TMS for Nicotine Addiction

Overseen By Nicole Lalta

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Central nervous system

Disqualifiers: Neurological disorder, Bipolar, Schizophrenia, others

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: 3

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Our primary goal will be to identify the optimal prefrontal-cingulate target by systematically measuring the efficacy of various image-based targeting techniques to increase the reward positivity using the 10-Hz TMS protocol in dependent smokers. Our secondary objective will be to measure the targets' effectiveness to increase decision-making capacity using the probabilistic selection task (PST). Our third objective will be to specifically assess whether the TMS targets has a differential impact on state levels of craving relative to baseline (Tobacco Craving Questionnaire \[TCQ\]. We plan to accomplish these three objectives using a randomized, controlled experiment involving 3 sessions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on uninterruptable central nervous system medication. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of this treatment for nicotine addiction?

Research shows that repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) can reduce cigarette craving and consumption. A large study found that smokers receiving active rTMS had a higher quit rate compared to those receiving a sham treatment, indicating its potential effectiveness in helping people quit smoking. ^{1 2 3 4 5}

Is TMS safe for humans?

TMS (Transcranial Magnetic Stimulation) is generally considered safe for humans, as it is a non-invasive method used to treat various conditions, including depression and addiction. Studies have shown that it can be safely administered, with the most common side effects being mild and temporary, such as headaches or scalp discomfort. ^{1 3 4 6 7}

How is TMS treatment different from other treatments for nicotine addiction?

TMS (Transcranial Magnetic Stimulation) is unique because it noninvasively stimulates the brain, specifically targeting the left dorsolateral prefrontal cortex (DLPFC), to reduce nicotine cravings and increase abstinence rates. Unlike traditional treatments like nicotine replacement or medications, TMS directly influences brain activity related to addiction without the use of drugs. ^{1 3 8 9 10}

Research Team

Travis E Lalta, PhD

Principal Investigator

Rutgers University

Eligibility Criteria

This trial is for individuals aged 18-55 with nicotine addiction who are in good mental and physical health, can follow the study plan, and haven't had substance abuse treatment recently. Pregnant women or those with brain lesions, metal implants affecting MRI scans, or certain neurological conditions cannot participate.

Inclusion Criteria

Not received substance abuse treatment within the previous 30 days

Be willing to provide informed consent

Nicotine dependent individuals (according to the Alcohol, Smoking and Substance Involvement Screening Test nicotine dependence score)

Exclusion Criteria

I have a history of brain-related autoimmune, endocrine, viral, or vascular disorders.

I have never been diagnosed with bipolar disorder, schizophrenia, PTSD, dementia, or major depression.

Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Session A

Participants undergo MRI scanning and receive structural, fMRI, DWI, and resting-state FC scans

1 day

1 visit (in-person)

Sessions B and C

Participants receive rTMS at different prefrontal targets and complete T-maze and PST tasks

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 10-Hz TMS to the DLPFC
• Sham TMS-DLPFC

Trial Overview The study tests whether a type of brain stimulation called 10-Hz TMS aimed at the DLPFC affects reward activity in smokers. It's a controlled experiment comparing real TMS to sham (fake) treatment over three sessions to see if it helps decision-making and reduces cravings.

Participant Groups

Group I: Active TMS Experimental Treatment 1 Intervention

Participants in the active condition will receive repetitive TMS (rTMS), delivered at 110% of participants' resting motor threshold at 10 Hz continuously over the predefined prefrontal target for a total of 1000 pulses. Within each of the two TMS sessions, two targets will be stimulated.

Group II: Sham TMS Placebo Group 1 Intervention

Identical parameters will be applied to the SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation.

10-Hz TMS to the DLPFC is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Post-Traumatic Stress Disorder (PTSD)

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)

Approved in Canada as rTMS for:

• Major Depressive Disorder (MDD)

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Findings from Research

A single session of high-frequency rTMS (10 Hz) over the left dorsolateral prefrontal cortex significantly reduced cigarette craving in 16 nicotine-dependent participants, demonstrating its potential efficacy as a noninvasive treatment.

The reduction in craving was notably greater with real rTMS compared to sham treatment, suggesting that rTMS may be a promising tool for aiding smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. Li, X., Hartwell, KJ., Owens, M., et al.[2022]

In a study involving 48 chronic smokers, ten daily sessions of high-frequency transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex significantly reduced cigarette consumption and nicotine dependence.

The rTMS treatment also effectively blocked cravings triggered by smoking-related cues, although the benefits appeared to decrease over time after the treatment ended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Amiaz, R., Levy, D., Vainiger, D., et al.[2022]

A pilot study involving 24 participants with severe nicotine dependence showed that 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the left frontal pole significantly reduced craving responses to both smoking-related and neutral cues, indicating its potential efficacy in treating tobacco use disorder.

The study found a correlation between improved verbal memory recall and reduced reactivity to neutral cues, suggesting that rTMS may influence craving experiences through its effects on memory systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left frontal pole repetitive transcranial magnetic stimulation reduces cigarette cue-reactivity in correlation with verbal memory performance. Marques, RC., Marques, D., Vieira, L., et al.[2022]

A multicenter double-blind RCT involving 262 chronic smokers showed that repetitive transcranial magnetic stimulation (rTMS) significantly increased the continuous quit rate (CQR) to 19.4% compared to 8.7% for the sham treatment, indicating its efficacy in promoting smoking cessation.

This study established a safe treatment protocol for rTMS, which has now received FDA clearance as an aid for smoking cessation, marking a significant advancement in addiction medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. Zangen, A., Moshe, H., Martinez, D., et al.[2021]

In a study involving 13 smokers with schizophrenia and 14 non-psychiatric controls, high-frequency repetitive transcranial magnetic stimulation (rTMS) did not significantly reduce tobacco craving or improve cognitive function after a short-term treatment period.

Despite the lack of efficacy in modifying craving and cognitive outcomes, the study found that rTMS was safe, with no significant adverse events reported, suggesting that further long-term studies are needed to explore its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls. Kozak, K., Sharif-Razi, M., Morozova, M., et al.[2021]

Excitatory repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral pre-frontal cortex significantly reduces craving for substances in patients with dependence, with a strong effect size (Hedges' g = -0.62) based on a meta-analysis of 26 randomized controlled trials involving 748 participants.

In addition to reducing cravings, rTMS also effectively decreases substance consumption, particularly when using excitatory stimulation protocols, indicating its potential as a therapeutic intervention for substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. Zhang, JJQ., Fong, KNK., Ouyang, RG., et al.[2020]

Transcranial magnetic stimulation (TMS) has been explored in 19 studies involving 316 adults for its potential to reduce drug cravings and use, particularly targeting the dorsolateral prefrontal cortex with high-frequency pulses.

While some studies showed promising results, such as decreased smoking and cocaine use, the treatment is still experimental, and the exact mechanisms and optimal parameters for rTMS in addiction treatment remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of substance addiction. Gorelick, DA., Zangen, A., George, MS.[2022]

In a study involving 42 nicotine-dependent smokers, 10 daily sessions of MRI-guided rTMS to the left dorsal lateral prefrontal cortex significantly reduced cigarette consumption and craving, with participants smoking fewer cigarettes per day during treatment and at a one-month follow-up.

Participants receiving active rTMS were more likely to achieve smoking cessation by their target quit date (23.81% vs. 0% in the sham group), indicating that rTMS can be an effective intervention for reducing smoking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial. Li, X., Hartwell, KJ., Henderson, S., et al.[2021]

High-frequency repetitive TMS (hf rTMS) applied to the left dorsolateral prefrontal cortex significantly reduces nicotine craving in smokers who have abstained for 6 hours, indicating its potential as a smoking cessation treatment.

The study found that hf rTMS also led to a decrease in EEG delta power, which is associated with the brain's reward system, suggesting that the craving reduction may be linked to changes in dopaminergic activity, although the craving and delta power changes did not directly correlate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation of the left dorsolateral prefrontal cortex decreases cue-induced nicotine craving and EEG delta power. Pripfl, J., Tomova, L., Riecansky, I., et al.[2022]

A pilot study involving 11 tobacco-dependent smokers found that repetitive transcranial magnetic stimulation (rTMS) significantly reduced cravings for tobacco compared to a placebo, suggesting its potential as a therapeutic intervention.

Given that traditional smoking cessation methods have low success rates (around 30% abstinence after 12 months), rTMS may offer a promising alternative to help increase tobacco abstinence rates in smokers looking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation for nicotine dependence]. Johann, M., Wiegand, R., Kharraz, A., et al.[2014]

References

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

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. [2022]

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

Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Left frontal pole repetitive transcranial magnetic stimulation reduces cigarette cue-reactivity in correlation with verbal memory performance. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. [2020]

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

Transcranial magnetic stimulation in the treatment of substance addiction. [2022]

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

Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial. [2021]

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

Transcranial magnetic stimulation of the left dorsolateral prefrontal cortex decreases cue-induced nicotine craving and EEG delta power. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation for nicotine dependence]. [2014]