A drug approved by the FDA for smoking cessation was associated with significant reductions in cannabis use only in men with cannabis use disorder (CUD), a new trial showed.

Following 12 weeks of treatment with varenicline, men reported significantly less cannabis use than those receiving a placebo, whereas women in the treatment group reported no significant difference in use.

However, women did report more symptoms of withdrawal and cravings after treatment with varenicline.

“Current pharmacological treatment options are very limited, and so our ability to help people reduce their cannabis use is also limited. Our study found that varenicline, a drug that helps people to reduce or stop smoking, may be effective at reducing cannabis use as well, but only for men,” lead author Aimee McRae-Clark, professor in the Department of Psychiatry and Behavioral Sciences at the Medical University of South Carolina in Charleston, South Carolina, said in a news release.

The study was published online on January 15th in Addiction.

A Growing Issue

Cannabis use in the US has doubled over the past decade as more than 30 states have legalized or decriminalized recreational use of the substance. CUD is also on the rise, with an estimated 3 in 10 cannabis users developing an addiction.

A study published last year showed that patients hospitalized for CUD had nearly three times the risk for death compared to those without the disorder, prompting some researchers to declare CUD a “public health crisis.”

A previous pilot trial by the South Carolina researchers demonstrated higher rates of cannabis abstinence among participants with CUD following treatment with varenicline.

The new study included 174 participants with CUD (mean age, 28 years; 65.5% male) who used cannabis at least three times a week. Participants were randomized to receive a placebo (n = 84) or varenicline (n = 90) for 12 weeks, with follow-up 1 week after the treatment period.

Exclusion criteria included those with psychotic disorders, noncannabis substance use disorder within the past 60 days, suicidal ideation in the past 10 year, or past year alcohol use disorder.

Varenicline was given at the standard dose of 0.5 mg daily for 3 days, upped to 0.5 mg twice a day for 4 days and then 1 mg twice daily for the remaining treatment period.

Participants also took part in a weekly medical management session to facilitate adherence to the treatment plan.

Cannabis and substance use was self-reported. Withdrawal symptoms and cravings were assessed weekly using the Cannabis Withdrawal Scale and Marijuana Craving Questionnaire, respectively.

Mental and physical health was evaluated using the Patient-Reported Outcomes Measurement Information System. Participants’ urine was tested weekly for various drugs and assessed for cannabinoids and creatinine.

The primary outcome was weekly sessions of cannabis use. Secondary outcomes included daily cannabis use sessions, cannabis withdrawal symptoms, marijuana cravings, number of participants who experienced adverse events, treatment adherence, and group differences in urine drug concentrations.

Benefits Only Among Men

Compared to placebo, there was no statistically significant decrease in weekly cannabis sessions among participants during the primary outcome period of weeks 6-12 (between group difference, 1.7; P = .41).

There were key differences by sex, however, with men reporting significantly fewer cannabis sessions than women, with a session defined as cannabis use separated by an hour of no cannabis use.

Among men, treatment with varenicline was associated with 4.3 fewer weekly cannabis sessions (P = .04) and 7.2 fewer weekly cannabis sessions during follow-up than placebo (P = .003). There was no association between treatment and reduced cannabis sessions in women.

Men using varenicline vs placebo reported fewer days of weekly cannabis use (3.8 days vs 4.7 days; P = .11), whereas women in the treatment group reported more cannabis use days (4.9 days vs 3.6 days; P = .09).

In the treatment group, men were more likely to have a negative urine cannabinoid test than women.

Higher Withdrawal Scores in Women

Women who received varenicline had significantly higher withdrawal scores than those taking placebo (21.4 vs 7.0; P < .001). They also had more cravings than men and more anxiety than those who received placebo.

During weeks 6-12, women taking varenicline had less medication adherence than placebo, which may indicate lower tolerability in women, the authors noted.

Overall, 70.1% of participants reported adverse events such as nausea and dream disturbances, with more adverse events reported by the varenicline group.

Limitations of the study were the low number of women compared to men and exclusion of patients with other substance use disorders or significant psychiatric histories.

“Our next step is to further explore varenicline for cannabis use disorder, using a larger sample size of women, to better understand this sex difference in the treatment outcome. In the meantime, we are encouraged that varenicline shows potential promise in treating this fast-growing problem,” McRae-Clark said.

This research was supported by the National Institutes of Health. McRae-Clark reported serving as a consultant for Indivior Pharmaceuticals and has received research support from Pleo Pharma.