rTMS for Methamphetamine Addiction

Overseen By Brandon J Cornejo, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

Must not be taking: Psychiatric medication

Disqualifiers: Neurological disorder, Psychiatric disease, Cardiovascular disease, Seizure disorder, 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: 18

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) can reduce cravings in people with methamphetamine use disorder. A special magnetic device targets a brain area believed to be involved in cravings. Participants will be divided into groups receiving either real or sham treatments and will view meth-related or neutral pictures to test their responses. This trial may suit someone who has used methamphetamine heavily for over a year, is currently abstinent, and wants to quit. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research on addiction treatment.

Will I have to stop taking my current medications?

The trial requires that participants do not currently take any psychiatric medications. If you are on such medications, you would need to stop taking them to participate.

What prior data suggests that this technique is safe for methamphetamine addiction treatment?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe. When used according to approved guidelines and with thorough pre-treatment screening, rTMS is usually well-tolerated. Serious side effects rarely occur. Most side effects, such as headaches or scalp discomfort, are mild and resolve quickly. In studies involving individuals with methamphetamine use disorder, rTMS has been used without major safety concerns. While rTMS is safe, individual responses can vary, making medical supervision essential. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about repetitive transcranial magnetic stimulation (rTMS) for methamphetamine addiction because it offers a non-invasive approach that targets brain activity directly. Unlike traditional treatments that focus on behavioral therapy or medications like bupropion and naltrexone, rTMS uses magnetic fields to stimulate nerve cells in the brain associated with addiction pathways. This method could potentially modulate cravings and improve self-control without the side effects associated with medications. By exposing participants to methamphetamine-related or neutral pictures, researchers aim to understand how visual cues impact treatment efficacy, which could lead to more personalized addiction therapies in the future.

What evidence suggests that this trial's treatments could be effective for methamphetamine addiction?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help reduce cravings in people with methamphetamine addiction. In this trial, participants will be divided into groups to receive either real or sham rTMS treatments. Studies have found a noticeable decrease in the urge to use methamphetamine with rTMS treatment. This method stimulates certain areas of the brain, potentially interrupting the brain circuits involved in craving. Early results suggest that rTMS could be a promising way to help people manage their methamphetamine addiction. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with methamphetamine use disorder who have used at least 0.5 g per day, five days a week, for over a year and are currently detoxed with a desire to quit. They must not have other drug abuses (except nicotine), serious mental health issues, neurological disorders, cardiovascular diseases or metal implants in the head/chest.

Inclusion Criteria

People who use methamphetamine must meet the criteria for a diagnosis of methamphetamine use disorder according to the DSM V.

People must meet four criteria in order to be considered for the study: they must have detoxified for at least four weeks, have a desire to stop using methamphetamine, not be pregnant, and not be taking medications that would interfere with the study.

To be eligible for this study, subjects must use METH at least 0.5 g per day, at least 5 days per week, and have a minimum 12-month history of METH abuse.

Exclusion Criteria

Present or past history of neurological disorder

The present history of a DSM IV Axis I or DSM V primary psychiatric disease (apart from MUD and depressive symptoms defined as a Hamilton Depression Scale Score < 7 ('normal')

Scores on the Hamilton Depression Scale > 8, possibly indicating clinical depression

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Induction

Participants receive 10 daily rTMS or sham treatments over 2 weeks, with visual cue exposure and craving assessments

2 weeks

10 visits (in-person)

Maintenance

Participants undergo maintenance phase with weekly rTMS or sham sessions and assessments for craving and relapse

4 weeks

6 visits (in-person)

Follow-up

Participants are contacted 6 months after treatment termination to assess long-term effects on craving and relapse

6 months

1 visit (phone)

What Are the Treatments Tested in This Trial?

Interventions

• Methamphetamine visual cues
• Neutral visual cues
• Repetitive transcranial magnetic stimulation

Trial Overview The study tests if high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) can reduce craving in meth users when directed at the brain's left frontal region. Participants will be randomly assigned to receive real or sham rTMS while being shown drug-related or neutral images over several weeks.

How Is the Trial Designed?

Group I: Treatment rTMS + meth pictures Experimental Treatment 2 Interventions

Participants in this group will receive real repetitive transcranial magnetic stimulation treatments. Before each rTMS session they will be exposed to a series of methamphetamine-related pictures to evaluate response to methamphetamine visual cues while receiving real rTMS treatments. This group will be referred to as real METH (RM).

Group II: Treatment rTMS + neutral pictures Active Control 2 Interventions

Participants in this group will receive real repetitive transcranial magnetic stimulation treatments. Before each rTMS session they will be exposed to a series of neutral pictures to evaluate response to neutral visual cues while receiving real rTMS treatments. This group will be referred to as real neutral (RN).

Group III: Sham rTMS + meth pictures Placebo Group 2 Interventions

Participants in this group will receive sham repetitive transcranial magnetic stimulation treatments. Before each rTMS session they will be exposed to a series of methamphetamine-related pictures to evaluate response to methamphetamine visual cues while receiving sham rTMS treatments. This group will be referred to as sham METH (SM).

Group IV: Sham rTMS + neutral pictures Placebo Group 2 Interventions

Participants in this group will receive sham repetitive transcranial magnetic stimulation treatments. Before each rTMS session they will be exposed to a series of neutral pictures to evaluate response to neutral visual cues while receiving sham rTMS treatments. This group will be referred to as sham neutral (SN).

Repetitive transcranial magnetic stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in Canada as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

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]

In a study involving 97 patients with severe methamphetamine use disorder (MUD), those who had better cognitive and emotional functioning were more likely to respond positively to repetitive transcranial magnetic stimulation (rTMS) treatment, indicating that these factors can help predict treatment outcomes.

Patients with MUD exhibited significant cognitive impairments and emotional disturbances compared to healthy controls, suggesting that addressing these issues may enhance the effectiveness of rTMS in reducing drug cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive and emotional predictors of real versus sham repetitive transcranial magnetic stimulation treatment response in methamphetamine use disorder. Chen, T., Su, H., Jiang, H., et al.[2021]

In a study involving 10 methamphetamine-dependent users and 8 healthy controls, low-frequency rTMS (1 Hz) of the left DLPFC significantly increased self-reported craving for methamphetamine in users compared to sham stimulation, indicating a potential mechanism for craving modulation.

The rTMS procedure was found to be safe and tolerable for all participants, suggesting that while it may enhance craving in certain individuals, it does not pose immediate safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex transiently increases cue-induced craving for methamphetamine: a preliminary study. Li, X., Malcolm, RJ., Huebner, K., et al.[2022]

Low-frequency repetitive transcranial magnetic stimulation (rTMS) effectively blocked methamphetamine-induced conditioned place preference in rats, suggesting its potential to inhibit the development of methamphetamine addiction.

The mechanism behind this effect involves a downregulation of GABABR1 expression in the dorsolateral striatum, indicating a specific neurobiological target for rTMS in treating drug addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency repetitive transcranial magnetic stimulation inhibits the development of methamphetamine-induced conditioned place preference. Wu, XQ., Zan, GY., Ju, YY., et al.[2019]

A study involving 60 participants with severe methamphetamine use disorder found that 20 sessions of intermittent theta burst rTMS significantly reduced drug cravings and induced neuroplastic changes in brain connectivity.

The reduction in craving was linked to increased functional connectivity between the left dorsolateral prefrontal cortex and the inferior parietal lobule, suggesting that rTMS may help rewire brain networks involved in addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroplastic changes in resting-state functional connectivity after rTMS intervention for methamphetamine craving. Su, H., Liu, Y., Yin, 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]

Intermittent theta burst stimulation (iTBS) applied over the dorsolateral prefrontal cortex (DLPFC) significantly reduced craving for methamphetamine and improved cognitive function and sleep quality in 126 participants with severe methamphetamine use disorder over a four-week period.

The study suggests that rTMS is a promising and safe treatment option for methamphetamine use disorder, indicating the need for further large-scale trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst transcranial magnetic stimulation for methamphetamine addiction: A randomized clinical trial. Su, H., Chen, T., Jiang, H., et al.[2021]

High-frequency repetitive transcranial magnetic stimulation (rTMS) at 10 Hz applied to the left dorsolateral prefrontal cortex (DLPFC) significantly improved behavioral adjustment in long-term methamphetamine (METH) addicts by reducing the post-error slowing effect in their response times.

After rTMS treatment, the response times of METH addicts during post-error trials became comparable to those of healthy individuals, indicating that this intervention may help restore normal cognitive functioning related to error processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intervention Effect of Repetitive TMS on Behavioral Adjustment After Error Commission in Long-Term Methamphetamine Addicts: Evidence From a Two-Choice Oddball Task. Liang, Q., Lin, J., Yang, J., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9197111/

Efficacy of Repetitive Transcranial Magnetic Stimulation in ... These meta-analyses reveal the effect of rTMS on methamphetamine cravings. In our study, the overall effect on craving was SMD = 0.983, CI = 0.620–1.345, p < ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178124002804

Transcranial magnetic stimulation for methamphetamine ... Review article. Transcranial magnetic stimulation for methamphetamine use disorder: A scoping review within the neurocircuitry model of addiction.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04883021

NCT04883021 | A Pilot Study of Repetitive Transcranial ... A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Treatment of Methamphetamine Use Disorders. ClinicalTrials.gov ID NCT04883021.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2762704

Effect of Low-Frequency Repetitive Transcranial Magnetic ... Findings In this randomized clinical trial, patients who use methamphetamine exhibited greater impulsivity than healthy control participants, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12060337/

Repetitive transcranial magnetic stimulation for stimulant use ... Cocaine and methamphetamine use disorders (CcUD/MtUD) have serious public health, medical, and psychiatric consequences.

6. medrxiv.org medrxiv.org/content/10.1101/2025.10.02.25337151v1.full.pdf

Repetitive Transcranial Magnetic Stimulation in Substance ... rTMS is generally considered safe when participants are properly screened and rTMS is applied within approved therapeutic protocols in many ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40336040/

protocol for a multi-site, double-blind, randomized controlled trial The study is a double-blind, sham-controlled trial seeking to recruit 160 participants with a current moderate to severe CcUD or MtUD diagnosis.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0165178122004954

High-frequency repetitive transcranial magnetic stimulation ... This study aims to explore the efficacy of high-frequency rTMS in reducing drug craving and increasing decision-making ability for methamphetamine use disorder ...