobacco self-administration by ethanol: A behavioural analysis. J. exp. Analysis. Behav., 2~, 279-292, (1976). BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢...m ¢..r7 O',,

-170- 83. Grlnspoon, L. DruS dependence: Non narcot£c aSencs. 1317-1331 in Freedman, A.N., Kaplan, H.I. mad Sadock, B.J. (@de). Cowprehens£ve Textbook of Psych£aCry/IZ. Vol. ZZ, 2rid edn. ~£11iams and Wilkins Co., Baltimore (1975). 8A. Gr£Cz, E.R., Baer-~e£ss, V. and Jarvik, M.E. T£eration of nleoClne intake with £u11-1ength cigarettes. CI/~. Phazmac. Ther., 20, 552-556, (1976). 85. Groll-F~aFp, E., ~aSue:, H., W-uck, H. and Rm£de:, M.~ E£~ects of low carbon monox£de concentrations on vlsilmnce and compute~-amaly-ed bra£n potenc£als. Scaub, Reinhal: Luf:., 32, 64-68, (1972). Guillerm, R., IdJm~rel, G., BrousJolle, ~., Byacln~he, R., Simon, A. and Hee, J. Cl/~ical and £uncC~onml resplraCoz7 effects of subst£cuclon of m cigarette ~r~eh comparatively non-irritant smoke gor ~he usual type of c~arette, in a group o£ heavy smokers. Bronches., 24, 209-231, (1974). 87. Hammer, O. S Jahre Bad llauhei~er raueher-ent~ohnamesthersple trod n£chtraucheroC=ai~ain$. Hunch. rod. wsch., II._~6, $65-$68, (197A). 88. Hmaaond, Z.C. and Gar£~kel, L. Chanses in cisareCte smoki~s. J. hath. Cancer Inst., 3_.3.3, 49-'64, (1964). 89. Bart, P., Farrell, G.C., Cooksley, W.G.E. and Fo~ell, L.W. Xnhanced drug metabolism in cigarette smokers. Bt. m~d. J., 2, 147-149, (1976) 90. Beimscra, N.W. The eJ~tacce o£ msokin8 ms mood change. 197-207 in Dunn, V.L., J:r. (ed). gmok/n8 Behavior: Motives and ZncsssCivee. Wlnsl:on amt Sons, Wmsbinl;con D.C., (1973). 91. lieimscrm, N,W., Bancroft:, li.R. and DeFock, A.L IKf£ecCs of Jmoklall upon susca/zssd pe=formance 4,, a e/smlacem d=ivinl cssk. Ann. lq.Y. Acad. Sc4., 1A2, 295-307, (1967). BAT Co LTD - MINNESOTA TOBACCO LITIGATION C.m O-,, x~

-171- 92. Herman, C.P. External and 4~te~al cues as data~In~nants of the mmoki~q~ behavior of lisht and heavy smokers. J. PtrJo~tlity tnd Soc. Psycho1., 30, 664-672, (197A). 93. Hit, key, R.J. and llarne~, E.G. E~holosical i~d biochemical /nteractions and rAm£r relationships to smoking. 267-282 ~n Dum~, W.L., Jr. (ed). Smoking Behmrlor: Motlvu ~d ~c~tives. Wi=ston and Sons, Washlng~on D.C., (1973). 94. Ho~, D. Why people smoke. 14~d. H1th., Dec., 26-31, (1975). 95. Hunt, W.A. and Bespalec, D.A. An evaluatlon of current methods of modifying smoki=g behavlor. J. cli~. FsychoZ., 30, A31-438, (1974). 96. Hunt, W.A. and Hacarazzo, £.D. Habit smchanimas £u mok£ng. 65-90 in Hunt W.A. (ed). Leaning Mechanisms in Smok;nK. A1d£ne Publlshlng Co., Chlca8o, (1970). 97. Hutchinson, R.R. and laley, G.S. Ztfeets of nicotine on avoidance, ¢ooditio~ed 8uppr~oion and al&~:eJslon zeilpouse measures in Ilnimalil and man. 171-196 in Duau, W.L., Jr. (ed). Smok~$ Behsvlor: Hotives snd Zncontlves. Wt=stou and Sons, Washington D.C., (1973). 98. ]]Lard, F.F., Green, D.E. and Bo~, D. A scale to dlf£eronciste beL~een types o£ smoking as relattd to management of affect. Int. J. Addict,, 4, 649-659, (1969). 99. 3~ard, 7.¥. and Toak/ns, S.S. The experience of a~£ect as • diti~'lllJ~l~ll~t O4F II~Ok~ bihIvtOr: A 8il~4ll Of vtl:lLd£ty stud£es. J. abnoxm. Psychol., 81, 172-181, (1973). 100. ~smac, ~.F. and Raud, H.J. Blood levels of ni:ot~ne and phys£olog~cal • ££ec~s a~t•r ~uhaljtlon o£ tobacco smoke. Eu=. J. Ftmnmco1., 8, 269-283, (1969). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-172- 101. Zsacssc~, S-O. and Jam,•n, L. Kesults of • quit-aaok{ul research p¢oject in • ¢azxlomly selected populatic~. Scand. J. Soc. Hed., 4_, 25-29, (1976). 102. Iril, T.M., UletC, G.A., Hsu, W., El~J3gemberg, H. ~ UXeCt, J.A. The dfects of ~k:LnS; urlchdra~al on qmmtitativtly analysad EEG. C1LzL~cal Electro~cephalolr~aphy, 2, 4~-57, (1971). 103. Jacobs, H.A., gnapp, P.H., Koseuthsl, S. and liaske11, D. Psycholog£c aspects of cigarette smoking ~n men. Psych•so•. )fed., 32, &69-/~95, (1970). 104. Jack, H.E. The role of nlcot:~ne ~J~ the Imok:~g l~b~t. 155-190 ";n Hu~t, W.A. (ed). Leaching bchat~um JJ~ Smokln8. &ld¢ne ?ublCJhlng Co., Chicago, (1970). 105. Jsz~ik, H.E. Further •bier-rations on n~cocinm as the =eJJ~orcing agent tn smokCnK. 33-49 4n Dram, W.L., Jr. (ed). Smoking Behavior= Motives and Encent4ves. W£nston and Sons, WuhCult~n D.C., (1973). 106. Jsc-v~J~, H.E., Glick, S.D. and NaJ¢anmTa, R.K. ~ibition o£ cigsmette smo~ns by o¢•11y adaubsisteted n~cotine. Clin. Pba~mac. Tber., 11, 574-576, (1970). 107. Jenkins, C.D., Zyr~ns~L, $.J. and Rose•tan, I.E. It•logical, psych•logical and socLal cl~¢&cte=ist:Lcs of smon ~Lth d:[ffeue=t ran•kinK habits. Health Sez~Lcss Rap., 88, 834-843, (1973). 108. Johns, M.W. The sleep habits sad X~i~estyl• o£ cigarette smokers. Msd. J. Jmst., 2, 808-811, (1974). 109. Johnston, L.M. Tobacco smoking and n4cot:Lne. Lancet, 2, 742, (1942). 110. Johnstcm, L. H£cotLnJ cheu~ug-lFun. Br. rood. J., 2, 585, (1976). BAT Co LTD - MINNF_.,,.CK3TA TOBACCO LITIGATION

-173- 1ll. F~mzler, H., Ja~fe, J.H. and Zeldenberg, F. Lon8- and short-term ~f£ect£vemas8 of • larKe--sc~Ze propriecaz~ 8~ok4ni cessation prof~mn - A 4-year follov-up of Smolumdern p~rticipaunts. J. olin. Psycho1., 32, 661-669, (1976). 112. i~eenan, A. and Johnson, F.N. Development of behavioral tolerance to n£cot~e in the rat. Ezpe=iemt£a., 28, 428-429, (1972). 113. Routzer, C.S., L£chtens~e~n, R. and Hmes, R.L. Hodificatlon of emok~aK beh~ior: A review. Psycho1. Dull., 70, 520-533, (1968). 114. Xhosla, T. and Lowe, C.lt. Obesity and emokinK habits. B:. mid. 3., 4_, 10-13, (1971). 115. ]L~Jsen, D.H. Psycho-sociaZ factors in c£garet~e amok~nS motivation: A revlev. Ked. 0£fr., 10_~_4, 365-372, (1960). 116. lr~zpp, P.K., Bliss, C.H. and Wells, H. Addlctive aspects in heavy cisa:et~e amokLu8. Jt~. J. ?qchitl:., 119, 996-972, (1963). 117. EnotC, V.J. and Venables, P.H. EEG alpha correlates o£ non-e~okers, smokers, 8mok/J2K mad 8mok:LnK depr£vatlon. Psychophysiology, 14, 130-].56, (1977). 118. F~zlowsk:L, L.T. E££ect~s o£ csJ~£e~.ne consumption on nlcot~ne consus~Cion. PsTchopharmacology, 4_~7, 165-168, (1976). 119. EozZowsk~, L.T., Jarvlk. H.E., m~d Gritz, I~.R. Nico:4ne resulmcion and cilarette smoking. Clin. Pbarmac. Ther., 17, 93-97, (1975). 120. Rreitler, S., Sbahar, A. mad Rreitle:, H. CoKnitive orientation, tTPe of smoker and behavior r.herapy of 8mok£ns. Br. J. mad. Psychol., 499, 167-175, (1976). 121. Lando, H.&. Sel£-pacLu$ ~n el~na~£n$ ~£c amok£ns: Selreaadipity revis~ted? Beh~. /'her., 7, 634-640, (1976). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-174- 122. Lando, B.A. and Davlson, G.S. CoKuitive dlssonance as • modifier of chronic muoklu4S behavior: A sereudlpltoum £~dins. 3. cc.~mult a~d clin. Psychol., 43, 750, (1975). 123. Lareon, P.5., Kam$, H.B. and S41vette, H. Tobacco. Zzparimmntal and C1/~i¢al Studies. A comprehensive account of the world literature. Willims and Wilklns Co,, Baltimore, (1981). 124. Larson, P.5. amd Silvecte, H. Tobacco. Kxper/mental and Clinical Studies, Suppler Z. W411ia~s amd WtLk/~s Co., 3altimore, (1968). 125. Larson, P.S. and SilveCCe, H, Tobacco. F-,cper/mmntal and Cliuicml Studies. Supplm~mt II. Williams and Wilkiu8 Co., Baltimore, (1971). 126. Larsou, P.S. and SilveC~e, H. Tobacco. F~cper/~mntal and Clin4cal Studies. Supplement ZTI. Williams and W£1kins Co., Baltimore, (1975). 127. Lebovits, B. and Ost£etd, &. SmoklnK and personality: A mchodoloKi~al aualys£8. 3. chron. DLs., _~_~, 813-821, (1971). 128. LevenberK, 8.B. and WaSher, H.K. 8mok4~g c8|smt4ou: 1xn~r-Cerm irrelevance o£ mode o£ treatment. J. ~ehav. Ther, sad Exp. P~bimc., 7, 93-95, (1976). 129. L4cbcanmtein, E., Larc4s, D.W., B4rchler, G.E., Wahl, J.M. and Schmahl, D.F. ComparLaon of t'apLd mokiu$, warm, ~k7 a£r, and attention placebo in the mod£flcaC4~ of 8mokin$ behavior. J. coasult, msd cli~. Frjcbol., 40, 92-98, (1973). 130. Lincoln, J.Z. We~KhC 8a~n 8fret cemsaticrn o£ emokLnK. J. Am. reed. &ss., 210, 1765, (1969). 131. Lindenthml, J.J., }/yecs, J.K. and Pepper, H.F. 8mok~, psTcholos4cml 8tmcus and stress. Soc. 8ci. and Mad., 6, $83-$91. (1972). BAT Co LTD - lvlINN~TA TOBACCO LITIC;ATION m "-4

-175- 132. Lubl£u, T., and Joslya, L. Averstye conditioning o£ cigarette addiction. Paper prese=ted at the m-et£nS of the American ~sychological Associatioo, Los AnKelts, September 1968. 133. Luccbesi, B.K., Schuster, C.R. and Emley, G.S. The role of nlcot/ne as a determinant of cigarette smoJ~Lug frequency /n man with observations of certain csrdiovucular e£fects associated with the tobacco allutlotd. C14~. Phatmac. TheE., 8, 789-796, (1967). 134. Halet~y, B.N. and glo~taE, 3. Smob£ng and alcoholism. Am. J. Psychiat., L3_~1, 44~-AA7, (1974). 135. HaEcc~its, E. On the natuze o£ 8ddlct~c~ to clgs~ecCes. J. Am. psychosnal. Ass., 17, 1074-1096, (1969). 136. l~usnaz, B. and Plait, E.S. Smok~g: A Beha~rloral ~alysls. PeEKamon PEess, (1971). 137. N:3[~mell, A.C. Zmplicattx~ for btlth education of social t~fluinces on smokiag. Am. J. pub1. Kith., 59, 1998-2004, (1969). 138. NcXemle11, A.C. Smoking :otivatton FaCtOES. BE. 3. SOC. olin. Psycho1., 9, 8-22, (1970). 139. ~=Emm~11, A.C. Is addictive smoking an iudepemient trait? T--t. J. Addict., 8, $05-509, (1973) • 140. NcEanne11, A.C. & comparison o£ two smok~ typolos£es. Rases:c~ Fspe: 12. ~obacco Zesearcb Cmmc£1, London, (1973). 141. )lcEmmo11, A.C. in • disc, sion o£ ib:sse11, K.A.H., Peto, J. and rate1, U.A. The clus~fLcat£on of msok~ug by £8ctc~ial structure of motives. J1. ]L. statist. Soc.&., 137, 313-333, (1974). 142. ~11, A.C. and Thomas, I.E. Adults' and adolescents' smok4~ hablts and attitudes. Government 8otis1 Survey, S.S.3S3/B. H.H.S,0. L~ndou," (1967). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-I76- 143. Harck Hauual 12th eda. Bolvey, g. (ed). Marek, Sharp and Dobme Kese&wch Laborator£es, (1972). 144. Hettlin, C. Peer and ocher influences on maoking behavior. J. Sch. High., 46, $29'-$36, (1976). 14S. Heyer, A.S., Friedman, L.H. and Lazars£eld, P.F. Hotlvatlonal co~licts engendered b7 the on'-Koi.n8 ~sc~ss£Gm of c£Karet:te smoking. 243--254 in Duma, W.L., Jr. (ed). Smoking Behavior: Hocives and Incent£ves. W£nston and Sons, Wasb£nston D.C., (1973). 146. Hlott, S.R. and Hlott, Y.D. Fantasy in indtvlduala who smoke, stopped smokinK and never maoked. J. c1~. PsTchol., 32, 415-418, (1976). 147. Hoses, F.M. Treating Imoking habiC by ~Scuss£on and hTpmosis. D£s. new. Syst., 23, 18A-188, (1964). 148. Hu~ee, H.B. Zlec:t;roencephaloFaph:Lc d£ects of ca££elne, ~co~me~ tobacco smok£=8, and slcobol. 22-36 ~ ztil, T.H. (ed). Prycbot:opic Drugs sad cbe Euma= EZG. Hod. Pz~bl. Pba:mscopsycb~at. Vol. 8., Earger, ~ssel, (1974). 149. Nurph:ee, R.B. and Schultz, R.g. Abstinence effects in smokers. Fed. Proc., 27, 220, (1968). 150. HTrsten, A-L., A=derssoD, L, FramkeDbaemmr, M. and E1gerot, A. T=mad~te effects o£ c~erette m~:qK a~ related to di££erent ~8 bAb£ce. Percept. Hot. Sk~lls, 40, 515-523, (1975). 1S1. Hyrsten, A-L., Zlse:ot, A. and g~:lm, B. ~£ects o£ 8bst~:eace fz~ tobacco Imo~g on physlolo$£cal and psycl~loglcal arousal levels in b~b~tual smokers. Pa~cbosom. H~I., ~9, 25-38, (1977). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-177- 152. Nesbitt, P.D. Smoking, physio!ogical a~ousal and ~otioml response. J. Personal£ty and Soc. Psycho1., 25, 137-144, (1973). 153. N£1sson, A. and TibblJm~, L. Personality coz~relmtes of smokers rite d£fferi=sg consumption o£ cisarettes. Psycho1. Ees. Bull., 12, 1-12, (1972) . 154. Norton, G.R. and Barske, G.R. The role of averslon in the rapid- smoking treatment procedure. Addlct. Behav., 2, 21-7.5, (1977). 155. Xovlist V. e-search with the Mood Adjective Check List. 352-389 in Tomk£ns, S.S. and Izard, C.E. (eds). Affect, Cognition, and Personality. Springer, New York, (1965). 156. 01dream, M. Smok.ing bahavlour: A st:udy of perscrnalJ.ty d:Lff~'mnces between smokers and non-smokers. File 463, June 1974. 157. Paton, W.D.M. Page 3 in SteLnbe:s, R. (ed). The Scienti££c Basis of Drug Dependence. Churchill, London, (1969). 158. Pederson, L.L. and Lefcot, N.M. A psycholoKical end behsvioural ccmpar£son of ex-smokers and s~oker8. X. chron. Dis., 29, 431-434, (1976). 159. Peters, 3.M. and TezT£s, B.G. MozTbolo$4cal constitut£on and smokin$. A £uEtha: evaluat£on. Arch. environ. Hlth., 14, 678-681, (1967). 160. ?flaum, 3. Smoking behsv£ot: A cEit£cal :s~lew of reseaxch. J. Appl. Behav. 8ci., 1, 195-209, (1965). 161. Pincherle, G. and Willlamson, J. Smok/nE and neurotlclsm. Lancet, 2, 981, (1971). 162. ]tesni.¢k, 3.K. Effects of stylus sat:/.a1:£on on the overlemraed umladapt4we =esponle of c~et~e tokenS- J. ¢oosult. and =lin. Psycho1., 32, 500-505, (1968). BAT Co LTD - MINNE,-,C~TA TOBACCO LITIGATION ",,,C

-178- 163. l~eyl~oldl, C. ~ lficholl, R. of cigarette smok/ng: One year follow-up. 251-258, (1976). 164. Robins, L.N., Davis, D.K. and Goodwin, D.W. Perionallc7 and behavlourml correZmce8 Psycho1. Rop., 38, I)-ruK use by U.S. enlisted men in Vietnam: A follow-up on their re~u~-n home. Am. J. Epldemiol., 99, 235-249, (1974) . 165. Russell, M.A.H. Smok/ng in BritaLin: Strafe&7 for future emsnelpatlon. Br. 3. Addict., 66, 157-166, (1971). 166. Russell, M.A.H. CiKarette dependence: Z - Nature and cZassLfication. Br. reed. J., 2, 330-331, (1971). 167. Russe11, M.A.H. CIKarette dependence: ZZ DocEorl role in man•Be•int. ar. mea. J., 2, 393-395, (1971). 168. RuIIeZ1, M.A.H. CiKarette 8mok~K: natural h£ltory of • dependence disorder. Br. J. med. Psycho1., 66_, 1-16, (1971). 169. Eusse11, M.A.H. ChamEe8 in ciKarttte price mid conmtnnption by men in Britain, 1966-71: A prelimlnmt'y smalyii8. BE. J. prey. 8oc. Mid., 27, 1-7, (1973). 170. Russell, M.A.H. The smokln8 habit and its cZasilflcatlon. Practltioner, 21_..22o 791-800, (1974). 171. Eussell, M.A.K. Eealistlc $os18 for mmokJmS msd health. • case £o3 iSLfer Iok~]8- ]daJlCeC, 1, 254--258, (1974). Also publlibd as; Smoking and heaLthz A critique of traditLonal Ko818. Jnl. R. CoZ1. Ken. Pract., 25, 39-~6, (1975). 172. Russell, M.A.H. Lou~tar medlum-n/cotine clSaurectes= • new approach to safer mnokin8. Br. mad. J., --1, 1430-tA33, (1976). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-179- 173. l~sse11, H.&.H. Tobacco amokin8 amd ~cotine dependence. 1-&7 G£bbi~s, R.3., Zsra~l, Y., Ealamt, H., Popham, R.E., Schmldt, W. and Saazt, R.G. (ads). Research Advamces in Alcohol and Dz~E Problema, Vol. 3, John ~£1ey and SoDs, (2976). 17A. Russell, M.&.H. Personal coammlcatiou (1977). • 175. Russell, H.&.H. Persmmsl comaunication (1977). 176. Russell, M.&.H., Fe)verabeDd, C. axed Cola, F.V. FlaJma D~cotine levels afte~ c~arette mol~ug and c~ ~¢ot~e &~m. Br. mad. J., 1, I043-1046, (1976). " 277. Russell, M.A.H., Peto, J. mud Pate1, U.A. The claasi£ic~t£on of smoking by £actor£al structure of motlves. 31. R. statist. 5oc. A., 137, 313-333, (1974). 178. Russell, H.A.H., Suttou, S.L, Yeyerabe~d, C., Cole, r.V. and Saloojee, Y. liicot:is:Le che~xug gum as a substitute for smoir~ng. a:. mad. J., 1, 1060-2063, (2977). 279. Russell, M.A.H., W£1aon, C., Feyerabezui, C. and Cole, P.V. Lf£ect of n£coti=, chafing gum on mo~L~S behav£ou: and as an aid to ciB~ette ~r~tbd~mml. Br. rod. J., 2, 391-393, (1976). 280. Russell, H.&.B., Wilson, C., Pate1, U.A., Cole, P.V. m~t Feyerab-md, C. Compsrisou of d£ect on tobacco couma:ptlon and carbon m:,:x~te abso~-pti~m of cha~aiu~ to h~gh and low ~cot~e c~$mrettes. ~. mmlo 3., ~, 512-526, (1973). 182, Russell, M.A.B., 9£1so=, C., Pat~l, U.A., Feye:abend, C. amd Cole, P.V. Plasma n~cot~ne levels after smok4-1~ c/4~arattes wiLth h~ab, msd£,m aml lo~ ZL~COtt:m yields. B:. umd. ~., 2, ~1~-416, (1975). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-180- 182. Ryan, F.J. Gold turkey in Greenlleld, Zow8: • £otlog-up study. 231-241 in Dunn, V.L., Jr, (ed). 8rooking Behavior= Hotlvoa and I~cemtives. Wimston and 8onsp Was~tGm D.C., (1973). 183. 8slbe:, E.J. and lto~D J.Z. PersGmality di~feremceo be•linen smokers and =m:-samke=s. A stu4y of sc~ol ch£1dreQ. Arch. euv£r. Slth., 8, 459-465, (1964). 18A. Schachter. S. Eu~cion. Obesity and Crime. Academic ]Pz'esso Hew Tork. (1971). 185. Sehachter, S. Nesbitt'8 Paradox. 147-155 in lknm, W.L., Jr. (ed). Smoking BeJ:svior: Hotives and Incentives. Winston and Sons, Wash~qEton D.C., (1973). 186. Schachter, S. H£coc~e :•BulaC£on in heaTy and liiht smokers. J. exp. Psycho1., 106, 5-12, (1977). 187. Scha~ht~r, S., Kozlmm~, L.T. and 8£1ve:ote~, B. ~tecto 0£ ~i~s:y pH on ciKazette amoki~4. 3. exp. Psycho1., 106, 13-19, (1977). 188. 8chachter, 8., S£1versce~, B., Koslowsk~, L.T., ~, C.P. and LieblinK, B. Lf£ecC8 of 8Cress ou ciimcette smokA~K and ur4vmzT pH. 3. exp. Psychol., 1_~, 24-30, (1977). 189. Schachter, S., Silverseein, B. and Perllck, D. Psycholo&~c81 and ph~x~scolosical sxpllmations o£ amok£ug under stress. J. exp. Psyehol., 106, 31-40, (1977). 190. Schechte:, )i.D. and Rand, N.J. F~£ect og a~ute deprivation 0£ smok:;.u8 on •ggresslon and hostLl£ty. PoychopharmacolosLa, 35, 19-28, (1974). 191. Sc~mhl, D.P., Lichc~steln, ~. and B~rr£8, D.~. Suecess£ul treament o£ habitual smokers with waz~, smoky air and rapid smoking. 3. consult, end elin. Prychol., 38, 105-111, (1972). BAT Co LTD - MINNESOTA TOBACCO LITIGATION c.m

-181- 192. SchwarCs, J.L. A critical revlew and evalumtlon of amokLu@ coatrol methods. Pub1. Etch. E~p., Wash., 8A, 483-506, (1969). 193. SeZtzar, C.C. Norpho!osic couat£tution and smoking. J. Am. reed. Ass., 183, 639"-6A$, (1963). 196. Seltzer, C.C., Frledmmn, G.D. and SieKelaub, A.B. Smok/~s msd dru~ consumption in white, black and oriental mmu and women. Am. 3. publ. UZth., 6A, &6~-A73, (1974). 19S. Sh££f~an, S.M. and ~mrv/~, M.L SmokinS Irlchdramal sTmpcams in Cvo weeks of absCinmuce. P~chopharmacolory, S_O0, 35-39, (1976). 196. S£1verste/~, a., Roslowmki, L.T. m~d $chmchter, S. Soc£aZ li£e, till•torte mmolk~u$, and mr~Jzaz7 pB~. J. exp. Psycho1., Z0__66, 20-23, (1977)o 197. 8mltb, G.H. literatu~re. FersonaliCy and amoking: & :ev£ew of the emp£:ical 42--61 in Bunt, W.X. (ed). ~Hecban~m in Smokins. &Idine Publtsbin~ Co. Chicaso, (1970). 198. Scepuey, L Behav/x~ral :afulacton o~ a~coctne Incakm in c/ssrecce smokers prmmamcedurlch • 'mhorcmned' c~4arm:ce. mace/a8 of Ohm lr£CiahPhmnsacolosic•l Soc£eCy. levcasCle Opon Tyn•. 13Ch-lSth Jul7 1977. Paper Sty-- at • UnivsrsiCy of 199. Stolenm=, Z.F., T/•k, 1. sad Jarvik, M.Z. Acute and chrma~c coZeranc• to n£coCln• msasured by acCtv£Cy 4. rste. Psycbophazmscololi•, 30., 329-342, (1973). 200. Scolerma=, I.T., Gold£arb, T., Ftnk, L mad 3arvik, M.E. Influencing ¢il;azmtte mm:~h~Lths~Leotine mstaKonLsts. Ps)~.hophaz3mcolos~a, ZS, 2~7-2~9, (1973). BAT Co LTD - MINNESOTA TOBACCO LITIGATION C~

--182- 201. Stungo, E. Drug addiction. Lancet, 2, 209, (1961). 202. Tarrlere, C. and Hartmaann, 7. Investigaci~ Into the •greets o£ tobacco smoke on • visual vi$ilance task. 525-530 ErKonOULiCS- Proc. 2nd I.E.A. CoaBress, Dort~md, (196h). 203. Thomas, C.B. The relatlonshlp of 0moklng mad hablts of nervous tension. 157-170 in Dunn, W.L., Jr. (e4). 0mokt~qZ Beh4vtor= Moclves Rnd lncenClves. Winstoa and Sons, Wuh/ngton D.C., (1973). 204. Thornton, R.E. lnternatlcmml wo~ksl].13p ~ ~ be]:La~wi~al ef£ecCs of nicotine. Zurich 16th/17th September, File 463, (1976). 205. Todd, G.F. Statistics of 01oking in the United r~nsdmn. Tobacco Research Council, (1969). 206. Tomkins, S.S. psychologica! model for smoklng behavior. Am. J. publ. Elth., $_~6, 17-20, (1966). 207. Tong, J.Z., Knott, V.J., NeGro, D.F. and Laish, G. 8moki~g mad human expe=immtal psychology. Bull. Br. psychol. 8oc., 27, 533--538, (1974). 208. ~t~bull, M.~. mud Kelvin, A.S. Cigarette depm~den~e. Be. mmi. J., 3, 115, (L971). 209. Turner, J.A.M¢)l., Sillett, R.W. mad Ball, K.P. Some effect8 of chanBing to low-C~ and low-nicotine ¢iSarettem. Lancet, 2, 737-739, (1974) • Z10. Ulett, J.A. ami Itil, T.H. quantitatlve elecc=oRnceptmlogram in smoking and smoking deprivation. Science, N.Y., 164, 969-970, (1969). 211. United States Department og Bealth, ~tucaef~m sad Delfare 8moher'8 S•lf-Test~n$ F~t. Public Baalth Settle• Publ~cation No. 1904, (1969). BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-183- 212. United Scares Public Health Service. 5mokinK and bLTCh. B~porC of the Advisory Co~LiCcee Co the SurKeou Gene~&l of the Public Health Service. Publ£caCton No. 1103, (1964). 213. Van Prooedij, C. Smok~nB: Its ~nflumce ou the tssdividual and its role in moc£al modici~. Elsevier Publ£mh~ Co. Amsterdam, (1960). 214. From Vain Proomd~j, C. Ned. T4jdschr. ~neemk., 114_t 1662-1667, (1970) in Larmon, P.S. mad Silvecce, H. Tobacco F~pe=immncal mad Cl~4cal Studies. Strpplemenc ZlI. Willimmm mad 9ilkinm Co. Baltimore, (1975). 215. Veldmma, D.J. and Bowum O.H. Personality mad pmr~oz~uace c~armcceriscics associated wieh c~KaucecCe mmokins mmm~ collele frem~amn. J. consult msd clin. Psycho1., 3.333, 109-119, (1969). 216. Walk.mrp R.Z., Nicolay, 1.C., l~lucsmy, R. and B£a~lml, R.G. PsycholoKiCLl cot-relaeem of smok~tg. J. c14~. PrycJ:ol., 25, 42-44, (1969) • 217. Walton, K.G. Smoki~$ and alcobol£mm: a bria£ report. ~an. 3. Psychiat., 128, 139-140, (1972). 218. W~rbu~Con, D.H. mad Meshes, R. M4cocLne and Aztamc£cm. iesulcs c4rcul~ced u T.X.C. Faper Q. 938. 219. ~k~acherley, D. Some personality correlates of the mb414Cy Co stop smoking cigarettes. 3. consult. Psycho1., 29, 683--485, (1965). 220. gaecerqvisC, H. Fo3rok.sve3:ksambecem for ~okmvTamjn~ v~d lamd8 LaJm.TeCC, 1966-1967. Lak~C£da~agess, 70, 3591-3595, (1973). As rmporCsd in Cbm 8uthorts 8bsermct in U.8. ~C of Jk~alth, Educatlon sad Wel£a:e, maoktnS and Bealth Bulletin, Hay 1974. BAT Co LTD - MINNESOTA TOBACCO LITIGATION r',o

-18h- 221. Wood. D.J. Theories o£ mmok~nS motivstion: • rmvimw o£ the literature. BAT Report No. KD. 926-R. 8.8.72. 222. Wood, D.J. Project WEYJLT - Yarc 2. U.K. stole ss~karss their reactions Co cigarettes of different ~4cotlne delivery as influenced by inner need. BAT ieport No. BD.1322 ~estricced, 30.1.76. Z23. Wood, D.J. ~d Wilkes, E.B. ]Project Ts31KA~ - P~t: 1. Cluster profiles of U.K. male luokmrs mad tlmir Bene~al smok~sS, hab4r.s. BAT itmport: No. ltD.1229-R. 10.7.75. 22A. World E~aXth Organ4sat£on. Zxpert Com~tCea on ~gs Liable to Product Addiction. 7th ~eport W.H.O. Techn. Lep. Set. So. 116, (1957). 225. World Health Orga~isation. The Use of Cannabis. g.H.O. Tmchn. Rep. Set. No. 478, (1971). 226. World Health Orsanisation. E~pett Committee on Drug Dependence. W.H.O. Techn. Rap. Set. No. 551, (197h). 227. World Health Organ~saCion. Sc4enc/~4c Group. 1valuation of Depmnd~nce Liabilit:y and Dmpasdence Potential o£ Drugs. W.ll.O. Techn. imp. Set. No. 577, (1975). BAT Co LTD - MINNESOTA TOBACCO LITIGATION c~

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