rTMS for Cannabis Use Disorder

Overseen By Victor Tang, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must be taking: Psychotropic medications

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Pregnancy, Bipolar, Schizophrenia, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

46 Participants Needed

Trial Summary

What is the purpose of this trial?

There has been a considerable rise in cannabis consumption in recent years, with estimates of 200 million individual users globally. Importantly, 3% of these individuals have cannabis use disorder (CUD), with this prevalence increasing to 33% amongst regular users, making it one of the most common substances use disorders (SUDs) worldwide. CUD is associated with substantial health, societal, and economic costs, and worsening of other psychiatric disorders. Despite this clinical burden, effective treatment options are limited. No pharmacological treatments have emerged as clearly efficacious, and psychotherapeutic interventions have shown tempered results. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain-based approach in which alternating magnetic fields are applied to the scalp to induce electrical currents in cortical tissue. As it can modulate neural circuits implicated in neuropsychiatric disorders, it is a promising brain-based approach in the treatment of addictions. Evidence has indicated its efficacy in reducing drug craving and consumption across numerous SUDs, although research into cannabis has been largely unexplored. Recently, a novel circular rTMS coil, the MagVenture MMC-140, has been developed with the capacity to modulate both the bilateral prefrontal cortex (PFC) and insula, both of which are implicated in the neurocircuitry of craving and executive function. As such, it shows potential for CUD treatment. This proof-of-concept clinical trial will evaluate the feasibility and tolerability of a 4-week course of rTMS to the PFC/insula using MMC-140 as a treatment for CUD. Feasibility of both high frequency (HF; excitatory) and low frequency (LF; inhibitory) stimulation parameters will be evaluated. In addition, pre/post rTMS changes in cannabis use outcomes (e.g., consumption, craving, and withdrawal), executive function, and PFC/insula functional connectivity will be explored. By comprehensively investigating clinical, cognitive, and neuroimaging effects of rTMS, this study could pave the way for the first brain-based intervention in CUD that could be widely adopted into clinical settings using a novel, cost-effective and accessible rTMS device.

Will I have to stop taking my current medications?

The trial requires that you be on a stable regimen of your psychotropic medications for at least 14 days before joining. However, if you are taking more than 2 mg of lorazepam (or an equivalent dose of another benzodiazepine) or any anticonvulsant medication, you may need to stop or adjust those medications during the treatment.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for Cannabis Use Disorder?

Preliminary studies suggest that rTMS, when applied to a specific brain area called the dorsolateral prefrontal cortex, may help reduce cravings and cannabis use in people with Cannabis Use Disorder. This treatment has shown promise in reducing cravings for other substance use disorders as well. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans and has been used for various neuropsychiatric disorders. Studies have shown it is feasible to deliver rTMS to people with substance use disorders, although specific effects related to different levels of substance use are not well understood. ^{1 2 4 5 6}

How is rTMS treatment different from other treatments for cannabis use disorder?

Repetitive Transcranial Magnetic Stimulation (rTMS) is a unique, non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, like the dorsolateral prefrontal cortex, to reduce cravings in substance use disorders. Unlike traditional therapies, rTMS does not involve medication and is still being explored as a novel option for cannabis use disorder, where few effective treatments currently exist. ^{1 2 4 5 7}

Eligibility Criteria

This trial is for adults aged 18-65 with cannabis use disorder, using cannabis at least 5 days a week and aiming to reduce or quit. They must have a certain level of dependency and be on stable psychiatric meds if any. Excluded are pregnant individuals, those with severe mental health disorders, other primary substance abuse issues, seizure history, significant head injury, unstable medical conditions, or specific medications.

Inclusion Criteria

I have been on the same mental health medication for at least 14 days.

I use cannabis most days of the week and want to reduce or stop using it.

I understand the details of the clinical trial and can make decisions about my health.

Exclusion Criteria

I have an active seizure disorder or a significant head injury with a confirmed lesion.

Pregnant or intending to be pregnant during the study

Presence of cardiac pacemaker, intracranial implant, or metal in the cranium

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 4-week course of rTMS to the PFC/insula using MMC-140 for CUD treatment

4 weeks

Weekly visits for rTMS sessions

Follow-up

Participants are monitored for changes in cannabis use outcomes, executive function, and PFC/insula connectivity

4 weeks

Follow-up assessments at 4 weeks post-treatment

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation

Trial Overview The study tests repetitive transcranial magnetic stimulation (rTMS) using the MMC-140 coil on people with cannabis use disorder over four weeks. It will assess how well this non-invasive brain stimulation works in reducing cravings and consumption by exciting or inhibiting brain activity related to addiction.

Participant Groups

Group I: High-Frequency (HF) Active Control 1 Intervention

10 Hz rTMS

Group II: Low-Frequency (LF) Active Control 1 Intervention

1 Hz rTMS

Repetitive Transcranial Magnetic Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraines

Approved in European Union as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Anxiety disorders

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Brain & Behavior Research Foundation

Collaborator

Trials

63

Recruited

2,900+

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex is safe and feasible for individuals with cannabis use disorder (CUD), based on a study involving 72 participants.

While there were no significant differences in craving reduction, those receiving active rTMS reported fewer days of cannabis use in the final two weeks of follow-up, suggesting potential therapeutic benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Preliminary Investigation Of Repetitive Transcranial Magnetic Stimulation Applied To The Left Dorsolateral Prefrontal Cortex In Treatment Seeking Participants With Cannabis Use Disorder. Sahlem, GL., Kim, B., Baker, NL., et al.[2023]

Repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex is safe and feasible for individuals with cannabis use disorder (CUD), based on a study involving 72 participants.

While there were no significant differences in craving reduction, those receiving active rTMS reported fewer days of cannabis use in the final two weeks of follow-up, suggesting potential therapeutic benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary randomized controlled trial of repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex in treatment seeking participants with cannabis use disorder. Sahlem, GL., Kim, B., Baker, NL., et al.[2023]

In a preliminary study involving 24 outpatients with schizophrenia and cannabis use disorder, high-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex was found to be safe and well-tolerated, with a high retention rate of about 90%.

The active rTMS group showed a trend towards reduced cannabis use and craving, along with significant improvements in psychiatric symptoms and attention, suggesting that rTMS may be an effective treatment option for cannabis use disorder in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia. Bidzinski, KK., Lowe, DJE., Sanches, M., et al.[2022]

The rise in cannabis use and cannabis use disorder (CUD) due to increased legalization highlights the urgent need for effective treatments, as current options have limited success and high relapse rates.

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a non-invasive treatment for substance use disorders, including CUD, and has received FDA clearance for smoking cessation, indicating its potential for broader applications in addiction therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation as a potential treatment approach for cannabis use disorder. Kearney-Ramos, T., Haney, M.[2022]

Repetitive transcranial magnetic stimulation (rTMS) can be safely and feasibly administered to individuals with cannabis use disorder (CUD), with 89% of participants completing the study without adverse effects.

However, a single session of rTMS did not significantly reduce cue-elicited craving for cannabis, suggesting that while the treatment is tolerable, it may not be effective for craving reduction in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) administration to heavy cannabis users. Sahlem, GL., Baker, NL., George, MS., et al.[2023]

Repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe and feasible for patients with neuropsychiatric disorders who also have a history of substance use, based on a review of 274 articles.

However, the impact of different levels of substance use on the safety and efficacy of rTMS remains unclear, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. Tang, VM., Ibrahim, C., Rodak, T., et al.[2023]

Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in reducing cravings for tobacco, alcohol, and cocaine when applied at high frequencies to the dorsolateral prefrontal cortex (DLPFC), based on a review of eight studies.

Repeated sessions of high-frequency rTMS over the DLPFC may be particularly beneficial for decreasing smoking and alcohol consumption, suggesting that rTMS could be a promising treatment option for drug addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. Barr, MS., Farzan, F., Wing, VC., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Preliminary Investigation Of Repetitive Transcranial Magnetic Stimulation Applied To The Left Dorsolateral Prefrontal Cortex In Treatment Seeking Participants With Cannabis Use Disorder. [2023]

2. Ireland pubmed.ncbi.nlm.nih.gov

A preliminary randomized controlled trial of repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex in treatment seeking participants with cannabis use disorder. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation as a potential treatment approach for cannabis use disorder. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) administration to heavy cannabis users. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. [2019]