Effects of tiagabine in combination with intravenous nicotine in overnight abstinent smokers.
BACKGROUND
Preclinical studies suggest that medications enhancing the brain gamma amino butyric acid (GABA) system attenuate the rewarding effects of stimulants including nicotine. These preclinical studies have not been followed up in systematic human studies.


OBJECTIVE
This study was conducted to examine the effects of a GABAergic medication, tiagabine, on acute physiological and subjective effects of intravenous (i.v.) nicotine and on tobacco withdrawal symptoms in overnight abstinent smokers. The proposed mechanism of action for tiagabine is selective inhibition of GABA transporter type I, which leads to increases in synaptic GABA levels.


METHODS
Eight male and four female smokers participated in a double-blind, placebo-controlled, crossover study. In each of three experimental sessions, participants were treated orally with a single 4- or 8-mg dose of tiagabine or placebo. Two hours following the medication treatment, participants received i.v. saline, followed 30 min later by 1.5 mg/70 kg i.v. nicotine.


RESULTS
Tiagabine treatment did not affect the heart rate or blood pressure changes induced by nicotine. There was a significant treatment effect for the subjective responses to nicotine, such that tiagabine, compared to placebo, attenuated the ratings of "good effects" and "drug liking." Tiagabine treatment at 8 mg attenuated the craving for cigarettes and enhanced the cognitive performance in the Classical Stoop Tests, compared to placebo or 4 mg tiagabine condition.


CONCLUSIONS
These results suggest that GABA enhancing medication tiagabine may reduce the rewarding effects of nicotine and improve cognitive performance in abstinent smokers. The utility of GABA medications for smoking cessation needs to be examined further in controlled clinical trials.
Sofuoglu
Mehmet
M
Department of Psychiatry, VA Connecticut Healthcare System, Yale University, 950 Campbell Ave., Bldg. 36/116A4, West Haven, CT 06516, USA. Mehmet.Sofuoglu@yale.edu
Mouratidis
Maria
M
Yoo
Sonah
S
Culligan
Kerry
K
Kosten
Thomas
T
D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D001288:Attention / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D009538:Nicotine / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D012201:Reward; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000523:psychology; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D000078308:Tiagabine