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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether repetitive Transcranial Magnetic Stimulation (rTMS) can reduce cravings and substance use in individuals with opioid use disorder. rTMS uses magnetic pulses to potentially enhance cognitive function and decrease the desire to use opioids. Participants must be enrolled in a program for treating opioid addiction and must avoid non-prescribed substances other than marijuana. As an unphased study, this trial provides a unique opportunity to contribute to groundbreaking research in addiction treatment.

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 prior data suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is safe for opioid use disorder?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe. The FDA has approved it for treating major depression, indicating a strong safety record. In studies on opioid use disorder, rTMS is described as a non-invasive treatment, meaning it doesn't involve surgery or entering the body.

Although specific data on using rTMS for opioid cravings is limited, treatments for other conditions have shown few serious side effects. Some individuals might experience mild headaches or scalp discomfort during or after the procedure, but these symptoms usually resolve quickly. Overall, rTMS appears to be a safe option with manageable side effects for those considering it as a treatment for substance use issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it offers a non-invasive approach to treating opioid use disorder by using magnetic pulses to stimulate specific areas of the brain. Unlike traditional treatments such as medication-assisted therapy (MAT) with methadone or buprenorphine, which primarily target opioid receptors, rTMS focuses on altering brain activity patterns linked to addiction. Researchers are particularly excited about rTMS because it has the potential to reduce cravings and improve mood without the need for medication, offering a promising alternative for individuals seeking non-drug-based therapies.

What evidence suggests that rTMS is effective for opioid use disorder?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS), the treatment under study in this trial, can help reduce opioid cravings. Some studies found that these reduced cravings can persist even after treatment ends. The treatment uses magnetic pulses to target specific brain areas, potentially helping to control cravings. Early evidence also suggests it can reduce cravings triggered by cues, such as seeing or thinking about opioids. While a single session might offer only short-term relief, ongoing treatments appear more promising. Overall, rTMS could be a useful tool for managing opioid use disorder. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39545446/

Repetitive transcranial magnetic stimulation in the ... TMS has been seen in some studies to significantly reduce cravings for opioids with effects beyond the last administrated treatment.

2. clinicaltrials.gov clinicaltrials.gov/show/NCT03538444

Repetitive Transcranial Magnetic Stimulation for Opiate ... As expected, single session studies have only found small temporary reductions in craving; however, these promising data have led to preliminary clinical trials ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12178270/

Deep Transcranial Magnetic Stimulation in Patients With ... This randomized controlled trial evaluated the efficacy of accelerated wide‐volume deep TMS using a double‐cone coil in patients with opioid use disorder.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352396420301845

The effects of repetitive transcranial magnetic stimulation ... Early evidence suggests that repetitive transcranial magnetic stimulation is effective in reducing cue induced craving for patients with opioid use disorder ( ...

5. wmpllc.org wmpllc.org/ojs/index.php/jom/article/view/3717

Repetitive transcranial magnetic stimulation in the ... TMS has been seen in some studies to significantly reduce cravings for opioids with effects beyond the last administrated treatment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8036083/

Effectiveness and safety of repetitive transcranial magnetic ... Studies suggest that repetitive transcranial magnetic stimulation (rTMS) can be used for the treatment of MD. However, there is still lacking evidence to ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05074524

Repetitive Transcranial Magnetic Stimulation to Reduce ... This study will use rTMS, a neuromagnetic and non-invasive treatment, to reduce opioid cravings in individuals who are diagnosed with opioid use disorder.

8. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20240403

Assessment and Management of Concurrent Substance ... Limited data are available to inform clinicians on how to manage concurrent substance use in the context of repetitive transcranial magnetic ...