Brain Stimulation for Opioid Use Disorder

Overseen By Julie A Desaulniers, M.S.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Butler Hospital

Must be taking: Buprenorphine, Methadone

Disqualifiers: Organic brain disorder, Bipolar, Schizophrenia, Psychosis, Suicidality, others

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

Compensation: Varies

Number of Visits: 5

Duration: 1 week

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS), can reduce opioid cravings and prevent relapse. Participants will undergo five sessions where tDCS targets specific brain areas linked to decision-making and self-control. Two groups will participate: one will receive active stimulation, and the other will receive a sham (fake) version. Ideal candidates are those currently dealing with opioid dependence and who recently started treatment with medications like buprenorphine or methadone. As an unphased trial, this study offers participants the chance to contribute to pioneering research that could lead to innovative treatments for opioid dependence.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it requires recent initiation of buprenorphine or methadone, so you may need to continue these medications during the trial.

What prior data suggests that this brain stimulation technique is safe for opioid use disorder?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe and low-risk. Studies have found it can help reduce cravings for opioids and other drugs like methamphetamine and cocaine. Past evaluations described tDCS as a noninvasive way to adjust brain activity without major side effects.

Participants in earlier studies reported tDCS as a well-tolerated treatment, with few instances of discomfort or negative effects. This treatment has been used not only for substance use disorders but also for managing chronic pain, demonstrating its versatility and safety across different conditions. Although side effects are rare, they may include mild headaches or skin irritation where the electrodes are placed. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial Direct Current Stimulation (tDCS) for opioid use disorder because it offers a novel approach compared to traditional treatments, which often include medications like methadone or buprenorphine. Unlike these medications, tDCS is a non-invasive brain stimulation technique that targets the dorsolateral prefrontal cortex (DLPFC), a region involved in cognitive control and decision-making. This method could potentially enhance cognitive function and reduce cravings without the need for medication. Additionally, tDCS sessions are relatively quick and could fit easily into daily routines, making it a potentially convenient option for patients.

What evidence suggests that transcranial direct current stimulation is effective for opioid use disorder?

Research has shown that transcranial direct current stimulation (tDCS) may help reduce cravings for opioids. tDCS is a noninvasive method to stimulate the brain, and studies have found it can lessen the desire for substances like opioids, methamphetamine, cocaine, and tobacco. In this trial, participants will be assigned to either an active tDCS arm or a sham tDCS arm. A review of noninvasive brain stimulation methods found that tDCS could improve outcomes for people dealing with opioid use. By targeting brain areas related to cravings and self-control, tDCS might help decrease the urge to use drugs and support recovery. Early findings suggest tDCS could be a low-risk option for those with opioid use disorder. ^{1 2 3 4 6}

Who Is on the Research Team?

Abrantes Abrantes, Ph.D.

Principal Investigator

Butler Hospital

Michael Stein, M.D.

Principal Investigator

Boston University

Are You a Good Fit for This Trial?

This trial is for individuals with Opioid Use Disorder. Participants should have a history of opioid dependency but are currently seeking treatment. The study excludes those who might have other medical conditions that could interfere with the trial or pose risks.

Inclusion Criteria

Current opioid dependence

I started taking buprenorphine or methadone less than 30 days ago.

Enrolled in Butler Hospital's Alcohol and Drug Inpatient Unit, Alcohol and Drug Partial Hospital Treatment Program, Intensive Outpatient Services, or Outpatient Services at Butler Hospital OR receive opioid-treatment services in the community

Exclusion Criteria

Current suicidality

I do not have a brain disorder like Parkinson's, Huntington's, MS, or brain infection.

Probation/parole requirements or an upcoming move that might interfere with protocol participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive five sessions of tDCS+CCN priming stimulation or sham tDCS+CCN priming over consecutive business days

1 week

5 visits (in-person)

Maintenance Treatment

Participants continue buprenorphine or methadone maintenance treatment while being monitored for opioid relapse and craving

24 weeks

Follow-up

Participants are monitored for long-term neurobehavioral outcomes, including opioid relapse and craving

6 months

What Are the Treatments Tested in This Trial?

Interventions

• tDCS

Trial Overview The study tests if tDCS, a non-invasive brain stimulation technique, can reduce opioid relapse by targeting the brain's cognitive control network. It compares active tDCS to sham (placebo) treatment in a randomized setup to see long-term effects on cravings and relapse.

How Is the Trial Designed?

Group I: active tDCS Active Control 1 Intervention

Each participant will undergo 5 consecutive (i.e., business days) sessions of active tDCS delivered to the DLPFC. During each session, participants are engaging in tasks that activate the cognitive control network.

Group II: sham tDCS Placebo Group 1 Intervention

Each participant will undergo 5 consecutive (i.e., business days) sessions of sham tDCS delivered to the DLPFC. During each session, participants are engaging in tasks that activate the cognitive control network.

Who Is Running the Clinical Trial?

Butler Hospital

Lead Sponsor

Trials

133

Recruited

16,700+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a pilot study involving 28 patients with opioid use disorder on buprenorphine-naloxone, adjunctive high-definition transcranial direct current stimulation (HD-tDCS) significantly reduced cravings and withdrawal symptoms compared to a sham treatment.

Despite the reduction in cravings and withdrawal, there were no significant changes in the levels of glutamate-glutamine and GABA in the left dorsolateral prefrontal cortex, suggesting that the mechanism of action for HD-tDCS may not directly involve these neurotransmitters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive High-Definition Transcranial Direct Current Stimulation in Brain Glutamate-Glutamine and γ-Aminobutyric Acid, Withdrawal and Craving During Early Abstinence Among Patients With Opioid Use Disorder on Buprenorphine-Naloxone: A Proton Magnetic Resonance Spectroscopy-Based Pilot Study. Kumar, AS., Khanra, S., Goyal, N., et al.[2023]

A single session of transcranial direct current stimulation (tDCS) applied to the bilateral frontal-parietal-temporal areas significantly reduced craving scores in 20 long-term heroin addicts, demonstrating its potential efficacy in managing addiction-related cravings.

No side effects were reported from the tDCS treatment, indicating that it is a safe intervention for reducing cue-induced cravings in heroin addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation of the frontal-parietal-temporal area attenuates cue-induced craving for heroin. Wang, Y., Shen, Y., Cao, X., et al.[2022]

Transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) significantly reduced drug cravings in 40 former crystalline-heroin users enrolled in methadone maintenance programs, indicating its potential as a treatment for addiction.

The study demonstrated that both anodal and cathodal tDCS effectively decreased cravings compared to sham stimulation, supporting the efficacy of tDCS in managing cravings across different types of substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Drug Craving in Crystalline-Heroin Users by Transcranial Direct Current Stimulation of Dorsolateral Prefrontal Cortex. Sharifi-Fardshad, M., Mehraban-Eshtehardi, M., Shams-Esfandabad, H., et al.[2022]

Anodal transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC) significantly reduced attentional bias towards drug cues in early-abstinent methamphetamine users, suggesting a potential therapeutic effect.

The study involved 90 participants and compared different electrode montages, with specific configurations showing effectiveness in modifying attentional bias, highlighting the need for further research on optimal tDCS protocols for addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Electrode Montages of Transcranial Direct Current Stimulation for Attentional Bias Modification in Early Abstinent Methamphetamine Users. Shahbabaie, A., Hatami, J., Farhoudian, A., et al.[2020]

In a study involving 31 male patients with opioid use disorder, active transcranial direct current stimulation (tDCS) significantly reduced impulsivity compared to sham treatment, suggesting it may enhance cognitive control in these patients.

Both active and sham tDCS reduced drug craving, but only active tDCS showed a significant effect on impulsivity, indicating its potential as a complementary noninvasive treatment for opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A sham-controlled clinical trial to examine the effect of bilateral tDCS on craving, TNF-α and IL-6 expression levels, and impulsivity of males with opioid use disorder. Eskandari, Z., Mostafavi, H., Hosseini, M., et al.[2021]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

In a clinical trial with 36 male crack-cocaine users, transcranial direct current stimulation (tDCS) significantly reduced craving for crack-cocaine compared to a sham treatment, with effects lasting for 4 weeks after the sessions.

tDCS also led to decreased anxiety and improved quality of life, suggesting that it may enhance prefrontal brain function to help regulate craving behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Placebo-Controlled Trial of Targeted Prefrontal Cortex Modulation with Bilateral tDCS in Patients with Crack-Cocaine Dependence. Batista, EK., Klauss, J., Fregni, F., et al.[2022]

In a pilot study involving 38 individuals with opioid use disorder, transcranial Direct Current Stimulation (tDCS) combined with cognitive training showed significant improvements in decision making under ambiguity and executive functions, suggesting a potential new treatment approach.

The study highlights that tDCS may help alleviate cognitive deficits associated with opioid use disorder, which are crucial for preventing relapse, indicating that this method warrants further investigation as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation combined with cognitive training improves decision making and executive functions in opioid use disorder: a triple-blind sham-controlled pilot study. Aksu, S., Soyata, AZ., Şeker, S., et al.[2023]

Transcranial direct current stimulation (tDCS) has been shown to positively impact clinical measures such as craving and abstinence in individuals with substance use disorders, based on a review of 43 studies.

Despite the promising results, there is a lack of uniformity in the treatment protocols used, indicating that optimal parameters for tDCS need to be established to enhance its effectiveness for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transcranial direct current stimulation in substance use disorders: an update]. Tobback, H., Deroost, N., Baeken, C., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7221269/

Effectiveness of Transcranial Direct-Current Stimulation ... The present study was aimed to compare the effectiveness of combined Transcranial Direct-Current Stimulation (tDCS) and emotion regulation training

2. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123005711

Targeting cravings in substance addiction with transcranial ... Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11528323/

A Systematic Review of Noninvasive Brain Stimulation for ... We conducted a systematic review of studies using noninvasive brain stimulation to affect clinical outcomes related to substance use for adults with opioid use ...

4. journal.ppcr.org journal.ppcr.org/index.php/ppcrjournal/article/view/86

Transcranial Direct Current Stimulation for Opioid use disorder It has been used to reduce craving in substance use disorder (SUD). tDCS may be used in opioid use disorder to reduce craving and drug use.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05863494

Transcranial Direct Current Stimulation and Chronic Pain The overarching goal of this project is to apply transcranial direct current stimulation (tDCS) as an alternative to opioids for the reduction in chronic pain.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10262281/

Impact of Transcranial Direct Current Stimulation on Ultra- ... We found that tDCS may promote the tolerability and efficacy of treatment approaches for opioid addiction using ultra-rapid opioid detoxification. 1. Background.