Elsevier

Biological Psychiatry

Volume 66, Issue 2, 15 July 2009, Pages 185-190
Biological Psychiatry

Research Report
Varenicline Reduces Alcohol Self-Administration in Heavy-Drinking Smokers

https://doi.org/10.1016/j.biopsych.2009.01.029Get rights and content

Background

Alcohol and tobacco dependence are highly comorbid disorders, with preclinical evidence suggesting a role for nicotinic acetylcholine receptors (nAChRs) in alcohol consumption. Varenicline, a partial nicotinic agonist with high affinity for the α4β2 nAChR receptor, reduced ethanol intake in rodents. We aimed to test whether varenicline would reduce alcohol consumption and alcohol craving in humans.

Methods

This double-blind, placebo-controlled investigation examined the effect of varenicline (2 mg/day vs. placebo) on alcohol self-administration using an established laboratory paradigm in non-alcohol-dependent heavy drinkers (n = 20) who were daily smokers. Following 7 days of medication pretreatment, participants were first administered a priming dose of alcohol (.3 g/kg) and subjective, and physiologic responses were assessed. A 2-hour alcohol self-administration period followed during which participants could choose to consume up to 8 additional drinks (each .15 g/kg).

Results

Varenicline (.5 ± SE = .40) significantly reduced the number of drinks consumed compared to placebo (2.60 ± SE = .93) and increased the likelihood of abstaining from any drinking during the self-administration period. Following the priming drink, varenicline attenuated alcohol craving and reduced subjective reinforcing alcohol effects (high, like, rush, feel good, intoxicated). Adverse events associated with varenicline were minimal and, when combined with alcohol, produced no significant effects on physiologic reactivity, mood, or nausea.

Conclusions

This preliminary investigation demonstrated that varenicline significantly reduced alcohol self-administration and was well tolerated, alone and in combination with alcohol in heavy-drinking smokers. Varenicline should be investigated as a potential treatment for alcohol use disorders.

Section snippets

Participants

Participants were eligible if they were ≥21 years and smoked ≥10 cigarettes per day. Women and men had to consume >7 or 14 drinks per week, and >3 or 4 drinks per episode at least once per week, respectively (35), in the previous 30 days. Exclusion criteria included alcohol dependence, illicit drug use (except for occasional cannabis use), past 30-day use of psychoactive drugs, treatment-seeking for alcohol or smoking, current Axis I disorders (except for nicotine dependence or alcohol abuse) (

Baseline Characteristics

Varenicline and placebo groups were well matched for baseline demographic variables, and smoking and drinking behavior with the exception of race/ethnicity (Table 1).

Pretreatment Period

During the medication titration period, rates of adverse events did not differ by medication (Table 2). All severity ratings were minimal or mild. No participants discontinued the study because of adverse events. There were no significant changes from baseline in alcohol or cigarette use during the 1-week drug titration period;

Discussion

Using an established alcohol self-administration paradigm (30, 31, 32, 33, 34), we found that varenicline compared with placebo significantly reduced the number of drinks consumed by heavy-drinking smokers and increased the likelihood of remaining completely abstinent during the 2-hour self-administration period. This result is consistent with preclinical findings (29) examining ethanol seeking and choice and further supports a role for nAChR effects in alcohol consumption. Varenicline also

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