rTMS for Reducing Smoking Cravings

Overseen By Mariya V Cherkasova, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: West Virginia University

Must not be taking: Antidepressants, Antipsychotics, Amphetamines, others

Disqualifiers: Epilepsy, Stroke, Brain lesions, 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: 3

Duration: 3-6 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different thinking strategies combined with repetitive Transcranial Magnetic Stimulation (rTMS) affect smoking cravings and brain activity. It targets smokers who smoke at least eight times a day and do not plan to quit soon. Participants will undergo rTMS while employing various mental techniques: considering the positives of smoking, the negatives, or not thinking about smoking at all. The study seeks smokers who can undergo brain scans and are not currently using other smoking treatments. As an unphased trial, it offers a unique opportunity to contribute to innovative research on smoking behaviors and brain activity.

Do I need to stop my current medications to join the trial?

The trial requires you to stop certain medications that lower the seizure threshold, such as some antidepressants and recreational drugs. If you're on varenicline or nicotine replacement therapy, you cannot participate. The protocol doesn't specify other medications, but it's best to discuss with the trial team.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that lower the seizure threshold, such as some antidepressants and recreational drugs. If you are currently using varenicline or nicotine replacement therapy, you will need to stop these before participating.

What prior data suggests that rTMS is safe for reducing smoking cravings?

Research shows that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe for helping people quit smoking. Studies indicate that it effectively reduces cravings and withdrawal symptoms. The FDA has approved rTMS for short-term use in adult smokers trying to quit.

Most clinical studies report only mild side effects, with headaches being the most common. No seizures have been reported. Overall, participants seem to tolerate rTMS well. While more research is needed, current findings are reassuring. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for smoking cessation, which often involve nicotine replacement therapies, medications like varenicline or bupropion, and behavioral counseling, the rTMS-concurrent Behavioral Priming treatment uses a novel approach by combining repetitive Transcranial Magnetic Stimulation (rTMS) with behavioral priming techniques. rTMS is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain, which can directly target brain areas involved in craving and addiction. By pairing this with behavioral priming that can either upregulate or downregulate craving responses, researchers hope to modify the brain's response to cravings more effectively. This unique combination could offer a new pathway to reducing smoking cravings, potentially leading to higher success rates in smoking cessation efforts.

What evidence suggests that rTMS-concurrent Behavioral Priming is effective for reducing smoking cravings?

Research shows that repetitive Transcranial Magnetic Stimulation (rTMS) can help reduce the urge to smoke. Studies have found that people who received rTMS reported feeling less dependent on nicotine and experienced fewer withdrawal symptoms. This suggests that rTMS might make resisting the urge to smoke easier. The treatment appears to work by influencing brain areas involved in addiction. Early results also suggest that rTMS could help people quit smoking for longer periods. In this trial, all participants will receive active rTMS paired with different types of behavioral priming to explore its effectiveness further. ^{4 6 7 8 9}

Who Is on the Research Team?

Mariya V Cherkasova, PhD

Principal Investigator

West Virginia University

Are You a Good Fit for This Trial?

This trial is for individuals who smoke at least 8 cigarettes daily, have no plans to quit in the next 3 months, and can safely undergo rTMS and fMRI. It's not specified who cannot participate, but typically those with metal implants or certain medical conditions may be excluded.

Inclusion Criteria

Able to provide written informed consent, and to follow study procedures

Dual use of cigarettes and e-cigarettes is permitted

Active cigarette smoker consuming at least 8 cigarettes a day for at least 6 months

Exclusion Criteria

Pregnancy

I have had a serious head injury in the past.

I may have a mental health condition based on a specific questionnaire score.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Training

Participants are trained on how to do upregulation and downregulation of craving

1 week

Treatment

Participants undergo 3 testing sessions with rTMS and fMRI, using different thinking strategies

3-6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in smoking cravings and brain activity

1 week

What Are the Treatments Tested in This Trial?

Interventions

• rTMS-concurrent Behavioral Priming

Trial Overview The study tests how different thinking strategies during rTMS affect smoking cravings and brain activity. Participants will try 'upregulation' (focusing on positive smoking experiences) and 'downregulation' (considering negative consequences) while viewing related images during sessions.

How Is the Trial Designed?

Group I: Active rTMS Experimental Treatment 1 Intervention

There is a single arm in this open-label pilot study. All participants will receive active rTMS paired with different types of behavioral priming (upregulation of craving, downregulation of craving, no regulation of craving).

rTMS-concurrent Behavioral Priming is already approved in United States for the following indications:

Approved in United States as rTMS for:

• Smoking cessation

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Published Research Related to This Trial

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 of 37 smokers with severe nicotine dependence, combining 1-Hz repetitive Transcranial Magnetic Stimulation (rTMS) with Nicotine Replacement Therapy (NRT) significantly increased abstinence rates, with 16 out of 18 participants in the active rTMS group remaining abstinent compared to 9 out of 19 in the sham group.

Active rTMS also led to a significant reduction in craving levels, particularly in the compulsive aspect of cravings, suggesting that rTMS may help manage withdrawal symptoms during smoking cessation, although the effects did not persist long-term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial. Trojak, B., Meille, V., Achab, S., et al.[2018]

A single session of repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) significantly reduced brain activity in areas associated with craving, specifically the medial orbitofrontal cortex (mOFC) and nucleus accumbens (NAc), in a study of 11 nicotine-dependent smokers.

These results suggest that rTMS may help decrease craving in smokers by modulating neural activity in key brain regions, indicating a potential mechanism for its anti-craving effects and supporting further research in addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers. Li, X., Sahlem, GL., Badran, BW., et al.[2018]

In a study involving 15 smokers, high-frequency rTMS (10 Hz) applied to the superior frontal gyrus (SFG) increased craving responses to smoking cues while reducing cravings for neutral cues, indicating a dual role of the SFG in craving modulation.

The findings suggest that the SFG can both enhance and inhibit craving responses, supporting its involvement in the brain's regulation of drug-seeking behaviors, which could inform future treatments for smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes. Rose, JE., McClernon, FJ., Froeliger, B., 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 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]

A single session of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex significantly reduces brain activity in the right insula and thalamus in non-treatment-seeking smokers, suggesting a potential mechanism for reducing craving.

The study, involving 10 nicotine-dependent smokers, also found that rTMS decreased connectivity between the left dorsolateral prefrontal cortex and the medial orbitofrontal cortex, indicating changes in brain networks related to craving and addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex reduces resting-state insula activity and modulates functional connectivity of the orbitofrontal cortex in cigarette smokers. Li, X., Du, L., Sahlem, GL., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12576856/

Repetitive transcranial magnetic stimulation reduces nicotine ... After 10 times of rTMS, the FTND, MNWS and VAS scores significantly decreased, when compared to baseline, and withdrawal symptoms were partially alleviated.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0925492725001325

a regional homogeneity study based on resting-state fMRI Our findings demonstrated that rTMS treatment may improve nicotine-related dependence by modulating local neural synchronization in the ...

3. mecp.springeropen.com mecp.springeropen.com/articles/10.1186/s43045-025-00558-2

Efficacy of repetitive transcranial magnetic stimulation for ... rTMS demonstrated notable potential in enhancing abstinence rates and possibly in reducing nicotine dependence with smoking cue. These effects, ...

4. academic.oup.com academic.oup.com/braincomms/article/7/2/fcaf101/8052715

Repetitive transcranial magnetic stimulation reduces smoking ... This study aimed to examine the effectiveness of rTMS in smoking cessation and to explore the underlying neural mechanism of the treatment effect.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9293555/

Repetitive Transcranial Magnetic Stimulation for Tobacco ... In general, rTMS was found to be safe for tobacco treatment with cancer patients. One participant reported back pain after sham treatment and recovered without ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8429333/

Repetitive transcranial magnetic stimulation for smoking ... Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163834325001070

Effectiveness and safety of repeated transcranial magnetic ... In this study, we conducted a meta-analysis of the effectiveness and safety of rTMS for smoking cessation based on included RCTs.

8. mecp.springeropen.com mecp.springeropen.com/articles/10.1186/s43045-025-00503-3

Efficacy and safety of repetitive transcranial magnetic ... In this study, we demonstrated that r-TMS effectively reduced withdrawal symptoms, craving, and nicotine dependence, as determined by the MNWS, ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8607981/

Transcranial Magnetic Stimulation Treatment for Smoking ... Safety outcomes were consistent with prior TMS smoking cessation trials, with no reported seizures and headache as the most common adverse event ...