High-dose THC products linked with adverse mental health outcomes, review shows
Cannabis products with more than 5 mg or 10% delta-9-tetrahydrocannabinol (THC) per serving are associated with risk of psychosis and cannabis use disorder, according to a review of nearly 100 studies and over 200,000 participants.
High-concentration delta-9-tetrahydrocannabinol (THC) cannabis products are associated with unfavorable mental health outcomes, including psychosis, schizophrenia, and cannabis use disorder, a systematic review found.
Researchers assessed 99 studies of 221,097 participants to better understand the association between cannabis products with greater than 5 mg or greater than 10% THC per serving, or labeled as “high-potency concentrate,” “shatter,” or “dab” (high-concentration THC), and anxiety, depression, psychosis or schizophrenia, and cannabis use disorder. Forty included studies were therapeutic, where cannabis was used to treat medical conditions or symptoms. Findings were published by Annals of Internal Medicine on August 26.
Of the included studies, 42% were randomized trials, 47% were observational studies, and 11% were other interventional studies. All were done between 1977 and 2023, and they came from 15 countries. Over 95% of studies had a moderate or high risk of bias.
In nontherapeutic studies, high-concentration THC products showed consistent unfavorable associations with psychosis or schizophrenia (70%) and cannabis use disorder (75%). No therapeutic studies showed favorable results for these outcomes. Fifty-three percent and 41% of nontherapeutic studies reported unfavorable associations for anxiety and depression, respectively, especially among healthy populations. Nearly half of therapeutic studies found benefits for anxiety (47%) and depression (48%); however, 24% and 30% found unfavorable associations, respectively. Almost all studies rated at low risk of bias showed unfavorable results, the researchers found.
The researchers were unable to quantify risk levels or specify THC thresholds at which risk escalates, they noted. Additional limitations to the study include a lack of data on frequency, duration of use, and titration practices.
Overall, the findings “do not provide the evidence needed by clinicians to provide clear answers to questions that they are receiving from patients and their families,” the researchers wrote. However, “there are authoritative conclusions that the risk for adverse consequences increases with THC dose,” they said.
An accompanying editorial reiterated that the review's findings are not definitive. “Although some studies signaled therapeutic benefits for anxiety and depression, occurring particularly among persons with cancer and neurologic conditions, many studies detected that use of high-concentration cannabis products was associated with adverse outcomes, especially among healthy persons,” they wrote.
The editorialists also highlighted limitations of the included studies, such as inconsistent measurement tools, unclear participant representativeness, and limited reporting. In the absence of rigorous research on THC concentrates, “physicians and other health care professionals should educate their patients who use marijuana about the potential harms related to the use of high-concentration cannabis products and that they may not be as safe as traditional plant-based marijuana products,” the editorial concluded.