rTMS and Cognitive-Behavioral Therapy for Cocaine Use Disorder

Overseen By Elizabeth Martinez

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: New York State Psychiatric Institute

Must not be taking: Antipsychotics, Lithium, Tricyclics, others

Disqualifiers: Depression, Bipolar, Schizophrenia, others

Compensation: Varies

Number of Visits: 27

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those taking medications that lower the seizure threshold or are ototoxic. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of this treatment for cocaine use disorder?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) can help reduce cocaine use and cravings by targeting specific brain areas involved in addiction. Studies have shown that rTMS can lead to long-lasting reductions in cocaine use and improve brain function related to decision-making and self-control. ^{1 2 3 4 5}

Is rTMS safe for treating cocaine use disorder?

Research suggests that rTMS is generally safe for humans, with serious side effects being infrequent. It has been used in studies for various addictions, including cocaine, and is considered a promising treatment option. ^{2 3 5 6 7}

How does the rTMS treatment differ from other treatments for cocaine use disorder?

The rTMS treatment is unique because it uses magnetic pulses to stimulate specific brain areas involved in decision-making and self-control, which may help reduce cocaine cravings and usage. Unlike traditional treatments, it is non-invasive and targets brain circuits directly, potentially offering a new approach for those who haven't responded to other therapies. ^{1 2 3 5 8}

What is the purpose of this trial?

The goal of this clinical trial is to compare the effects of active repetitive transcranial magnetic stimulation (rTMS) to sham (placebo) rTMS prior to cognitive-behavioral therapy (CBT) as a treatment for adults with cocaine use disorder. The main questions it aims to answer are: * Is rTMS safe and feasible as an augmentation for CBT for the treatment of cocaine use disorder? * What is the brain mechanism of rTMS? * Will active rTMS (compared to sham rTMS) followed by CBT help adults with cocaine use disorder achieve abstinence from cocaine? Participants will: * Have two brain MRI scans; * Undergo 3 weeks of daily rTMS (or sham) treatments (15 sessions), and; * Have 12 weeks of once-weekly cognitive-behavioral therapy for the treatment of cocaine use disorder. Researchers will compare active (real) rTMS to sham (placebo) rTMS. All participants will receive cognitive-behavioral therapy. The former principle investigator, Dr. Derek Blevins, has vacated his position (February 2025), and has transferred the principle investigator role to Dr. John Mariani, the STARS Clinic Director.

Research Team

John Mariani, MD

Principal Investigator

New York State Psychiatric Institute

Eligibility Criteria

This trial is for adults aged 18-65 with moderate to severe cocaine use disorder who are seeking treatment. They must have used cocaine on at least 9 days in the last month and agree to limit alcohol intake and avoid certain drugs. Women must use effective contraception.

Inclusion Criteria

You are capable of providing informed consent and adhering to study protocols.

You fulfill the diagnostic criteria for current moderate to severe Cannabis Use Disorder as specified in the DSM-5 and are seeking treatment.

Age 18-65;

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

rTMS Treatment

Participants undergo 3 weeks of daily rTMS (or sham) treatments (15 sessions) targeting the mPFC/dACC

3 weeks

15 visits (in-person)

Cognitive-behavioral Therapy

Participants receive 12 weeks of once-weekly cognitive-behavioral therapy for the treatment of cocaine use disorder

12 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Active H7-coil repetitive transcranial magnetic stimulation (rTMS)
• Sham H7-coil repetitive transcranial magnetic stimulation (rTMS)

Trial Overview The study compares active rTMS, a non-invasive brain stimulation technique, with sham (placebo) rTMS before cognitive-behavioral therapy sessions for treating cocaine addiction. It explores safety, feasibility, brain mechanisms of rTMS, and its effectiveness in aiding abstinence.

Participant Groups

Group I: Active (high-frequency) rTMS Active Control 1 Intervention

Daily high-frequency (10 Hz) repetitive transcranial magnetic brain stimulation for 3 weeks (15 sessions).

Group II: Sham (placebo) rTMS Placebo Group 1 Intervention

Sham rTMS uses the same device and mimics the auditory and scalp sensations without stimulating the brain.

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Findings from Research

In a study of 44 patients with cocaine use disorder, 5-Hz repetitive transcranial magnetic stimulation (rTMS) significantly reduced cravings and impulsivity over a 2-week treatment period, indicating its potential efficacy as an adjunctive therapy.

The treatment also led to increased functional connectivity in brain regions associated with decision-making and impulse control, with effects lasting for up to 3 months, although they diminished by 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Functional Connectivity Outcomes of 5-Hz Repetitive Transcranial Magnetic Stimulation as an Add-on Treatment in Cocaine Use Disorder: A Double-Blind Randomized Controlled Trial. Garza-Villarreal, EA., Alcala-Lozano, R., Fernandez-Lozano, S., et al.[2022]

In a pilot study involving 18 participants with cocaine use disorder, high-frequency rTMS (10 Hz) significantly reduced cocaine-seeking behavior compared to baseline, indicating its potential as a treatment option.

No significant effects were observed in the low-frequency (1 Hz) or sham groups, suggesting that the efficacy of rTMS may depend on the frequency of stimulation applied to the prefrontal cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study. Martinez, D., Urban, N., Grassetti, A., et al.[2022]

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]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a noninvasive treatment for substance use disorders (SUDs) like cocaine and opioid use disorders by inducing neuroplastic changes in the brain, which can help reduce cravings and drug use.

The field faces several 'known unknowns' that need to be addressed to optimize rTMS for SUDs, including selecting the right cortical targets, understanding subcortical circuit engagement, and determining the best treatment sequences, highlighting the need for collaborative research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. Steele, VR., Maxwell, AM.[2023]

In a study of 284 outpatients with cocaine-use disorder, 3 months of repetitive transcranial magnetic stimulation (rTMS) led to significant long-lasting reductions in cocaine use, with a median time to first lapse of 91 days.

The treatment was well-tolerated, with infrequent serious adverse events, and the frequency of cocaine use dropped to less than one day per month for most patients, indicating rTMS could be a promising intervention for cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcome of Repetitive Transcranial Magnetic Stimulation in a Large Cohort of Patients With Cocaine-Use Disorder: An Observational Study. Madeo, G., Terraneo, A., Cardullo, S., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in reducing cravings for tobacco, alcohol, and cocaine when applied at high frequencies to the dorsolateral prefrontal cortex (DLPFC), based on a review of eight studies.

Repeated sessions of high-frequency rTMS over the DLPFC may be particularly beneficial for decreasing smoking and alcohol consumption, suggesting that rTMS could be a promising treatment option for drug addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. Barr, MS., Farzan, F., Wing, VC., et al.[2019]

Repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe and feasible for patients with neuropsychiatric disorders who also have a history of substance use, based on a review of 274 articles.

However, the impact of different levels of substance use on the safety and efficacy of rTMS remains unclear, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. Tang, VM., Ibrahim, C., Rodak, T., et al.[2023]

References

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

Clinical and Functional Connectivity Outcomes of 5-Hz Repetitive Transcranial Magnetic Stimulation as an Add-on Treatment in Cocaine Use Disorder: A Double-Blind Randomized Controlled Trial. [2022]

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

Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Outcome of Repetitive Transcranial Magnetic Stimulation in a Large Cohort of Patients With Cocaine-Use Disorder: An Observational Study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. [2019]

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

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. [2023]

8. France pubmed.ncbi.nlm.nih.gov

Efficacy of high-frequency (15Hz) repetitive transcranial magnetic stimulation (rTMS) of the left premotor cortex/dorsolateral prefrontal cortex in decreasing cocaine intake (the MagneTox study): A study protocol for a randomized placebo-controlled pilot trial. [2019]