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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