A Preliminary Investigation of Pre-Frontal Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Cannabis Use Disorder

Cannabis Use Disorder Clinical Trial

Official title:

A Preliminary Investigation of Pre-Frontal Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Cannabis Use Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03144232
• Other study ID #: 56294
• Secondary ID: K23DA043628
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2017
• Est. completion date: July 30, 2022

Study information

• Verified date: August 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This investigation will preliminarily determine if a course of high-frequency rTMS applied to the left dorsolateral prefrontal cortex, will reduce behavioral craving, and fMRI cue-reactivity in treatment-seeking cannabis use disordered participants.

Description:

The overarching goal of this proposal is to investigate if a course of excitatory DLPFC rTMS results in reduced cannabis behavioral craving in treatment-seeking individuals with CUD (Aim1). Additionally, the investigators seek to explore the mechanistic underpinnings of any observed effect, by collecting functional magnetic resonance imaging data during cannabis cue administration before and after the treatment course (Aim 2). These aims will be addressed through a nine-week, double-blind, randomized, sham-controlled study in which 72 treatment-seeking cannabis use disordered participants (36/group) will be given 20 sessions of either Active or Sham excitatory rTMS applied to the DLPFC. rTMS will be delivered over five weeks (2 sessions each day, two days each week). rTMS will be applied in conjunction with a validated three-session Motivational Enhancement Therapy (MET) behavioral intervention.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: July 30, 2022
• Est. primary completion date: July 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Participants must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.

2. Participants must be between the ages of 18 and 60.

3. Participants must meet DSM-5 criteria for at least moderate Cannabis Use Disorder, with use of at least 20 out of the last 28 days.

4. Participants must express a desire to quit cannabis.

5. Participants must have a Positive UDS for cannabis during their baseline visit (confirming they are regular users).

Exclusion Criteria:

1. Participants must not be pregnant or breastfeeding.

2. Participants must not meet moderate or severe use disorder of any other substance with the exception of Nicotine Use Disorder.

3. Participants must not be on any medications that have central nervous system effects.

4. Participants must not have a history of/or current psychotic disorder or bipolar disorder.

5. Participants must not have any other Axis I condition requiring current treatment and must have a HRSD24 =10 indicating no clinically relevant depressive symptoms.

6. Participants must not have a history of Dementia or other cognitive impairment.

7. Participants must not have active suicidal ideation, or a suicide attempt within the past 90 days.

8. Participants must not have any contraindications to receiving rTMS (e.g. metal implanted above the head, history of seizure, any known brain lesion).

9. Participants must not have any unstable general medical conditions.

Related Conditions & MeSH terms

• Cannabis Use Disorder
• Marijuana Abuse

Intervention

Device:
• Active rTMS
rTMS will be delivered via a MagPro double blinded rTMS Research System (MagVenture, Denmark) with a Cool-B65 Butterfly Coil (a combined active and sham coil). We will use a standard resting motor threshold (rMT) determination to determine the TMS dose. Study-treatment will be delivered at 120% rMT. Each active rTMS study-treatment will consist of a total of 4000 pulses of 10Hz stimulation (5s-on,10s-off). Study-treatments will be delivered at the EEG coordinate for F3 (which approximates the left DLPFC), and will be found using the Beam-F3 method.
• Sham rTMS
Sham sessions will be delivered using an electronic sham system consisting of a coil that mimics the appearance and sound of rTMS, combined with a TENS device which produces a small electric shock mimicking the feeling of active rTMS. This type of sham has been demonstrated to be indistinguishable from active rTMS.

Locations

Country	Name	City	State
United States	Stanford University	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Marijuana Craving Questionnaire-Short Form Score as a Measure of Behavioral Craving	The investigators hypothesize that as compared to those participants receiving sham rTMS, those participants receiving active rTMS will have a reduced level of behavioral cannabis craving prior to their final rTMS session as compared to prior to their first rTMS session. The investigators will measure behavioral cannabis craving using the marijuana craving questionnaire. Score range: 12 to 84, higher scores represent more craving.	Baseline (pre) and Week-5 (post)
Primary	Cue Reactivity	The investigators hypothesize that as compared to those participants receiving sham rTMS, those participants receiving active rTMS will have a reduced BOLD response in reward structures (dorsal striatum, ventral striatum, and anterior consulate cortex) during a validated cue-reactivity fMRI paradigm prior to their final rTMS session as compared to prior to their first rTMS session (change score). The following beta scores represent the change score (post-pre) in scans in the drug stimuli minus neutral stimuli subtraction map. Generally, more activation (a positive score) represents more cannabis image cue-reactivity, and the reported range represents standard units as output in the fMRI.	Baseline (pre) and Week-5 (post)
Secondary	Abstinence	Number of weeks (out of a total of 4 possible), in the follow-up period, where participants were abstinent from cannabis. Missing data was conservatively assumed to be non-abstinant. More weeks of abstinence is more favourable	4-weeks