TI-NDBS for Nicotine Addiction

Overseen By Kendall Moore, BS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Must not be taking: Smoking cessation, Reward processing

Disqualifiers: Seizures, Migraines, Cardiovascular, Neuropsychiatric, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new brain stimulation method can help reduce cravings and nicotine use. The technique, called temporal interference (TI), sends gentle electrical currents through the scalp to target brain areas linked to addiction. Participants will be divided into three groups: one receiving stimulation to the nucleus accumbens, another to the anterior insula, and a third group receiving a placebo. The trial targets individuals who vape frequently, using at least 15 mg of nicotine daily, and are willing to try a session after an 8-hour break from vaping. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on addiction treatment.

Do I have to stop taking my current medications for the trial?

The trial requires that you are not on any current smoking cessation treatment or medications that affect reward processing. If you are taking such medications, you may need to stop them to participate.

What prior data suggests that this non-invasive brain stimulation method is safe for reducing nicotine cravings?

Previous studies have shown that temporal interference (TI) stimulation is safe for humans. Research indicates that people generally tolerate TI stimulation well. Reports from those who have experienced it confirm that TI does not cause serious side effects when used on areas like the nucleus accumbens. Similarly, studies targeting the anterior insula with TI stimulation suggest it is safe and well-tolerated.

Non-invasive brain stimulation techniques, including TI, have effectively treated tobacco addiction. These methods work without surgery, reducing risk by focusing on stimulating specific deep brain areas involved in addiction.

While researchers continue to study TI stimulation for nicotine addiction, previous research supports its safety in humans. This makes it a promising option for those considering participation in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the TI-NDBS treatments for nicotine addiction because they use a novel technique called temporal interference (TI) stimulation. Unlike traditional methods that rely on medications or behavioral therapy, these treatments directly target specific brain regions involved in addiction. The TI Stimulation - Nucleus Accumbens arm aims to modulate the brain's reward center, potentially reducing cravings more effectively. Meanwhile, the TI Stimulation - Anterior Insula arm targets a region linked to craving and smoking behavior. By precisely stimulating these areas, TI methods could offer a new, non-invasive way to manage nicotine addiction, providing hope for those who struggle with current options.

What evidence suggests that this trial's treatments could be effective for nicotine addiction?

This trial will compare different approaches of temporal interference (TI) brain stimulation for nicotine addiction. Research has shown that TI can reach deep brain areas involved in addiction. Participants may receive TI stimulation targeted to the nucleus accumbens, which studies suggest can help people quit smoking more effectively than a fake treatment. Another group will receive TI stimulation targeted to the anterior insula, a brain area connected to cravings, where early trials suggested TI might reduce cravings by changing brain activity. These findings offer hope that TI could help decrease nicotine cravings and use in people who vape. A sham stimulation group will serve as a control, mimicking the initial sensation of active stimulation without sustained current. ^{1 2 6 7 8}

Who Is on the Research Team?

Joshua Brown

Principal Investigator

Indiana University, Bloomington

Are You a Good Fit for This Trial?

This trial is for individuals struggling with nicotine addiction from vaping. Participants must have been abstinent from nicotine for at least 8 hours before the session. The study excludes those who are pregnant, have metal implants in their head, a history of seizures, or any condition that might interfere with brain stimulation.

Inclusion Criteria

Nicotine dependent and vape at least 15 mg nicotine per day

Must have a phone with internet access

I am between 21 and 50 years old.

Exclusion Criteria

Metal implants in the head or under the scalp (excluding dental implants)

Active alcohol use disorder or history of alcohol withdrawal

My blood pressure is higher than 150mmHg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Stimulation Session

Participants undergo a single 60-minute session of temporal interference (TI) stimulation targeting either the nucleus accumbens or anterior insula, or receive sham stimulation. Craving and nicotine use are measured in real time.

1 day

1 visit (in-person)

Follow-up

Participants track nicotine use and cravings using a smartphone app for one week following the stimulation session.

7 days

Remote monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Temporal Interference Methods

Trial Overview The study tests a new non-invasive brain stimulation method called temporal interference (TI) to see if it can reduce cravings and usage of nicotine in vapers. It compares TI targeting two different brain areas against a sham (fake) treatment over one session and tracks results using an app for a week.

How Is the Trial Designed?

Group I: TI Stimulation - Nucleus Accumbens Experimental Treatment 1 Intervention

Participants in this arm will receive 60 minutes of temporal interference (TI) stimulation targeted to the nucleus accumbens (NAcc). TI will be delivered using two electrode sets, with placement determined to optimize stimulation of this region. Stimulation will use up to 2 mA per electrode at carrier frequencies of 2000 Hz and 2020 Hz, producing a 20 Hz beat frequency. Craving ratings will be collected every 10 minutes, and nicotine vapor use will be measured in real time.

Group II: TI Stimulation - Anterior Insula Experimental Treatment 1 Intervention

Participants in this arm will receive 60 minutes of temporal interference (TI) stimulation targeted to the anterior insula (AI). TI will be delivered using two electrode sets, with placement determined to optimize stimulation of this region. Stimulation will use up to 2 mA per electrode pair at carrier frequencies of 2000 Hz and 2020 Hz, producing a 20 Hz beat frequency. Craving ratings will be collected every 10 minutes, and nicotine vapor use will be measured in real time.

Group III: Sham Stimulation Placebo Group 1 Intervention

Participants in this arm will receive sham temporal interference (TI) stimulation that mimics the initial sensation of active stimulation. The current will ramp up over 30 seconds and immediately ramp back down, with no sustained current. This procedure controls for sensory experience and participant expectations. Electrode placement will mirror that used in the active conditions. Participants will complete the same craving assessments and use the same custom vape device as in the experimental arms.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

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

Temporal Interference Methods for Addiction Treatment The primary outcome is the change in self-reported craving from baseline (pre-stimulation) to the final rating at the 60-minute time point. This measure will ...

2. reporter.nih.gov reporter.nih.gov/search/DOSpEaX_vUCQOvdR2_97_g/project-details/11119339

Temporal interference methods for non-invasive deep brain ... This project explores temporal interference (TI) electrical neurostimulation as a potential new technology to test causal hypotheses about deep brain function ...

3. nature.com nature.com/articles/s41598-024-71841-1

Non-invasive temporal interference brain stimulation ... The main objective of the current study is to evaluate the effect of temporal interference (TI) brain stimulation on addictive behaviors of morphine-induced ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/00469580231221286

Transcranial Electrical Neurostimulation as a Potential ... We are investigating a new method of non-invasive deep brain stimulation, called temporal interference electrical neurostimulation (TINS), which ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11486613/

Efficacy and safety of non-invasive brain stimulation ... In terms of smoking cessation, NIBS may improve smoking abstinence rates from 3 to 6 months after quitting smoking, compared with sham [24].

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763422003104

A review of functional brain differences predicting relapse ... Neuroimaging studies have identified a variety of brain regions whose activity predicts substance use (i.e., relapse) in patients with substance use ...

7. issup.net issup.net/knowledge-share/resources/2025-10/temporal-interference-neurostimulation-novel-non-invasive

Temporal Interference Neurostimulation as a Novel Non- ... The success of the pilot study paves the way for our trial investigating TI's effects on craving and nicotine use. If validated, TI could offer ...

8. researchgate.net researchgate.net/publication/376811880_Transcranial_Electrical_Neurostimulation_as_a_Potential_Addiction_Treatment

Transcranial Electrical Neurostimulation as a Potential ... In particular, we review temporal interference electrical neurostimulation, which allows non-invasive and focal stimulation of deep brain regions. This provides ...