Summary: A comprehensive systematic review of 99 studies involving 221,097 participants found that high-concentration delta-9-tetrahydrocannabinol (THC) cannabis products are linked to negative mental health outcomes, most notably psychosis, schizophrenia, and cannabis use disorder (CUD). While some clinical studies suggested possible benefits for anxiety and depression, those findings were inconsistent and of low quality. Overall, the evidence points to greater mental health risks with higher THC concentrations, and investigators call for stronger, better-designed research to guide clinicians and the public.
The review evaluated a wide range of study designs published between 1977 and 2023 and deliberately included both studies that tested therapeutic effects and observational research examining associations. Researchers defined high-concentration THC products as those containing more than 5 mg THC per serving or exceeding 10% THC by weight per serving, or products specifically labeled as “high-potency concentrate,” “shatter,” or “dab.”
Key Facts
- Psychosis and Schizophrenia: High-THC products were consistently linked to increased risk of psychotic symptoms and schizophrenia, particularly in studies not intended to test therapeutic use.
- Cannabis Use Disorder (CUD): Associations with CUD were common, with a substantial portion of studies reporting unfavorable outcomes.
- Anxiety and Depression: Non-therapeutic studies more often reported adverse associations for anxiety (53%) and depression (41%). Therapeutic trials produced mixed results—almost half reported benefit for anxiety (47%) and depression (48%), while a meaningful minority showed harm.
- Quality and Consistency: More than 95% of included studies carried moderate or high risk of bias, and contemporary high-potency products were underrepresented, limiting certainty.
Source: American College of Physicians
The systematic review appears in the journal Annals of Internal Medicine. Investigators from the University of Colorado Anschutz Medical Campus and collaborating institutions screened multiple databases through mid-2025 to identify studies that reported mental health outcomes after exposure to high-concentration THC products. Mental health outcomes assessed included anxiety, depression, psychosis or schizophrenia, cannabis use disorder, and other substance use disorders.
To organize findings by timing, reviewers categorized effects as acute (within 12 hours), post-acute (after consistent use for one to two months), and long-term (after consistent use for more than one year). They also separated studies intended to evaluate therapeutic effects from observational and other non-therapeutic research.
Across studies that did not test cannabis as a therapy, high-THC products showed a robust and consistent pattern of unfavorable associations with psychotic outcomes (reported in roughly 70% of such studies) and with CUD (around 75%). In contrast, no therapeutic trial reported favorable effects on psychosis or schizophrenia. For mood and anxiety symptoms, results differed by study purpose and population: observational studies often found adverse associations for anxiety and depression, while nearly half of therapeutic trials reported symptom improvement—yet many of those trials were small or otherwise limited.
The authors emphasize that heterogeneity in product types, dosing, participant characteristics, and study designs, along with frequent methodological limitations, reduces confidence in causal conclusions. Contemporary high-potency formulations common in legal markets were not extensively evaluated in many older studies, which further constrains applicability to present-day products.
About this psychosis and THC research news
Author: Angela Collom
Source: American College of Physicians
Contact: Angela Collom – American College of Physicians
Image: The image is credited to Neuroscience News
Original Research: Closed access. “High-Concentration Delta-9-Tetrahydrocannabinol Cannabis Products and Mental Health Outcomes: A Systematic Review” by Jonathan M. Samet et al., Annals of Internal Medicine (DOI: 10.7326/ANNALS-24-03819)
Abstract
High-Concentration Delta-9-Tetrahydrocannabinol Cannabis Products and Mental Health Outcomes: A Systematic Review
Background:
The legalized cannabis marketplace has rapidly shifted toward products with higher concentrations of delta-9-tetrahydrocannabinol (THC), prompting concern about mental health consequences across populations.
Purpose:
To systematically evaluate associations between high-concentration THC cannabis products and mental health outcomes including anxiety, depression, psychosis or schizophrenia, and cannabis use disorder (CUD).
Data Sources:
Searches included Ovid MEDLINE through May 2025 and EMBASE, Allied and Complementary Medicine Database, Cochrane Library, Database of Abstracts of Reviews of Effects, CINAHL, and Toxicology Literature Online through August 2024.
Study Selection:
Two independent reviewers selected studies that met the high-concentration THC definition (greater than 5 mg THC or greater than 10% THC per serving, or products labeled as “high-potency concentrate,” “shatter,” or “dab”). Both therapeutic and non-therapeutic studies were included.
Data Extraction:
Reviewers extracted outcomes related to anxiety, depression, psychosis or schizophrenia, and CUD, classifying results by whether associations were favorable, unfavorable, or mixed and by study characteristics, including whether cannabis was used therapeutically.
Data Synthesis:
Ninety-nine studies (221,097 participants) met inclusion criteria: randomized trials (42%), observational studies (47%), and other interventional designs (11%). Most individual studies had moderate to high risk of bias. In non-therapeutic research, the majority of studies reported unfavorable associations for psychosis or schizophrenia (70%) and for CUD (75%). For anxiety and depression, non-therapeutic studies reported unfavorable associations in 53% and 41% of cases, respectively. Therapeutic studies were mixed—approximately half reported improvements in anxiety and depression, but a notable share reported harms.
Limitation:
The body of evidence is limited by moderate to high risk of bias across most studies and incomplete assessment of modern high-potency products commonly available today.
Conclusion:
High-concentration THC cannabis products are associated with unfavorable mental health outcomes, particularly psychosis or schizophrenia and cannabis use disorder. Available evidence for therapeutic benefit in anxiety and depression is inconsistent and generally low quality, underscoring the need for rigorous, contemporary research to inform clinical guidance.
Primary Funding Source:
Colorado General Assembly, House Bill 21-1317.