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High-frequency rTMS over left DLPFC associated with reduced cannabis dependence and severity in small CUD study

High-frequency rTMS over left DLPFC associated with reduced cannabis dependence and severity in smal…
Photo by Logan Voss / Unsplash
Key Takeaway
Consider rTMS over left DLPFC as a potential experimental approach for CUD, but efficacy requires confirmation in larger trials.

This open-label randomized study examined the short- and long-term effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) in 18 participants (12 men, mean age 24.89 years) with moderate to severe cannabis use disorder (CUD). Participants were randomized to receive the same rTMS intervention across three different treatment schedules: 2, 4, or 5 weeks, with outcomes assessed over 12 months of follow-up.

High-frequency rTMS was associated with improvements across multiple secondary outcomes over the 12-month period. Psychological dependence (measured by SDS), craving (MCQ-SF), DSM-5 defined CUD severity, frequency of cannabis use, and cannabis-related problems all showed statistically significant improvement (all p < 0.05), with effect sizes (Hedge's g) ranging from -1.86 to -0.76. However, no consistent differences were observed between the three treatment schedules in terms of clinical outcomes.

Regarding safety, all rTMS sessions were well tolerated with no significant adverse events reported. The study's key limitation is its small sample size of 18 participants and its open-label design, which limits causal inference. The authors explicitly note that further large-scale studies are needed to differentiate optimal treatment scheduling and confirm these preliminary findings.

For clinical practice, this study provides preliminary support for the safety and potential long-term treatment effects associated with high-frequency rTMS over the DLPFC for reducing cannabis dependence and CUD severity. However, given the small sample, open-label design, and lack of a sham control, these findings should be interpreted cautiously as hypothesis-generating rather than establishing efficacy.

Study Details

Study typeCohort
EvidenceLevel 3
PublishedMar 2026
View Original Abstract ↓
AimHigh-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.MethodsIn 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.ResultsAll 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 ps < 0.05, hedge’s g ranged -1.86 – -0.76). No consistent differences were observed between the three schedules.ConclusionsThese 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 Registrationclinicaltrials.gov, identifier NCT05292547.
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