Repetitive Transcranial Magnetic Stimulation for Cannabis Use Disorder

Development of a Novel, Scalable, Neurobiologically-Guided Transcranial Magnetic Stimulation Protocol for the Treatment of Cannabis Use Disorder

There has been a considerable rise in cannabis consumption in recent years, with estimates of 200 million individual users globally. Importantly, 3% of these individuals have cannabis use disorder (CUD), with this prevalence increasing to 33% amongst regular users, making it one of the most common substances use disorders (SUDs) worldwide. CUD is associated with substantial health, societal, and economic costs, and worsening of other psychiatric disorders. Despite this clinical burden, effective treatment options are limited. No pharmacological treatments have emerged as clearly efficacious, and psychotherapeutic interventions have shown tempered results.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain-based approach in which alternating magnetic fields are applied to the scalp to induce electrical currents in cortical tissue. As it can modulate neural circuits implicated in neuropsychiatric disorders, it is a promising brain-based approach in the treatment of addictions. Evidence has indicated its efficacy in reducing drug craving and consumption across numerous SUDs, although research into cannabis has been largely unexplored. Recently, a novel circular rTMS coil, the MagVenture MMC-140, has been developed with the capacity to modulate both the bilateral prefrontal cortex (PFC) and insula, both of which are implicated in the neurocircuitry of craving and executive function. As such, it shows potential for CUD treatment.

This proof-of-concept clinical trial will evaluate the feasibility and tolerability of a 4-week course of rTMS to the PFC/insula using MMC-140 as a treatment for CUD. Feasibility of both high frequency (HF; excitatory) and low frequency (LF; inhibitory) stimulation parameters will be evaluated. In addition, pre/post rTMS changes in cannabis use outcomes (e.g., consumption, craving, and withdrawal), executive function, and PFC/insula functional connectivity will be explored. By comprehensively investigating clinical, cognitive, and neuroimaging effects of rTMS, this study could pave the way for the first brain-based intervention in CUD that could be widely adopted into clinical settings using a novel, cost-effective and accessible rTMS device.

Inclusion Criteria:

1. Must be deemed to have capacity to provide informed consent
2. Age between 18 to 65
3. Diagnosis of cannabis use disorder according to the DSM-5 and the Structured Clinical Interview for DSM-5 (SCID for DSM-541)
4. Report cannabis as the primary drug of concern, a frequent pattern of use (≥5 days per week), and a goal of reduction or abstinence of cannabis use
5. CUDIT-R score ≥12
6. Marijuana Contemplation Ladder ≥7
7. Cannabis positive urine drug screen, with Narcochek baseline THC-COOH level of >150 ng/ml.
8. On a stable regimen of their psychotropic medications for 14 days before enrolment.

Exclusion Criteria:

1. Pregnant or intending to be pregnant during the study
2. Diagnosis of bipolar disorder, schizophrenia spectrum disorder, or other active concurrent psychiatric disorder that is too unstable and may preclude safe participation in the trial as deemed by the PI.
3. Substance use disorder other than cannabis or nicotine, that is of moderate severity or greater, or is the primary substance of concern based on the SCID for DSM-5
4. Known active seizure disorder, significant head injury with an imaging verified lesion
5. Unstable medical illness
6. Presence of cardiac pacemaker, intracranial implant, or metal in the cranium
7. Participants taking > 2 mg lorazepam (or a benzodiazepine at an equivalent dose) or taking any anticonvulsant medication during treatment.