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. i v.^ y.....+.v..a 17 8 v Mtmeu.lavawat V / 7 Puffing Frequency a- -' Nicotine Intake in Cigs - tte Smokers HEATHER ASHTON,' a.nt., m.a.c.r. ; D. W. WATSON,t s.A., M.PHIL. wax TxE TEcxrnus. essisrAxca oa R. MARSH,$ erm J. SADLERS _aria,hef*6wlJow"r, ttrro, s, 679-6ai Summary: The smoking behaviour of 36 subjects smok- ing rigsrettes with different filter retention efGdea- eies for nicotine was studied. Subjects were observed while performing various tasks on a driving simulator and also during a resdng period after the tasks. Smokers of eigarettes with high-retention filters took more frequent puffs and obtained nearly the same amount of nicotine as smokers of cigarettes with low-retention filters, both while performing the tasks and during the resting period. Smokers of both types of cigarettes took significantly morc ;affs and obtained more nicotine per unit time dur- ion tt=e resting period than during the tasks. The results ar . rompatible with the possibility that smokers antotna- ti,.+?y adiust the nicotine dose obtained from a cigarette to some "optimum" level which tnay vary with different activities. Introduction .41 -During the course of e:tperiments designed to test the effect of stnoking on complex perceptual-motor tasks it became apparent that subiects smoked different types of dgarettes at different rates. Armitage at aT. (1968) suggested that sonte people smoke in order to dose themselves with nicotine and pointed out that a cigarette smoker has "titerally finger-tip con-t of how much nicotine he takes into his mouth." Thus ,•it i nble that smokers may unconsciously adjust their nico- tine _.,se to some desired level, and for this reason it was of interest, as part of the Luger study, to investigate the smok- ing behaviour of subjects given cigarettes with filters of dif- fering retention efficiency for nicotine. To obtain a given quantity of nicotine from a cigarette with a high-tetendoti filter the smoker would need to take more puffs or longer ~-and deeper puffs than if he were smoking a cigarette with a less efficient filter. Methods A total of 36 voluateer subjects were studied, 15 women and 21 mea. All were smokea and their notmal daily cfgar- ~ erte consumption ranged from 3 to 30. The age range was fzota 19 to 35 years. Many of them were univrssiry students, but the group also iaetuded hospital staff and clerical pesson- ne1 frotn an indust:ial fitat. C"agarettes were kindly supplied by the Tobacco Research Council and were of two types: (a) low-nicotine cigarettes and (b) high-nicotine cigarettes. The filters and blends of tobacco '-tued were -such that if the cigarettes were smoked in an ana- Iptical smoking-taachine with 25-mL puffs of 2 seconds' dura- tion taken once per minute and smoked to a butt length of 20 mm. (the average manner of smoking among a population) (Ar:aitage er mL, 196g), the tip retention efficiency for nicotine was 61010 and 22% and the mainstream smoke eontained 1-0 and 2•1 m& nicotine in types (a) and (b) respectively. There ~ aras no detectable diffetence in flavour or other qualities br m the two types of dgarettes • Leauter in Phumacolop Hoooruy Setior Resesch A..odate. F]ecavme Tedinieiaa. Technicm. uaoeat of Phaera.oo4p , Voi.eniry of Neweude upon Tyne, md Departa+eot of t~iaid P6.rmaaology, Royal Victoria lnArmary, Newcastle upon Tyee. Fsperimental Procedure The subjects performed tasks on a driving simulator, the details of which will be published later. Briefly, the tasks consisted of "driving" to a film projected on to a screen in front of the subject and responding to certain light signals an a panel below the sereen requiring braking, steering, and movements of the ttaffiator switch. There were 122 such signals in each task Two 20-minute tasks were used which differed in the degree of "stress" they induced in the subjeet. Task level I involved driving to a film and responding to light signals that corre- sponded with the requirements of the ft7m. Task level 2 Involved driving to the same fi2ta but also responding to light signals that were sometimes intentionally contradictory to the driving requirements of the f'im. Task level 2 was thus the more difficult and stressful because of the ttncertainty induced by the conflicting signals. The tasks were performed consecutively in a random order with a resting period of 5 to 10 minutes between each task. During tlie.first half of each task the subjects smoked one cigarette with no restrictions on the manner or nte of smok- ing. Nineteen subjects smoked high-nicotine cigarettes and 17 subjects smoked low-nicotine cigarettes. After completion of the two tasks a further half dgarette (approximately) was smoked during a resting period. Ideally a whole cigarette should have been smoked during the resting period. Some of the subjects, however, were not accustomed to smoking as many as three cigarettes In an hour, and in~ order to obtain a more natural smoking pattern it was decided to limit their nicotiae intake where possible. The two groups thus smoked 2} cigar- ettes in a 60-minute period with at least 15 minutes of non- smoking between the end of one cigarette and the start of the nest Measurements Puff Frsqueney. Fach puff at a cigarette taken by the subjects during the tasks and resting periods was recorded by an observer operating a marker on the pen recorder, and the time of starting and finishing each cigarette was a4so noted. All subiects were told that they were smoking "ordinary" tipped cigarettes and none was aware that their puff frequency was being observed. Analysis of Cigarette Stubs for Nicotine Corttsnt. The cigarette stubs were analysed for nicotine content by Mr. C. Grant, (yemistry Departntent, Tobacco Research Council. Since the tip tetention efficiency of the filter and the amount of nicotine retained in the tip were known, it was possible to estimate the amount of nicotine presented to the smoker for each cigarette as follows: TR>:tip retention efficiency Ns=nicotine preseated to smoker Nr=niaotine retained in tip " Nr TR= Ns+Nr Ns(TR)+Nr'TR)=I~ Nr (1-TR) Ns= TR The nicotine presented to the smoker represented the total amount of nicotine taken into the mouth for each cgarette.

IRtY1yt Iuua,Yi i i In the absence of suitable methods foLdetenaitting blood nico- tine levels it was not posspale to :ermine how much of ' this nicotine was absorbed from the buccal mucosa or fraat the lungs. Other Msasurenurtts.-Respiratoty rate was measured by impedance pneumography by means of two Devices skin electrodes applied to the ninth intercostal space in the mid- axillarq line connected to an Impedance Rheograph (E. and M. Instrument Company) and recorded on a Beckman Dynograph recorder. An indication of the depth of each res- piration was also obtained by observation of the amplitude of the tracing, and the measurement was thus semiquantitadve. Subjects' reaction times to the panel light signals during the task, and physiological functions ipcluding heart rate, blood pressure, and calf blood flow were also reeorded. Detatls of these measureatetus will be reported separately. Results Differences Between Groups Smoking Different Cigarettes A comparison was made of the smoking behaviour of the subjects smoking the high- and low-nicotine cigarettes. Puff Frsqusrtcy.-During both of the driving tasks and during the resting period after the tasks the subjects smoking. the low-nicotine cigarettes took more frequent puffs than those smoking the high-nicotine cigaremes. These differences were highly significaat. The puff frequencies in the two groups under the various conditions are shown in the Chart and the Table. As would be expected from the inaeased puff frequency, the average time taken to finish a cigarette was less in the groups smoking the low-nicotine cigarettes. Records of respiration made during the smoking showed no differences in overall rate or in the depth of respiration at or after each puff between the two groups of smokers. Hence these results suggest that the subjects smoking the low-nico- tine cigarettes were attempting to compensate for the high filter retention of nicotine by a faster puffing rate. The puff volume appeared to be relatively constant, though small differences may not have been detected. Nuotins Dslivnsd to Smoker per CiYarstts.-During the less exacting level 1 task and during the resting period there was no significant difference in the amount of nicotine deliv- ered to the smoker from the two types of cigarettes. Thus, under these conditions, iaceased puffing rate compensated LEVEL I  Low-raieoti•e eiqerettes s O Nl~ieotiee cl~eretfes 4 • J 2 1 { O ~ S r LEVEL j • 4 o 0 z 5 4 3 2 i 0 Rf STINt; 24681012141618 Subletts for higher filter --tention, so that smokers extracted about the same amount o :otine from both types of cigarettes. In the 1eve12 task, however, the smokers of the low-: •i--otine cigarettes obtained slightly less nicotine than the smv.: rs of the high- nicotine cigarettes. It is possible that the motcr demands of the more stressful task level limited the rate of smoking, since sub- jects in the low-nicotine group were commonly observed to cut short an attempt to t;ke a puff when a driving sigr-al appeared on the sceen in front of them. These results are also shown in the Chart and the Table. Differences within the Smoking Groups Differences were also observed within the groups of smokers. Both groups had a higher puff rate during the rest- ing period after the tasks than during the tasks themselves. As mentioned before (see Methods), only half a cigarette was smoked during the resting period. Less nicotine is available to the smoker in the first half of a cigarette, since nicotine condenses in the remaining tobacco as a cigarette is• smoked. Therefore puff fiequency calculated from the first half of a cigarette might be expected to be greater than that calculated M.awptt~ Rare, T'tm. Taiet te Soroke Cgarate, md 1lricetir. Dslioered to Snteleer dnriryt~ Tor.b LetnL eed Resrirt~ Period after Tar+Es for Sewkeri eJ Lots- end Xigb-nfeoti+u Cigarstta M.ro 1.ew.tQieedn• Ciqretta (tbeans of 17 subjew) w~,.Nteetiee Cipretces (meuu a[ tta subjeets) slvLitanee t:e+.ls a! Dilferences lteaween t•o.r- and Hich-lqlcotine Qprettn Toas pet n nttts: ' 1 Le.a . • 1•74 o9a P<o-0Ot (vos v~ t>.r ds.) a dw (+ r v~ ° t.e.et 2 . o: , r<o at (13-M pufts trerd4) •2 p (a•a9 puCs ~ ) ) 0•o01 T • ~ ds. amaked) (aate } 94 (qnir i eie. smoked) < 'lta+e takee te smoke u>s eiearette (mirr.)z Z.MeI t T•ss 9•tt r<o•ot Lnrel2 7•!a s•t! P<o•Ot tdteedne deu.a~e to smoker ~ t L1 . ~ 1T2•c! 179•S3 Btat sipiiliant dW (t•2a y.e (t•s1 as.) 14 - ~W _ • ' 1~ ~~ • 40 1 P<o•OS (I se as. Oer o4) a•~ ms. pQ as.) Rnriitti • •214•~0 •2?3 30 Not si"eant (edy f da. rawked) (onty I eig. sreoked) '•Net• that puff rsa estd ttieedoe deli.ered vrert ereater(P<o•O1) during teseine ~d ttue during palarmeoee ol tnks tae both low- eed hieh-nieodne eistatenes Z..e tad. 400 ` 700 20o ~ IW ~ O 0 i o j ; ffl~ • eI 24CO I ( JOC ili'!lllltltIfllFtfIrIlrI'c i~ . 24681012141618 Sebjeett Pu![ frequency and aicotine prtaented to smoker In subj•et ttooking bw- stsd bigh-oicoeine aieeeetta during perfoentaaee of dri.ing essks Ierelt I and 2, and during ttasdrtf period. Pult frequency is siani6eantlr greater in smokers' of bw-oieotine cigarettes under stl conditions (a, e, and e).• There is no sigtti6cant ditierence in aieotine pmentad to smokers during task level I attd restins period (b end f), but during task level 2 the anokers of low-nicotine cigarettes obtained slightly less nicotine (P <0•0S) (d). N O

y z-,cprcmucr ry ru lvicoune- lntat:c ln lagarette Jmokers-As/:ton and Watson v:or1 a,whole cigarette. Allowance was made f' this factor, ow•es%r, lsy comparing the resting puff -rate pe. .iinute with .ie puff rate per minute for the first half of the cigarette only uring the driving tasks. When compared in this way the rest- zg r'` rate was siill significantly grcater than that during le lcvels (I'<0•01). In addition, the nicotine obtained `^otn L,.e cigarettes per unit time was also significantly greater zan during the tasks in both groups. This finding suggests ze possibility that the subjects were striving for a higher nico- :ne dose during the resting period. There was also a ten- ency-in both the high- and low-nicotine cigarette groups to ike -more puffs and obtain more nicotine during the level 2 ssk than during the level 1 task. These differences did not each statistical significance, but they suggest again that ifferent nicotine doses arc °optimum" for different activities. hese results are included in the Table. Diacussion Tkls Investigation shovrs that under varying conditions ~ mokers of low-nicotine cigarettes had a higher puff requency and drew into their mouths nearly the same mounr of nicotine as smokers of high-nicotine cigarettes. In he absence of suitable methods for determining blood levels tf nicotine there is unfortunately no way of measuring how auch of the nicotine taken into the mouth was absorbed into he body; but all subjects inhaled when smoking and there ,. +as no detectable difference in the mean depth of respiration -et.veen the groups smoking different cigarettes. These fnid- igs are thus consistent with the poss'bility that thero e3dsts n"optimum" nicotine dose for a given activity and that mokers uncvrtsciously modify their smoking patteras in an nempt to obtain this dose. This proposition in tttrn sugges that nicotine exerts in sar e central pharmacological action. Subjective evidence ron. nokers that they are either "cranqmlliied° or stimulated" by smoking a cigarette (Armitage et aL, 1968) rould seem to support this thesis. Several authors have ttempted to obtain objective evidence in tnan. For esample, Izuses st al. (1958) and Wechsler (1959) observed changes in i.EG. patterns in subjects smoking cigarettes, but these ` banges also occurred to some estent when dmieot;nized igarettes were used. Murphree sr aL (196 ,T), however, stated 5at smoking cigarettes or cigars caused changes in S.SG. •atterns, usually of a type associated with stimulation rather san uanquilliadoa Limbiue and Sesa (1957) also onduded that smoking caused short-lived flattening of :_E.G. potentials. In animals there is now good evidence that nicotine given !y intermittent intravenous injection or by cigarette smoke :Iown into the lungs, in amounts comparable to those btained by a human subject iahaliag a cigarette, causes hanges in electrocortical activity and in cortical acetylcholine elease (Armitage st el., 1963, 1969; Hall, 1970). Small requent doses of nicotine tend to cause effects assodated :ith central stimulation (desyncbsoaization of electrocortico- ` tatn and increased cortical aeetyleholine release), while ~ ~ 681 larger doses given less freq• '-*'tly sometimes cause depressant effects (decrease in cortical ._tivity an4 cortial acetylcholine output). The results of behavioural studies in rats and mice (Morrison, 1967, 1968a, 1968b) fit in with these observations, since small frequent intravenous doses of nicotine tend to stimulate bar-pressing behaviour and learning rate while less frequent larger doses sometimes have a depressant effect on these activities. These findings in animals have yet to be demonstrated in man, but it may be that the smokers in the present tests were striving for a nicotine alerting effect while performing the task levels. It is of interest that with both types of cigarettes the puff rate rose significantly during the resting period after the tasks, and the amount of nicotine obtained per unit of tuae also rose during this period. Under these resting condi- tions the subjecu may have been attempting to obtain the "tranqut7Iizing" effect of higher doses of nicotine. In addition, with both the high- and the low-nicotine cigarettes the sub- jects appeared to abstract slightly more nicotine during the tnore stressful level 2 task than during the relatively straight- fon.ard level 1 task. These observations fit In with the sug- gestion of Armitage at cl. (1968) that the effects of nicotine in man probably depend critically on the dose and rate of self- adnninistrarion by smoking. It would also appear from the present experiments that the rate of self-administration in man is controlled more by the puff rate than by the depth or duration of iahalation of each pufL The question of whether the "optirttum" dose of nicotine, and thus the smoking behaviour, alters significaatly at different levels of stress and relasadon in conditions where motor activity does not affect puffing rate would require further study in a carefully selected group of subjects. The differences in the speed and accuracy of performance at the different task levels between the groups of smokers and a comparison with a group of non-smokers will be reported in a separate paper. The work was supported by a grant from the Tobacco Research Counal We would like to thank Professor J. W. Thompson, depart- meat of pharmacology, University of Newcastle upon Tyne, for help and advice at all stages of the israrestigatiod We also thank Mrs. M. Russell for help In analysiag the racords aad Mts. R. Telford for help in the calculations. Requests for reprints should be seat to Dr. Ii Ashtoa Rgam+Qs Atmitase, A.1C, Hiil, G. H« and Morrisoa, G F. (1968). Natvre, 217, 331. Asmita=e, A. K., Iiall, G. H., and Sellets, G M. (1969). B+ftiu+i /ourwe! of P/m+eaaslonr, 35,152. Hsll, G. H. (1970). Bntiuh Jmmul eJ PMnweeeWry, 3= 271. Haaaer, FL, 3eLwrarz, 8. Ea Roth, f3 , u~d Hiekford, R. G. (1958). Et:co.- .oeepidft.aphy aad Clndea! Nnvepl,ydoloCy. 10. 576 P. Lmbiasa, M.~and S~sa~ G(1957). .4as Ne~se7ariu, 12, 473. Mosrisoo, G. (1967). Iater+meiowel7eaeeel of Nneephanwaolov, 6, 229. Moerifoo, C. F. (196E1.). PsyehopJanwaceloria, 12, 176. Matisn, G F. (196lb). BritirAi 1w.r+mJ o/ Plurn,awloty .nd Cbewwdwapy, 32, 2s. Mmphree, H. B., Pfc3lfa, G C., and Priee, L M. (1967). .l,wL e/ dio NesYw+l itcadewr of Sdraees, 142, 247. Wedtaler, R L(197Zi). F.derae:en F: wxdi+tn, 17,169. t' m :