Associations between Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) and Cannabis Use: A Scoping Review

Background and Purpose: Globally, cannabis is the most widely used drug, and frequent use increases the risk of cannabis use disorder (CUD). The move toward federal legalization of recreational cannabis use draws nearer in the U.S. as legalization becomes more common at the state level. Despite the increased potential for legal cannabis use, there are currently no FDA-approved medications for CUD treatment, emphasizing the need for research into new pharmaceutical therapies. Emerging research suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of medications traditionally used for type 2 diabetes mellitus (T2DM) and obesity, may reduce the use of substances like alcohol and nicotine. However, potential effects of GLP-1RAs on cannabis use behavior are relatively unexplored. To address this gap, we conducted a scoping review to identify and map studies assessing the use of GLP-1RAs to address cannabis use patterns in human and animal models.

Methods: Articles published in English, regardless of publication year, were identified using pre-specified Boolean search terms (e.g., including but not limited to “glp-1” AND “cannabis” OR “marijuana”) in Academic Search Complete, APA PsycInfo, Psychology and Behavioral Sciences Collection, SocINDEX with Full Text via EBSCOHost, Article First, PubMed, WorldCat, Google Scholar, and ProQuest Dissertations for gray literature. Following duplicate removal, 1,492 articles were imported into Covidence for screening, and 40 articles were considered under full-text review. A total of 2 articles met all eligibility criteria, and we extracted data on each study’s purpose, design, participant characteristics, intervention(s), outcomes, and results. Findings were reported following PRISMA-ScR guidelines.

Results: Both studies used retrospective cohort designs to analyze U.S. electronic health record data. In particular, the studies examined the association between semaglutide, a commonly prescribed GLP-1RA, and cannabis misuse and disorder. While one study found a significant reduction in CUD among adults with obesity and a significantly reduced risk of CUD in adults with T2DM, the second study found no significant reduction in cannabis misuse risk associated with semaglutide among adults with T2DM when compared to three non-GLP-1RA antidiabetic medications.

Conclusions and Implications: Although there is emerging evidence of potential associations between GLP-1RAs—specifically semaglutide—and cannabis misuse and disorder, our scoping review highlights the gap in knowledge on the use of GLP-1RAs to address an array of cannabis use patterns, including those that are non-disordered. There is a need for future research to explore these associations with greater nuance and clarity. For instance, both studies only included adults with T2DM and/or obesity who were prescribed semaglutide, excluding other widely used GLP-1RAs and individuals without either condition who were also eligible for these medications. As GLP-1RAs become increasingly affordable and accessible to a wider range of populations, it is critical that the social work profession understand their potential effects on cannabis use, as well as the broader context of substance use treatment and care. Future research may also assess outcomes such as frequency of and motivations for use to inform broader GLP-1RA applications related to cannabis.