Major Review: High-THC Cannabis Products Tied to Psychosis and Addiction, Mixed Results for Anxiety and Depression | Research

The takeaway

Across 99 studies and 221,000 participants, high-concentration THC products showed consistently unfavorable associations with psychosis and cannabis use disorder, while evidence for anxiety and depression was mixed depending on whether use was therapeutic or recreational.

Cannabis consumers choosing between product potencies; policymakers considering THC concentration limits; clinicians advising patients on cannabis risks

99 studies, 221,097 participants reviewed

What the researchers found

In non-therapeutic studies, high-concentration THC showed unfavorable associations with psychosis/schizophrenia (70% of studies) and cannabis use disorder (75%). For anxiety, 53% of non-therapeutic studies found unfavorable associations, while 47% of therapeutic studies found benefits. For depression, 41% non-therapeutic studies were unfavorable while 48% of therapeutic studies showed benefits. No therapeutic studies reported favorable results for psychosis.

Why it matters

As legalized cannabis markets increasingly feature high-potency products, this landmark review provides the clearest picture yet of mental health risks. The distinction between therapeutic and recreational use reveals an important nuance: context matters for whether high-THC products help or harm.

The numbers in context

99 studies; 221,097 participants; 70% showed unfavorable psychosis associations; 75% showed unfavorable CUD associations; 47% therapeutic benefit for anxiety; 48% therapeutic benefit for depression; >95% of studies had moderate or high risk of bias

How the study worked

Systematic review searching MEDLINE through May 2025 plus five additional databases through August 2024. High-concentration THC defined as >5mg or >10% THC per serving, or labeled as concentrate/shatter/dab. 99 studies (221,097 participants) including 42% RCTs, 47% observational, 11% other interventional. Published in Annals of Internal Medicine.

What this study cannot tell us

Over 95% of included studies had moderate or high risk of bias. Limited evaluation of contemporary products (concentrates, vapes). Definition of "high concentration" varied across studies. Cannot establish causation from observational studies.

How to read the evidence

Large-scale systematic review published in a top-tier medical journal, though over 95% of included studies had moderate or high risk of bias.

When this study was published

Published in 2025 with searches through May 2025.

The bigger picture

This is one of the most comprehensive reviews to date on high-potency cannabis and mental health. Its publication in Annals of Internal Medicine signals mainstream medicine taking the potency question seriously. The therapeutic vs. non-therapeutic distinction could reshape how we think about cannabis regulation.

Questions still open

Should cannabis regulations include THC concentration caps? At what potency threshold do mental health risks increase sharply? Why do therapeutic and non-therapeutic contexts produce different anxiety and depression outcomes?

Common questions

Are high-THC products more dangerous than lower-potency cannabis?

This review found consistently unfavorable associations between high-THC products and psychosis (70% of studies) and cannabis use disorder (75%). The evidence is strongest for these two outcomes.

Can high-THC cannabis help with anxiety or depression?

The results were mixed. In therapeutic contexts (using cannabis to treat a condition), about half of studies found benefits for anxiety and depression. In non-therapeutic use, unfavorable associations were more common.

What counts as high-concentration THC?

The review defined it as more than 5mg or more than 10% THC per serving, or products labeled as concentrates, shatter, or dab. Many products in legal markets exceed these thresholds.

Read the original research

High-Concentration Delta-9-Tetrahydrocannabinol Cannabis Products and Mental Health Outcomes : A Systematic Review.

Annals of internal medicine, 178(10), 1429-1440

View on PubMed ↗Publisher’s paper ↗

Citation

Rittiphairoj, Thanitsara; Leslie, Louis; Oberste, Jean-Pierre; Yim, Tsz Wing; Tung, Gregory; Bero, Lisa; Riggs, Paula; Hutchison, Kent; Samet, Jonathan; Li, Tianjing. (2025). High-Concentration Delta-9-Tetrahydrocannabinol Cannabis Products and Mental Health Outcomes : A Systematic Review.. Annals of internal medicine, 178(10), 1429-1440. https://doi.org/10.7326/ANNALS-24-03819