Varenicline attenuates some of the subjective and physiological effects of intravenous nicotine in humans.
BACKGROUND
Varenicline, a partial nicotinic acetylcholine receptor (nAChR) agonist, is approved for smoking cessation. A few preclinical studies examined the pharmacological effects of varenicline, alone or in combination with nicotine. How varenicline affects the pharmacological effects of pure nicotine has not been examined in humans. The goal of this study was to characterize varenicline's actions on nicotine's dose-dependent effects in abstinent smokers.


METHODS
Six male and six female smokers participated in a double-blind, placebo-controlled, crossover study. Smokers had two 4-day treatment periods, assigned in random sequence, to varenicline (1 mg/day) or placebo treatment. On day 4 of each treatment phase, smokers had an experimental session, where they received three escalating doses of intravenous (IV) nicotine (0.1, 0.4, and 0.7 mg/70 kg), in 30-min intervals. Varenicline's effects were assessed through subjective, physiological, and cognitive performance outcomes to nicotine administered via IV route.


RESULTS
In response to IV nicotine, varenicline treatment attenuated the rating of drug strength, high, head rush, and stimulated. Varenicline also attenuated nicotine-induced increases in heart rate. Varenicline had mixed effects on cognitive performance. Smokers under varenicline treatment, compared with placebo, reported enhanced positive mood measured with the Positive and Negative Affect Schedule.


CONCLUSIONS
These findings provide new insights into the mechanisms of action of varenicline in smoking cessation.
Sofuoglu
Mehmet
M
Department of Psychiatry and VA Connecticut Healthcare System, Yale University School of Medicine, 950 Campbell Ave., Bldg. 36/116A4, West Haven, CT 06516, USA. Mehmet.Sofuoglu@yale.edu
Herman
Aryeh I
AI
Mooney
Marc
M
Waters
Andrew J
AJ
D000328:Adult; D000339:Affect / Q000187:drug effects; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D003367:Cotinine / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011810:Quinoxalines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016540:Smoking Cessation / Q000379:methods* / Q000523:psychology; D014029:Tobacco Use Disorder / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D016896:Treatment Outcome; D000068580:Varenicline
D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D009538:Nicotine; D003367:Cotinine; D000068580:Varenicline
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