Cannabis Use DisorderPhase 2NCT03144232
A Preliminary Investigation of Pre-Frontal Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Cannabis Use Disorder
A Phase 2 study testing Active rTMS in people with Cannabis Use Disorder, run by Stanford University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Cannabis Use Disorder
- What is being tested?
- Active rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2017to 30 Jul 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Participants must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
- Participants must be between the ages of 18 and 60.
- 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.
- Participants must express a desire to quit cannabis.
- Participants must have a Positive UDS for cannabis during their baseline visit (confirming they are regular users).
Who cannot join
- Participants must not be pregnant or breastfeeding.
- Participants must not meet moderate or severe use disorder of any other substance with the exception of Nicotine Use Disorder.
- Participants must not be on any medications that have central nervous system effects.
- Participants must not have a history of/or current psychotic disorder or bipolar disorder.
- Participants must not have any other Axis I condition requiring current treatment and must have a HRSD24 ≤10 indicating no clinically relevant depressive symptoms.
- Participants must not have a history of Dementia or other cognitive impairment.
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- Participants must not have active suicidal ideation, or a suicide attempt within the past 90 days.
- Participants must not have any contraindications to receiving rTMS (e.g. metal implanted above the head, history of seizure, any known brain lesion).
- Participants must not have any unstable general medical conditions.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Conditions
- Cannabis Use Disorder
- Being tested
- Active rTMS, Sham rTMS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active rTMSDevice
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 rTMSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS | Experimental | 10 Hz rTMS applied to the left DLPFC Receives: Device: Active rTMS |
| Sham rTMS | Sham comparator | Sham rTMS applied to the left DLPFC Receives: Device: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (pre) and Week-5 (post)
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.
Measured: Baseline (pre) and Week-5 (post)
Secondary outcomes (1)
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
Measured: 4-weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2017
- Study start1 Aug 2017
- Primary completion30 Jul 2022
- Study completion30 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cannabis Use DisorderStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Gregory Sahlem, Stanford University
- Investigators
- Gregory Sahlem, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03144232
- Sponsor's protocol ID
- 56294
- Other IDs
- K23DA043628
- Status last verified
- Aug 2023
- First submitted
- 4 May 2017
- Last updated
- 9 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Preliminary Investigation of Pre-Frontal Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Cannabis Use Disorder
- ClinicalTrials.gov ID
- NCT03144232
- Acronym / sponsor ID
- 56294
- Conditions
- Cannabis Use Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 30 Jul 2022 (actual)
- Study completion
- 30 Jul 2022 (actual)
- First posted
- 8 May 2017 (actual)
- Results
- Posted 9 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active rTMS | Experimental | Device: Active rTMS10 Hz rTMS applied to the left DLPFC |
| Sham rTMS | Sham comparator | Device: Sham rTMSSham rTMS applied to the left DLPFC |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Participants must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
- Participants must be between the ages of 18 and 60.
- 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.
- Participants must express a desire to quit cannabis.
- Participants must have a Positive UDS for cannabis during their baseline visit (confirming they are regular users).
Key exclusion criteria (9 listed)
- Participants must not be pregnant or breastfeeding.
- Participants must not meet moderate or severe use disorder of any other substance with the exception of Nicotine Use Disorder.
- Participants must not be on any medications that have central nervous system effects.
- Participants must not have a history of/or current psychotic disorder or bipolar disorder.
- Participants must not have any other Axis I condition requiring current treatment and must have a HRSD24 ≤10 indicating no clinically relevant depressive symptoms.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active rTMSrTMS 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. | Device | Active rTMS |
| Sham rTMSSham 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. | Device | Sham rTMS |
Primary outcome
Marijuana Craving Questionnaire-Short Form Score as a Measure of Behavioral Craving
Time frame: Baseline (pre) and Week-5 (post)
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.
Cue Reactivity
Time frame: Baseline (pre) and Week-5 (post)
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.
1 secondary outcome
Abstinence
Time frame: 4-weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory Sahlem, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Active rTMS in people with Cannabis Use Disorder, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Marijuana Craving Questionnaire-Short Form Score as a Measure of Behavioral Craving (time frame: Baseline (pre) and Week-5 (post)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2023; AzTrials last refreshed its copy on 7 Nov 2026.