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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how transcranial magnetic stimulation (TMS), a type of brain stimulation using magnetic pulses, might assist individuals using opioids like heroin or methadone. The research examines TMS's effects on decision-making processes related to managing opioid use. Individuals diagnosed with an opioid use disorder and currently on stable medication-assisted treatment may qualify. Participants will undergo brain scans and complete tasks with both active TMS and a placebo version to assess TMS's impact on brain activity. As an unphased trial, this study allows participants to contribute to innovative research that could lead to new treatment options for opioid use disorder.

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 prior data suggests that TMS is safe for treating opioid use disorder?

Research has shown that transcranial magnetic stimulation (TMS) is safe and well-tolerated for people with substance use disorders (SUDs). Studies indicate that the side effects of TMS for individuals with SUDs are similar to those in other groups, suggesting it doesn't cause many unexpected problems and is a safer choice for these individuals.

The FDA has already approved TMS for treating certain mental health issues and substance use problems, which adds reassurance about its safety. Some studies have demonstrated that TMS can help reduce cravings for opioids, offering promise for those seeking to manage opioid use with fewer side effects.

Overall, TMS has proven to be a safe treatment option with manageable side effects, consistent with its other uses. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Transcranial Magnetic Stimulation (TMS) for opioid use disorder because it offers a completely different approach compared to standard treatments like medication-assisted therapies (e.g., methadone, buprenorphine). While most treatments focus on managing withdrawal symptoms and reducing cravings through medications, TMS is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain. This new technique could potentially target the brain's reward and addiction pathways directly, offering a novel way to curb addiction. Additionally, TMS is known for having minimal side effects, which could make it a more appealing option for individuals who cannot tolerate or prefer not to use medications.

What evidence suggests that TMS might be an effective treatment for opioid use disorder?

Research shows that transcranial magnetic stimulation (TMS) might help reduce cravings in people with opioid use disorder. In this trial, participants will receive either Active TMS or Sham TMS. Studies have found that TMS can significantly decrease the desire for opioids, with effects continuing even after treatment ends. One study discovered that TMS can enhance decision-making skills, potentially helping individuals better manage their opioid use. TMS uses magnetic pulses to stimulate specific brain areas, altering brain activity related to addiction. Overall, early evidence suggests TMS could be a promising treatment for reducing opioid cravings and supporting recovery. ^{2 5 6 7 8}

Who Is on the Research Team?

Kathryn C Biernacki, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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) 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]

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]

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