Deep Brain Stimulation for Opioid Use Disorder

Overseen By Donald Whiting, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Must be taking: Methadone, Buprenorphine, Suboxone

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Prior brain surgery, Seizures, Dementia, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 24 months

3 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether deep brain stimulation (DBS) can aid individuals with opioid use disorder (OUD) who have not improved with other treatments. DBS uses electrical impulses to target a specific brain area, potentially reducing opioid cravings and relapse. The trial seeks individuals who have struggled with OUD for at least five years, have repeatedly relapsed despite treatment, and have tried various treatment options without success. Participants must not currently abuse other substances and should have completed certain medical evaluations. As an unphased trial, this study offers a unique opportunity to explore a novel treatment approach for those who have exhausted other options.

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 mentions that participants should not have active illicit substance abuse and must be part of a medication-assisted treatment program, which may include methadone or buprenorphine.

What prior data suggests that deep brain stimulation of the nucleus accumbens is safe for opioid use disorder?

Research has shown that deep brain stimulation (DBS) of the nucleus accumbens (NAc) is safe and generally well-tolerated for individuals with opioid use disorder. Studies have found that DBS of the NAc can help reduce drug use and cravings and may also improve emotional issues related to opioid addiction. In earlier trials, individuals with severe opioid addiction that did not respond to other treatments experienced fewer cravings and a lower chance of relapse with DBS of the NAc. Importantly, these studies found no major safety concerns, suggesting this treatment could be a promising option for those struggling with opioid addiction. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Deep Brain Stimulation (DBS) for Opioid Use Disorder because it offers a novel approach by directly targeting the brain's reward system. Unlike standard treatments like methadone or buprenorphine, which work by managing withdrawal symptoms and reducing cravings, DBS involves implanting electrodes in the brain's nucleus accumbens (NAc) to modulate neural activity. This method has the potential to alter the brain circuits involved in addiction, providing a new avenue for those who haven't responded to traditional therapies. By potentially addressing the root neurological pathways of addiction, DBS could revolutionize how we treat opioid dependency.

What evidence suggests that DBS of the NAc might be an effective treatment for opioid use disorder?

Research has shown that deep brain stimulation (DBS) of the nucleus accumbens (NAc) can aid individuals with opioid addiction. Studies have found that DBS reduces cravings and helps prevent relapse over time. In individuals with severe addiction, DBS proved safe and decreased drug use and cravings. Another study suggested that DBS might improve factors that increase the risk of substance use. Overall, evidence suggests that DBS of the NAc could benefit those dealing with opioid addiction. Participants in this trial will receive bilateral DBS of the NAc to further evaluate its effectiveness. ^{3 5 6 7 8}

Who Is on the Research Team?

Nestor Tomycz, MD

Principal Investigator

Allegheny Health Network

Are You a Good Fit for This Trial?

This trial is for adults over 22 with a primary diagnosis of opioid use disorder (OUD) based on DSM-V, who have struggled with OUD for at least 5 years and failed multiple treatments. Participants must not have severe psychiatric disorders or other substance abuse issues, should be in good physical health without serious infections or blood clotting problems, and cannot be pregnant.

Inclusion Criteria

Has completed a neuro-psychological evaluation to the satisfaction of a neuropsychologist

OUD must be the primary disorder

Negative blood cultures to rule out bacteremia

Exclusion Criteria

I have severe brain shrinkage or fluid/blood under my skull's lining.

I have signs of heart valve infection.

Have any other medical condition that, in the opinion of the Investigator, makes the subject unsuitable for enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Recovery

Participants undergo DBS brain electrode implantation and are admitted post-operatively for an overnight stay

1 week

1 visit (in-person, surgical)

Post-Surgery Programming and Adjustment

Two weeks after surgery, subjects undergo systematic testing and programming of DBS settings

2 weeks

Multiple visits (in-person)

Treatment

Participants receive ongoing DBS treatment with routine outpatient visits for parameter adjustments

24 months

Routine outpatient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• DBS of the NAc

Trial Overview The study tests deep brain stimulation (DBS) of the nucleus accumbens (NAc) as an additional treatment for those with hard-to-treat opioid addiction. It will include only three individuals who continue to relapse despite being in a drug treatment program.

How Is the Trial Designed?

Group I: NAc DBS Experimental Treatment 1 Intervention

Subjects will receive bilateral DBS of the NAc

Who Is Running the Clinical Trial?

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Lead Sponsor

Trials

52

Recruited

13,000+

Abbott

Industry Sponsor

Trials

760

Recruited

489,000+

Dr. Etahn Korngold

Abbott

Chief Medical Officer

MD, Harvard Medical School

Robert B. Ford

Abbott

Chief Executive Officer since 2020

Bachelor's degree from Boston College, MBA from UC Berkeley, Haas School of Business

Published Research Related to This Trial

Deep brain stimulation (DBS) targeting the nucleus accumbens (NA) shows promise in reducing addictive behaviors related to substances like alcohol and cocaine, supported by both animal studies and preliminary human observations.

While initial results from small patient series indicate potential benefits of DBS for addiction, larger, well-structured studies are necessary to establish its efficacy and safety as a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleus Accumbens as a Novel Target for Deep Brain Stimulation in the Treatment of Addiction: A Hypothesis on the Neurochemical and Morphological Basis. Vannemreddy, P., Slavin, K.[2020]

This study will evaluate the safety and efficacy of deep brain stimulation (DBS) targeting the nucleus accumbens and anterior limb of the internal capsule in 60 patients with refractory opioid dependence over a 25-week follow-up period.

The primary outcome will be the abstinence rate confirmed by urine tests, while secondary outcomes will assess changes in craving, psychological health, and overall well-being, providing a comprehensive view of DBS's impact on opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of deep brain stimulation of nucleus accumbens/anterior limb of internal capsule for opioid relapse prevention: protocol of a multicentre, prospective and double-blinded study. Qu, L., Ge, S., Li, N., et al.[2020]

High-frequency deep brain stimulation (DBS) in the nucleus accumbens (NAc) effectively prevented the reinstatement of morphine-seeking behavior in morphine-dependent rats, suggesting its potential as a treatment for opiate addiction.

The study demonstrated that DBS accelerated the natural decline of drug craving without negatively impacting learning and memory, indicating a promising therapeutic approach for severe morphine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens. Ma, Y., Chen, N., Wang, HM., et al.[2013]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAc) shows promise in reducing alcohol cravings and achieving long-term abstinence in individuals with alcohol use disorder (AUD), supported by both animal and initial human studies.

The review highlights the NAc as a key area in AUD treatment and discusses the potential of DBS as a neuromodulation strategy, while also addressing challenges and future directions for research in this field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nucleus accumbens and alcoholism: a target for deep brain stimulation. Ho, AL., Salib, AN., Pendharkar, AV., et al.[2021]

Deep brain stimulation (DBS) targeting the Nucleus Accumbens/Ventral anterior internal capsule was found to be safe for a participant with severe treatment refractory opioid and benzodiazepine use disorders, with no serious adverse events reported over a 12-month follow-up.

DBS significantly reduced substance cravings, particularly for benzodiazepines, and showed trends toward improved executive functions and heart rate variability, suggesting potential benefits for treating substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the nucleus accumbens/ventral capsule for severe and intractable opioid and benzodiazepine use disorder. Mahoney, JJ., Haut, MW., Hodder, SL., et al.[2022]

High-frequency stimulation (HFS) at 120 Hz in the nucleus accumbens during the extinction phase of morphine addiction increased conditioned place preference (CPP) scores, indicating a temporary enhancement of addictive behavior.

In contrast, HFS applied during the postextinction phase significantly reduced relapse CPP scores, suggesting that this timing of stimulation can effectively suppress drug-seeking behavior after withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of High-Frequency Electrical Stimulation of Bilateral Nucleus Accumbens on the Behavior of Morphine-Induced Conditioned Place Preference Rats at Extinction and Reinstatement Phases. Yang, C., Qiu, Y., Hu, X., et al.[2022]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAc) shows promise as a treatment for patients with treatment-refractory addiction, based on a review of 14 human studies.

The safety profile of DBS in addiction treatment is generally good, suggesting it could be a viable option for patients with severe addiction issues, particularly for those addicted to substances like heroin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleus accumbens as a stereotactic target for the treatment of addictions in humans: a literature review. Sobstyl, M., Kupryjaniuk, A., Mierzejewski, P.[2021]

This study is the first to report on deep brain stimulation (DBS) of the nucleus accumbens (NAc) in nonhuman primates, indicating its potential as a target for treating psychiatric disorders.

The bilateral electrical stimulation of the NAc was found to be safe, with no significant changes in behavior or locomotor activity observed during the stimulation period, suggesting that this model could aid in future research on NAc stimulation's clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the bilateral nucleus accumbens in normal rhesus monkey. Li, N., Gao, L., Wang, XL., et al.[2012]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12534431/

Effects of deep brain stimulation of the nucleus accumbens ... The present study suggested that DBS of the NAc/ALIC is effective for reducing heroin craving and preventing relapse in the long term and may ...

2. nature.com nature.com/articles/s41398-024-03060-1

A systematic review of deep brain stimulation for substance ... DBS targeting primarily the nucleus accumbens (NAcc), with or without the anterior limb of the internal capsule, presented encouraging levels of efficacy in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1094715922009424

O130 / #985 NUCLEUS ACCUMBENS DEEP BRAIN ... DBS of the NAc/VC is safe and well-tolerated in treatment-refractory OUD with a potential for reducing substance use, craving and ameliorating risk factors ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8422285/

Deep Brain Stimulation of the Nucleus Accumbens/Ventral ... In a participant with severe, treatment refractory opioid and benzodiazepine use disorder, DBS of the NAc/VC was safe, reduced substance use and craving, and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02440152

The Effectiveness of Deep Brain Stimulation for Opioid ... There is evidence that deep brain stimulation (DBS) of the NAcc exerts a positive effect on individuals with severe heroin addiction via inhibitory action . The ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37329519/

Safety and feasibility clinical trial of nucleus accumbens deep ... DBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD.

7. nature.com nature.com/articles/s41398-025-03635-6

Effects of deep brain stimulation of the nucleus accumbens ... The present study suggested that DBS of the NAc/ALIC is effective for reducing heroin craving and preventing relapse in the long term and may ...

8. thejns.org thejns.org/view/journals/j-neurosurg/140/1/article-p231.xml

Safety and feasibility clinical trial of nucleus accumbens deep ... DBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD.