High-Intensity Exercise and Hippocampal Integrity in Adults With Cannabis Use Disorder: A Randomized Clinical Trial.

Importance: Cannabis is the most commonly used illicit drug, with 10% to 30% of regular users developing cannabis use disorder (CUD), a condition linked to altered hippocampal integrity. Evidence suggests high-intensity interval training (HIIT) enhances hippocampal structure and function, with this form of physical exercise potentially mitigating CUD-related cognitive and mental health impairments.

Objective: To determine the impact of a 12-week HIIT intervention on hippocampal integrity (ie, structure, connectivity, biochemistry) compared with 12 weeks of strength and resistance (SR) training in CUD.

Design, Setting, And Participants: This randomized, single-blind, comparator-controlled clinical trial (Brain Exercise and Addiction Trial [BEAT]) assessed the efficacy of a 12-week exercise intervention for improving hippocampal integrity. Participants were adults with moderate to severe CUD and were not required to cease cannabis consumption. In-person assessments and interventions were conducted at Monash University's BrainPark facility (Melbourne, Australia). The trial was conducted from 2018 to 2022 and the data analysis from September 2022 to February 2023.

Intervention: HIIT (3 times a week, high lactate condition) for 12 weeks, compared with 12 weeks of SR (3 times a week, low lactate, active control condition) to 12 weeks. Exercise interventions were supervised by exercise physiologists and tailored to target specific (lactate) and personalized physiological mechanisms.

Main Outcomes And Measures: The primary outcome was hippocampal integrity as indicated by a composite of 3 magnetic resonance imaging (MRI) measures: anatomical volume, fractional anisotropy, and N-acetylaspartate. Secondary outcomes included cognitive and mental health measures. Outcomes were assessed at baseline and at the end of the intervention. Adverse events were tracked throughout participation.

Results: Fifty-nine participants with moderate to severe CUD were randomized 1:1 to receive HIIT or SR. The mean (SD) age was 27.0 (6.3) years (range, 20-53 years); 47 participants (80%) were male and 12 (20%) female. Overall, 47 participants (80%) completed the 12-week intervention, attending a mean of 29 of 36 exercise sessions (80%). Hippocampal integrity did not increase after 12 weeks of HIIT (estimated marginal means [SE], -0.14 [0.43] at baseline; 0.10 [0.45] after intervention) or SR (0.38 [0.37] at baseline; -0.16 [0.37] after intervention).

Conclusions And Relevance: This trial found that a 12-week HIIT intervention did not improve hippocampal integrity or associated cognitive or mental health impairments while people continued to consume cannabis. However, results indicated that people with CUD can engage in regular physical exercise programs and highlighted exercise as a potential strategy to reduce cannabis craving.

Trial Registration: ClinicalTrials.gov Identifier: NCT04902092.