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

Trial Summary

What is the purpose of this trial?

Investigators will measure behavioral and brain responses following transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) (anode on right DLPFC, cathode on the left DLPFC) delivered during cognitive control network (CCN) priming. In Phase I, the EEG provided validation of expected changes in these networks following tDCS stimulation of the DLPFC. In this current phase (II), the investigators will perform a larger randomized clinical trial (RCT) (active vs. sham control) to address long-term neurobehavioral outcomes, including opioid relapse, craving, and sustained EEG changes.

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 data supports the effectiveness of this treatment for opioid use disorder?

Research shows that transcranial direct current stimulation (tDCS) can reduce drug cravings in people with opioid use disorder and other addictions, like heroin and crack-cocaine. It works by stimulating specific brain areas, which helps decrease the desire to use drugs. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Research shows that tDCS is generally safe for humans, with no reports of serious adverse effects or irreversible injury in over 33,200 sessions across various conditions, including potentially vulnerable populations. ^{1 2 6 7 8}

How is transcranial direct current stimulation (tDCS) unique in treating opioid use disorder?

Transcranial direct current stimulation (tDCS) is unique because it uses a non-invasive method to deliver a small electrical current to specific brain areas, which can help reduce cravings and improve decision-making and cognitive functions in people with opioid use disorder. Unlike traditional drug treatments, tDCS directly targets brain activity and can be combined with cognitive training to enhance its effects. ^{1 2 5 6 9}

Research Team

Abrantes Abrantes, Ph.D.

Principal Investigator

Butler Hospital

Michael Stein, M.D.

Principal Investigator

Boston University

Eligibility Criteria

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

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

Current opioid dependence

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

Exclusion Criteria

Current suicidality

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

I don't have conditions like seizures, metal in my head (except dental work), scalp issues, severe headaches, recent brain injury, or implants affected by magnets.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A Randomized Placebo-Controlled Trial of Targeted Prefrontal Cortex Modulation with Bilateral tDCS in Patients with Crack-Cocaine Dependence. [2022]

3. Iran pubmed.ncbi.nlm.nih.gov

Modulation of Drug Craving in Crystalline-Heroin Users by Transcranial Direct Current Stimulation of Dorsolateral Prefrontal Cortex. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing Electrode Montages of Transcranial Direct Current Stimulation for Attentional Bias Modification in Early Abstinent Methamphetamine Users. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation of the frontal-parietal-temporal area attenuates cue-induced craving for heroin. [2022]

6. England 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. [2021]

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

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

[Transcranial direct current stimulation in substance use disorders: an update]. [2023]

9. England 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. [2023]