Accelerated TMS for Methamphetamine Addiction

Overseen By Joseph T Sakai, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Psychotic disorders, Bipolar, Neurological disorders, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 5 days

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you have no change in your current psychiatric medication regimen for at least 4 weeks before joining. If you're not on any psychiatric medications, you can participate as well.

What data supports the effectiveness of the treatment Accelerated TMS Protocol for methamphetamine addiction?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce cravings and improve decision-making in people with methamphetamine addiction. High-frequency rTMS has been found to lower drug cravings and enhance cognitive function, suggesting it could be a promising treatment for methamphetamine use disorder. ^{1 2 3 4 5}

Is accelerated TMS safe for humans?

Accelerated TMS, including various forms like rTMS and Deep TMS, has been studied for safety in humans, showing it is generally well-tolerated with no serious adverse events reported in studies for conditions like major depression and methamphetamine addiction. ^{1 3 6 7 8}

How is Accelerated TMS different from other treatments for methamphetamine addiction?

Accelerated TMS (Transcranial Magnetic Stimulation) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, which can help reduce cravings and improve decision-making in methamphetamine addiction. Unlike traditional treatments, it does not involve medication and can be tailored with different frequencies to target specific brain functions. ^{1 2 3 4 7}

What is the purpose of this trial?

The investigators will evaluate the effects of an accelerated Transcranial Magnetic Stimulation (TMS) protocol of the left dorsolateral prefrontal cortex (DLPFC) for moderate to severe methamphetamine use disorder. This is a randomized parallel group design to assess feasibility and safety, evaluate efficacy (use, craving) and identify magnetic resonance imaging (resting state and cue craving) associated with group/outcomes.

Eligibility Criteria

This trial is for individuals with moderate to severe methamphetamine addiction. Participants must meet certain health criteria and be able to undergo MRI scans. Specific details on who can or cannot participate are not provided.

Inclusion Criteria

Able to provide informed consent

Meets DSM-5 criteria for past-year moderate or severe methamphetamine use disorder

Provides a urine drug screen positive for methamphetamine

Exclusion Criteria

Presence of a clinically significant abnormality on baseline MRI

Lifetime non-substance-induced psychotic disorders, schizophrenia, schizoaffective disorder or bipolar disorder defined by DSM-5

Current diagnosis of DSM-5 drug use disorder other than stimulant, cannabis or nicotine use disorder

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a 5-day accelerated iTBS protocol (40 treatments) to the left dorsolateral prefrontal cortex during a short inpatient stay

5 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment with weekly study visits

12 weeks

12 visits (weekly, in-person)

Treatment Details

Interventions

• Accelerated TMS Protocol

Trial Overview The study tests an accelerated TMS protocol targeting the left DLPFC, comparing active TMS treatment against a placebo-like sham TMS, to see if it's feasible, safe, and effective in reducing meth use and cravings.

Participant Groups

Group I: Active TMS Experimental Treatment 1 Intervention

Participants have baseline assessments/evaluation, are admitted to the inpatient research unit, randomized via permuted block design to 5 days of active TMS, and then have weekly study visits for the next 12 weeks.

Group II: Sham TMS Placebo Group 1 Intervention

Participants have baseline assessments/evaluation, are admitted to the inpatient research unit, randomized via permuted block design to 5 days of sham TMS, and then have weekly study visits for the next 12 weeks.

Accelerated TMS Protocol is already approved in United States, European Union, Canada, China for the following indications:

Approved in United States as Accelerated TMS Protocol for:

• Treatment-resistant depression
• Obsessive-compulsive disorder
• Migraine with aura
• Smoking cessation

Approved in European Union as Accelerated TMS Protocol for:

• Major depressive episodes
• Anxiety disorders
• Chronic pain

Approved in Canada as Accelerated TMS Protocol for:

• Major depressive disorder
• Bipolar disorder

Approved in China as Accelerated TMS Protocol for:

• Depression
• Anxiety disorders
• Substance use disorders

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

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]

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]

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 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]

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]

Accelerated Deep TMS protocols, applied multiple times a day, demonstrated an impressive 80.2% response rate and 50.5% remission rate in 111 patients with major depressive disorder, indicating their efficacy as a treatment option.

The study found that these protocols were safe, with no serious adverse events reported, and showed long-term durability of effects, with 86.7% of patients maintaining benefits after 60 days and 92.9% after 180 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world efficacy and safety of various accelerated deep TMS protocols for major depression. Roth, Y., Hanlon, CA., Pell, G., et al.[2023]

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]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

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

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. Ireland pubmed.ncbi.nlm.nih.gov

Real world efficacy and safety of various accelerated deep TMS protocols for major depression. [2023]

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

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

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]