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

Trial Summary

What is the purpose of this trial?

This pilot study is designed to test feasibility and superiority of rTMS types and target locations for the optimal rTMS intervention for individuals seeking treatment for Alcohol Use Disorder (AUD) or Opioid Use Disorder (OUD). The critical questions this study seeks to answer are: which rTMS type applied to l-dlPFC in OUD participants will induce the greatest reduction of opioid use post-treatment? Is inhibitory rTMS applied to medial prefrontal cortex (mPFC) more effective than excitatory rTMS applied to l-dlPFC at reducing alcohol use post treatment in AUD participants?

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 data supports the effectiveness of the treatment rTMS for substance addiction?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce cravings and drug use in individuals with cocaine and heroin addiction. It works by altering brain activity in areas linked to cravings, suggesting it may be a promising treatment for substance addiction. ^{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, as it is a non-invasive brain stimulation method used in various studies, including those for addiction and psychiatric disorders. Large trials, such as those for smoking cessation, have established safe treatment protocols, and the US Food and Drug Administration has cleared rTMS for certain uses, indicating its safety profile. ^{4 6 7 8 9}

How does the treatment rTMS differ from other treatments for substance addiction?

Repetitive transcranial magnetic stimulation (rTMS) is unique because it uses magnetic fields to stimulate specific brain areas, like the dorsolateral prefrontal cortex, to reduce cravings and drug use. Unlike traditional treatments, rTMS is non-invasive and directly targets brain networks involved in addiction, offering a novel approach for those who may not respond to standard therapies. ^{1 4 8 10 11}

Research Team

Vaughn R Steele, PhD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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) 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]

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]

References

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

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

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

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

3. Ireland pubmed.ncbi.nlm.nih.gov

Transient alcohol craving suppression by rTMS of dorsal anterior cingulate: an fMRI and LORETA EEG study. [2013]

4. United States 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. [2022]

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

A generalizable functional connectivity signature characterizes brain dysfunction and links to rTMS treatment response in cocaine use disorder. [2023]

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

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

7. Italy pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. [2019]

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

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

State-Dependent Effects of Ventromedial Prefrontal Cortex Continuous Thetaburst Stimulation on Cocaine Cue Reactivity in Chronic Cocaine Users. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study. [2022]