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7'2-04I07. Ague, C. Nicotine Content of Cigarettes and the Smoking Habit: 'Iheir Relevance to Subjective Ratings of' Preferences in Srttokets. Psychophatntacologa 24(2)326:33I0; March 16, 1972. , . One tettuce4eaf and three tobaceo1 cigarettes with different nicotine content were smoked by 24 habitual' smokers in the course of' four successive sessions. Their previous srnoking habits were found to be scgrticicantly reil<ted to their preferences for the various ciprettes. 1Vhile the heavy smokers (more than 10 cigarettes per day) preferred, only the tobacco cigarettes and stroneely disliked the lettuce-leaf, light smokers disliked mostly the highest nicotinecigan:tte. These r,atings were also relat.ed to differences in the nicotine intake. These Finditugs support the importance of nicotine in the smoking habit, although other factors may be related to the likibleness of tobacco smoking. The relesrance of'this type of' study isdiscuxse.d. (Auth: Abs. Mod.) i 79-0629 ltnderson, u. H. liultifactrrial A'spects of the Chronic B'sonehitis-- EnphYsema C'omplex, pp. 327-3i42. 1977, In: Clark, :1', A, (Editor) , Pulmonsrr Disease• Defense ri'echan'.sms and F'opulations alt Risk, Proceedings of the Tobacco~and' •H'ealth Research Inistittste Symposium 2, Lexington, Kentucky, 7CFri1 12-14, 1977, Tobarco and Health Research Institute, English. Quantitative smoking characteristics were eoapared in a group of' 2016' individuals without cardiopulmonary disease and in a group of' 114 subjects with evidence o'_ airways obstructior, as a measure of ehronic obstructive puleonarp disease (CaPD), lto d'iff erences in such eharacteristics as to number of ci?arettes smoked, puff volume or nutnber, nicotine and tar exposure, an3 smoking ti®e were deronstreated. Therefore, the fact that one. group hiad' CCPD and the other did not must be explained by something other than the qualitaitive and quantitative o.anner, of smoking cigarettes. Studies of airway function were done in chronic cigarette smokers before, S minutes after and 15 inutes afte= smoking either a cigarette with more than 25 mig of tar and 1.5 mg of nicotine or a 2otr tar and nicotine cigarettte containing less than 5.g of' tar and less than 0.5 sq of nicotine. Those who smoked the low tar and nicotit:e ciyarettes smoked more insofar as the volume, duration of puff' and total volume of smoke from each, cigarette was eoneerned. Iieither the smoke from the high- nor the 1oV-tar cigarettes changed the F'rY 70-1144. Ashton, H., Watson, D. W. Puffng Ftequency and Nicotine Intake in Cigarette Sznokers British Medical Journal 3(5724):b7!9-6S'1i, September 19, 1970: , The smoking behavior of 36 subjects szttokin, cigar:ttes with different filter retentionieffciencies for nicotinewas, studied. Subjects were observed while performing vardou.s tasks on a driving simulator and also durin; a, resting period after the tasks. Smokers of cigarettes with high-retention filters took more frequent puffs and obtaine& nearly the same amount of nicotine as smokers of cigarettes with low-retention GIters; both while performing the tasks and'during the resting,period. Smokers of both types of'cigaret!tes took significantly more pu6fs and obtaitted more nicotine per unit time during the resting period' than during the tasks: The resuUta are compatible wit;h, the possibility that smokers automatically adjust the nicotine dose obtained from a cigarette to sornc "optiaturn" level which may vary withi different activities. (Auth: Abs••.) ~' 1005052842.

73-0925. Ashton, S'., Telford', 8. Smoking and Carbozyhaemoglobin. (Letter). Lancet 2(,7833) : 857-858, October 13', 1973, EEnglish. In response to the assertion of Russell and colleagues that an extra- mild (low-nicotine) cigarette causes a smaller rise in blood i carb!oxyhezoglobin (COSb) than a nonmild cigarette when both are' puffed at the same controlled rate, the authors claim that this is unlikely'to be trne for smokers smoking in their natural manner. For smokers whose '" puffing is not controlled, puffing rate is greater vhen they are smoking low-nicotine cigarettes than when they are smoking, high-nicotinie cigarettes, and the nicotine obtained from the two types of cigarettes does not differ sig,nificantly. People appear to smoke for a given dbse - of nicotine and to alter their puffing rate unconsciously in such a way as~ to obtain this dose fron different types of cigarettes. . Since the amount of carbon monoxide obtained from a cigarette depends, like nicotine intake, on puffing rate and depth of inhalation, a greater rise of COEb vill occur with mild cigarettes, the opposite of 8ussell's results in controlled conditions. To publish Co yield as well as tar and nicotine content of different brands of cigarettes, as suggested by Russell, could thus be misleading.. See Abstract 73-09591. 73•3:23 british Hedical Journal. Do People Snake for Nicotine? Erit~'.ish ~r: iedical .lcurral 2,(6094) : )©41- tQU2,. October 22', 1977. English. •~~ . . I Euaber of Fublished studies on the possible, role of nicotine im determinisg smoking behavior are- cited. Peeli=gs of deprivation uiponcessaticn of.nicotin!e injection have been reported, but recarded nicotine .abstinence syndromes may have more accurately been tobacco-abstinence .syndromes. Although puff frequency and propcrticn of nicotine absorbed' fron i': a cigarette appear to increase as cigarettes of__lomer nicotine yield are `_smc]ced, lou-nicctine cig;are.ttes also ha.e. low yields of other constituents ttat,ccntribute to taste and satisfaction; difficultl in. liqhtiag• and snoking some loti,-nicotiae cigar Ettes may be acre. responsible than nicotine for increased' depth of inhalation -or rate of Fuffing...A'lthough gun chewing ccnsinerably reduced cigarette consumption. in one study, chewing gus containizg nicotine: led to. little more reduction than. did. chewing n"'ptacebo"' gum. In other studies, a. limited red'ucticn in- smoJcing! folloeing i,r..tusion cf nicotine supports. the hypothesis that nicotine has a def iaiti ve, b nt small, role in the smoki8g habit.. I'nother: study polnt ed up differences in the diegree to Yhicb inhalation of' saoke _and intratemous nicatine affect the subject's subsequent desire to smoke.. Although nicotine content ct cigarettes has declined by about halE in.the Onited States and Great Britain in the last 15-20 years, -cigarette.consuoption has not doub2ed. The suaaar7 concludies by noting that. tcbaccole dependence is a complex Fhenomenon; ia addition to nicoti3e,•contribating factors likely include the ritual ef sanipuLating cigarettes in the'_ hand and' lips, the pleasures of taste and smell, the relief of ten_ion, and the enhancement of sociabilizY. 100505284'3'.

,- , 76-1291 Cherry, V. h. Recent Studies on Less fiarmfdl Cigarettes at the uiniversity of xaterloa, Ontario, Canada. pp. 1'03-11i0. 1976, Ia: aynder, E. L.; H'ofimann, D.; Gbri, G. S. (,Ed'itors). tiioliifying the Risk for the Smoker, Volume 1. Proceedinqs of the 3rd World Conference on Sdokinq and Kealtih, choiogical addiction as a function of nicotina content of cigarettes smoked was examined. There appears to be some Fs y telationshap, although it is not the most prominent dosagF factor, between nicotine and pslrchological addiction to eigarettes. Investi;ations of phy,siologicaU or pharmacological addiction to ci;arett~es have concentrated upon the primary ortance of nicotine in the addictive process. Results of the analyses performed sug;est the independence of' int p psychological' addiction to ci; zettes from thrunvalidated concept of physolo;icai' or pharrnaeolagical add'iction. (Auth~. Abs. Mod.) . vhica affect these dialiveries. Finally, tae possibility of using increasedd cigarette prices, brouqst about by increased taxes, is discussed, as a method os' discouraqisq cigarette soioKinq, particularly amonq the lower- income group or younq people, where there is evidence of'increasinW use ot cigarettes in Canada, especially by girls. 8vidence for the feasibility of tais approach is presented, including uorb usinq econometric models, andd some of the difiiculzies are also discussed. (Auth. Abs.) studies on individual smokers are described!, which indicate that the majority o,i' smokers can sxitch to a cigarette deliver~'inq less tar and nicotine without a marKzd attempt to coapeasate for the reductions by smoxiaq more intensely. Thirdly, vays oi modifying nicotine and carbon monoxid!e deliveries are discussed in terms of the cigarette c@aracteristics nicotiae deliveries o:: Canadian cigarettes is discussed' as a factor in the trend' toWards cigarettes with decreasing deliveries over the last few years in Canada.In addition, data are presented vhich indicate that this trend has not markedly affected the relative share of the market devoted to specific brands. It is hoped that the puDlicatioa of tar and nicotine deliveries on the cig,arette packages, starting on July 1, 1975, will further promote the trend to lower deliveries, since there is a continuinq slotr increase in Canadian per capita cigarette consumption. Secondly, Work is described oa several methods ot rzducinq the health hazards associated vith cigarette smoking. First, ta2 publication of tar and New York, June 2-5, 1975. DH-*-:*i Publication :io. (hii2i) 76-1221!,, Euqilish. 7'I-1077. Eisin,er, RA.Nicotine and Addiction to Cigarettes. British JourRtal of Addiction 66(2):1S0-156„ 1!971.

! 1 C C 78'-'J0'17 Eaal_, J. F. Pharmacology of b- cotize. pp,. 561-567. 1577', Ia: StainfEld, 3. ;~ G_iffiths, W. ; Ball, !i. ; iallor, H. ti. (Lait crs) . Health Consaqlien'ces, Ed'QCat'ion, CEssat-on Ac'ziv'1t:.as, aII,3' GJvcrnmental Action, . oluae II. Proctedli::gs oi the Third iorld Co:tErea'c- on Szoking and Health, New York, Jure 2-5, 1975. DSEW ' &ublicatiou No. (NIFO 77-1C13', English. The cliLicmS Fuar.t3colog,i'cal effects oz LicotinE as it is present in the main saokE s_ream d'2aand on the phy'sjo..oy;ical state of the subject,a the degree of' nicotine absorption, the eitent of thc habit, and the psychoiog'ical p_eaisposition of' the sWoxer, to mention only a' feVl coLtributing factors. It is to be noted also taat the poarnzcoloqicaS effects ot smoucir:g are not solely relalted to nico:.ine but are the end result of' the sWoka pE'r se and all oI its piarLlclllate matt'et. Tle' pcarmacology of r.i:.otine.als it bears airtc..iy on the smouing habit and' th= pha:macological inter9er.tion in, smoki.ng cessation are rEvieLed. There are, of c'aursa, many factors which itflu_Lcz tWe ansorptioa of nicctin'e from smoking. . A'mWng these are the form of tobacco, the contact time of' tobacco smok:ag with mucous membranes, the pii oi the boay fluial with which the ' smoke comes in contact, the degree and aepth of inhalation, the dEgree' of ha!":ttla_lon of th3 sGCJk=z, the ni'cot;:le con':.Bat ot tnle toba,ccosII'ok'ed, the moisture cron:en't of th= tobacco s'auokca, the l'1's2' of', a filter, the alkal:nitj or acidity of th= tobacco smokE and tn_ ru=f fr~quency. The human system rapidly develops a tQiiErance to nicoL-Ine. Zmr eic:tation, nausea, salivation disappesr. on the other soma smoxers aLa hy,pers.nsitive to n_cotine and exuibit increased blood prEssur_, pulse rate and decreased sr.-,;n temperatIIze aLter smoking a siL"41;z c;.yarette. N_cot'ine produces a nailtituae of Efi'ects re3atedl to behavioral caanges, cardiovascular =esponsas, a:.d pulmonary actions, efieczs vhiich are pr_dlictatle for the most part but whica are also in'lluencEd by tnle backqrolu:.d, t-Jo;log:'cal and ,sych olog ical activity of tn e smoker. , I z is. tnis ulbiquitous nat ure of nieo_ine which coazouz3's phairmacological intervention oi its aeti,on in smoking behavior. 7T-J134'5 Freedman, S. ; FLetcher. C. tS. hicstine, Tobacco Substitutes, and' SmoKina Babits. (Letter).. British dedicall Journal 2(61032) • 419, AuaUst 14, 1970. Enc711sh. Tnis is a comment on Dr. . Ba'wbone 's articAe in British bedical Journal (Jnly 17, 1976) . The authors do not beliewe that svitchinq to low-nicoitine ci:v3rettes should!necessarily lead to a m'arked increase in ciQarette cons!umption4 Previous data are cited in w"ch the con'sumDtion increasedd from mean 32 to mean 3u. Th_y also aqree tiith the observaltion that when nen accustomedl to a low-nicotine intake svitc'L back to hiqher nicotine ' ciq3ret'tes they trY to keec the consuaption lov. Studies conducted by the alutnors show that estimalted nicotine dei.iviaries may differ from the macnine-smokinQ delivarTbq as nuchl as 01.4 mq. They snqge'st that reQular measure'ments of carbiorvhemoalobin levels c:ould be a, useful indicator of total szoke inhalation. See also Abstract 77-0357. , 1005052845

71-0327. Frith, C. D. The Effect of Varying t;he Nicotine Content of Cigarettes on He::aan Smoking Behavior. P,ycho- pbarrnacolo;ia 19("?):1I8S-192, January, 21D, 1'9711. Nine subjects were given: cigarettes to smoke contrinin;, three dif -rent amounts of nicotine. It was found that the laroer the cont:nt of nicotine in the cigarettes offered tHe srnaller was the number, smoked during tlte eight-hour periiod.A linear relationship between nicotine content and'time to smoke a single~cigarette was found such that the more.nicotinee there was ia a cigarette, the longer a subject took to smoke it: (Auth. Abs:) i 70-0495. Goldfarb; T: L, Jarvdc, 141: E., G1ick, S. D. Cigarette Nicotine Content as a Determnnant of. Hur;iaaSmoking Bzhavior. Psirchopharmacologia 17(1):39-93, P970. bSeasures of smoking rate and psychologicall effects of cigarettes with varying nicotine content were made in IS subjects. While subjects did perceive differences in strength and quality -of the experimental lettuce cigarettes as compared to their own brartds, their smoking,rates did not decrease diffrrcntially over the nicotine grad'uent•. The decrement in: smoking due to the eXperimental cigarettes persisted when subjects resumed smoking their own cigarettes. However, the smoking that did occur in the absence of ' both tobacco and nicotine indicates that the habit iuelf often exhibits functirDnal autonomy from the physiological effecLs of nicotine. (Aut~h~ Abs.) 76-0576 Go I dfarb, T.; Gr i tze E. R.; Jairv i k, H. E.; Sto t eratan, I. P. Reactions to, Cigarettes, as a Function of Acotine and ^Tar''. CtinicaC P'harmaco I ogy and Therapeut i cs 19t b),: 767-772, June 1976. Engt i sh. ExveriRents-were carr'ied out to exatci'ne the, effects of ntcotine and' tar"' on the extent of, and! stibJect i've reactions to e i garette sznok i ng. It was conf i'rmed that sir.okers rate commerciat , low-nicotine cigarettes as less ""'strong" and, less "°satisfying•' than their usual brands. Since such cigarettes deliver reduced amounts of tar as wetl as of nicotine, an experiment to di.stingui!s!h between the two was c.arr iett out with speci'al cigarettes~. Ratings of ""'strengthr'' were directly rel'ated to nicotine: but were not af'fiected by tar. The numbers of c igarettes smoked fel'.1 sl ightliy, as their estimatedl del iveryc of' nicoti'ne Increased, but tar had no effect om this i'ndex. The ur inary excretion of n1coti'ne was corre.l!aited wiiit'h the rated yiletds of nicotirie toc the ditferent c1g'arettes, but there was also evidence that s'ubjects tended to! adjust their manner of smok1ng~so as to titrate their doses of, nicotine. The results are fnterpretedr as i'ndi'cating a role for nieotine, but not for tar, in the maint enance of cigarette s.a.oking behavior, and as support for the v lew that less harmful cigarettes should have a high: yilelld of nicotine relative to tar.iJ,'uth. Abs.lt 100505284& ~~.

\1 0 7'6-1!1d0l Gritr. E. B.; Baer-.eiss, V.; iarvi's, h. Z. Titration oi Sicotine. Intake ;iith r'ull-Leaqthl and Ba1f-Lenqth Ciqarettes. Clinical Pharmacology ind Theralpeutics 20 (5) : 552-556, aolvember 1976. Eaglish. Titration, tae selt-raqulation of' nicotine intak2, vas studied in 12 smokers by gals chromatoqraFh assays of urinary nicotine levels. Results demonstrated that excretion of urinary nicotine in the proximal condition (',half cigarette closer to the filter) did not differ significantly from the whole cigarette coudi tion; ho+:ever, less nicotine was excreted in the distal condition (half cigarette farther from the filter) because oi' a rod filtration eiiect. 3ubjActs extracted proportionately morz nicotine from % the hai,cl than from tua vhoLe cigarettes; titration was approximately the same in both half-ciqar=tte conditions. On scales of strength and satisfaction, fu11-1ength cigarettes Yere given the highest rating, followed by proximal and then distal cigarettes. It was suggested that in future studies of the various parameters of' puifinq, such as number of puffs,, depth of inhalation, and duration of puff, these parameters shouldd be co@pared among tae proximal, distal, and ful11-length cigarettes. (Auth. Abs. . C!'od . )' . 79-0516 Gritz, E. R. Patterns of Puffing, in Cigarette Smokers. National Institute oi' Drug Azuse Researcn Monograph Series 20: 221-235. July 1978'. English. An initial attempt to assess some of the parameters of puffing are presented. Paid volunteers wh!o normally saoked an average of one pack of cigarettes per day were ask:ed!to smoke cigarettes through a modifiedd plastic holdlEr containing a thermistor which was activatedd whenever air passea over it. ln some experiments, volunteers used smoke screens and - subjiects need only turn~ their heads to take a puff of a cigarette. Puf fing seconds or greater) and short (less than 5 seconds) puff to puff' (',P-P) intervals and a grouip who had almost exclusively long,P-P intervals. The former, were, on the average, heavy smo&ers (mean=30 cigarettesJday ) and were older (mean=5w years) compared to the latter group who were, on the average, lighter smorers (',mean-1l8 ci garettes/day ) and younger (mean=30 years). Light smoKers did not increase the number of'P-P intervals even when given quadruple the baseline number of cigarettes. However, heavy smoaezs increased' the number of' both long and short P-P' intervals when, the baseline cigarette number was doublecz or quadrupled. Smoking was depressed in the opaque screen ccnditi'on for all subjects. Puff duration and volume was significantly smaller when subjects had'abst3ined from smoking. Nicotine content of cigarettes affected only maximum rate of inhalation, or peakediness of the puff. Nicotine-free cigarettes vere inhaled' more sharply. when subjects were deprived, the maximuim rate of innalation was greater on the nicotine-free than on the nicotine cigarettes. by puffing pattern were revealed: a group who had a mixture of long (5 - :s.conditions of deprivation or no deprivation. Two Qistinct types of smokers T'parameters were also analyzed using nicotine-free tobacco cigarettes under 100'505284'7

75,-(5°S Jaff'e, J. F.: C.arzler, ". E, Tozacco~ and Nicotine Self- A'-'rir.istratioW ir. Mu.ans: '"he Eve1!Ltion of a nethoidolocy, pp. 2^i-22C. July In: Krasne_cr, i~,P, (',T_ditor). Self-Ad'sinistration of Abuse Su:atalces, aEt:.::ds fcz Study. t~~.ticn_1 Znstitute on Drug Abuse Research ?!cnec'r3'ph S'e'rles, Fo. 2., °_irelis::'. .::e, sElf-_':mtnist=_ti,on of nicctir.e by human.s vas exaoined in a latcrstory _tudy. "reii'rin-ry ezceric.en~ts were done to investigate how sroking varies as a ftncticr: of resroase cost. Sufl jects performed simple taskr and ti=re rewardeW r;:tF: a cicarette. Results showed that consumFtio~n .ent down as re_-or.=e Ccst i'rcreased aa'_ then rose again, but not to the st=rting pci'nt, a_ rez_zn_e cost was lowered. Ir, the mai!n test, the relationsbif betwee.n cveczil re_Fense costs and nicotine content of the ei.;arette purcras_a ::as ex_c,ire~, The 23', ss,okers (1'.5' wo©er., 7 men), were asxed to save ci.._rette buttr dL_inc a 2' veek b,aseline observation period ani each tiae the =urject cha*ced' bran3s. Isticates of daily, nicotine intake were y3Ce, Results 1rGi,c2ted b^havlCral differences between the'men, ar.d thp wozEr. Fewer ¢err trar. va;en_voluntEered f'or the study and only, four of tx~e severd coc::lEtec the tl2 yetk stu3y, The oPn who Aftnished shored sl7[uSCaS.t2'al r'e:llIIct.Qt'.s' 1'n,nlccflr.e and tar consumDtion,, Ttielve of the 16 vomen crrrleted' the study. All =~cre3 a rapid drop irn the intake level of nicotine in the tir3t E weeks and the jecline continued' aore 3,radua117, foLr the rest of t^e =tu'y. Pcortrric incentive_ did not seem to influence the sutjects to ss+itct. tc lox niccti: E ar.3 tar cigarettes. Subjects ter.ded to coasuGe sore o:' the cicaret'tP as the nicotine content decreased,. The teadenc} to inc,ale cere did not result in higher earbon monoxide Ievels. F.:esu:t= indicate that cci_1! factcss, coff'Ee or alcohol consumption aindi health eon:ce:as Qay tiay a rcl'e in deter:.ining the nuaber of cigarettes smokeC per day. Pcssitilitie_ for icaccuzate measurements in the test Yere actei

Jaffe, J, F, ; t;ar,rler, r, P*; alyinic Wh'at We iCno'v From other ltaaictionsc ?'27-?`.7c. In. 5_chw.,rt2 - 1 - . J. L. (rditor) , Proctess 1n' 5'mo'siay Cessatioc, f•rcceed'ic cs af Intzrnaticnal Co'r.ferencE on Smoking Cessation, New Yorx, J'une 21I-2., 1575, :nerican Cancer Society, Eaglish, Sicilarities and d_.':erer.cES between snoking and other forms of druwc use a're ex;lcre:, vi~to:ic=1'lp, cruS use in the United States and Great Eritalin has been suhject to the so'c-L&l cliGate, the cost and the availability of ,i the drug, ~s- t:ze _ocial e'siEZte ctarge's with re'g3ir3 to the aeceptability of , a 3rue, the characteri:tics cf the u'szr chances. Cass p'rodu'ced cigarettes of.Er2d a cheap, o:.ur.da: t sucr?y c: tobaece for the Fublic. Drug and' -._ t-0lo_cco c€?v,L,ny' is ittCnsif,iFW !2 sight of the subs't3nc'$. Patterns o',f ulse' for tobacco and c'ruc_ v_ry and the im_3et on health and social behavior may nct ccrrelata Ri'th the intake cf the 3'.I'ictive substanee, It is Fossible th_t d'ru;s or nicct:r;e have s;ecial a3aptive value for some individuals. Of the 3:, nill'ion z:or.ers vho have storpe3l smickina since 196,4, about 95 percent Qt3'Tt' on thEir o,wn. SCestici.'s '1r',ei ra2Seld about th!o'se who do not stop l1siL-, to'b3c'c?' or :ErC1ri hut s6::t,lt'ute lAwEr' t'ar' and'' nicotine cigarettes or, methadlome in an ef:'ctt t.' use less h.r_rdous substances, l compensatory increase in tt.e Frc; ortier~ er nucter of cigarettes smokeC was not generally otserved aesong, tncse whose ssitci:ed' to lover tar and, nicotine ciaare'ttes ' an_ rratev Er increases tterE werE were not suf'ficienit to offset the decrease in tzr sn d r.icetin e, In of' the lowered tar an3 nicotine romtf;;t, iil but t;:e' very lc.est had equal carbcn monoaide d'eliver7. Studies indicate the f.rezt cb;:acitv of the dr',ule user to deny the pos_ibili!ty of' aeverse effects ar:c de,:'ay, cFang,in'q beha'vior. Smokers, oore th'3fr, alcoholics acd cri_te u'sers, rasist c,haag,e.

75-CE54 Jaffe, J. P,; Kanizler, r, Seokiag as an Addictive Disorder, pp. 4- 23I. January 1979, In: Krasneccr, F, A,. (Editor). Cigarette Smoking as a De;endecce Process, National rnstitute on Drvg, Abuse Research !lonograph. Series, Ko. 23, DkE,w Publication Fo. (AD1) 79-$'00, English. This overview of the ad'dictive nature of' the smoking habit points out se1'ected sir•ilarities ar.d' d'ifferFnces between tobacco usaae and the drug u_ing behavior comdcnlr viewed as addiction in our societT. Speculation on the nature and extent of tobacco consumption in the future ils also made. Fsychol'ocical parallels related' to initial use are: (1)', exFeriaentation and, recular use beSinninc in youth;, (2) tendency for users to have extro.erted personalities; and (?) tendency of the majority of new users to quit eventuallY. A survey of studies on pharaacoloqical factors affeeting ' continued use cor.cer.trates or. the reinforcing role pla7ed by nicotine. Biolocical factors,, such as eEnetic predisposition, raT also affect smoking, haibit. Wi:thdratial symptom:s caused by cessation of'smoking are chiazacterizpd'. Titration and ni'cctine manipulation experiments revealed that a perfect eorrelaticn betveern nicotine levels and smoking levels does not exist, vhich, is still consistent with classic add!i!etions. Cessation, studies revealed that recidivism rates are identical for heroin, alcohol and ciearette users. Tobacco addiction differs from other types in the absence of toxicity due to overd¢sace, lox cost, and high degree of social acceptability. Chanqes in tetacco consumption predicted'for the future include: rrduction, but not elia:inatioa of' the smoking, habit; changes in characteristics of'the Forulation that smokes; and continued reduction inn tar az3 nicotine content in cicazettes. Concern is roiced that widespread use of less hazardous cicarettes vil'1 undermine t1ie ef:fo=t to deter sackinq in younq people, 79-0323 Jarvik, B. E. ; Popek, P. ; Schneid'er, , g. ' G. ; Baer-Weiss, 9. ; Gritz, E. E'. Can Cigarette Size and Nicotine Ccntent InflIIence S3oking, and Puf_ing Rates? Psgchopharaacology 58 (3) : 303-306, 1978. Eng,lish. The stimuli controlling the rate at vhich people smoke ciqa,rettes have not been clearly def ined'. On the hypothesis that smoking is bas icallp nicotine seekingi behavior, nicotine avaflable tc the smb ject was experimentally manipulated through controlling cigarette size and nicotine content. In Elperiaent I, sub jects given their osra, cigarettes in whole, half, quarter, and eighth lengths, increased' the number of cigarettes smoked and number of puffs to compensate for reductions in-size. Satisfaction ras directly related to cigarette length. In Experiment II', sub jects given special cigarettes deli9erin g 0. 2' or 2.0 ag nicotine/cigarette smoked s3gnificantZj more of the low than, of' the hig'hh nicotine cigarettes and took significantZy :ore puffs. ls in EzFeriaent I, signi',ficantly- more quarter length than fall length cigarettes were smoked, but total number of puffs did not differ. These results support the hypothesis that nicotine controls smoking behavior. (huth. lbs. ) 100505-2850

79-0519 Jarvik, M. E. Self-Administrat,ion of, Cigarettes With Varying designed to examine these variables. Paid volunteers were tested using A smoker can control his nicotine intake by varying th~e rate at which he lights cigarettes or by, modifying his puffing rate. Experiments were . . Tobacco and Nicotine Ccntent. National Ins.titute of Drug Ablise Atesearca Monograph Series 20: 236-243. July 19'75. English. trendi (F = 1!8.30, p<0.03 ). T-tests performed bet:reeni all p~ossible, pairs of occasions these same brands were given in whole, half, quarter and one eighth lengths in random order. As the cigarette length decreased, the number of ci'gatettes smoked increased (F = 14.85, p<0.001 ) with a linear .. d'ay, volunteers smotced' their own brand of' cigarettes and on successive special cicarette holders which recorded puffs against time. On the first = means for number of ciQarettes were si3nificant at the .01 level except 0 .betWeen half and quarter lengths. The number of puffs was greater for shorter ci5arettes and the differences were significant ( F= 3.9'1 , p<0 .01) and linear ( F=6.33, p<0.03 ). Differences between whole and quarter, half and quarter, and half and eighth, were significant by t-tests. The average numoer of puffs per cigarette decreased with decreasing lengtn.. Satisfaction was inversely proportional to lengtn, i.e., shorter cigarettes were less satisfying. These changes were also~highly significant. The seconc experiment was designed to examine the effects of varying both nicotine content and length of cigarettes. Experimental cigarettes delivering 0.2 mg or 2.0 mg nicotine per cicarette were used. Suojects smoiced ainC puffea more: on low-nicotine than on hich-nicotine cigarettes. S1,milarl'y, subjects smoked more quarter length tnan full lenigth cigarett'es. All of these differences were highly siignificant. The subjects puffed proportionately more on the short cigarettes. The number of puffs per cigarette remained constant in the face of crnanging, nicotine content. This indicates that number of cigarettes smoked and not puff'ing rate was, used too compensate for cnarnge in nicotine content. The satisfaction ratios were low and approximately equal for noth nicotine content and length. There is a suggestion that subijects dis3iked'all of these experimental cigarettes ... since their satisfaction rating, ranged around' 4.0 or lower, wnereas subjects rated their own cigarettes in the previous experiment about 5.2.. It is very likely, that the nicotine deliveries were either too hich or too: low,.certairaly not the middle range of 1.0 to 1.5 that the smOieers were accustomed: to.

n ~ ~J. 75-0190. Kozlovski, L. T. ; Jarvik, n. E. ; Gritz, E. R. Nicotine Regulation and Cigarette Smoking. Clinical Fharmacology and Therapeutics 1!7 (1) : 93-97, January 1975, English. , study was conducted to determine +rhether there is nicotine re!gulatioui in cigarette snoking. Both cigarettes- and a chewing, gum ccntaining nicotine were administzred as '•1prelaad's''. Since tar comsuimption covaries with nicotine in cigarette preloads, the purest test of a regulation effect is found by looking at the effect of nicotine level in all nicotine gum.conditions combined. The 56 subjectsin the blind study had a m~ean average daily cigarette consumFtion of 20.75 cigarettes and had smo~ked on the average 5.9 years. The results shoved! evidence of nicotine regulation. digh, nicotineprelload vithcigare~ttes (1.3 mgi nicotine, 191 mig tar) produced a significantly, lcnger latency period to the next cigarette than low nicotine loading (0.3 ag nicotine, 1u ag ta=) . With chewing gum, high nicotine prelolading (4 mg nicotine) significantly shortened the total puff-time duraiticn compared' to a low nicotine preload (1 mg nicotine). The different ef.ects of nicotine in cigar,ettes versus nicotine in chewing gum are discussed. 7'9-0592' Lader, M, Xicotine and Sr.cking 3iehaviouir, 9'ritish Journal of depeadeace, A potential major contribution to, the stud7 of nicotine andd szokinig in the recent dIevelopeent of techniques for estimating nicotine and' its eajor aetabiolite, cotinine, in body fluids. The significance of studies on.nicotine excretion, in the urine is also discussed. It is noted' that the route of' nicotine adcinistration is of si'gnificant i!aportance, since inhaling produces more pleasurarle effects than ingestion or injection. N . Q Q. CJ1 ~Q • AI ~ M electroenceFhalogras ac.cificatioir., assessaent of effects of nicotine.on behavioral tastes are also evaluated, and incl'ude observations of changes in smoking characteristics and task performance when the nicotine content in eiaarettes is aodified,. In a series of dif'ferent experiments, it was found that smokers vary their hatits onlY, slightly to adjust to nicotine content. Tobacco dependence aFgears to involve nore than nicotine ;depression of spinal reflexes; respiratory stimulation; and Clinical Pharmacology 5(v.): 2P°-292, April 1978. English,. In this editorial, evidence that nicotine is the habit maintaining agent in cisarette smoking is reviexFd. The physiological actions of nicotine which are repilicated by cigarette szokinig are described'. These include: stimulation and deFression of chclinoceptors in autonomic ganglia and neuromiuscular j'unctions; catectolamine release from adrenal aedulla; ~

77'-3357' Hawbone, B. G. Hlirotine. ;ooacco >,Lbstitutes, and Smokinv H'abits. (Li= _a_Y. British !!ad'ical Journal 2'(1E0,-o) . 177, .dulY 1'7', 1970. EnuLish. Dsirica 1975 the author inv=_stiQated sub3ects smoking the tobacco su!bstitutes hSM (new smokina material)' aL,;. Cvtrel. Subjects smoked both 3 p;oiurt containinai 40 merceat substitute ai.d a matchzd control containinu .10i0 percent tobacco oroduct. each for 24 aours srith an intervening period of seven days. Follo:inaeacro sm'okinQ oer.od five cigarettes were clhain- smoxed and the butts collected! and anaiyzt_s in terms of length and filter nicntine. An estimate of tLa smokers' aost of nicotine (observed nicotine) was calculat:ed'froim the filter nicotinea..,s ""filterretention fact:or: "' I • for each sublect an indication of the m3nLar in which the ciaarettes had bean smoked' may then be obtained by consiaeri,nq the ratio between the obse=ve3 nicotine and the nicotine viaL3 c,s machine smoking (expected, aicotine) . The results indicate: (1) tLat the HSH product was smoked to a :siqxificantlv shorter butt length than thw control: (2) that all subjects received sianif icaintly less nicotine LaEn smoJciac the substitute prod'ucts: (3) that the substitute croducts vere beiLu sianificantlv ""overssoked,'''' rrhizh miQht su!acest an attempt to comm~=E,snte for the reduction in nicotine.. See also Abstract 77'-03W5. - 7'u-0422'. Russell, !!. ~. H. Realistic Goals' for S'moking and' &ealth. -A Case for S'afer Svoking.,S.ancet 1(17'851') : 254!-25,8, February 16, 197'4, English. ,. Evidence is preseated' demonstrating the-crucial role of' nicotine in the generation and maintenance of cigarette dependence, the potency of srhich ensures that almost anyone who smokes at all becomes dependent. It is suq'qested' that this high d'eaendence-oroducina flotencv and the nniversal - : a eal of the eflfects of nicotine lie behi d th t fail f ki ,,~ k pp n ures o e pas smo ng ,control programs.. Zn this cuntezt, the goal of abstinence and thee abolition of all smoking is unrealistic and d'oomed to fail. The more realistic goal of safer smoking is explored. It is argued that the carbon ~•-` sonox'ide (iC0) yield of' cigarette brands should be, adde& to the official .tar and nicotine tables and that the safer cigarette is likely to be the one with low tar and CO yields -but a high, rather than low, nicotine yield!. However, the nlti,ate goal of acceptably safe, light to moderate, controlled smoking will probably require the virtual elimination of cigarette smoking in favor of noninhaled smoking of pipes or sediQm to larqe cigars. With the combined effects of health education coupled too selective taxation directed at this more realistic goal, success is not only possible but probable. O1uth..Abs.)

75-1i2 41. Eussel1, Y:A.S'. Safer Cigarettes. (Letter),. British If_d'ical laurnal 3(,5974) ; 41 , July 5, 1975, English. The int:oduction of safer, cigarettes is commemdable as a me.asure' to reduce smoking-'related diseases. Efforts in this area are more likely to be productive than tr dlitional antismoking methods. Filtered cigarettes were the first measures in safe smoking. Ventilated filters made it possible to red'uce tar, nicotin'e', and carbon monoxid''e yields. The' disadvantage apparen't here was that smokers ccmpensat2 fcr lover nicotine intake by inhaling a greater volume of smoke~ and eventually changing to high-nicotine cigarettes. This evidence sugg;ests that the ideal cigarette would have a medium nicotine yield, approximaltely 1.0 mgi, and low yiel'ds of ta: and carbon monoxide. While~ such cigarettes would nat h'e completely safe, thiey roul'd satisfy smokers who require nicotine, and reduce both lung cancer, which is associated with tar, and cardiovascular disease-, vhich' is associated with carbon monoxide. C 79-1'^3 P.ussell, r..3,li, To}acc'Q Ilecen'_ence: Is NicotinE F'ewarding, or Aiversive?' -F, 1:~s'-122. January 1!97'S, In: K'rasnecor, 1!. A. (rlitor). Ci.;arette 5':cokir.g as a r.eper.d'Ence ?rocess, F_tional I'nstitute on Drug Abuse R ESe?rch' l10CD'crLph Series, SG, :2 , ::1Y11St1. The role of' nicotine in totacc.c deoe'n3er.ce is discussed''.. Peview of thee data availatle irn tse literature raises many questions but provides fev, answers bleycnd the :cl~lcvir.c crrclusio'ns• (1) r~harQacolocical reinforce~sen't is not a'n essential fe-turE of ac?'ictive~behavior; (2), There are many nonc;arc3colioaical factors involvec' in tobacco sWokin,, and these ap'gear to be sufficient to generate strong decenlence in =::okers who do not inhale; (3') The low acce, ta:,ait}° of 1c.-r.icctine cigarettes is not necessarily du'.e to the reduced nicotine conttr.t, aor.phac:acologica'1 factors are a1so, involved:. (,n)' Smok'ers yllio i.atale iii~Qem to, tolerate a decrease in, nicotine intake better' than an increasE;, (,S) Simply, because nicotine has many pharc~acological effects in sccl:ir.c cosesi, i't does not follow that these effects are reinforcing rcther thar. aversive; ('6): E'vidence is scanty that~ ar.ir.als will' self'-inject nicotine as avid'l'y as they, do otf:er addictive drugs; (7) Rpart :roQ circur.startial histoiricall evi-d''emce that people have never shown, a str'on; ir:clin:: ticn to iatiale smok'e tr.at does not contai'n a psycholactive druc,, there is no direct exFerimental study which shows that nicotine is pharmacclocic3lly re+a.:diny, or reinforcing' in hiumans; (8) k'hzther or r,ot nicotine is p'tarr:ecoloqically rE4arding' in optimal dose's, it seems to become averrive vhE* these doses are exceer:'ed; (~9)i The hypothesis that people smoke and inF._le for ner.ohararaeological rewards, including thee taste and irritatcy of nicoticQ itsel'f, bu't are inhibited'from smoking more because they finic excessive r.;cctir,e pharmacologically aversive, has not yet b'eer, disproved; and! (1,) Tf;p ir.Flicaticns for safer cigarettes remain the same aoi matter wFethtr nz'cotir.e is rewardi:na or aversive, The sa'fer cigacette s~hould have a low-tar, lov-earbon monoxide eontent, but medium to hi_h (rather th'ar, low) nicotine yie13', 100'50528'S4

4. , 78-0719 Schachter, S. Studies of the Interactioa of Psycholcqxcal and Pharaacological Oeterminents of Smokzng. 1. Hilcotine BegalatioL in Heavy and Light Smokers. Jou!rnal of E'zFerimental Fsychoiogy 1'06 (1) : 5-12, 1977. Eb g,li sh. The resQ1'ts oi a research program concerned wyth the interaction of pharmacological and' psychological determinants of cigarette sacx.ing are presented. The hypothesis that smokers rrguliate nicotine intake is tested' by having surj~ects smoke cigarettes of aiym or low nicotine content on alternating weeks. Longtime heavy smoxars ao, regulate because they consistently smoke more low than high, nicotine cigarattes. GivEm this indication tnat heavy smokers ad just taaa,r saoxing rate to xeep nicotine at a roughly ccnstant level, the hypothesis that the rate of' saaxing depends on the etabolic fate and excretion rate of nicotine is ezaQined. Pharmacological evidence indicates that although most nicotinb is rapidly metabolizad, a fraction of nicotine Escates datozicatioa and is eliminated in the urinie. The proportion of nicotine tnat escapes metahciism depends on the acidity oi the urine. The 'ore acid the urine, the greater the excretion cf unmetabolized nicotine.-(huthl. abs~.) 78'-0552' Schmidt, F. Sind Z+Qarmtten mit her3bqe_etztem 8ikotin- und Teeraehal t veaiaer qasundi:_itsschaldlichL f Are Lcw-Tar and aicotine Ciqar_ttes Less Hazardous to alialth? ) tied_zinische Va1t 28 (,27) 1180-11 83, .- Ju19, 8. 1577, German. . 'The decision wheth_r smoxinQ of low-tar and nicotine ci'qarettes is less decreases the number of' smakan ciqarattes. The civarettes of varyinW nicctine content (1. 5l mq, 1.0 i6q, 0.5 mQ) and the so-called nico t.ine-fres. eiaarsttes were tested. Fo:tr-seven smokers sackad 45,0'00 test c:qarettess in 1.400 days. :hle smioki'nq raLe did' d'ecrease 15 pe=cent, in smokers of 1.0 aq ciQarEttes. A alueztiott:,d-':a administe,red to s!mckeLS of' ciaarette's with filters troved that those smo,.trs do inhale less. The sn'Ckinq of ciqarettes r,ith filters did not, hotaver, prove to be less damaqinq to health. The nicotine deficiency is also ba..LancEd by the s,mckers cf lo ti-tar/nicotinE ciaarettes by' deecer inhalaticx,. the nicotine def.~'c:ency. Oc tnt colatrary incrsased' nicotine content . ,,.. usually the danaer the consumation of cigar_ttes will increase to balance ~`-• danaerouls is ccn_rovarsial. IL loNerinq the content of n~cctine there is 1U05452855

7b-1200 Silverstein, cs. An Addiction, Explanation of Ciqarenr.z-induc.ed celaxation. 68 pp. 13,761, boctoral Dissertation, Columbia lDniversity, New Yor~k, NewYorY, EaqIlisa,._ sypotheses based: on an addiction model of ciqiarette smokinq were tested in two experiments. Botn involved the use of a sh ocK-endurance anxiety me3sure as the depen:ent variable. In the first experiment, comparisons wers made between aonsmokers, smokers waol ware allowed to smoJce! a ciqarette wit.h either a high or a low nicotine content and smokers who were not allowea to smoke a cigarette. Results were consistent with the hypothesis- taat the calminq efszct attributed to smoking a cigarette is due to the action of nicotine in preventinq*withdrawal; rather than to, a tranquilizinq, property ot ciqarette smokinq. In the second experiment, the urinary pff of': some of the sublects was maintained' al;caline. Results indicated that smosers with high urinary ph will not extibit withdrawal as soon as saokers with low urinary pii'. Zmalications of these finda.nqs for an explanation of ci4,arette smokinqi were discussed. (Auith. Ams.) 77-0713 Wyatt, T. Classification, of Cigarettes. (Zetter) . British Medical Jouraal 2(6032): 4201, l'uigust 114, 1'976'. EWqlish. _ ,. tl T'he author' agrees yith n.1.8. Russell's suggestion (J'uae 12, 1976) that aokers. cbange their brand of cigarettes toi gain a satisf ying nicotine `' s intake for the.least iatake of tar. The author carries the idea a step further by suqq,esting taat smokers may be better able to make such, a change in brands ii' the tar, and' nicotine yields were printed on the cigarette pacYets~. A.s the situa tion, in the IInited' Kingdo 4 exists: no w, only the cateqorT (i. e. , A"low tar, ""'"low to aiddle: tar'"')' is printed o'n the ci4arette packety as opposed to the exact figures for the tar and nicotine yields. The range of yizld!s for each category is relatively large:. For example, in the "'"low tar'' category the range is from 1..25 to 9.58 mig per cigarette, With this type of system, it is impossible!for a smoker to detergine how much difference in exposure a: change in brands wiould make, especially, if the brand change is within thz saae cateq,orq. It is concluded that at a tise when increasing quantification of, tar (and aicotine) values are souqht, the present systes of classification is outdiated. 1oosos,28ss