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 E. Hutchison, Jonathan Samet, Tianjing Li
Annals of Internal Medicine October 1, 2025 DOI: 10.7326/annals-24-03819 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Sample size | 221,097 |
| Population | Participants in studies of high-concentration THC cannabis products |
| Topics | Cannabis |
| Citations | 12 |
| Key findings | High-concentration THC products are consistently associated with unfavorable mental health outcomes, particularly psychosis or schizophrenia and cannabis use disorder. |
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.
Comparable studies
Other systematic reviews and meta-analyses on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of cannabis use on outcomes of psychotic disorders: systematic review People with psychotic disorders, as examined in 13 longitudinal studies | 2008 | Systematic review | |
| The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample Patients with established schizophrenia (meta-analysis: 572) and patients with... | 2010 | Meta-analysis and cross-sectional observational study | n = 700 |
| Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review | 2020 | Systematic review | |
| Neuroimaging in cannabis use: a systematic review of the literature Cannabis users and controls in neuroimaging studies | 2009 | Systematic review | |
| Human Laboratory Studies on Cannabinoids and Psychosis. Healthy human subjects and individuals with schizophrenia | 2016 | Systematic review |
Citations in the library
Cited by 3
- Cannabis, psychosis, and violence: case reports and comprehensive evidence review Frontiers in Psychiatry July 21, 2026
- Cannabis and Mental Health: A Review. JAMA Internal Medicine May 1, 2026
- THE INFLUENCE OF CANNABIS ON THE DEVELOPMENT OF SCHIZOPHRENIA - A REVIEW International Journal of Innovative Technologies in Social Science March 27, 2026
Cites 32
- Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Current Pharmaceutical Design September 12, 2012
- The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial PLoS One March 17, 2021
- Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males Translational Psychiatry November 29, 2016
- The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double‐blind, placebo‐controlled, crossover experiment Addiction February 8, 2023
- Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence Psychological Medicine April 28, 2020
and 27 more in the library