Transcranial Magnetic Stimulation for Methamphetamine Addiction

Overseen By Ryan Carnahan, PharmD, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Iowa

Must not be taking: Clozapine, Stimulants

Disqualifiers: Epilepsy, Schizophrenia, Neurological disorder, others

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

Compensation: Varies

Number of Visits: 16

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with methamphetamine use disorder. It employs dual target transcranial magnetic stimulation (TMS), a technique that uses magnets to stimulate specific brain areas. The researchers aim to determine if this treatment can reduce cravings and improve mental health in those actively receiving support for methamphetamine use. Individuals diagnosed with methamphetamine use disorder and engaged in psychosocial treatment may be suitable for this study. Participants will undergo 16 TMS sessions over four weeks and will be monitored for changes in mood, sleep, and substance use habits over three months. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically clozapine or stimulants, if you are currently on them.

What prior data suggests that this dual target transcranial magnetic stimulation is safe for methamphetamine use disorder?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe and well-tolerated. Studies report common side effects such as mild pain in the scalp, eyes, jaw, and neck, experienced by about 39% of participants. Nausea and dizziness occur in 4% to 11% of cases. Hearing problems are rare, affecting 1% to 2% of participants. Serious side effects, like seizures, are very rare but have been reported.

Dual target TMS, which combines different TMS methods, has also demonstrated safety. One study found this type of TMS to be well-tolerated, with positive effects lasting for six months. While TMS is approved for treating major depressive disorder, its safety for methamphetamine use disorder is still under investigation. Overall, TMS remains a safe option with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about dual target Transcranial Magnetic Stimulation (TMS) for Methamphetamine Use Disorder because it offers a novel approach compared to existing treatments, which often include behavioral therapies and medications like bupropion and naltrexone. Unlike these traditional options, dual target TMS directly stimulates specific areas of the brain—the medial prefrontal cortex (MPFC) and the dorsolateral prefrontal cortex (DPFC)—which are involved in decision-making and impulse control. This method could potentially reduce cravings and withdrawal symptoms more effectively by targeting the brain circuits associated with addiction. Moreover, TMS is a non-invasive procedure, offering a less intrusive treatment option for patients.

What evidence suggests that this dual target transcranial magnetic stimulation is effective for methamphetamine use disorder?

Research has shown that transcranial magnetic stimulation (TMS) may reduce cravings and substance use in individuals with various substance use disorders. Studies involving hundreds of adults who received TMS have reported positive results in lowering drug cravings and usage. In this trial, participants will receive dual target TMS. One group will first receive stimulation of the dorsolateral prefrontal cortex (DLPFC) using intermittent theta burst stimulation (TBS), a method already approved for treating major depression, underscoring its safety and potential effectiveness. The other group will first receive stimulation of the medial prefrontal cortex (MPFC) using continuous TBS, which has been studied for reducing cocaine cravings and may also help with methamphetamine use. Overall, these findings support the potential of using TMS on two brain areas to manage methamphetamine use disorder by possibly altering brain activity linked to addiction. ^{6 7 8 9 10}

Who Is on the Research Team?

Ryan Carnahan, PharmD, MS

Principal Investigator

University of Iowa

Alison C Lynch, MD, MS

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

Inclusion Criteria

Diagnosed with an active methamphetamine use disorder

Is engaged in psychosocial treatment or articulates a plan to engage in psychosocial treatment for methamphetamine use disorder during the study period

Able to consent for treatment and research participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dual target transcranial magnetic stimulation (TMS) daily for 2 weeks, followed by three times weekly for 2 weeks

4 weeks

16 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of depressive symptoms, anxiety, sleep, craving, quality of life, and methamphetamine use

12 weeks

Monthly follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Dual Target Transcranial Magnetic Stimulation

How Is the Trial Designed?

Group I: MPFC first Experimental Treatment 1 Intervention

Participants in this arm will undergo all study procedures including consent; pre-, during, and post-psychological assessments; pre- and post- MRI and fMRI; 16 treatments of dual target TMS over a 4-week period; and substance use-related assessments to include substance use, withdrawal symptoms, and cravings to use. This arm will receive the medial prefrontal cortex stimulation first.

Group II: DPFC first Experimental Treatment 1 Intervention

Participants in this arm will undergo all study procedures including consent; pre-, during, and post-psychological assessments; pre- and post- MRI and fMRI; 16 treatments of dual target TMS over a 4-week period; and substance use-related assessments to include substance use, withdrawal symptoms, and cravings to use. This arm will receive the dorsolateral prefrontal cortex stimulation first.

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Ryan M. Carnahan

Lead Sponsor

Trials

2

Recruited

44,500+

University of New Mexico

Collaborator

Trials

393

Recruited

3,526,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

In a meta-analysis of 93 randomized controlled trials involving repetitive transcranial magnetic stimulation (TMS), the overall incidence of adverse events (AEs) was found to be higher in the active TMS group (29.3%) compared to the placebo group (13.6%), indicating a 2.60 times greater risk of experiencing AEs with active treatment.

Despite the higher incidence of AEs, TMS is considered a safe and well-tolerated intervention, with common side effects including headache and dizziness, highlighting the importance of recognizing nocebo effects in both clinical trials and practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. Zis, P., Shafique, F., Hadjivassiliou, M., et al.[2022]

The study introduces a novel electronic targeting method for transcranial magnetic stimulation (TMS) using a set of overlapping coils, allowing for faster and more precise stimulation of specific brain areas without the need for physical coil movement.

With just two coils, the device can adjust the stimulation location along a 30-mm line in the cortex, demonstrating a significant advancement in TMS technology that could enhance research and therapeutic applications in brain stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-locus transcranial magnetic stimulation-theory and implementation. Koponen, LM., Nieminen, JO., Ilmoniemi, RJ.[2019]

Mild adverse effects (MAEs) from transcranial magnetic stimulation (TMS) occur in about 5% of sessions, with most symptoms like headache and nausea reported after the sessions, particularly during initial treatments.

The study found no significant links between participant characteristics (age and gender) or TMS parameters (frequency and intensity) and the occurrence of MAEs, suggesting that initial participant anxiety may play a role in these reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. Maizey, L., Allen, CP., Dervinis, M., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

Transcranial magnetic stimulation (TMS) is a non-invasive and painless method used since 1985 to stimulate the brain and cranial nerves, with applications in both diagnostics and treatment.

Repetitive TMS can modify the excitability of the cerebral cortex, making it a promising therapeutic tool for investigating neural circuitry and treating various neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in clinical practice. Alisauskiene, M., Truffert, A., Vaiciene, N., et al.[2018]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

In a study of 63 obese individuals undergoing a 5-week rTMS treatment for weight control, the treatment showed a reassuring safety profile with no unexpected adverse events reported up to one year after treatment.

The most common side effects were moderate headaches (40.4%) and local pain/discomfort (19.2%), particularly more frequent in the high-frequency rTMS group, but overall, rTMS was well tolerated in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. Ferrulli, A., Massarini, S., Macrì, C., et al.[2021]

In a study involving 49 patients with bipolar disorder and treatment-resistant depression, sequential bilateral repetitive transcranial magnetic stimulation (rTMS) did not show a significant difference in reducing depression scores compared to sham stimulation.

The findings suggest that active sequential bilateral rTMS may not be effective for treating bipolar depression, indicating a need for future research to explore unilateral rTMS approaches instead.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A negative double-blind controlled trial of sequential bilateral rTMS in the treatment of bipolar depression. Fitzgerald, PB., Hoy, KE., Elliot, D., et al.[2019]

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