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

Trial Summary

What is the purpose of this trial?

The primary aim of this project is to use a randomized single-blind sham-controlled study to investigate if high frequency repetitive transmagnetic stimulation (HF-rTMS) can modulate cue-induced craving in adult methamphetamine (METH) users. The investigators hypothesize that HF-rTMS directed at left dorsolateral prefrontal cortex (DLPFC) will result in a reduction in craving for METH compared to sham-controlled rTMS in adults with methamphetamine use disorder (MUD) as evidenced by validated measures of METH craving. Neurobiologically, the investigators anticipate rTMS mediated stimulation of the DLPFC could result in inhibition of cue-induced craving through potential disruption of involved circuitry. The current project proposes that participants who are recently abstinent from METH will be randomized into four experimental groups to provide two rTMS conditions (real versus sham) and two picture cues conditions (METH versus neutral). The experiment will have an induction phase where each subject will receive 10 daily treatments within 2 weeks. Just before each rTMS/sham session participants will be shown visual cues (METH or neutral). Participants will then undergo a maintenance phase for an additional month with assessments to evaluate craving and relapse. Urine samples for urine drug screening (UDS) will be collected at screening day and on days 1, 5 and 10. Just before each rTMS/sham session participants will be shown visual cues (METH and neutral). VAS craving scores will be assessed before and after picture presentation and after the rTMS/sham session. Before the first and 10th treatment session, participants were evaluated by the the Stimulant Craving Questionnaire (STCQ) and the Severity of Dependence Scale (SDS) questionnaires. Participants will then undergo a maintenance phase for an additional month. During the first week of maintenance, three rTMS/sham sessions will be administered. During each of the following 3 weeks, one rTMS/sham session will be given per week. As with the induction phase, urine samples will be collected for screening and STCQ and the SDS questionnaires will be completed at each maintenance session. To evaluate the long-term effects of the rTMS treatment, the investigators plan on contacting participants 6 months after treatment termination for all subjects who completed the 10 treatment sessions. During that phone conversation, craving and relapse will again be assessed.

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 data supports the effectiveness of this treatment for methamphetamine addiction?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce drug cravings and improve decision-making in people with methamphetamine addiction. Studies also indicate that rTMS can change brain activity in ways that help reduce cravings and improve behavioral responses, making it a promising treatment option. ^{1 2 3 4 5}

Is rTMS safe for treating methamphetamine addiction?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered a safe and non-invasive treatment, as it has been used for various conditions like depression and neuropsychiatric disorders. Studies suggest it may also be safe for methamphetamine addiction, with no major safety concerns reported in the research. ^{1 4 6 7 8}

How does rTMS treatment differ from other treatments for methamphetamine addiction?

Repetitive transcranial magnetic stimulation (rTMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, which can reduce drug cravings and improve decision-making in methamphetamine addiction. Unlike other treatments, rTMS can induce beneficial changes in brain connectivity and neurotransmitter systems, offering a novel approach where no effective medical treatments currently exist. ^{1 2 3 4 7}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Neuroplastic changes in resting-state functional connectivity after rTMS intervention for methamphetamine craving. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Cognitive and emotional predictors of real versus sham repetitive transcranial magnetic stimulation treatment response in methamphetamine use disorder. [2021]

5. Singapore 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. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Intermittent theta burst transcranial magnetic stimulation for methamphetamine addiction: A randomized clinical trial. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Low-frequency repetitive transcranial magnetic stimulation inhibits the development of methamphetamine-induced conditioned place preference. [2019]

8. Ireland 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. [2022]