Exercise-induced brain changes in cannabis use disorder: a longitudinal MRI study of a 12-week supervised HIIT program

OBJECTIVE: Cannabis use disorder (CUD) is highly relapsing and has been associated with structural brain alterations (e.g., white matter and cortical thickness) in pathways and regions critical for a healthy brain. The development of non-abstinence-based interventions is essential for restoring structural alterations in CUD. Physical exercise, particularly aerobic exercise, may promote neuroplastic changes in brain structure. METHODS: In this novel randomised, single-blind, comparator-controlled trial, we recruited 59 individuals with CUD (76% classified with severe CUD; median age = 25 years, 22% female, without requiring abstinence during intervention). They were randomly allocated to receive 12-weeks of 45 min, three times/week of either: (i) High Intensity Interval Training (HIIT) aimed to achieve 80% of participants' maximum heart rate (above the lactate release threshold); or (ii) active control Strength and Resistance training (S&R). The main outcome was brain structural organisation (fractional anisotropy and cortical thickness) measured via advanced diffusion and anatomical MRI scans conducted before and after 12 weeks. RESULTS: The HIIT group showed significant increases in FA in the left uncinate fasciculus (p = 0.012) and cortical thickness in the right pars opercularis of the inferior frontal gyrus (p = 0.016), revealed by time-by-group interaction. These exercise-induced changes in white matter and cortical thickness significantly correlated with total hours spent with heart rates > 80% (r = 0.32, p = 0.027 and r = 0.41, p = 0.001) and the time spent above the lactate release threshold (r = 0.27, p = 0.061 and r = 0.40, p = 0.004). CONCLUSION: Overall, a 12-week HIIT exercise intervention, without requiring abstinence from cannabis consumption, can enhance brain plasticity.