Deep Repetitive Transcranial Magnetic Stimulation for Cannabis Use Disorder

Study Overview
=================
Brief Summary
-----------------
There is a credible basis for lateral prefrontal cortex and insula deep repetitive transcranial magnetic stimulation (dTMS) stimulation as a treatment for cannabis use disorder (CUD), but no studies to date have examined this. Evidence of benefit could expand the treatment options available for CUD but require randomized controlled trials (RCTs) to evaluate its efficacy. Toward an RCT of this intervention, the proposed study is a phase 1 open-label pilot trial of dTMS for adults with CUD. This study will establish the viability of an H4 protocol constituting an active arm of a future double-blind RCT.

Detailed Description
-----------------
Deep repetitive transcranial magnetic stimulation (dTMS) is a technique that stimulates areas of the brain using magnetic pulses and is an approved treatment for several mental health and substance use disorders. The treatment uses head coils to deliver the magnetic pulses. A dTMS coil called the H4 coil stimulates the lateral prefrontal cortex and insula, and has been approved for the treatment of tobacco use disorder. No studies have been conducted on the H4 coil for treat cannabis use disorder. The purpose of this pilot study is to determine feasibility and tolerability of a dTMS H4 protocol. The goal is to lay the foundation for randomized controlled trials of dTMS as a treatment for adults with moderate-to-severe cannabis use disorder.

Official Title
-----------------
Phase 1 Open-Label Pilot Trial of Deep Repetitive Transcranial Stimulation of the Lateral Prefrontal Cortex and Insula for Adults With Moderate-to-Severe Cannabis Use Disorder

Conditions
-----------------
Cannabis Use Disorder

Intervention / Treatment
-----------------
* Device: dTMS stimulation via the H4 coil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult, age 25-65 DSM-5 CUD, moderate or higher (4+ DSM-5 symptoms) Daily cannabis use at enrollment Most common route of administration is dried flower Urinary THC of >150mg/ml at enrollment Treatment-seeking (i.e., self-reported readiness to change of 7 or greater on a 0-10 readiness ruler) Stable domicile and reliable transportation. Exclusion Criteria: Current comorbid substance use, mood, anxiety, stress-related or psychotic disorders other than tobacco use disorder. Current unstable medical condition (e.g., diabetes) rTMS Contraindications: intracranial or metal implants in the head or nearby regions that cannot be safely removed; history of epilepsy or seizures; pregnancy (female participants only); pacemaker and/or implantable cardioverter-defibrillators). Medication contraindications (e.g., bupropion >300 mg/day due to risk of seizures, benzodiazepine equivalent dose to lorazepam >2 mg/day). History of recurrent headache or migraine (past year) Significant literacy, visual, or hearing problems

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: H4 dTMS<br>The participants will receive 18 H4 dTMS sessions over 4-6 weeks as an adjunct to evidence-based standard care for CUD (i.e., motivational interviewing and contingency management). | Device: dTMS stimulation via the H4 coil<br>* Deep repetitive transcranial magnetic stimulation (dTMS) uses transient electromagnetic fields to stimulate the brain and is approved by Health Canada and the FDA for the treatment of depression, anxious depression, obsessive-compulsive disorder, and tobacco use disorder. Compared to the traditional TMS, dTMS is able to target brain depths ranging from 2 to 6 cm. With the use of various H-coils, dTMS has been used to target specific neural networks with the aim of producing desired clinical effects in psychiatric populations. The intervention in this study is the H4 dTMS coil which stimulates the lateral prefrontal cortex and the insula in the brain.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of H4 deep dTMS coils in adults with cannabis use disorder. | To determine the protocol feasibility, the percentage of intervention sessions completed by the participants will be examined | End of intervention period ( 4 weeks) | 
| Tolerability of H4 deep dTMS coils in adults with cannabis use disorder. | To determine the protocol tolerability, the percentage of withdrawn participants will be examined | End of intervention period ( 4 weeks) | 
| Safety of H4 deep dTMS coils in adults with cannabis use disorder. | To determine the protocol safety, weekly adverse events reported will be examined | End of intervention period ( 4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of H4 deep rTMS on cannabis use frequency | Cannabis use frequency, as measured by percentage of cannabis use days in the past 7 days. | End of intervention period ( 4 weeks) and 1-month follow-up | 
| Effects of H4 deep rTMS on Cannabis craving | Cannabis cravings will be measured by the Marijuana Craving Scale (12-item scale, higher scores indicate more cravings). | End of intervention period ( 4 weeks) and 1-month follow-up | 
| Effects of H4 deep rTMS on motivation to quit Cannabis | Motivation to quit Cannabis use will be measured by the Readiness Ruler (0-10 scale), higher scores indicate more motivation to quit. | End of intervention period ( 4 weeks) and 1-month follow-up | 
| Effects of H4 deep rTMS on resting state neural activity | Resting state electroencephalography (EEG) will be assessed to examine neural activity changes in the brain. | End of intervention period ( 4 weeks) and 1-month follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
H4 coil, Transcranial Magnetic Stimulation