Transcranial Magnetic Stimulation for Stimulant Use Disorder

Overseen By Melnie Stimac

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Minnesota

Disqualifiers: Organic brain disorder, Psychotic disorder, others

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

Compensation: Varies

Number of Visits: 3

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The study will recruit 50 adults with stimulant use disorder currently in treatment and abstinent for at least 2 weeks. The study will also recruit up to 10 healthy controls (adults without StUD) for initial study configuration. The study will consist of five steps that are expected to be completed over two lab visits. Step 1: The 3T MRI scan will provide accurate prefrontal cortex anatomy for using neuronavigation for TMS. In addition, the study will use an analysis of resting fMRI connectivity to determine the location in the left DLPFC that has the maximum connectivity with the incentive-salience network. Step 2: The study will use the data collected at the MRI to select the individual TMS location. EEG will be used to collect TEPs in response to single pulse TMS at the left DLPFC. Participants will then be randomized to one of three conditions: A) TMS unsynchronized with EEG, B) TMS synchronized with EEG theta frequency trough, and C) TMS synchronized with EEG theta frequency peak. The stimulation will be applied with an intensity of up to 120% of the resting motor threshold (which is a safe and common practice; Rossi et al., 2021). The intensity can be decreased for individual participants. Step 3: Following randomization, the study will administer a pre-iTBS assessment. Step 4: The study will compare brain and behavioral responses before and after the iTBS session with TMS and EEG synchronization as assigned by their randomized group. Step 5: The study will administer a post-iTBS assessment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether participants must stop taking their current medications. However, participants must be abstinent from substance use (other than caffeine or nicotine) for at least 2 weeks before joining the study.

What data supports the effectiveness of the treatment for stimulant use disorder?

Research suggests that transcranial magnetic stimulation (TMS) can help reduce cravings and drug use in people with cocaine and methamphetamine use disorders by changing brain activity. Studies have shown that TMS can alter brain chemicals and improve brain connections, which may help people with addiction. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS) is generally considered safe for humans and is already approved by the FDA for treating depression. Studies have shown it can be safely used in people with substance use disorders, although more research is needed to fully understand its effects in this group. ^{2 6 7 8 9}

How does the treatment differ from other treatments for stimulant use disorder?

Transcranial Magnetic Stimulation (TMS) is unique because it is a non-invasive brain stimulation technique that targets specific brain areas to reduce cravings and improve decision-making in stimulant use disorder. Unlike traditional treatments, TMS directly modulates brain activity and neurotransmitter function, offering a novel approach to managing addiction. ^{2 4 8 10 11}

Research Team

Kelvin Lim

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adults with stimulant use disorder who have been abstinent for at least two weeks and are currently in treatment. It also includes up to 10 healthy controls without the disorder. Participants must be able to undergo an MRI scan and TMS, and they will be excluded if any condition prevents safe participation.

Inclusion Criteria

Intention to remain in an addiction treatment program until intervention completion (does not apply to healthy control participants)

Confident level of English language proficiency

Ability to provide consent and comply with all study procedures

Exclusion Criteria

I have a brain condition like a stroke or brain injury.

TMS contraindication (history of seizures, metallic cranial plates/screws or implanted device)

MRI contraindications (unapproved metallic implants, pacemakers or any other implanted electrical device, shrapnel, metallic braces, non-removable body piercings, pregnancy, breathing or movement disorder, claustrophobia)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Configuration

Recruitment of healthy controls for initial study configuration and MRI scan to determine TMS location

1 visit

1 visit (in-person)

Randomization and Pre-iTBS Assessment

Randomization of participants to TMS conditions and administration of pre-iTBS assessment

1 visit

1 visit (in-person)

iTBS Session and Post-iTBS Assessment

Administration of iTBS session with TMS and EEG synchronization, followed by post-iTBS assessment

1 visit

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Optimizing Transcranial Magnetic Stimulation

Trial Overview The study tests three types of transcranial magnetic stimulation (TMS) on individuals with stimulant use disorder: unsynchronized TMS, synchronized TMS at EEG theta trough, and peak frequencies. The goal is to optimize brain responses using individualized neuronavigation based on MRI scans.

Participant Groups

Group I: Group 3 Experimental Treatment 1 Intervention

Participants assigned to closed-loop-trough

Group II: Group 2 Experimental Treatment 1 Intervention

Participants assigned to open-loop

Group III: Group 1 Experimental Treatment 1 Intervention

Participants assigned to closed-loop-peak

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

In a study involving 10 treatment-seeking cocaine addicts, bilateral repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex did not show a statistically significant difference in cocaine intake compared to sham treatment over time.

However, exploratory analysis revealed a trend towards reduced cocaine consumption in the active rTMS group, with significant reductions observed at 3 months and at the end of treatment, suggesting potential long-term benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study. Bolloni, C., Panella, R., Pedetti, M., et al.[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]

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]

Transcranial magnetic stimulation (TMS) is a promising non-invasive technique that may help reduce cravings and the risk of relapse in individuals with substance use disorders, particularly methamphetamine use disorders.

The study introduces three alternative TMS settings designed specifically to target and regulate brain function related to methamphetamine addiction, suggesting potential for broader application in similar brain-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A transcranial magnetic stimulation protocol for decreasing the craving of methamphetamine-dependent patients. Chen, T., Su, H., Li, R., et al.[2022]

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]

Non-invasive brain stimulation (NIBS), including transcranial electrical stimulation (tES) and transcranial magnetic stimulation (TMS), shows promise as a treatment for substance-use disorders (SUDs), supported by preclinical research linking brain circuits to drug behavior.

The paper emphasizes the need for standardized methods and outcome measures in NIBS research for SUDs, aiming to improve the translation of neuroscience findings into effective clinical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead. Ekhtiari, H., Tavakoli, H., Addolorato, G., et al.[2023]

Nonsmokers were significantly more likely to remain eligible for an rTMS study and complete it compared to smokers, with eligibility rates of 84.2% versus 57.4% and completion rates of 87.5% versus 59.3%.

The study suggests that smokers may require more careful screening for drug use and brain abnormalities before receiving rTMS treatment, highlighting a potential need for increased awareness of incidental MRI findings in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recruitment and Retention of Smokers Versus Nonsmokers in an rTMS Study. Sheffer, CE., Brackman, S., Mennemeier, M., 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) is generally safe and feasible for patients with neuropsychiatric disorders who also have a history of substance use, based on a review of 274 articles.

However, the impact of different levels of substance use on the safety and efficacy of rTMS remains unclear, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. Tang, VM., Ibrahim, C., Rodak, T., et al.[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]

High-frequency repetitive transcranial magnetic stimulation (rTMS) significantly reduced drug craving in patients with methamphetamine use disorder, as evidenced by lower Visual Analog Scale (VAS) scores compared to the sham group.

The 10-Hz rTMS group also showed improved decision-making abilities on the Iowa Game Test (IGT), particularly in later blocks, indicating that rTMS may enhance cognitive function in addition to reducing cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex reduces drug craving and improves decision-making ability in methamphetamine use disorder. Wang, W., Zhu, Y., Wang, L., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study. [2022]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

A transcranial magnetic stimulation protocol for decreasing the craving of methamphetamine-dependent patients. [2022]

5. 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]

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

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead. [2023]

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

Recruitment and Retention of Smokers Versus Nonsmokers in an rTMS Study. [2023]

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

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

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

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. [2023]

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

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

11. Ireland pubmed.ncbi.nlm.nih.gov

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex reduces drug craving and improves decision-making ability in methamphetamine use disorder. [2023]