Neurostimulation for Addiction

Overseen By Joshua Brown, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Must not be taking: Psychotropics, Cancer meds, Epilepsy meds

Disqualifiers: Seizure disorder, Cognitive impairments, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new brain stimulation technologies to help people with opioid use disorders (OUDs). Researchers aim to observe how different brain areas respond to these treatments and whether they can reduce or disrupt addiction. Participants may receive various forms of brain stimulation, including traditional transcranial direct current stimulation (tDCS) and a newer method called temporal interference non-invasive deep brain stimulation (TI-NDBS). Ideal candidates are adults who smoke at least three-quarters of a pack of cigarettes daily and have a phone with internet access. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for OUDs.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain medications for ADHD, mental illness, cancer, epilepsy, migraines, or other neurological conditions.

What prior data suggests that this neurostimulation technology is safe for treating opioid use disorders?

Research shows that both treatments in this study, TI-NDBS and tDCS, are generally safe for people.

For TI-NDBS (temporal interference non-invasive deep brain stimulation), studies suggest it is well-tolerated. This method uses gentle electrical currents on the scalp to reach deep brain areas without surgery. Although it's a newer technique, no major safety issues have been reported so far.

For tDCS (transcranial direct current stimulation), extensive safety information is available. Reviews and studies indicate that tDCS does not cause lasting harm or permanent side effects. It is considered safe, even with repeated use.

Both treatments have shown minimal side effects, making them promising options for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the new neurostimulation approaches being tested for addiction because they offer innovative ways to engage the brain. Unlike traditional medications that alter brain chemistry, these treatments use electrical stimulation to directly influence brain activity. Temporal interference non-invasive deep brain stimulation (TI-NDBS) targets specific brain regions without invasive procedures, potentially offering a safer alternative with fewer side effects. Additionally, transcranial direct current stimulation (tDCS) is non-invasive and can be administered repeatedly over several days, potentially providing quick results. These approaches might open new pathways for treating addiction by altering brain circuits associated with cravings and compulsive behaviors.

What evidence suggests that this trial's treatments could be effective for opioid use disorders?

This trial will compare different neurostimulation techniques for addiction treatment. Research has shown that temporal interference non-invasive deep brain stimulation (TI-NDBS), which participants in this trial may receive, can target specific brain areas linked to addiction. Studies have found that stimulating the nucleus accumbens (NAcc) can help people stop using opioids. Non-invasive deep brain stimulation has been tested in humans and can reach deep brain areas to alter their activity.

Another method tested in this trial is transcranial direct current stimulation (tDCS). Research supports that tDCS can reduce both cravings and withdrawal symptoms in opioid addiction. Both TI-NDBS and tDCS show potential in altering brain activity related to addiction, offering hope for those struggling with opioid use disorders. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-40 who smoke at least three-quarters of a pack of cigarettes daily, can speak and read English, have at least a 6th-grade education, and own a phone with internet. Excluded are those with cranial abnormalities or metal implants, IUD users without safety documentation for MRI, pregnant individuals, those over 440 lbs., pacemaker users, people on certain medications including psychotropics or with cognitive impairments.

Inclusion Criteria

You need to smoke at least 15 cigarettes per day.

Must have phone with internet access

Must have the ability to speak and read English

Exclusion Criteria

I am on medication for ADHD, mental illness, cancer, epilepsy, migraines, neurological syndromes, or AIDS.

You have had holes or openings made in your skull in the past, or you have known cracks or breaks in the bones of your head.

I weigh less than 440 lbs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Device Feasibility

Identify the best locations for electrode placement for TI-NDBS

4 weeks

Phase 3 Treatment

Participants receive active or sham TI-NDBS for 60 minutes on one day

1 day

Phase 4 Treatment

Participants receive active TI-NDBS, sham stimulation, or traditional tDCS for 60 minutes over 5 days

5 days

Follow-up

Participants are monitored for changes in nicotine craving and smoking behavior

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Active TI-NDBS
• Sham TI-NDBS
• tDCS

Trial Overview The study is testing new non-invasive neurostimulation technologies—Active TI-NDBS and tDCS—against a sham (placebo) intervention to treat opioid use disorders by targeting specific brain regions. The goal is to disrupt addiction behaviorally and neurally as groundwork for future clinical trials.

How Is the Trial Designed?

Group I: Phase 4 TI-NDBS Experimental Treatment 1 Intervention

Participants assigned to this condition will receive active temporal interference non-invasive deep brain stimulation for 60 minutes for 5 days and will be compared to sham stimulation and tDCS.

Group II: Phase 3 Active TI-NDBS Experimental Treatment 1 Intervention

Participants assigned to this condition will receive active temporal interference non-invasive deep brain stimulation. Participants will receive stimulation for 60 minutes on one day.

Group III: Phase 4 Traditional tDCS Active Control 1 Intervention

Participants assigned to this condition will receive traditional transcranial direct current stimulation for 60 minutes for 5 days.

Group IV: Phase 4 Sham stimulation Placebo Group 1 Intervention

Participants assigned to this condition will receive sham temporal interference non-invasive deep brain stimulation, in which they will have electrodes attached to the scalp but the device is only turned on for a few seconds. Participants will be in the scanner for 60 minutes for 5 days. This will be used as the control condition and compared with TI-NDBS and tDCS.

Group V: Phase 3 Sham TI-NDBS Placebo Group 1 Intervention

Participants assigned to this condition will receive sham temporal interference non-invasive deep brain stimulation, in which they will have electrodes attached to the scalp but the device is only turned on for a few seconds.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Indiana University School of Medicine

Collaborator

Trials

194

Recruited

181,000+

Published Research Related to This Trial

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 38 healthy adults, temporal interference transcranial alternating current stimulation (TI-tACS) was found to be safe, with no significant adverse effects reported after active stimulation at 2 mA for 30 minutes.

The study showed no significant differences in neurological and neuropsychological measurements between the active TI-tACS group and the sham group, indicating that TI-tACS does not negatively impact brain function under the tested conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Employing Temporal Interference Transcranial Alternating Current Stimulation in Human Studies. Piao, Y., Ma, R., Weng, Y., 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]

Transcranial Direct Current Stimulation (tDCS) has shown cumulative effects in reducing methamphetamine cravings and associated cognitive impairments in a methamphetamine-dependent subject, indicating its potential as a therapeutic intervention.

Booster sessions of tDCS may further help in managing psychological stress and cravings, suggesting that ongoing treatment could enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative and booster effects of tdcs sessions on drug cravings, lapse, and cognitive impairment in methamphetamine use disorder: A case study report. Shariatirad, S., Vaziri, A., Hassani-Abharian, P., et al.[2022]

Non-invasive neurostimulation techniques, specifically repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), significantly reduce craving levels in individuals with substance dependence and for high palatable food, with a medium effect size of 0.476 based on 17 studies.

The analysis found no significant differences in effectiveness between rTMS and tDCS, or among different substances of abuse, indicating that both techniques are similarly effective in targeting cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of non-invasive neurostimulation on craving: a meta-analysis. Jansen, JM., Daams, JG., Koeter, MW., et al.[2022]

Transcranial direct current stimulation (tDCS) shows promise in reducing food cravings in individuals with behavioral addictions, particularly in studies focusing on eating disorders.

Only seven studies were reviewed, indicating a need for more research on the efficacy of tDCS for various behavioral addictions beyond just eating disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) in behavioral and food addiction: a systematic review of efficacy, technical, and methodological issues. Sauvaget, A., Trojak, B., Bulteau, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07210268

Temporal Interference Methods for Addiction Treatment Deep brain stimulation (DBS) of the NAcc has resulted in remission of opioid and alcohol use, while disruption of the AI has led to spontaneous ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07215299

Temporal Interference Methods for Non-invasive Deep ... The investigators will investigate whether TI stimulation can increase BOLD activity in targeted deep brain regions including the nucleus accumbens (NAcc) and ...

3. nature.com nature.com/articles/s41593-023-01456-8

Non-invasive temporal interference electrical stimulation of ... Here we report the validation of the non-invasive DBS concept in humans. We used electric field modeling and measurements in a human cadaver to ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12162641/

Advances in the application of temporal interference stimulation TIS can effectively penetrate the cerebral cortex and modulate neural activity in deep brain regions.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024055130

Quantitative analysis of noninvasive deep temporal ... Animal studies have shown promising results in using DBS to modulate brain circuits involved in addiction-related behaviors [4,17,18]. DBS is a ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04432064/temporal-interference-neurostimulation-and-addiction?activelyRecruiting=false&page=245&id=219&slug=addictions

Temporal Interference Neurostimulation and Addiction The investigators hypothesize that temporal interference non-invasive deep brain stimulation (TI-NDBS) will be well tolerated and effective ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11638170/

The safety and efficacy of applying a high-current temporal ... This study aimed to introduce a high-current TI electrical stimulation protocol to enhance its intensity and evaluate its safety and efficacy

8. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X2400130X

Temporal interference electrical neurostimulation at 20 Hz ... Temporal interference electrical neurostimulation (TI) is a relatively new method of non-invasive neurostimulation that may be able to stimulate deep brain ...