Brain Stimulation for Substance Addiction

Overseen By Vaughn R Steele, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Neurological disorders, Cardiac implants, Schizophrenia, others

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

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a brain stimulation technique called rTMS, which uses magnetic fields to stimulate specific brain areas, in reducing substance use. It targets individuals with Alcohol Use Disorder (AUD) or Opioid Use Disorder (OUD). The study compares different rTMS methods and brain targets to determine the most effective approach. Ideal participants are those already receiving treatment for AUD or OUD. As an unphased trial, this study provides a unique opportunity to contribute to cutting-edge research that could enhance future treatments.

Will I have to stop taking my current medications?

The trial requires that you stop using benzodiazepines at least 48 hours before starting the study. If you are currently using medications with anti- or pro-convulsive effects, you may also need to stop taking them.

What prior data suggests that this rTMS technique is safe for individuals with AUD or OUD?

A previous study found repetitive transcranial magnetic stimulation (rTMS) to be a safe treatment for alcohol use disorder (AUD), helping to reduce cravings and alcohol consumption without major side effects. Research has shown that patients tolerate rTMS well, making it a promising option for those seeking help with AUD.

For opioid use disorder (OUD), studies suggest that rTMS can safely reduce cravings. Evidence indicates that rTMS is as safe for substance use disorders as it is for other mental health conditions.

Overall, rTMS appears to be a safe treatment for both AUD and OUD, with research showing it is well-tolerated and effective at reducing cravings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using repetitive transcranial magnetic stimulation (rTMS) for substance addiction because it offers a non-invasive approach that directly targets brain areas involved in addiction, like the prefrontal cortex. Unlike traditional treatments such as medication or counseling, rTMS uses magnetic fields to stimulate nerve cells, which could potentially alter the neural pathways associated with addiction. This method might offer a quicker onset of effects and fewer side effects compared to medications, making it a promising option for individuals with alcohol use disorder (AUD) and opioid use disorder (OUD). By specifically targeting brain regions linked to cravings and self-control, rTMS could provide a new avenue for reducing addiction-related behaviors.

What evidence suggests that rTMS could be an effective treatment for AUD and OUD?

This trial will examine the effects of repetitive transcranial magnetic stimulation (rTMS) on individuals with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD). Studies have shown that rTMS can help reduce alcohol use and cravings in people with AUD. Research indicates that high-frequency rTMS not only decreases the number of heavy drinking days but also improves attention and reduces impulsive reactions to alcohol-related triggers.

For individuals with OUD, rTMS has effectively reduced cravings triggered by certain cues. Early findings suggest that applying rTMS to the left dorsolateral prefrontal cortex, a brain area involved in decision-making, helps manage opioid cravings. Overall, rTMS shows promise in aiding those with substance use disorders by targeting specific brain areas linked to addiction. Participants in this trial will be randomly assigned to receive different rTMS applications based on their specific disorder, AUD or OUD. ^{1 2 3 6 7}

Who Is on the Research Team?

Vaughn R Steele, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals seeking treatment for Alcohol Use Disorder (AUD) or Opioid Use Disorder (OUD). Specific eligibility criteria are not provided, but typically participants must meet diagnostic criteria for these conditions and be stable enough to participate in the study.

Inclusion Criteria

Be able to give valid informed consent in English

Absence of cognitive impairment: IQ equivalent of ≥ 70 on the WRAT

Receiving treatment for either AUD or OUD

Exclusion Criteria

Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted medication pumps or sensors, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object in the body that precludes rTMS administration

Lifetime history of schizophrenia, bipolar disorder, mania

TMS contraindications

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rTMS treatment over 5 visits within 2 weeks

2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview The study tests different types of repetitive transcranial magnetic stimulation (rTMS) on two brain areas: the left dorsolateral prefrontal cortex (l-dlPFC) for OUD and medial prefrontal cortex (mPFC) for AUD. It aims to find which rTMS type and target location most effectively reduce substance use post-treatment.

How Is the Trial Designed?

Group I: OUD Experimental Treatment 1 Intervention

Individuals receiving treatment from HHC for OUD. Participants will be asked to complete a battery of tasks at the prior to the first rTMS session and after the last rTMS session. Each rTMS eligible participant will be scheduled for 5 rTMS visits (to be completed within 2 weeks from start to finish). Each rTMS session will start with finding motor hotspot, the rTMS dose, then application of rTMS. Within OUD participants, random assignment of rTMS type (cTBS vs iTBS ) applied to l-dlPFC will occur in sets of 6 thus increasing rTMS site distribution even if a small sample is collected.

Group II: AUD Experimental Treatment 1 Intervention

Individuals receiving treatment from HHC for AUD. Participants will be asked to complete a battery of tasks at the prior to the first rTMS session and after the last rTMS session. Each rTMS eligible participant will be scheduled for 5 rTMS visits (to be completed within 2 weeks from start to finish). Each rTMS session will start with finding motor hotspot, the rTMS dose, then application of rTMS. Within AUD participants, random assignment of rTMS site (cTBS at mPFC vs iTBS at l-dlPFC) will occur in sets of 6 thus increasing rTMS site distribution even if a small sample is collected.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

A multicenter double-blind RCT involving 262 chronic smokers showed that repetitive transcranial magnetic stimulation (rTMS) significantly increased the continuous quit rate (CQR) to 19.4% compared to 8.7% for the sham treatment, indicating its efficacy in promoting smoking cessation.

This study established a safe treatment protocol for rTMS, which has now received FDA clearance as an aid for smoking cessation, marking a significant advancement in addiction medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. Zangen, A., Moshe, H., Martinez, D., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a non-invasive treatment for cocaine and methamphetamine use disorders by potentially inducing beneficial changes in brain circuits related to addiction, particularly affecting dopamine and glutamate systems.

Clinical studies indicate that rTMS can alter brain network connectivity, which may help reduce cravings in individuals with substance use disorders, suggesting a new avenue for effective treatment where no FDA-approved options currently exist.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders. Moretti, J., Poh, EZ., Rodger, J.[2020]

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 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]

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) 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 study of 44 patients with cocaine use disorder, 5-Hz repetitive transcranial magnetic stimulation (rTMS) significantly reduced cravings and impulsivity over a 2-week treatment period, indicating its potential efficacy as an adjunctive therapy.

The treatment also led to increased functional connectivity in brain regions associated with decision-making and impulse control, with effects lasting for up to 3 months, although they diminished by 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Functional Connectivity Outcomes of 5-Hz Repetitive Transcranial Magnetic Stimulation as an Add-on Treatment in Cocaine Use Disorder: A Double-Blind Randomized Controlled Trial. Garza-Villarreal, EA., Alcala-Lozano, R., Fernandez-Lozano, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8878126/

rTMS Reduces Craving and Alcohol Use in Patients with ... These findings suggest that rTMS might be an effective add-on in treating patients with AUD and warrant replication in future large-scale ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006322321018266

Repetitive Transcranial Magnetic Stimulation in Alcohol ... Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04773691

Effectiveness of High-frequency rTMS in Reducing Alcohol ... The hypothesis to be tested is that repeated transcranial magnetic stimulation allows a reduction in alcohol consumption in patients with an alcohol use ...

4. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05940-z

Efficacy of repetitive transcranial magnetic stimulation (rTMS ... Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.869014/full

Effect of High-Frequency Repetitive Transcranial Magnetic ... The results suggested that high-frequency rTMS could improve the attention bias of alcohol-related cues and impulsivity for patients with AUD.

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

Assessment and Management of Concurrent Substance ... Clinical practice recommendations for the assessment and management of alcohol use during repetitive transcranial magnetic stimulation (rTMS) ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03191266

NCT03191266 | Transcranial Magnetic Stimulation for the ... At least 60% of Veterans with an alcohol use disorder will relapse within 6 months of treatment, irrespective of the type of treatment they receive.