CUD is characterized by continued use of cannabis despite ‘clinically significant impairment’ such as ignoring important social, occupational, or recreational activities and persistent use despite physical or psychological problems associated with cannabis.  Cannabis use is also associated with psychosis, sleep disorders, withdrawal, and mood and anxiety disorders.

Varenicline is an effective medication for quitting tobacco.  This trial, conducted at the Medical University of South Carolina and published in Addiction, tested whether varenicline could help with CUD. Results showed it helped men reduce cannabis use, but not women. (Varenicline works equally well for both sexes as a stop-smoking aid.)

The trial included 174 participants with CUD who used cannabis at least three days per week.  Participants were randomized to varenicline (working up to a dose of 1 mg twice daily) or placebo for 12 weeks.  Participants also received a weekly brief medical management session to encourage their adherence to both the medication and the treatment plan.

The men in the study who received varenicline used cannabis fewer times per week than the men on placebo.  Specifically, the varenicline group averaged 7.9 cannabis sessions per week during the study and 5.7 sessions in the week following the study, compared with more than 12 weekly sessions for the placebo group.  The male varenicline group also used cannabis an average of 3.8 days per week, compared with 4.7 days per week for the male placebo group.

The women in the study who received varenicline did not differ in their cannabis use from the women on placebo.  The varenicline group averaged just over 10 sessions per week, compared with the placebo group’s 9.2 weekly sessions (which dropped to 8.2 in the week following the study).  The female varenicline group used cannabis an average of 4.9 days per week, compared with 3.6 days for the female placebo group.

The female varenicline group showed higher withdrawal and craving scores and higher anxiety than any of the other groups.  Perhaps connected with that, women receiving varenicline reported lower medication adherence than women receiving placebo.

Lead author Professor Aimee McRae-Clark says “Cannabis use disorder is rising quickly in the United States. 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.  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.”

This Open Access paper is available on the Wiley Online Library from the embargo date (https://onlinelibrary.wiley.com/doi/10.1111/add.70296) or you may request an early copy from Jean O’Reilly, Editorial Manager, Addiction, jean@addictionjournal.org.

Full citation for article: McRae-Clark AL, Gray KM, Baker NL, Sherman BJ, Tolliver B, Burt J, Steplight A, Chapman E, and Wagner A.  Varenicline for cannabis use disorder: A randomized controlled trial.  Addiction. 2026. DOI: 10.1111/add.70296

Primary funding:  This work was supported by the National Institutes of Health (UH3DA043231).

Declaration of interests: Dr. McRae-Clark has served as a consultant for Indivior Pharmaceuticals and has received research support from Pleo Pharma. Dr. Gray has served as a consultant for Indivior Pharmaceuticals and received research support from Aelis Pharma. The other authors report no interests to be disclosed.

Addiction is a monthly international scientific journal publishing peer-reviewed research reports on alcohol, substances, tobacco, gambling, editorials, and other debate pieces. Owned by the Society for the Study of Addiction, it has been in continuous publication since 1884.

The findings, to be published June 5 in JAMA Network Open, suggest that most patients reported using cannabis for symptom management, despite identifying as recreational users, indicating the need for routine cannabis screening.   Currently few healthcare systems offer this screening in primary care settings.

“Patients may not tell their primary care providers about their cannabis use, and their doctors may not ask about it,” said lead author Dr. Lillian Gelberg, professor of family medicine at the David Geffen School of Medicine at UCLA and of health policy and management at the UCLA Fielding School of Public Health  “Not asking patients about their cannabis use results in a missed opportunity for opening up doctor-patient communication regarding use of cannabis generally and for management of their symptoms. “

Thirty-eight states, three US territories and the District of Columbia allow cannabis for medical use, and 24 of these states also permit recreational use. Stigma over cannabis use has fallen likely due to these legal moves. While there has been an increased perception that its use is risk free, cannabis potency has increased.

The U.S. Preventive Services Task Force recommended in 2020 that primary care physicians screen their adult patients for use of cannabis and other substances. The following year the investigators implemented the UCLA universal electronic health record-based, self-administered survey on cannabis use and medical cannabis use. Patients complete this survey as pre-visit screening prior to their primary care visits as sent to them via the Epic patient portal.

The researchers used patients’ de-identified electronic health records at UCLA collected from January 2021 to May 2023 to determine the prevalence, correlates and reasons for current cannabis use. The UCLA Health system is one of the few to ask patients to voluntarily complete cannabis use surveys during pre-appointment check-ins. The survey used the WHO Alcohol Substance Involvement Screening Test (ASSIST) to assess cannabis use.

Nearly 176,000 patients completed surveys. Of those, nearly 30,000 (17%) reported cannabis use among whom 35% had results suggesting moderate- to high-risk for a cannabis use disorder, defined as a score of 8 or higher on the screening survey. Among users, 40% used cannabis once or twice in the previous three months, 17% used monthly, 25% used weekly and 19% used it daily or almost daily.

Other findings included:

• Cannabis use was lowest among people living in the most disadvantaged neighborhoods (14%), yet the risk for disordered use was highest among this group
• Inhaled modes of cannabis use were as common as ingestion (65.0% and 64.7%), including 29% who vaped
• 47% used cannabis for medical reasons
• 76% used it to manage symptoms such as mental health symptoms or stress (56%), sleep (56%), and pain (37%).  Further, most patients who reported using cannabis only for recreational reasons had also used it at some point to manage a symptom.

The study has some limitations. The findings are based on patients’ self-reported use and though cannabis is legal in California, some patients may still have been reluctant to disclose using it. Much of the data were from screenings taken during the COVID-19 lockdown, during which cannabis use may have been higher than it might have been otherwise. In addition, the findings may not be applicable to other health systems, particularly in states where cannabis use is still illegal.

However, “given the high rates of cannabis use and medical cannabis use that we found in this large urban healthcare system, it is essential that healthcare systems implement routine screening of all primary care patients,” the researchers write.  “Integrating screening efforts to include information regarding cannabis use for symptom management could help enhance the identification and documentation of medical cannabis usage, particularly in the healthcare context.”

Study co-authors are Dana Beck, PhD, MSN; Julia Koerber, MPH; Whitney N. Akabike, PMP, MSPH; Lawrence Dardick, MD; Clara Lin, MD; Steve Shoptaw, PhD; and Marjan Javanbakht, MPH, PhD.

The study was funded by the University of California Tobacco-Related Disease Research Program (grant #T29IR0277) and the National Institutes of Health National Center for Advancing Translational Science (NCATS) UCLA CTSI (grant #UL1TR001881).

Article: [citation] doi:10.1001/jamanetworkopen.2024.14809