Transcranial Magnetic Brain Stimulation to Reduce Cannabis Use in Heavy Cannabis Users

Study Overview
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Brief Summary
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The growing legalization of cannabis across the U.S. is associated with increases in cannabis use, and accordingly, an increase in the number of individuals with cannabis use problems, including cannabis use disorder (CUD). While there are several medications being investigated as treatment options for CUD, none have been FDA-approved, and there is limited efficacy of traditional behavioral therapy approaches for this population. Consequently, there is a pressing need for the development of new treatments, including approaches that specifically target the brain areas associated with problematic cannabis use behaviors. Elevated attention to drug cues is one of the primary causes of relapse in heavy cannabis users. Preliminary data suggests that transcranial magnetic stimulation (TMS), a non-invasive form of brain stimulation, may be a novel brain-based tool to decrease heightened attention to drug cues in people with CUD. Building on prior data, the primary goal of this study is to evaluate the feasibility and effectiveness of TMS as a tool to decrease attention to drug cues and reduce cannabis use. This study will evaluate whether 2 weeks of rTMS can be used to decrease attentional bias to cannabis cues and reduce cannabis use in heavy cannabis users. We will recruit sixty (60) non-treatment seeking, near-daily cannabis users to receive 10 daily sessions of either real or sham (aka placebo) rTMS over a 2-week period. Participants will live on a residential research unit for 3 weeks. During the residential stay, data on cannabis use (measured using standard human laboratory measures of choice to smoke cannabis) and relevant brain activity (measured using drug cue exposure fMRI tasks) will be collected before and after the course of 10 daily rTMS sessions. We will aim to show whether real rTMS treatment reduces brain response and attentional bias to cannabis cues and reduces cannabis use levels.

Official Title
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Imaging the Effects of Intermittent Thetaburst Stimulation on Cannabis Self-Administration in Heavy Cannabis Users

Conditions
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Cannabis

Intervention / Treatment
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* Device: iTBS
* Device: iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males/non-pregnant females, 18-60 years old Current cannabis user Able to perform all study procedures Exclusion Criteria: Use of other illicit drugs If medical history, physical and psychiatric examination, or laboratory tests performed during the screening process reveal any significant illness that the study physician deems contraindicated for study participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br> | Device: iTBS<br>* Six trains of active intermittent thetaburst stimulation (iTBS) using neuronavigation-guided cortical targeting to the left dorsolateral prefrontal cortex location using figure-of-8 TMS coils.<br>* Other names: Intermittent theta-burst stimulation;|
| Sham Comparator: Sham<br> | Device: iTBS<br>* Six trains of sham intermittent thetaburst stimulation (iTBS) using neuronavigation-guided cortical targeting to the left dorsolateral prefrontal cortex location using figure-of-8 TMS coils.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cannabis self-administration (laboratory) | During the inpatient phase, there will be three cannabis self-administration sessions: one 1 day before the intermittent thetaburst stimulation (iTBS) intervention begins, one on inpatient day 10, and one 1 day after the full 10-day course of iTBS treatment. On cannabis self-administration days, participants will be given 6 opportunities throughout the day at 1.5-h intervals (start at 9 am) to purchase 0-6 puffs of a cannabis cigarette from their study earnings, up to 36 puffs per day. For each participant, we will quantify the total number of puff choices (0-36) they made to self-administer cannabis on Inpatient Day 3 (baseline; 1 day before the iTBS treatment) and compare it to Inpatient Day 18 (follow-up; 1 day after the full course of iTBS treatment). | Baseline (Inpatient Day 3), approx. half-way (Inpatient Day 10), and 2 weeks (Inpatient Day 18) | 
| Change in Salience Network drug cue reactivity [functional brain data during Cannabis Stroop functional magnetic resonance imaging (fMRI) task] | Relative brain activity to cannabis vs neutral visual stimuli will be assessed during the Cannabis Stroop fMRI task from the first (baseline) to the last (2.5 weeks) timepoint. | Baseline (Inpatient Day 2) and 2.5 weeks (Inpatient Day 19) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first cannabis use (outpatient) | The outcome will be 'time to first use' of cannabis, which is the time latency (in days) until the first day that the participant endorses using cannabis during the post-inpatient outpatient EMA period (which occurs on Days 1-14 after inpatient discharge). Endorsing the use of cannabis is given by a participant responding Yes to the daily Yes/No prompts sent via mobile phone each evening at 10pm which ask if they have used cannabis that day/timeframe. | Post-inpatient Outpatient Days 1 - 14 | 
| Change in Frequency of cannabis use (outpatient) | The outcome will be 'frequency of cannabis use,' which is the total number of days/week during the 2-week post-inpatient outpatient EMA period that a participant endorses using cannabis (by responding Yes to the daily evening mobile phone prompt asking them if they used cannabis that day; daily prompts occur on Days 1-14 after inpatient discharge. The frequency of use (total # of days/week used during the 2-week outpatient period) is computed independently for the pre-inpatient (baseline) and post-inpatient (follow-up) outpatient periods, and then the follow-up period is compared relative to baseline to get a measure of change following iTBS treatment. | Baseline (Pre-Inpatient) Outpatient Days 1 - 14 and Post-inpatient Outpatient Days 1 - 14 | 
| Change in Quantity of cannabis use (outpatient) | The outcome will be 'quantity of cannabis use' which is the total number of grams during each 14-day outpatient period that a participant endorses using (by responding Yes to the mobile phone prompt asking them if they used cannabis that day, and then entering the quantity in the following mobile phone prompt asking them How many total grams did you use? The quantity (total # of grams used over the 14-day period) is computed independently for the pre-inpatient (baseline) and post-inpatient (follow-up) outpatient periods, then the follow-up period is compared relative to baseline. | Baseline (Pre-Inpatient) Outpatient Days 1 - 14 and Post-inpatient Outpatient Days 1 - 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cannabis, self administration, transcranial magnetic stimulation, repetitive transcranial magnetic stimulation, intermittent theta burst stimulation, functional magnetic resonance imaging, functional neuroimaging, functional brain imaging, marijuana, cannabis smoking, marijuana smoking, recreational marijuana use, stroop task, attentional bias, drug cue reactivity, intervention, treatment, double blind, sham, sham controlled, residential, inpatient, ecological momentary assessment, randomized controlled clinical trials, randomized clinical trials, neuronavigation, personalized cortical targeting, biomarker development, brain mapping, neuroendophenotypes, neurobiomarkers