High-frequency repetitive transcranial magnetic stimulation is associated with sustained improvement in cannabis use disorder: a one-year, two-phase, three-arm randomized study.

Aim: High-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) shows promise in treating substance use disorders, but its efficacy for cannabis use disorder (CUD) is less well established. This 12-month, two-phase, three-arm, prospective, open-label study evaluated the short- and long- term effects of high-frequency rTMS over the left DLPFC in individuals with moderate to severe CUD across three treatment schedules. Methods: In the "active rTMS phase", 18 participants (12 men, mean age 24.89) were first randomized in a 1:1:1 ratio to receive 20 rTMS sessions with 2400 pulses of 15 Hz per session over three treatment schedules for 2, 4, or 5 weeks. All participants then entered a 12-month observational "maintenance phase" without further active rTMS treatments. Outcome assessments included Severity of Dependence Scale (SDS) score, MCQ-SF, CUD severity, frequency of use, abstinence, and CPQ at baseline, post-treatment, and at 3, 6, and 12 months. Results: All rTMS sessions were well tolerated with no significant adverse events. Across all groups, rTMS was associated with improved psychological dependence and reduced craving, DSM-5 defined CUD severity, use frequency, and related problems over 12 months (all Conclusions: These findings provide support for the safety and the potential short- and long-term treatment effects associated with high-frequency rTMS over the DLPFC for reducing cannabis dependence and severity of CUD. Further large-scale studies are needed to differentiate the optimal treatment scheduling when using rTMS for CUD. This study was registered at clinicaltrials.gov (NCT05292547). Clinical Trial Registration: clinicaltrials.gov, identifier NCT05292547.