Transcranial Magnetic Brain Stimulation to Reduce Cannabis Use in Heavy Cannabis Users
ConditionCannabis
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorDuke University
About this trial
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 repetitive transcranial magnetic stimulation (rTMS), 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.
In this study, fifty (50) treatment-seeking, near-daily cannabis users will be recruited to receive either active or sham (placebo) repetitive TMS (rTMS). Participants will complete a total of 25 treatment sessions, delivered as five sessions per day across five days, with sessions flexibly scheduled over a two-week period. Measures of cannabis use and brain activity will be collected before and after treatment using real-time self-report assessments and functional magnetic resonance imaging (fMRI), respectively. Specifically, cannabis use will be assessed in participants' everyday environments using brief text-message surveys during a two-week baseline period, the two-week treatment period, and a four-week follow-up period.
The study aims to determine whether active rTMS reduces brain activity in response to cannabis cues, decreases automatic attention to cannabis cues, and leads to meaningful reductions in cannabis use compared to sham treatment.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Males/non-pregnant females, 18-65 years old
Current cannabis user
Able to perform all study procedures
Disqualifiers
Regular 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
Trial design
Design model
Parallel
Treatments tested in this trial
iTBS
DeviceSixty trains of active intermittent thetaburst stimulation (iTBS) (1 train = 10 sec of 2 sec ON, 8 sec OFF; 3-pulse bursts at 5 Hz; 15 pulses/sec \[30 pulses/train\]; 60 trains/session; 1,800 pulses/session) using neuronavigation-guided cortical targeting to the left dorsolateral prefrontal cortex location using figure-of-8 TMS coils.
iTBS
DeviceSixty trains of sham intermittent thetaburst stimulation (iTBS) (1 train = 10 sec of 2 sec ON, 8 sec OFF; 3-pulse bursts at 5 Hz; 15 pulses/sec \[30 pulses/train\]; 60 trains/session; 1,800 pulses/session) using neuronavigation-guided cortical targeting to the left dorsolateral prefrontal cortex location using figure-of-8 TMS coils.
Treatment groups
50 Participants
are divided into 2 treatment groupsGroup A: ActiveExperimental treatment 1 intervention
Group B: ShamSham comparator 1 intervention
Trial outcomes
Primary outcomes
1
Frequency of cannabis use
On each study day, participants will receive EMA text surveys on their cellphones. For each participant, cannabis use frequency will be measured as the number of days per week they report cannabis use. During the two-week pre-treatment period, we will calculate the baseline frequency as the average number of use days per week across those two weeks. Cannabis use frequency will then be assessed during each of the two treatment weeks (Week 0-1) and during the four-week follow-up period (Weeks 2-5), and the follow-up period will subsequently be compared relative to baseline. This is corroborated by TLFB.
Time frame
Two-week Pre-treatment/Baseline phase (Days 1-14), Two-week Treatment phase (Days 15-28), Four-week Post-treatment phase (Days 29-56)2
Quantity of cannabis use
On each study day, participants will receive EMA text surveys on their cellphones. For each participant, cannabis use quantity will be measured as the average number of grams used per use-day during each week in which they report cannabis use. During the two-week pre-treatment/baseline period (Days 1-14), we will calculate the baseline quantity as the average daily grams used per use-day across those two weeks. Cannabis use quantity will then be assessed during the treatment phase (Days 15-28) and during the 4-week follow-up period (Days 29-56), and the follow-up period will subsequently be compared relative to baseline. This will be corroborated by TLFB.
Time frame
Two-week Pre-treatment/Baseline phase (Days 1-14), Two-week Treatment phase (Days 15-28), Four-week Post-treatment phase (Days 29-56)Secondary outcomes
1
Salience Network drug cue reactivity
Brain activity in response to cannabis-related versus neutral cues will be assessed using the Cannabis Stroop fMRI task, in which visual stimuli are presented and the Salience Network (SN) typically shows greater activation to drug cues than to neutral cues. This pattern reflects heightened SN drug-cue reactivity, or an attentional bias toward drug-related information. First, a data-driven approach called independent component analysis (ICA) will be used to identify and extract the SN timecourse and spatial map from the Stroop fMRI task data. Second, a general linear model (GLM) analysis will be used to relate each participant's SN timecourse to the task design (timing model of cue presentation blocks), allowing us to quantify SN activity during cannabis versus neutral cue task conditions. The primary outcome will be each participant's SN contrast beta value, a statistic derived from the ICA-GLM analysis that reflects the magnitude and direction of SN drug cue reactivity.
Time frame
Pre-treatment/Baseline (Day 14), Immediate Post-treatment (Day 28), 4-Week Post-treatment Follow-up (Day 56)2
Feasibility (attendance)
Feasibility will be measured as the percentage of scheduled TMS sessions completed by participants in each treatment group. For participants randomized to a TMS treatment group (active vs. sham) who attend at least one TMS session, we will quantify the total number of sessions completed. Feasibility will then be calculated as the percentage of planned TMS sessions that were successfully completed by each participant.
Time frame
Two-week Treatment phase (Days 15-28)3
Tolerability (withdrawals)
Tolerability will be measured as the proportion of participants who withdraw from the study before completing all planned TMS sessions. Among participants randomized to a TMS treatment group (active vs. sham) who attend at least one TMS session, we will identify those who discontinue prior to completing their final scheduled TMS session. Tolerability will then be quantified as the percentage of participants who withdraw before completing the full course of planned TMS treatments.
Time frame
Two-week Treatment phase (Days 15-28)4
Safety (AEs)
Safety will be measured as the frequency, type, and severity of treatment-related adverse events (AEs) reported during and after the TMS treatment period, categorized according to standard AE reporting guidelines. Among participants randomized to a TMS treatment group (active vs. sham) who attend at least one TMS session and receive any amount of TMS, we will quantify the number, type, and severity of subsequent treatment-related AEs. Adverse event profiles will then be compared between the active and sham treatment groups.
Time frame
Two-week Treatment phase (Days 15-28)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Duke University
Lead sponsor
National Institute on Drug Abuse (NIDA)
Collaborator
Source ClinicalTrials.gov