High-Concentration Delta-9-Tetrahydrocannabinol Cannabis Products and Mental Health Outcomes : A Systematic Review.
Thanitsara Rittiphairoj, Louis Leslie, Jean-pierre Oberste, Tsz Wing Yim, Gregory Tung, Lisa Bero, Paula Riggs, Kent Hutchison, Jonathan Samet, Tianjing Li
Annals of internal medicine October 1, 2025 Peer reviewed DOI: 10.7326/annals-24-03819 via PubMed
Summary
High-concentration THC cannabis products are consistently associated with unfavorable mental health outcomes, especially psychosis or schizophrenia (70% of studies) and cannabis use disorder (75% of studies). For anxiety and depression, over half of non-therapeutic studies reported unfavorable associations, particularly in healthy populations. Among therapeutic studies, nearly half found benefits for anxiety (47%) and depression (48%), though some also found unfavorable associations. Evidence quality was limited, with over 95% of the 99 studies (221,097 participants) having moderate or high risk of bias.
Study at a glance
| Design | systematic review |
|---|---|
| Sample size | 221,097 |
| Population | participants in studies of high-concentration THC cannabis products |
| Key finding | High-concentration THC products are associated with unfavorable mental health outcomes, particularly for psychosis or schizophrenia and cannabis use disorder, with some low-quality evidence for therapeutic benefits for anxiety and depression. |
Abstract
Rapid changes in the legalized cannabis market have led to the predominance of high-concentration delta-9-tetrahydrocannabinol (THC) cannabis products. To systematically review associations of high-concentration THC cannabis products with mental health outcomes. Ovid MEDLINE through May 2025; EMBASE, Allied and Complementary Medicine Database, Cochrane Library, Database of Abstracts of Reviews of Effects, CINAHL, and Toxicology Literature Online through August 2024. Two reviewers independently selected studies with high-concentration THC defined as greater than 5 mg or greater than 10% THC per serving or labeled as "high-potency concentrate," "shatter," or "dab." Outcomes included anxiety, depression, psychosis or schizophrenia, and cannabis use disorder (CUD). Results were categorized by association direction and by study characteristics. Therapeutic studies were defined by use of cannabis to treat medical conditions or symptoms. Ninety-nine studies (221 097 participants) were included: randomized trials (42%), observational studies (47%), and other interventional study designs (11%); more than 95% had moderate or high risk of bias. In studies not testing for therapeutic effects, high-concentration THC products showed consistent unfavorable associations with psychosis or schizophrenia (70%) and CUD (75%). No therapeutic studies reported favorable results for psychosis or schizophrenia. For anxiety and depression, 53% and 41% of nontherapeutic studies, respectively, reported unfavorable associations, especially among healthy populations. Among therapeutic studies, nearly half found benefits for anxiety (47%) and depression (48%), although some also found unfavorable associations (24% and 30%, respectively). Moderate and high risk of bias of individual studies and limited evaluation of contemporary products. High-concentration THC products are associated with unfavorable mental health outcomes, particularly for psychosis or schizophrenia and CUD. There was some low-quality evidence, inconsistent by population, for therapeutic benefits for anxiety and depression. Colorado General Assembly, House Bill 21-1317.