Repetitive Transcranial Magnetic Stimulation for Cannabis Use Disorder
ConditionCannabis Use Disorder
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorCentre for Addiction and Mental Health
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Must be deemed to have capacity to provide informed consent
Age between 18 to 65
Diagnosis of cannabis use disorder according to the DSM-5 and the Structured Clinical Interview for DSM-5 (SCID for DSM-541)
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
Disqualifiers
Pregnant or intending to be pregnant during the study
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.
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
Known active seizure disorder, significant head injury with an imaging verified lesion
Trial design
Design model
Parallel
Treatments tested in this trial
Repetitive Transcranial Magnetic Stimulation
DevicerTMS is a non-invasive neuromodulatory technique that applies alternating magnetic fields to the scalp to induce electric currents in localized cortical tissue. The intervention (LF or HF rTMS) will be administered daily 5 days/week for 4 weeks, using the MagVenture MMC-140 circular coil, with the brain regions targeted as the bilateral prefrontal cortex and the insula.
Treatment groups
46 Participants
are divided into 2 treatment groupsGroup A: High-Frequency (HF)Active comparator 1 intervention
Group B: Low-Frequency (LF)Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
Feasibility of study completion as assessed by completion rates
Feasibility is determined by completion of the study and all associated study assessments, without withdrawing or being withdrawn from the study. Withdrawal from the study can be dropping out for any reason, including intolerability, serious adverse events, or inability to adhere to study procedures.
Time frame
The timeframe is through study completion, beginning from baseline to end of rTMS treatment week 4, an average of 8 weeks, the event determined by withdrawal from the study.2
Tolerability of Intervention as assessed by adverse event reporting
This will be assessed through a side effect report at each treatment session. Safety monitoring will be implemented through the documentation and monitoring of adverse events (AEs) and serious adverse events (SAEs) using incidence tables by severity, relationship to treatment and baseline parameters.
Time frame
The timeframe is through study completion, beginning from baseline to end of rTMS treatment week 4, an average of 8 weeks. The events being counts of adverse events or serious adverse events.Secondary outcomes
1
Cannabis Use
Determined through self-report on the Timeline Followback (TLFB). Endpoints of interest will include percentage of days per week using cannabis, number of use sessions per day, 7-day point prevalence abstinence. Semi-quantitative analysis of cannabis use will be obtained through a THC Pre-Dosage Test (Narcocheck ®, Villejuif, France) to confirm.
Time frame
Baseline (pre-rTMS), Weekly (end of each week of rTMS), Follow-up (4-weeks post-rTMS), up to a total time frame of 8 weeks. Events are counted as self reported instances of cannabis use on the Timeline Followback.2
Cannabis Craving
Changes in cannabis craving assessed through the Marijuana Craving Questionnaire (MCQ). Minimum score is 3 and maximum score is 84. Higher scores indicate greater cannabis craving (worse outcome).
Time frame
Baseline (pre-rTMS), Weekly (end of each week of rTMS), an average of 8 weeks from baseline assessment to end of rTMS, Follow-up (4-weeks post-rTMS),3
Cannabis Withdrawal
Changes in cannabis withdrawal symptoms assessed through the Marijuana Withdrawal Checklist (MWC)
Time frame
Baseline (pre-rTMS), Weekly (end of each week of rTMS), an average of 8 weeks from baseline assessment to end of rTMS, Follow-up (4-weeks post-rTMS),4
Prefrontal cortex and Insula Connectivity
Assessed by seed-based resting state connectivity on functional magnetic resonance imaging (fMRI). Seeds are defined as the medial prefrontal cortex, dorsolateral prefrontal cortex, and the insula. Measurement will be of change in strength of connectivity between these seeds pre- to post-rTMS, and comparing between groups (high or low frequency stimulation).
Time frame
Baseline (pre-rTMS), End of rTMS (end of treatment week 4 of rTMS)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Centre for Addiction and Mental Health
Lead sponsor
Brain & Behavior Research Foundation
Collaborator
Source ClinicalTrials.gov