tDCS + TUS for Opioid Use Disorder

Recruiting at 1 trial location

Overseen By Megan Miller

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Case Western Reserve University

Must be taking: Methadone

Must not be taking: Antiepileptics

Disqualifiers: Pregnancy, Illegal stimulant use, Neurological disorders, Severe depression, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for individuals with opioid use disorder and chronic pain. It employs two techniques: transcranial Direct Current Stimulation (tDCS), a form of non-invasive brain stimulation, and Transcranial Ultrasound (TUS). The trial aims to determine if these methods can reduce drug use and improve mental health compared to a placebo treatment. Individuals who have struggled with opioid addiction for over six months or experience cravings despite treatment may be suitable candidates. Participants must live nearby and plan to remain in the area. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could significantly enhance quality of life.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have recently started on antiepileptic drugs, you may not be eligible to participate.

What prior data suggests that this protocol is safe for treating opioid use disorder?

Research has shown that using transcranial Direct Current Stimulation (tDCS) and Transcranial Ultrasound (TUS) together is generally safe and well-tolerated. A review of noninvasive brain treatments found that these methods can improve outcomes related to substance use, with few side effects reported. Previous studies suggest that tDCS is a low-risk way to help reduce cravings for opioids and other substances. Although data on side effects for this combination is limited, existing evidence from these studies supports their safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of transcranial direct current stimulation (tDCS) and transcranial ultrasound (TUS) for opioid use disorder because these non-invasive brain stimulation techniques offer a unique approach compared to traditional treatments like medications and behavioral therapies. Unlike the standard treatments that primarily focus on managing withdrawal symptoms or reducing cravings through pharmacological means, tDCS and TUS aim to directly modulate brain activity involved in addiction. This could potentially lead to a more targeted and effective way to alter the neural circuits associated with addictive behaviors, offering hope for improved outcomes in those struggling with opioid use disorder.

What evidence suggests that tDCS and TUS might be effective for opioid use disorder?

This trial will compare the effects of active transcranial Direct Current Stimulation (tDCS) combined with active Transcranial Ultrasound (TUS) against sham treatments. Research has shown that tDCS can reduce cravings for opioids by altering brain function, which is crucial for individuals with opioid use disorder. TUS also shows promise in influencing brain activity, potentially aiding in addiction treatment. Although using tDCS and TUS together is a newer approach, early studies suggest they may enhance each other's effectiveness. This combination aims to reduce drug use and improve overall well-being for those dealing with addiction and chronic pain. ^{6 7 8 9 10}

Who Is on the Research Team?

Ciro R Estebanez, MD, PhD

Principal Investigator

University Hospitals Cleveland Medical Center/ Case Western Reserve University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with opioid use disorder (OUD) and chronic pain, who have been diagnosed according to DSM-5 criteria. Participants must consent to the study, live locally without relocation plans, and can't be on high doses of methadone. Excluded are pregnant individuals, those with a history of illegal stimulant use or certain neurological disorders, recent brain surgery patients, or those on new antiepileptic drugs.

Inclusion Criteria

I have severe depression based on standard tests.

I currently have cancer.

You have metal in your head or implanted brain devices.

Exclusion Criteria

I have had fainting spells that doctors couldn't explain.

I have not consumed poppy seeds or herbal teas that could affect drug tests.

The subject is pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial Direct Current Stimulation (tDCS) and Transcranial Ultrasound (TUS) for the treatment of addiction in opiate use disorder with chronic pain

6 weeks

Weekly visits for stimulation sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Optimization of NIBS for Treatment of Addiction

Trial Overview

The study tests if transcranial Direct Current Stimulation (tDCS) combined with Transcranial Ultrasound (TUS) helps treat addiction in people with OUD and chronic pain. It compares active stimulation's effects on drug use reduction and psychosocial improvement against sham (fake) treatments.

How Is the Trial Designed?

Group I: Active (tDCS) + Active TUS Active Control 1 Intervention

Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS)

Group II: Sham (tDCS) + Sham TUS Placebo Group 1 Intervention

Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS).

Who Is Running the Clinical Trial?

Case Western Reserve University

Lead Sponsor

Trials

314

Recruited

236,000+

Highland Instruments, Inc.

Industry Sponsor

Trials

11

Recruited

650+

Published Research Related to This Trial

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]

In a study involving 13 alcoholics, repeated anodal tDCS over the left dorsolateral prefrontal cortex significantly reduced craving and depressive symptoms compared to a sham treatment, indicating its potential efficacy in managing alcohol dependence.

However, there was a concerning trend showing a higher relapse rate in the tDCS group (66.7%) compared to the sham group (14.3%), suggesting that while tDCS may improve mood and reduce cravings, it could also increase the risk of relapse, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral effects of transcranial direct current stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence. da Silva, MC., Conti, CL., Klauss, J., et al.[2022]

Transcranial direct current stimulation (tDCS) has been shown to significantly reduce cravings for substances like opioids, methamphetamine, cocaine, and tobacco, based on a systematic review of 43 randomized trials involving over 2,000 participants.

The most effective tDCS application involved bilateral stimulation with the anodal electrode on the right dorsolateral prefrontal cortex, using current intensities of 1.5 to 2 mA for 20 minutes, indicating a promising noninvasive approach to managing addiction cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting cravings in substance addiction with transcranial direct current stimulation: insights from a meta-analysis of sham-controlled trials. Chan, YH., Chang, HM., Lu, ML., et al.[2023]

In a study involving 30 patients with heroin dependency, transcranial direct current stimulation (tDCS) effectively reduced the objective measure of cigarette smoking, as indicated by lower expired CO concentrations after 5 days of treatment.

Both the active tDCS and sham control groups reported a decrease in the number of cigarettes smoked, but there was no significant difference in craving levels between the two groups, suggesting that while tDCS may help reduce smoking behavior, it does not significantly impact the desire to smoke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) may reduce the expired CO concentration among opioid users who smoke cigarettes: a randomized sham-controlled study. Lin, SH., Chen, PS., Chen, KC., et al.[2022]

Transcranial direct current stimulation (tDCS) significantly reduced negative affect in overnight abstinent smokers, as evidenced by lower scores on the Profile of Mood States (POMS) after real tDCS compared to sham stimulation.

While tDCS showed promise in improving mood, it did not significantly affect cigarette craving or attention, indicating that while it is safe and may help with negative emotions, its overall efficacy in treating tobacco dependence needs further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation reduces negative affect but not cigarette craving in overnight abstinent smokers. Xu, J., Fregni, F., Brody, AL., et al.[2021]

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 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 involving 60 participants with methamphetamine use disorder, active transcranial direct current stimulation (tDCS) did not significantly reduce self-reported drug craving compared to sham stimulation, indicating limited immediate efficacy in craving reduction.

However, neuroimaging results showed that active tDCS led to increased brain activation and connectivity in key areas associated with craving response, suggesting potential mechanisms by which tDCS may modulate neural responses to drug cues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation to modulate fMRI drug cue reactivity in methamphetamine users: A randomized clinical trial. Ekhtiari, H., Soleimani, G., Kuplicki, R., 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]

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