A recent study suggests that semaglutide (brand names: Ozempic, Rybelsus, and Wegovy) may have the potential to reduce the risk of developing and relapsing into cannabis use disorder. This discovery offers a promising avenue for treatment, especially since no medications are currently approved for cannabis use disorder. The findings have been published in Molecular Psychiatry.
Cannabis use disorder is a condition characterized by the compulsive use of cannabis despite significant negative consequences in a person’s life. This disorder is diagnosed based on criteria that include a strong desire to use cannabis, difficulties controlling its use, prioritizing cannabis use over other activities and obligations, and continued use despite experiencing social or interpersonal problems.
“Cannabis is the most frequently used illicit drug in the United States. Cannabis use disorder is associated with significant adverse outcomes. Currently, there is no FDA-approved medication for treating Cannabis use disorder. Therefore, there is an urgent need for identifying strategies to prevent or treat it,” said senior author Rong Xu, a professor and director of the Center for AI in Drug Discovery at Case Western Reserve University.
Semaglutide is a medication approved for use in treating type 2 diabetes and for weight management. It functions as a glucagon-like peptide-1 (GLP-1) receptor agonist, which means it works by enhancing the action of a hormone that stimulates insulin secretion in response to meals. This not only helps control blood sugar levels but also reduces appetite and food intake, contributing to weight loss.
Recently, semaglutide has drawn interest for its potential effects on addiction based on observations that it may reduce cravings and consumption of substances like alcohol and tobacco. The intriguing reports of semaglutide reducing cravings in other forms of substance dependency led researchers to investigate whether these effects could also extend to cannabis.
“We are always interested in the promise of new addiction treatments. Anecdotes from patients and results from early studies have pointed to the potential of semaglutide and other GLP-1 receptor agonist medications to treat an array of substance use disorders,” explained study author Nora Volkow, the director of the National Institute on Drug Abuse at the National Institutes of Health.
“We wanted to explore this further. With access to a massive database of electronic health record data at our disposal, we looked for noticeable associations in these data between semaglutide use and incidence of cannabis use disorder. What’s exciting about GLP-1 receptor agonist medications is their potential to treat addiction more broadly, meaning they may be able to treat different kinds of addictive disorders, as well as help people with addiction to multiple drugs.”
The study employed a retrospective cohort design, utilizing a large electronic health record database to explore the potential effects of semaglutide on cannabis use disorder. The database, TriNetX, contains de-identified and aggregated medical records from approximately 105.3 million patients across 61 large healthcare organizations in various geographic and demographic contexts.
The researchers focused on two specific groups: patients diagnosed with obesity and those diagnosed with type 2 diabetes. These groups were chosen because semaglutide is prescribed for weight management and diabetes treatment, respectively. The study included patients who were newly prescribed semaglutide or other non-GLP-1 receptor agonist medications for obesity or diabetes from June 2021 to December 2022. The non-GLP-1RA medications served as comparators and included treatments like bupropion and metformin among others.
The researchers found that semaglutide, when compared to non-GLP-1 receptor agonist medications, was associated with a reduced risk of developing new cannabis use disorder cases and a decreased likelihood of cannabis use disorder recurrence among those with a prior history.
For patients with obesity and no prior cannabis use disorder diagnosis, the incidence of cannabis use disorder was 0.28% in the semaglutide group compared to 0.48% in the group treated with other anti-obesity medications. This finding indicates a 44% reduction in the risk of developing cannabis use disorder among semaglutide users, highlighting its potential as a preventative treatment option.
Similarly, among patients with obesity who had previously been diagnosed with cannabis use disorder, semaglutide was effective in reducing the recurrence of the disorder. The rate of cannabis use disorder recurrence was 13.0% in the semaglutide cohort compared to 20.4% in the comparator group, translating to a 38% lower risk with semaglutide treatment.
Among patients with type 2 diabetes, semaglutide again demonstrated a protective effect against both new and recurrent cannabis use disorder. For type 2 diabetes patients without a previous cannabis use disorder diagnosis, the incidence rate of cannabis use disorder was significantly lower in the semaglutide group (0.21%) compared to the non-GLP-1 receptor agonist medication group (0.48%).
For type 2 diabetes patients with a prior history of cannabis use disorder, the findings were consistent with those observed in the obesity group, showing a reduced risk of recurrence though the difference was not statistically significant. This slight variation underscores the complexity of cannabis use disorder management in different patient populations and indicates the need for further research.
“While this study shows the potential of semaglutide to treat cannabis use disorders, this is a retrospective study with many inherent limitations,” Xu told PsyPost. “To support clinical use of semaglutide, randomized clinical trials are necessary.”
“Our study is just one of many needed before we can draw more concrete conclusions, but it shows us that it’s worth exploring semaglutide in the context of cannabis use disorder,” Volkow added.
Despite promising results, the study has some limitations to note. Its retrospective nature and the reliance on existing medical records mean causality cannot be established. The researchers suggest that future studies should include longer follow-up periods and placebo-controlled methodologies to validate and expand upon these findings.
“This study was inherently limited by its retrospective and observational nature, and controlled trials would be the ideal next step to better understand the effects of semaglutide on those with addiction,” Volkow explained. “Double-blind, randomized clinical trials that include large and diverse cohorts are the gold standard for analyzing these types of associations.”
The researchers also hope to untangle the “underlying molecular mechanisms of how semaglutide may target cannabis use disorder,” Xu said.
The study, “Association of semaglutide with reduced incidence and relapse of cannabis use disorder in real-world populations: a retrospective cohort study,” was authored by William Wang, Nora D. Volkow, Nathan A. Berger, Pamela B. Davis, David C. Kaelber, and Rong Xu.
