rTMS for Opioid Use Disorder

Overseen By James J. Mahoney, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: West Virginia University

Must be taking: Buprenorphine/naloxone

Must not be taking: Tricyclics, Antipsychotics, Amphetamines, others

Disqualifiers: Pregnancy, Major psychiatric illness, 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: 5

Duration: 3 weeks

Trial Summary

What is the purpose of this trial?

The purpose of this study is to understand the role of repetitive Transcranial Magnetic Stimulation (rTMS) in reducing opioid and other substance use and craving and improving thinking skills.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but certain drugs that lower the seizure threshold may require careful evaluation by a physician. If you are taking medications like Imipramine, Amitriptyline, or others listed, you may need to stop or adjust them before participating.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for opioid use disorder?

Research suggests that rTMS may help reduce cravings and improve symptoms like depression and impulse control in people with opioid use disorder, although it did not significantly reduce heroin use in one study. Additionally, rTMS has shown promise in reducing cravings for other substances like tobacco, alcohol, and cocaine, indicating its potential as a treatment for various addictions. ^{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, but it has been associated with some risks, such as seizures. Guidelines have been developed to ensure its safe use, including monitoring and setting limits on stimulation parameters. ^{1 2 3 6 7}

How does the treatment rTMS differ from other treatments for opioid use disorder?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, potentially reducing cravings and improving impulse control and attention in people with opioid use disorder. Unlike traditional medication-assisted treatments, rTMS targets brain circuits directly and may offer benefits for those who do not respond well to medications. ^{1 2 3 5 7}

Eligibility Criteria

This trial is for individuals enrolled in the COAT Program, who are abstinent from opioids and illicit substances (except marijuana), confirmed by a drug screen. They must meet criteria for Opioid Use Disorder, have stable mental health (with specific criteria on suicide risk assessment), and agree to use contraception. Exclusions include major cognitive disorders, pregnancy, certain medical conditions that make rTMS unsafe, prior rTMS treatment, and severe psychiatric illnesses other than depression.

Inclusion Criteria

I haven't used opioids or illegal drugs, except for prescribed buprenorphine/naloxone and marijuana, confirmed by a urine test.

Columbia-Suicide Severity Rating Scale score < 4

Willing to practice contraception to avoid pregnancy the duration of the study

Exclusion Criteria

Pregnancy

Positive responses to the TMS Adult Safety Screen or the MRI checklist

Major Cognitive Disorder (as evidenced by a score of <21/30 on the Mini Mental Status Exam (MMSE)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive 9 sessions of active rTMS over 3 weeks

3 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit per week (in-person)

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study investigates how repetitive Transcranial Magnetic Stimulation (rTMS) might help reduce opioid use and cravings while improving cognitive functions in people with Opioid Use Disorder. It's an open-label trial where all participants receive the intervention without any placebo or control group.

Participant Groups

Group I: Study Group Experimental Treatment 1 Intervention

Participants will receive a type of TMS called repetitive TMS (rTMS) wherein the magnetic pulses delivered will be close together in a rapid sequence. They will receive excitatory rTMS with a stimulation frequency of 10 Hz or higher.

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

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Findings from Research

In a pilot trial involving 22 participants with opioid use disorder undergoing methadone maintenance therapy, repetitive transcranial magnetic stimulation (rTMS) did not significantly reduce cravings or heroin use compared to a sham treatment.

However, rTMS was associated with significant improvements in depressive symptoms, impulse control, and attention, suggesting potential benefits for mental health aspects in individuals with opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy. Tsai, TY., Wang, TY., Liu, YC., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a noninvasive treatment for substance use disorders (SUDs) like cocaine and opioid use disorders by inducing neuroplastic changes in the brain, which can help reduce cravings and drug use.

The field faces several 'known unknowns' that need to be addressed to optimize rTMS for SUDs, including selecting the right cortical targets, understanding subcortical circuit engagement, and determining the best treatment sequences, highlighting the need for collaborative research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. Steele, VR., Maxwell, AM.[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]

In a randomized clinical trial with 30 methamphetamine-addicted patients, real rTMS significantly reduced cue-induced craving after 5 sessions compared to sham stimulation.

Real rTMS also improved cognitive functions such as verbal learning and memory, indicating it is a safe and effective intervention for reducing cravings in methamphetamine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex for methamphetamine use disorders: A randomised clinical trial. Su, H., Zhong, N., Gan, H., et al.[2022]

Excitatory repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral pre-frontal cortex significantly reduces craving for substances in patients with dependence, with a strong effect size (Hedges' g = -0.62) based on a meta-analysis of 26 randomized controlled trials involving 748 participants.

In addition to reducing cravings, rTMS also effectively decreases substance consumption, particularly when using excitatory stimulation protocols, indicating its potential as a therapeutic intervention for substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. Zhang, JJQ., Fong, KNK., Ouyang, RG., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a novel intervention for opioid use disorder (OUD), with a case report indicating a significant reduction in cravings for heroin and cocaine by approximately 60% to 82% after 7 sessions targeting the left dorsolateral prefrontal cortex.

This case highlights the potential of rTMS to augment medication-assisted treatment (MAT) for individuals with OUD, especially for those who continue to experience cravings despite comprehensive treatment, suggesting a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report illustrating the effects of repetitive transcranial magnetic stimulation on cue-induced craving in an individual with opioid and cocaine use disorder. Mahoney, JJ., Marshalek, PJ., Rezai, AR., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy. [2021]

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

Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. [2019]

4. Ireland pubmed.ncbi.nlm.nih.gov

High frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex for methamphetamine use disorders: A randomised clinical trial. [2022]

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

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. [2020]

6. Ireland pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]

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

A case report illustrating the effects of repetitive transcranial magnetic stimulation on cue-induced craving in an individual with opioid and cocaine use disorder. [2021]