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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how Transcranial Magnetic Stimulation (TMS) might assist individuals with stimulant use disorder (StUD). Researchers will test various TMS applications to determine which most effectively influences brain and behavior responses. They seek adults who have been in recovery from stimulant use for at least two weeks and are currently in treatment. Participants must not have brain injuries or certain medical devices that could interfere with the study. This research aims to discover improved methods for supporting recovery from stimulant addiction. As a Phase 1 trial, the focus is on understanding how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative approach.

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 prior data suggests that transcranial magnetic stimulation is safe for treating stimulant use disorder?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally safe and well-tolerated for individuals with substance use disorders. Most side effects are mild and similar to those experienced by others undergoing TMS. The primary concern is a very low risk of seizures, occurring in less than 1% of cases. However, factors such as alcohol use or lack of sleep may increase this risk. Despite this, TMS remains widely used and considered safe for many, including those with stimulant use disorders. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about transcranial magnetic stimulation (TMS) for stimulant use disorder because it offers a unique, non-invasive approach to treatment. Unlike traditional methods that often rely on counseling or medications, TMS uses magnetic fields to stimulate specific brain areas, potentially reducing cravings and withdrawal symptoms. This technique is being optimized in different ways, like closed-loop and open-loop systems, each designed to deliver tailored brain stimulation. By directly targeting brain circuits involved in addiction, TMS holds promise for quicker and more effective relief compared to existing treatments.

What evidence suggests that transcranial magnetic stimulation is effective for stimulant use disorder?

Research has shown that transcranial magnetic stimulation (TMS) holds promise for treating stimulant use disorder. This trial will explore various TMS approaches, including closed-loop-peak, closed-loop-trough, and open-loop methods. Studies have found that repetitive TMS (rTMS) can significantly reduce cravings for stimulants, with positive effects lasting at least 30 days after treatment in some cases. Another study found that TMS helped individuals reduce cocaine use over an extended period. These findings suggest that TMS could aid in reducing stimulant use and managing cravings more effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Kelvin Lim

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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) 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 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]

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]

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]

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/PMC12060337/

Repetitive transcranial magnetic stimulation for stimulant use ... Additionally, the study aims to evaluate the efficacy of rTMS in reducing stimulant use and craving, the impact of rTMS on mood, anxiety, sleep, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2451902225001259

Deep Transcranial Magnetic Stimulation Efficacy in ... The results showed a significant and large effect of real dTMS in reducing craving scores (SMCC = −1.26; 95% CI, −1.67 to −0.86; p < .001). High ...

3. nature.com nature.com/articles/s41386-023-01776-0

A systematic review and meta-analysis of neuromodulation ... We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most ...

4. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.00158/full

Long-Term Outcome of Repetitive Transcranial Magnetic ... Conclusions: This is the first follow-up study to show that rTMS treatment is accompanied by long-lasting reductions in cocaine use in a large cohort.

5. mdpi.com mdpi.com/2035-8377/15/1/21

Transcranial Stimulation for the Treatment of Stimulant Use ... Results showed that rTMS was effective in female methamphetamine users, and the effect lasted for at least 30 days after the 20-day treatment regimen [45]. In ...

6. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(25)00373-0/fulltext

Evidence for Safety and Tolerability of Transcranial Magnetic ... TMS is safe and well-tolerated for people with SUDs. The prevalence of side effects from TMS in people with SUDs is comparable to that in the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7732158/

Transcranial Magnetic Stimulation (TMS) Safety with ... While TMS has a risk of seizure that is generally <1% overall, some situations may increase that risk, such as alcohol use, brain injury, sleep deprivation, ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1388245720305149

Safety and recommendations for TMS use in healthy ... We provide an update on TMS-induced seizures, which remains the most serious risk of this technique, although by now it is certain that such a risk is very low.

9. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression.

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

Assessment and Management of Concurrent Substance ... Regarding safety, the most important consideration is the potential elevation of the risk of rTMS-induced seizures. For the management of ...