Varenicline (Chantix) for Smoking Cessation and Alcohol Use Disorder?
Smoking Cessation with Varenicline (Chantix) Among Patients with Alcohol Use Disorder May Also Reduce Craving and Prolonged Use of Other Drugs

Alcohol and tobacco are responsible for increased morbidity and mortality. Cigarette smoking is less prevalent than it was a decade ago but among those with substance use disorders it remains highly prevalent. The social and cultural sanctioning of smoking and drinking peaked with the World War II generation, where cigarette smoking and drinking were associated like a hand in a glove. The relationship between cigarette addiction and alcohol use disorder was so common that few had researched the relevance. Some of my early work established that cigarette smoking has antidepressant and anxiolytic effects. Anecdotally, treatment professionals have long noted that smoking usually increases during treatment for SUD.

As a result, the issue of whether or not to allow SUD patients to smoke during treatment was controversial, given the clean air legislation in the 1980s and 90s. Not allowing patients to smoke during treatment is associated with fewer admissions and a decrease in treatment adherence and completion. As a result, most centers today allow patients to smoke outside in designated areas. But the question remains—as health professionals, we understand the harms associated with tobacco use and advise our patients to seek treatment. Yet, the reward sensitivity and cognitive flexibility in the mesocorticolimbic system affected by acute smoking abstinence and stimulation of the nicotinic acetylcholine receptors in dependent smokers via varenicline is not well understood, but are the outcomes improving?

Varenicline (Chantix) is the newest pharmacologic treatment for smoking addiction. The mechanism of varenicline’s action is thought to reduce cigarette craving via a blockade of the reinforcing action of nicotine through partial agonist activity at the nicotinic acetylcholine receptors, which would also affect dopaminergic activity and availability in the midbrain.Ask the Expert

When nicotine enters the brain, it binds steroselectively to nicotinic/ acetylcholine receptors—in part because nicotine is molecularly similar to acetylcholine, which affects the sympathetic and para sympathetic bodily functions, including respiratory rate, heart rate, blood pressure as well as cognitive deficits in learning and memory. Acetylcholine also affects several additional neurotransmitters that mediate appetite, mood, and recall. Nicotine selectively binds to various receptors in nuclei where acetylcholine would normally exert its action, creating the similar effects, including the release of dopamine, which is central for the pleasure/reward sensation produced by all potentially addictive substances. To put it mildly, smoking addiction is a very complicated and stubborn thing—especially when co-occurring with alcohol use disorder.

In the current JAMA paper the authors tested the efficacy of varenicline among patients with alcohol use disorder and comorbid smoking dependence who were seeking treatment for alcoholism. This was a randomized, double-blind, parallel group, placebo-controlled trial of 131 participants who were randomized to either varenicline or placebo.

The results?

Investigators found that varenicline vs placebo resulted in a larger decrease in percentage of heavy drinking days (PHDD) in men (least square mean difference in change from baseline, 0.54; 95% confidence interval, −0.09 to 1.18; P = .09) and a smaller decrease in women (least square mean difference, −0.69; 95% CI, −1.63 to 0.25; P =.15). No heavy drinking days were reported by 29% of men taking varenicline vs 6% taking placebo. For women, no heavy drinking days occurred in 5% and 25% of those taking varenicline and placebo, respectively. Thirteen percent of those taking varenicline and none taking placebo achieved prolonged smoking abstinence.

The result of this excellent study revealed that among men, varenicline with medical management resulted in a statistically significant decrease in heavy drinking and increased smoking abstinence in the overall sample. In men with these dual addictions, varenicline use was associated with promoting improvements.

With medical management, varenicline resulted in decreased heavy drinking among men and increased smoking abstinence in the overall sample.

Why Does This Matter?

Stephanie O’Malley is one of the world’s experts on Medically Assisted Treatment (MAT) for addictive disease. Among her astute analysis, Dr. O’Malley revealed important gender difference in response to Naltrexone’s efficacy in smoking cessation—in favor of females, which we reported in 2006.

Second, even though varenicline primarily produces its effects via the dopaminergic reward systems and not by neural mechanisms that mediate nicotinic receptors, researchers have failed to see, nor assess other potential benefits for this medication in treating addictive disease beyond smoking. Any substance of behavior that elevates central dopamine is potentially addictive. Accordingly, any therapeutic that can readily cross the blood brain barrier and target dopaminergic systems is not only rare, but potentially significant mediating the effective of other addictive substances or behavior. We have not needed complex placebo controlled studies to know that most drinkers smoke and most smokers drink. Helping addicted patients recover from their addiction is indeed lifesaving, but expanding our understanding and approaches to address concurrent disorders and health risk behaviors in relation to alcohol and tobacco use disorder are desperately needed.


Stephanie S. O’Malley, PhD1; Allen Zweben, PhD2; Lisa M. Fucito, PhD1; et al. Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking A Randomized Clinical Trial. JAMA Psychiatry. Published online December 20, 2017. doi:10.1001/jamapsychiatry.2017.3544

Naltrexone augments the effects of nicotine replacement therapy in female smokers. Byars JA, Frost-Pineda K, Jacobs WS, Gold MS. J Addict Dis. 2005;24(2):49-60.