TMS for Opioid Use Disorder

Overseen By Kathryn C Biernacki, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: National Institute on Drug Abuse (NIDA)

Must be taking: Methadone, Buprenorphine, Naltrexone

Disqualifiers: Psychotic disorders, Neurological disorders, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 2 sessions

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: The purpose of this study is to understand how a type of brain stimulation, transcranial magnetic stimulation (TMS), may help those who use opioids such as heroin or methadone. TMS uses brief magnetic pulses to affect brain activity, and is approved by the FDA to treat some mental health problems and substance use. We will evaluate how TMS may help make it easier to make certain kinds of decisions that could help one manage their opioid use. Our findings may provide support for the use of brain stimulation as a treatment to reduce opioid use. Objective: To understand how TMS affects brain activity associated with decision making in people who do and do not use opioids. Eligibility: People aged 18 to 60 years with an OUD. Healthy volunteers are also needed. Design: Participants will have up to 3 clinic visits over 1 to 3 months. All participants will be screened to check if they are eligible to take part in this study. This study is completed in two parts. All eligible participants will complete the first part of the study. In the first part, you will receive one baseline magnetic resonance imaging (MRI) scan so we can take pictures of your brain while you complete computer tasks in the scanner. In these tasks, you will be asked to identify colors of words, view different images and play a game in which you can win money. If you can safely receive TMS, you will be invited to complete the second part of the study. In this part of the study, you will receive TMS and MRI over 2 sessions. For TMS, a coil will be placed on your head and a short electrical current will pass through the coil to create a magnetic pulse that stimulates your brain. You will also repeat the MRI scan and computer tasks. During one of the TMS visits you will receive active or real TMS. In the other, you will receive sham or placebo TMS, which feels like real TMS but does not affect the brain. You will receive both types of TMS. In all sessions, your urine and breath will be tested for drugs and alcohol, and you will complete questionnaires about mood and health.

Will I have to stop taking my current medications?

The trial requires participants with opioid use disorder to be on a stable dose of their medication-assisted treatment (like methadone, buprenorphine, or naltrexone) for at least 4 weeks before joining. If you are on other medications, the protocol does not specify if you need to stop them.

What data supports the effectiveness of the treatment TMS for Opioid Use Disorder?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) may help reduce depressive symptoms, improve impulse control, and enhance attention in individuals with opioid use disorder. Additionally, rTMS has shown promise in reducing cravings in heroin-dependent individuals by affecting brain networks involved in addiction. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS), including its repetitive form (rTMS), is generally considered safe for humans and has been used in various studies for different conditions. It is a noninvasive method that has been applied to treat neuropsychiatric disorders and substance use disorders, with no major safety concerns reported in the studies reviewed. ^{1 3 6 7 8}

How is TMS treatment different for opioid use disorder?

Transcranial magnetic stimulation (TMS) is unique because it is a noninvasive 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, TMS does not involve drugs and targets brain circuits directly to induce changes. ^{1 3 7 9 10}

Research Team

Kathryn C Biernacki, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Eligibility Criteria

This trial is for people aged 18 to 60 who either have an opioid use disorder (OUD) or are healthy volunteers. Participants with OUD may be using opioids like heroin or methadone. All participants must pass a screening and be able to safely receive TMS, which will be determined by the study team.

Inclusion Criteria

Participants in the opioid-using group can meet DSM-5 criteria for other substance use disorders (such as alcohol, nicotine, or cocaine use disorder) currently or in the past but must also meet criteria for an OUD

I have been diagnosed with an opioid addiction, either active or in remission.

I am on a stable dose of medication for opioid addiction for at least 4 weeks.

Exclusion Criteria

Participants must not have met criteria for a moderate or severe alcohol or cannabis use disorder in the last 12 months

I use cannabis no more than once a week and under 1g or 50mg THC.

Participants must not currently consume more than 8 standard alcoholic drink units per week

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-3 months

1 visit (in-person)

Baseline Assessment

Participants receive a baseline MRI scan and complete computer tasks to assess decision-making capacity

1 visit

1 visit (in-person)

Treatment

Participants receive TMS and MRI over 2 sessions, including both active and sham TMS, and complete computer tasks

2 sessions

2 visits (in-person)

Follow-up

Participants are monitored for changes in decision-making and substance use-related outcomes

1-3 months

Treatment Details

Interventions

• TMS

Trial Overview The study tests how transcranial magnetic stimulation (TMS), a brain stimulation technique, affects decision-making in those with and without OUD. It involves MRI scans while doing computer tasks and two sessions of both real and placebo TMS over one to three months.

Participant Groups

Group I: Active TMS Active Control 1 Intervention

Participants will be blinded as to which sessions involve active TMS or sham. Those study staff involved in interacting with the participant will also be blinded. Participants will be randomized into either active-sham or sham-active session order.

Group II: Sham TMS Placebo Group 1 Intervention

Participants will be blinded as to which sessions involve active TMS or sham. Those study staff involved in interacting with the participant will also be blinded. Participants will be randomized into either active-sham or sham-active session order.

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

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]

Transcranial magnetic stimulation (TMS) is emerging as a promising noninvasive treatment for substance dependence, potentially filling a gap in addiction therapies, as it is already FDA-approved for depression.

Repetitive TMS (rTMS) has shown potential in altering behavior and brain activity related to addiction, and future studies may benefit from combining rTMS with medications and cognitive behavioral therapies to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications for Addiction Treatment Development. Hanlon, CA., Dowdle, LT., Henderson, JS.[2019]

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]

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique that has shown promise as a safe and cost-effective treatment for substance use disorders (SUDs), impacting neural activity and promoting neuroplasticity.

Evidence from both preclinical and clinical studies supports the efficacy of repetitive TMS in modulating the brain circuitry associated with addiction, suggesting it could be a valuable intervention for treating SUDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rewiring the Addicted Brain: Circuits-Based Treatment for Addiction. Madeo, G., Bonci, A.[2019]

In a study of 30 heroin-dependent individuals receiving 10 sessions of rTMS over one week, treatment significantly reduced cravings and withdrawal symptoms, indicating its efficacy in managing addiction.

The study found that rTMS altered the coupling between brain regions in the default mode network, particularly the left inferior parietal lobe, which correlated with reduced cravings, suggesting a potential mechanism for its anti-craving effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Default mode network mechanisms of repeated transcranial magnetic stimulation in heroin addiction. Jin, L., Yuan, M., Zhang, W., et al.[2023]

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) 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]

Transcranial magnetic stimulation (TMS) has been explored in 19 studies involving 316 adults for its potential to reduce drug cravings and use, particularly targeting the dorsolateral prefrontal cortex with high-frequency pulses.

While some studies showed promising results, such as decreased smoking and cocaine use, the treatment is still experimental, and the exact mechanisms and optimal parameters for rTMS in addiction treatment remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of substance addiction. Gorelick, DA., Zangen, A., George, MS.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment recently approved for smoking cessation, showing promise in reducing cravings and consumption in various substance use disorders (SUDs).

The therapeutic efficacy of rTMS is thought to involve modulation of neural circuits related to executive control and salience, particularly targeting areas like the dorsolateral prefrontal cortex (DLPFC) and insula, although further research is needed to explore its potential direct effects on dopamine pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation as a Tool to Promote Smoking Cessation and Decrease Drug and Alcohol Use. Harmelech, T., Hanlon, CA., Tendler, A.[2023]

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

Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications for Addiction Treatment Development. [2019]

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

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

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

Rewiring the Addicted Brain: Circuits-Based Treatment for Addiction. [2019]

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

Default mode network mechanisms of repeated transcranial magnetic stimulation in heroin addiction. [2023]

6. 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]

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]

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

Transcranial magnetic stimulation in the treatment of substance addiction. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation as a Tool to Promote Smoking Cessation and Decrease Drug and Alcohol Use. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Rehabilitating the addicted brain with transcranial magnetic stimulation. [2022]