454 



467 



Wesnes et al. 1983). However, the pharmacokinetics of 

 nicotine (and other cigarette smoke constituents) follow- 

 ing inhalation are quite different from those seen follow- 

 ing slow IV infusion or buccal absorption of nicotine 

 from chewing gum (Benowitz 1988). Conclusive evidence 

 for the "nicotine primacy" hypothesis can only come 

 from inhalation-route studies. 



Knott (1991) has shown that the EEG is affected dif- 

 ferently by smoking "familiar" and "novel" cigarettes, 

 presumably reflecting differential nicotine absorption by 

 the subjects. Pritchard (1991) reported that subjects who 

 had a small pre- to px)st-smoking rise in expired air CO 

 (and were assumed to have absorbed small amounts of 

 nicotine) exhibited a decrease in magnitude in lower- 

 frequency EEG bands (EEG activation). In contrast, 

 subjects who had a large change in pre- to post-smoking 

 expired air CO (and were assumed to have absorbed 

 larger amounts of nicotine) exhibited an increase in mag- 

 nitude in the fast-frequency beta2 EEG band; a change 

 associated with anxiety relief Some studies of smoking 

 and cognitive performance have reported differential ef- 

 fects of varying cigarette nicotine yield. Wesnes and War- 

 burton (1983) reported that smoking cigarettes that 

 yielded 1.65 mg but not 0.28 or 0.71 mg nicotine facili- 

 tated performance of a sustained reaction time (RT) 

 task. Similar results were obtained by Wesnes and War- 

 burton (1984; effects for 1.3, 1.5, and 1.7 mg but not 

 0.9 mg nicotine-yield cigarettes). However, other studies 

 of smoking and cognitive performance have varied ciga- 

 rette nicotine yield and found no differential effects (Wil- 

 liams 1980; Suteret al. 1983; Edwards et al. 1985; Revell 

 1988). Finally, two investigations employed nicotine-frec 

 control cigarettes, e.g.. commercially-available "herbal" 

 cigarettes (Wesnes and Warburton 1983; West and Hack 

 1991). However, the laste, and the "tar" and CO yields 

 of such cigarettes are unknown, and it is extremely 

 doubtful that subjects would smoke them in a manner 

 similar to tobacco cigarettes in terms of puff volume, 

 puff intensity, number of puffs, etc. 



Although the results of these studies are consistent 

 with the hypothesis that nicotine is responsible for the 

 psychopharmacological effects of smoking, they are also 

 not conclusive. This is because the manipulations em- 

 ployed in these studies that presumably affected nicotine 

 absorption (agarette design/nicotine yields, subjects" 

 puffing and inhalation patterns; see Nil and Battig 1989) 

 would also have affected the absorption of other main- 

 stream smoke components (again, CO or one of the 

 other compounds contained in the particulate fraction 

 or gas phase of smoke). 



To dissociate the psychopharmacological effects due 

 to nicotine absorbed from cigarette smoke versus other 

 compounds absorbed from the particulate or gas phase, 

 one would require a cigarette that yielded little or no 

 nicotine in the mainstream smoke, but did yield similar 

 levels of "tar" and gas-phase components. A commer- 

 cial cigarette that fulfilled these criteria was recently sold 

 for a short penod of time in limited test markets. The 

 cigarette was manufactured with tobaccos which had 

 been processed such that nearly all the nicotine had been 

 extracted and therefore yielded extremely small quanti- 



ties of nicotine in the mainstream smoke. The cigarette 

 did, however, yield levels of "tar" and CO typical of 

 leading "lights" category cigarettes. We tested this ciga- 

 rette in an attempt to dissociate psychopharmacological 

 responses related to nicotine absorbed from tobacco 

 smoke from those related to components absorbed from 

 the particulate or gas phase. 



The specific goals of the present study were to deter- 

 mine the behavioral and psychophysiological impact of 

 smoking two cigarettes, one yielding typical levels of 

 "tar", nicotine, and CO (Control cigarette), and the 

 other yielding similar levels of "tar" and CO. but mini- 

 mal nicotine (Test cigarette). The two psychophysiologi- 

 cal variables measured were HR and EEG. Subjects' 

 puffing patterns ("puff-profile"), breathing patterns, 

 and plasma mcotine, blood carboxyhemoglobin 

 (%COHb), and expired-air CO concentrations were also 

 monitored to determine the impact of smoking the Con- 

 trol and Test cigarettes on these variables. 



Materials and methods 



Subjects and cigareites. Subjects were Tive male employees of the 

 RJ. Reynolds Tobacco Company who volunteered to participate 

 in the study. Employee volunteers were used because they were 

 known to the experimenters to be inhaling smokers who could 

 be relied on to comply with pre-experimental smoking restrictions. 

 Subjects gave their informed consent prior to participating in the 

 study and all procedures used were approved by the human re- 

 search review board. The consent form described the procedures 

 to be used and the measurements to be made, but did not disclose 

 the purpose of the test or the charactensiics of the cigarettes to 

 be used (other than that the cigarettes to be tested were commer- 

 cially available brands). Subjects were tested individually beginning 

 al 0830 hours following 48-h abstention from tobacco-product use. 

 Subsequent analysis of plasma samples for nicotine and cotinine 

 indicated that all subjects had complied with the tobacco-use re- 

 strictions. 



Mainstream smoke yields for the two cigarettes used in this 

 test as determined by the US Federal Trade Commission Method 

 (Pillsbury et al. 1969) are reported in Table I. 



Blood sampling (plasma nicoiine and %COHb) A sterile indwelling 

 Teflon™ catheter (Becton-Dickinson, 21 ga) was inserted into the 

 antecubital vein m one arm and cappied with a rubber stopper 

 This technique allows multiple blood samples to be drawn with 

 only one vein puncture and no discomfort to the subject following 

 the initial needle stick. Individual blood samples were drawn into 

 7 ml Vacutainer™ tubes containing EDTA as the anticoagulant 

 ("purple-top"). Samples were stored in the dark in an ice water 

 slurry until centrifuged (usually within I h of the stari of the test). 

 Plasma samples were aliquoted and stored at — 70* C for subse- 

 quent analysis of nicotine and cotinine (Davis 1986). 



Percent carboxyhemoglobin was determined for selected (see 

 below) pre- and post-smoking whole blood samples using a Model 

 IL482 (io-Oximeter. These determinations were made within 5 min 

 of drawing the sample. Expired air CO concentrations were deter- 

 mined using an Ecolyzcr™ CO Analyzer and were made «?<hin 

 I min of taking the breath sample. 



