High concentration THC associated with schizophrenia, psychosis, and other unfavorable mental health outcomes

Embargoed for release until 5:00 p.m. ET on Monday 25 August 2025   

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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.   
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1. High concentration THC associated with schizophrenia, psychosis, and other unfavorable mental health outcomes

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-03819

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-02585

Summary for Patients: https://www.acpjournals.org/doi/10.7326/ANNALS-24-03819-PS

URL goes live when the embargo lifts             

A systematic review analyzed associations of high-concentration delta-9-tetrahydrocannabinol (THC) cannabis products with mental health outcomes. The review found that high-concentration THC products are associated with unfavorable mental health outcomes, particularly for psychosis or schizophrenia and cannabis use disorder (CUD). However, there are limitations to currently available evidence and the researchers call for studies with improved designs to provide more accurate guidance for clinicians and the public. The review is published in Annals of Internal Medicine.  

Researchers from University of Colorado Anschutz Medical Campus and colleagues analyzed 99 studies comprising 221,097 participants completed between 1977 and 2023. Study selection was intentionally broad and included studies examining associations between high-concentration cannabis products and mental health outcomes regardless of whether the study had the purpose of evaluating therapeutic effects. High-concentration cannabis products were defined as having THC concentration exceeding 5 mg THC or 10% THC per serving or products described as “high-potency concentrate,” “shatter,” or “dab.” The mental health outcomes of interest included anxiety, depression, psychosis, schizophrenia, CUD and other substance use disorders. The researchers defined acute effects (within 12 hours), post-acute effects (after consistent use for 1 to 2 months), and long-term effects (after consistent use for > 1 year). In studies not testing for therapeutic effects, high concentration THC products were associated with psychosis, schizophrenia, and cannabis use disorder. No therapeutic studies found favorable effects on psychosis or schizophrenia. Of non-therapeutic studies, 53% identified unfavorable associations with anxiety and 41% found unfavorable associations with depression. Among therapeutic studies, some suggested beneficial effects for anxiety (47%) and depression (48%), while others suggested unfavorable effects (24% for anxiety and 30% for depression).  The findings reinforce previous conclusions that higher THC concentrations increase the risk for adverse mental health outcomes; however, they fall short of providing the definitive evidence needed to provide clear advice to patients.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Jonathan M. Samet, MD, MS, please email Jon.Samet@cuanschutz.edu. 

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2. Mediterranean diet combined with physical activity and weight loss cuts diabetes risk by 31%

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00388

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-02748

Summary for Patients: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00388-PS   

URL goes live when the embargo lifts             

A secondary outcome analysis of a randomized controlled trial evaluated whether an energy-reduced Mediterranean Diet (erMedDiet) plus physical activity reduced diabetes incidence compared to a standard MedDiet in adults with overweight or obesity and metabolic syndrome. The study found that following a MedDiet with caloric reduction, physical activity and modest weight loss was more effective at reducing diabetes incidence than an ad libitum MedDiet. The study is published in Annals of Internal Medicine. 

Researchers from Centro de Investigación Biomédica en Red (CIBER) in collaboration with different Institutes of health research and Universities from Spain conducted a secondary outcome analysis of the PREDIMED-Plus trial, a multicenter, randomized, parallel-group, single-blind, lifestyle intervention trial aiming to assess the effects of a weight-loss intervention with an erMedDiet and increased physical activity (intervention group) versus a control MedDiet group for primary cardiovascular prevention. Diabetes incidence was a predefined secondary endpoint of the PREDIMED-Plus trial. Participants in this analysis included 4,746 adults aged 55 – 75 years with overweight or obesity, without document cardiovascular disease or diabetes at baseline, and with metabolic syndrome. Participants were randomly allocated 1:1 to one of the study arms. Participants in the intervention group were instructed to follow an erMedDiet with physical activity recommendations and behavioral support for weight loss. The control group received educational sessions on the traditional MedDiet with ad libitum caloric intake following the PREDIMED-1 trial recommendations. Both groups received 1 L per month of extra-virgin olive oil to support adherence and retention. Diabetes incidence was assessed yearly for seven years of follow-up, with the American Diabetes Association criteria being used to ascertain incident diabetes. After 6 years, the adjusted absolute risk difference for incident diabetes between the intervention and control groups was −2.4% (95% CI, −3.1 to −1.8), corresponding to a 31% (CI, 18% to 41%) relative risk reduction in the intervention group as compared with the control group. This reduction was consistent across subgroups of age, education, and baseline metabolic status, with a greater effect observed in men than women. The results indicate that the MedDiet could be a beneficial dietary strategy plan for diabetes prevention, especially when combined with moderately reduced energy intake and physical activity. This multicomponent lifestyle modification represents a practical and sustainable strategy that could be incorporated into routine clinical practice for diabetes prevention. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Jordi Salas-Salvadó, MD, PhD, please email Begoña Navarro at comunicacion@ciberisciii.es.

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3. Study suggests large amount of unnecessary testing for long term toxicity monitoring in patients with rheumatoid arthritis

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-01598

URL goes live when the embargo lifts             

A retrospective cohort study determined the cumulative probabilities of abnormal and very abnormal of long-term routine laboratory toxicity monitoring (lt-RLTM) test results in patients with rheumatoid arthritis (RA) using disease-modifying antirheumatic drugs (DMARDs). The study also aimed to characterize the clinical context for the incidence of new very abnormal results. The study found that very abnormal lt-RLTM results are uncommon in patients using long-term DMARD treatment, and most were already clinically anticipated and often occurred after dose escalation. The results suggest that strategies for lt-RLTM warrant reconsideration. The study is published in Annals of Internal Medicine.

Researchers from the rheumatology department of the Sint Maartenskliniek in The Netherlands studied data from 4,774 patients with RA undergoing lt-RLTM after at least six months of DMARD use between July 2008 to April 2020. Routine laboratory toxicity monitoring was conducted in all patients at weeks 4, 8, 12, and 24 after the start of DMARD treatment, followed by lt-RLTM every 3 to 6 months. The DMARDs included in this study consisted of regularly used csDMARDs (methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, and azathioprine) and bDMARDs (adalimumab, certolizumab, etanercept, golimumab, infliximab, abatacept, rituximab, sarilumab, tocilizumab, and anakinra). The test set included 5 laboratory parameters: alanine aminotransferase (ALT), estimated glomerular filtration rate (eGFR), hemoglobin (Hb), leukocyte count, and platelet count. Results were categorized as abnormal and very abnormal, with cutoffs based on guidelines, clinical treatment recommendations, or expert opinion. The primary outcome was the cumulative incidence of new abnormal or very abnormal lt-RLTM results at 2 and 5 years after initiation of individual or combination DMARD therapy, calculated overall and by drug type or combination. The researchers found that among 297,775 lt-RLTM tests during the study period, 17,343 (5.8%) results were abnormal, and 2,064 (0.69%) results were very abnormal. Abnormal results obtained during the first 6 months of use of an individual DMARD or combination therapy were rare for ALT, leukocyte count, and platelet count, occurring in 0.9% to 1.3% of patient–DMARD exposure periods, and were slightly more common for eGFR (5.3%) and Hb (12%). Very abnormal results during the first 6 months of DMARD use were rare. A considerable proportion of abnormalities were judged to be unrelated to DMARD use, and the main causes of new very abnormal results included renal and urinary disorders unrelated to DMARD use. The results suggest that the practice of performing frequent lt-RLTM in all patients with RA using DMARDs should be reconsidered, as the findings call into question the value of nontargeted monitoring.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Evy Ulijn, MD, MSc please email e.ulijn@maartenskliniek.nl.

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