TMS for Cocaine Use Disorder

Overseen By Jessica Vincent

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Antidepressants, Antipsychotics, Stimulants, others

Disqualifiers: Substance use disorder, Heart disease, Stroke, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate sessions

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a brain stimulation method called intermittent theta burst stimulation (iTBS) to determine its effectiveness for individuals with cocaine use disorder. The researchers aim to understand how this treatment affects brain responses related to reward and attention. Participants will receive various types of brain stimulation, including a placebo version, to compare effects. This trial may suit adults who are not seeking treatment for their cocaine use but have experienced moderate symptoms and at least one positive cocaine test.

As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on innovative treatments for cocaine use disorder.

Do I need to stop taking my current medications for the trial?

The trial requires participants to stop taking certain medications that increase the risk of seizures, such as clozapine, chlorpromazine, bupropion, and others, during the study. If you are on any of these medications, you will need to stop taking them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that transcranial magnetic stimulation (TMS) targeting the dorsolateral prefrontal cortex (dlPFC) is generally safe for individuals with cocaine use disorder. Some studies found that this treatment is usually well-tolerated, with minor side effects like mild headaches or scalp discomfort, which typically resolve quickly.

For the dorsomedial prefrontal cortex (dmPFC), studies also suggest that TMS is safe and tolerable. Similar to the dlPFC studies, side effects are usually mild and temporary. Overall, both types of TMS have demonstrated a good safety record in research settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using transcranial magnetic stimulation (TMS) for treating cocaine use disorder because it offers a non-invasive alternative to traditional treatments like behavioral therapy and medications. Most treatments work by targeting the brain's reward system, but TMS directly stimulates specific brain regions involved in addiction, such as the dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC). This approach could potentially reduce cravings and improve self-control without the need for pharmaceuticals. Additionally, TMS can be precisely targeted and adjusted, allowing for personalized treatment plans, which is a unique feature not typically available with standard therapies.

What evidence suggests that this trial's treatments could be effective for cocaine use disorder?

This trial will evaluate the effects of transcranial magnetic stimulation (TMS) on different brain areas to reduce cocaine use and cravings. Studies have shown that TMS applied to specific brain regions can significantly reduce cocaine use. In this trial, participants will receive TMS targeting either the dlPFC or the dmPFC, or a sham iTBS as part of different treatment sequences. Research indicates that patients who received TMS on one part of the brain experienced long-lasting reductions in cocaine use, while TMS applied to another nearby area has shown promise in reducing cravings. A small initial study found this treatment safe and suggested it could benefit those struggling with cocaine addiction. Both treatments change brain activity in areas linked to addiction, which may help reduce the urge to seek drugs. ^{1 4 6 7 8}

Who Is on the Research Team?

Heather Webber, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults with cocaine use disorder who are not seeking treatment, have moderate to severe symptoms, and a recent positive urine test for cocaine. They must understand the consent form and provide contact details. Excluded are those with other substance disorders (except marijuana or nicotine), certain medical conditions, suicidal or homicidal risks, metal implants incompatible with TMS, unsafe medication doses, specific drug use within a week of enrollment or during the study.

Inclusion Criteria

Be able to understand the consent form and provide written informed consent

I have tested positive for cocaine use.

Meet DSM-5 criteria for current cocaine use disorder of at least moderate severity (≥ 4 symptoms)

Exclusion Criteria

I have moderate-to-severe heart disease.

Taking stimulants other than cocaine

Conditions of probation or parole requiring reports of drug use

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent theta burst stimulation (iTBS) to left dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) compared to sham

Immediate sessions

Multiple sessions (in-person)

Follow-up

Participants are monitored for changes in electrophysiological indices of reward sensitivity and motivated attention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sham iTBS
• TMS to dlPFC
• TMS to dmPFC

Trial Overview The study tests intermittent theta burst stimulation (iTBS) on two brain regions: left dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC), compared to sham treatment. It aims to see how iTBS affects reward sensitivity and attention in individuals with cocaine use disorder.

How Is the Trial Designed?

Group I: shami iTBS then dmPFC then dl PFC Experimental Treatment 3 Interventions

Group II: sham iTBS then dlPFC then dmPFC Experimental Treatment 3 Interventions

Group III: dmPFC then sham iTBS then dlPFC Experimental Treatment 3 Interventions

Group IV: dmPFC then dlPFC then sham iTBS Experimental Treatment 3 Interventions

Group V: dlPFC then sham iTBS then dmPFC Experimental Treatment 3 Interventions

Group VI: dlPFC then dmPFC then Sham iTBS Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

A proof-of-concept study involving 19 individuals with cocaine use disorder showed that administering intermittent theta-burst stimulation (iTBS) to the left dorsolateral prefrontal cortex was well-tolerated and safe, even in participants actively using cocaine.

Participants who completed at least 26 of the 30 iTBS sessions reduced their weekly cocaine use by 78% in spending and 70% in frequency, indicating that iTBS may effectively modulate addiction-related circuits and reduce substance use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. Steele, VR., Maxwell, AM., Ross, TJ., et al.[2020]

Intermittent theta burst stimulation (iTBS) and conventional 10 Hz repetitive transcranial magnetic stimulation (rTMS) showed similar effectiveness in reducing drug cravings and improving withdrawal symptoms in 20 male patients with methamphetamine use disorder (MAUD) after 12 treatments.

Both treatment methods were effective, suggesting that iTBS could be a viable alternative to 10 Hz rTMS, potentially enhancing the accessibility and cost-effectiveness of treatment for MAUD, although further large-scale studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation vs. High-Frequency Repetitive Transcranial Magnetic Stimulation in the Treatment of Methamphetamine Patients. Liu, Q., Sun, H., Hu, Y., et al.[2022]

Transcranial magnetic stimulation (TMS) can effectively reduce cravings in cocaine-dependent individuals by targeting the medial prefrontal cortex (MPFC), which is linked to limbic arousal, as shown in a preliminary study of 11 participants.

Unlike traditional TMS approaches that focus on enhancing cognitive control in the dorsolateral prefrontal cortex (DLPFC), this study suggests that decreasing MPFC activity may be a promising new strategy for treating substance cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals. Hanlon, CA., Dowdle, LT., Austelle, CW., et al.[2022]

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]

Intermittent theta burst stimulation (iTBS) of the prefrontal cortex has shown effects on reducing cocaine craving and consumption that are comparable to traditional high-frequency rTMS (15 Hz) in a study of 25 treatment-seeking cocaine addicts.

Both iTBS and 15 Hz rTMS demonstrated similar safety and tolerability profiles, with low dropout rates, suggesting that iTBS could be a more efficient treatment option due to its shorter duration (3 minutes) compared to the 15-minute standard protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study. Sanna, A., Fattore, L., Badas, P., et al.[2020]

Bilateral intermittent theta-burst stimulation (iTBS) of the prefrontal cortex showed a long-term therapeutic effect in reducing cocaine use disorder (CUD), with 69.7% of patients remaining abstinent after 12 months following treatment.

Patients who adhered to a maintenance treatment after iTBS had significantly lower dropout rates (29.63%) compared to those who did not follow maintenance (58.82%), highlighting the importance of ongoing treatment for sustaining abstinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of maintenance treatment on long-term efficacy of bilateral iTBS of the prefrontal cortex in treatment-seeking cocaine addicts: A retrospective analysis. Sanna, A., Bini, V., Badas, P., et al.[2022]

Intermittent theta burst stimulation (iTBS) over the left DLPFC and continuous theta burst stimulation (cTBS) over the right DLPFC significantly reduced cue-induced craving in abstinent methamphetamine-dependent subjects, indicating their potential efficacy as treatments for addiction.

The study involved 83 participants and showed that while iTBS had higher self-reported adverse effects initially, both stimulation methods were feasible and tolerable, suggesting a promising approach to reduce craving with shorter treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-Daily Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex Reduces Methamphetamine Craving: A Pilot Study. Zhao, D., Li, Y., Liu, T., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9379076/

Transcranial magnetic stimulation of dorsolateral prefrontal ... Out of 13 patients who completed Stage 1 in the control group, 10 patients received rTMS treatment during Stage 2 and showed significant improvement with ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178123004419

Effects of transcranial magnetic stimulation on cocaine ... A systematic review of randomized controlled trials (RCTs) was conducted on the efficacy and tolerability of rTMS in treating cocaine use disorder (CUD).

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.00158/full

Long-Term Outcome of Repetitive Transcranial Magnetic ... Conclusions: This is the first follow-up study to show that rTMS treatment is accompanied by long-lasting reductions in cocaine use in a large cohort.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03333460

Transcranial Magnetic Stimulation for Cocaine Addiction Preliminary data suggest that rTMS may help reducing cocaine craving and consumption. Researchers want to learn how the brain and the drug-seeking behavior may ...

5. medrxiv.org medrxiv.org/content/10.1101/2024.09.16.24313754v1.full.pdf

Transcranial magnetic stimulation of dorsomedial ... Transcranial magnetic stimulation of dorsomedial prefrontal cortex for cocaine use disorder: A pilot study. Heather E. Webber. 1. , L. Elliot ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26655188/

Transcranial magnetic stimulation of dorsolateral prefrontal ... We employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03607591

Study Details | NCT03607591 | Efficacy of Repetitive ... The study evaluates the efficacy of 3 weeks of repetitive transcranial magnetic stimulation (rTMS), 5 sessions/weekly, in reducing cocaine consumption ...

8. nature.com nature.com/articles/s41386-023-01776-0

A systematic review and meta-analysis of neuromodulation ... Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: a pilot study. Eur Neuropsychopharmacol. 2016;26:37 ...