rTMS for Methamphetamine Addiction

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Approved in 3 Jurisdictions

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

Trial 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 (Behavioural Intervention)
• Neutral visual cues (Behavioural Intervention)
• Repetitive transcranial magnetic stimulation (Procedure)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Veterans Affairs Portland Health Care System Portland, OR

Who Is Running the Clinical Trial?

Oregon Health and Science University Lead Sponsor

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] Methamphetamine abuse is escalating worldwide. Its strong and irreversible neurotoxicity generally causes structural and functional changes in the brain. Repetitive transcranial magnetic stimulation (rTMS) as a non-invasive tool can be used to modulate neuronal activity, cortical excitability, and dopaminergic neurotransmission. This study aims to explore the efficacy of high-frequency rTMS in reducing drug craving and increasing decision-making ability for methamphetamine use disorder patients. Sixty-four methamphetamine use disorder patients were randomized to sham rTMS group and 10-Hz rTMS group. Visual analog scale (VAS) and Iowa game test (IGT) were used to evaluate drug craving and cognitive decision-making ability before and after treatment. Before the treatment, the two groups had no differences in the scores of VAS and IGT. After the intervention, VAS scores of 10-Hz rTMS group were significantly lower than that of sham rTMS group. In addition, the two groups had significant differences in the net score of IGT on block 4 and block 5, which favoured the 10-Hz rTMS group. Taken together, the present results suggest that High-frequency rTMS can be used to reduce drug craving and improve decision-making function for methamphetamine use disorder.

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

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders. [2020] Cocaine use disorder and methamphetamine use disorder are chronic, relapsing disorders with no US Food and Drug Administration-approved interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool that has been increasingly investigated as a possible therapeutic intervention for substance use disorders. rTMS may have the ability to induce beneficial neuroplasticity in abnormal circuits and networks in individuals with addiction. The aim of this review is to highlight the rationale and potential for rTMS to treat cocaine and methamphetamine dependence: we synthesize the outcomes of studies in healthy humans and animal models to identify and understand the neurobiological mechanisms of rTMS that seem most involved in addiction, focusing on the dopaminergic and glutamatergic systems. rTMS-induced changes to neurotransmitter systems include alterations to striatal dopamine release and metabolite levels, as well as to glutamate transporter and receptor expression, which may be relevant for ameliorating the aberrant plasticity observed in individuals with substance use disorders. We also discuss the clinical studies that have used rTMS in humans with cocaine and methamphetamine use disorders. Many such studies suggest changes in network connectivity following acute rTMS, which may underpin reduced craving following chronic rTMS. We suggest several possible future directions for research relating to the therapeutic potential of rTMS in addiction that would help fill current gaps in the literature. Such research would apply rTMS to animal models of addiction, developing a translational pipeline that would guide evidence-based rTMS treatment of cocaine and methamphetamine use disorder.

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

Neuroplastic changes in resting-state functional connectivity after rTMS intervention for methamphetamine craving. [2021] Amphetamine-type stimulants are the second most commonly abused illicit drug worldwide, with no effective medical treatments currently available. Previous studies have demonstrated that high frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) reduced cue-induced craving in patients with methamphetamine dependence. However, the neuroplastic mechanism underlying rTMS intervention in methamphetamine users remains to be elucidated. Sixty participants (40 males) with severe methamphetamine use disorder according to DSM-5 were randomized to receive either intermittent theta burst protocols (iTBS) (short bursts of 50 Hz rTMS repeated at a rate in the theta range (5 Hz), 2-sec on, 8-sec off for 5 min; 900 pulses) or sham rTMS over the DLPFC over four weeks (20 daily sessions). Resting state functional connectivity magnetic resonance imaging was acquired before and after rTMS intervention. Participants received drug related cue exposure and rated their craving before and after stimulation. Seed-based functional connectivity analysis was performed to probe rTMS-induced neuroplastic reorganization of brain functional networks. Results showed that twenty daily rTMS sessions decreased craving, increased functional connectivity between left DLPFC and inferior parietal lobule, and decreased functional connectivity between insula and inferior parietal lobule, medial temporal lobe and precuneus. Moreover, the increase of functional connectivity between DLPFC and inferior parietal lobule correlated with craving reduction. This study suggests that neuroplastic changes of frontoparietal functional connectivity contributes to craving reduction, shedding light on the therapeutic effect of rTMS on methamphetamine use disorder. This article is part of the special issue on Stress, Addiction and Plasticity.

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] Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) can effectively reduce cravings in methamphetamine use disorder (MUD). However, a considerable group still fails to respond. Cognitive and emotional disturbance, as well as impulsive features, are widespread in patients with MUD and might mediate the treatment response of rTMS. The purpose of this study is to figure out whether these variables can help predicting patients' responses to rTMS treatment.

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] Behavioral adjustment plays an important role in the treatment and relapse of drug addiction. Nonetheless, few studies have examined behavioral adjustment and its plasticity following error commission in methamphetamine (METH) dependence, which is detrimental to human health. Thus, we investigated the behavioral adjustment performance following error commission in long-term METH addicts and how it varied with the application of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Twenty-nine male long-term METH addicts (for > 3 years) were randomly assigned to high-frequency (10 Hz, n = 15) or sham (n = 14) rTMS of the left DLPFC during a two-choice oddball task. Twenty-six age-matched, healthy male adults participated in the two-choice oddball task pretest to establish normal performance for comparison. The results showed that 10 Hz rTMS over the left DLPFC significantly decreased the post-error slowing effect in response times of METH addicts. In addition, the 10 Hz rTMS intervention remarkably reduced the reaction times during post-error trials but not post-correct trials. While the 10 Hz rTMS group showed a more pronounced post-error slowing effect than the healthy participants during the pretest, the post-error slowing effect in the posttest of this sample was similar to that in the healthy participants. These results suggest that high-frequency rTMS over the left DLPFC is a useful protocol for the improvement of behavioral adjustment after error commission in long-term METH addicts.

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

Intermittent theta burst transcranial magnetic stimulation for methamphetamine addiction: A randomized clinical trial. [2021] Methamphetamine is the most commonly used illicit drug in China. We previously demonstrated that 10 Hz rTMS over the DLPFC reduces craving in methamphetamine users. Here, we applied intermittent theta burst stimulation (iTBS), a new form of rTMS, in a large sample at four clinical centers. 126 participants (age 31.64 ± 6.33; 106 men) with severe methamphetamine use disorder according to DSM-5 were randomized to receive either iTBS or sham over the DLPFC for four weeks (20 daily sessions, 900 pulses per day). Cue-induced craving and cognitive function were assessed before and after rTMS intervention. Relapse was followed up by urine test after discharge from the rehabilitation center. iTBS significantly reduced craving and improved cognition and sleep quality. This study suggests that rTMS may be a useful and safe treatment option for methamphetamine use disorder, warranting future large scale trials.

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

Low-frequency repetitive transcranial magnetic stimulation inhibits the development of methamphetamine-induced conditioned place preference. [2019] The abuse of amphetamine-type stimulants (ATS) has become a global public health issue in recent years, these new-type drugs can cause addiction and serious cognitive impairment. However, there are no effective methods for the prevention and treatment of ATS addiction at present. Repetitive transcranial magnetic stimulation (rTMS) is a painless and non-invasive new therapeutic approach that has been used for the treatment of depression and other neuropsychiatric disorders, but whether it can be used to treat drug addiction is unclear. In the present study, we investigated the possible effects of rTMS on methamphetamine(METH)-induced conditioned place preference (CPP). High-frequency (10&#8239;Hz) and low-frequency stimulation patterns (1&#8239;Hz) were applied to test the effect of rTMS on METH-induced CPP. The results showed that low-frequency but not high-frequency rTMS could block METH-CPP, accompanied with a downregulation of gamma-aminobutyric acid type B receptor subunit 1 (GABABR1) expression in rat dorsolateral striatum. These results suggested that low-frequency rTMS could effectively inhibit the development of METH addiction and shed light on the rTMS as a potential approach for the prevention of drug addiction.

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] Repetitive transcranial magnetic stimulation (rTMS) can temporarily interrupt or facilitate activity in a focal brain region. Several lines of evidence suggest that rTMS of the dorsolateral prefrontal cortex (DLPFC) can affect processes involved in drug addiction. We hypothesized that a single session of low-frequency rTMS of the left DLPFC would modulate cue-induced craving for methamphetamine (MA) when compared to a sham rTMS session.