Brain Stimulation for Nicotine Addiction

Overseen By Brett Froeliger, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Missouri-Columbia

Must not be taking: Psychotropic, Antiepileptic

Disqualifiers: Neurological illness, Psychosis, Cardiac, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 3 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a type of brain stimulation called continuous theta burst stimulation (cTBS) to determine its effectiveness in helping people reduce or quit smoking. Researchers focus on how this treatment affects decision-making areas in the brain. Participants will receive stimulation in different brain areas to identify the most effective site. Individuals who have smoked at least 8 cigarettes a day for over 2 years or used 15 or more electronic cigarettes a day for over 1 year may be eligible to join. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new methods for quitting smoking.

Will I have to stop taking my current medications?

The trial requires that you have not used psychotropic (mind-affecting) or antiepileptic (seizure-preventing) medications in the last month. If you are taking these types of medications, you would need to stop before participating.

What prior data suggests that this brain stimulation technique is safe for nicotine addiction?

Previous studies have shown promising safety results for repetitive transcranial magnetic stimulation (rTMS). This technique, which includes continuous theta-burst stimulation (cTBS), is generally well-tolerated. Research shows that applying cTBS to different brain areas can help reduce cigarette cravings and consumption. For example, one article highlighted that rTMS reduced cigarette cravings without significant side effects. Another study found that cTBS, a type of rTMS, is usually safe and does not cause major side effects in participants.

These findings are encouraging, but anyone considering joining a trial should discuss potential risks and benefits with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using repetitive transcranial magnetic stimulation (rTMS) for nicotine addiction because it offers a non-invasive approach that directly targets specific brain areas involved in addiction. Unlike standard treatments such as nicotine replacement therapy and medications like varenicline or bupropion, rTMS uses magnetic fields to alter brain activity, potentially reducing cravings and withdrawal symptoms more effectively. This technique, particularly the continuous theta-burst stimulation (cTBS) applied to different regions of the prefrontal cortex, could lead to faster and more targeted results by modifying neural circuits directly linked to addiction behaviors.

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

Research shows that repetitive transcranial magnetic stimulation (rTMS), including continuous theta burst stimulation (cTBS), may help people quit smoking. In this trial, participants will receive cTBS targeting different brain areas. Studies have found that applying cTBS to the dorsomedial prefrontal cortex has helped people stop smoking. Evidence also suggests that targeting the ventrolateral prefrontal cortex with cTBS can alter brain processes related to smoking, leading to reduced smoking. Additionally, using cTBS on the vertex area of the brain has been linked to fewer nicotine cravings and less smoking. Overall, these findings support the potential of cTBS as a non-invasive treatment to help people quit smoking. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults who have been smoking at least 8 cigarettes a day for over 2 years or using e-cigarettes similarly. They must show signs of nicotine dependence, have functional vision (corrective lenses are okay), and be fluent in English. It's not suitable for those with certain conditions that the study doesn't specify.

Inclusion Criteria

I am fluent in English.

I can see well enough with glasses or contacts.

I have been a heavy smoker or vaper for at least a year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive continuous theta burst stimulation (cTBS) over 3 weeks to different brain areas to assess effects on cognitive control and smoking behavior

3 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of side effects and cognitive control

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study tests if a brain stimulation technique called continuous theta burst stimulation (cTBS) can improve cognitive control and help smokers reduce or quit. Participants will undergo cTBS sessions across four visits over three weeks, totaling about 12 hours.

How Is the Trial Designed?

Group I: cTBS to Vertex Experimental Treatment 1 Intervention

Continuous theta-burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. cTBS will be applied to the vertex.

Group II: cTBS to Ventrolateral Prefrontal Cortex Experimental Treatment 1 Intervention

Continuous theta-burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. cTBS will be applied to the ventrolateral prefrontal cortex.

Group III: cTBS to Dorsomedial Prefrontal Cortex Experimental Treatment 1 Intervention

Continuous theta-burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. cTBS will be applied to the dorsomedial prefrontal cortex.

Repetitive Transcranial Magnetic Stimulation (rTMS) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Published Research Related to This Trial

In a study involving 42 treatment-seeking smokers, 10 sessions of repetitive transcranial magnetic stimulation (rTMS) significantly reduced daily cigarette consumption by 62.93% compared to a 39.43% reduction with sham treatment, indicating its efficacy in tobacco use disorders.

fMRI results showed that rTMS increased activity in brain areas associated with executive control (dorsal anterior cingulate cortex and DLPFC) while decreasing activity in reward-related areas (medial orbitofrontal cortex), suggesting a mechanism of action that enhances self-control and reduces craving.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial. Li, X., Caulfield, KA., Hartwell, KJ., et al.[2023]

In a study of 23 participants, repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex showed that increasing the duration of treatment significantly improved the odds of smoking abstinence by 7-8 times, while increasing the intensity of sessions doubled the odds.

The research suggests that delay discounting rates, which relate to impulsivity in decision-making, could be a valuable target for smoking cessation therapies, with both duration and intensity of rTMS treatment contributing to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for Long-Term Smoking Cessation: Preliminary Examination of Delay Discounting as a Therapeutic Target and the Effects of Intensity and Duration. Shevorykin, A., Carl, E., Mahoney, MC., et al.[2022]

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 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]

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]

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 35 male schizophrenia patients, high-frequency rTMS (10Hz) over the left dorsolateral prefrontal cortex significantly reduced cigarette consumption compared to a sham treatment, with effects observed as early as the first week of stimulation.

The treatment did not correlate with changes in negative or depressive symptoms of schizophrenia, suggesting that rTMS specifically targets smoking behavior rather than overall psychiatric symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. Prikryl, R., Ustohal, L., Kucerova, HP., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11088513/

A Randomized Controlled Trial of Intermittent Theta Burst ... This study aimed to evaluate the clinical efficacy and safety of administering intermittent theta burst stimulation (iTBS) to the medial prefrontal cortex ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7113524/

Twice-Daily Theta Burst Stimulation of the Dorsolateral ... Here, we aim to compare the clinical efficacy and tolerability of intermittent and continuous theta burst stimulation protocols targeting left ...

3. withpower.com withpower.com/trial/phase-tobacco-use-disorder-2-2024-700f5

Brain Stimulation for Nicotine Addiction The purpose of the study is to examine the effects of continuous theta burst stimulation (cTBS) on different forms of cognitive control in adults who smoke ...

4. nature.com nature.com/articles/s41386-025-02106-2

Comparing neuromodulation targets to reduce cigarette ... Conventional TMS has also led to reductions in heaviness of smoking [2, 3, 8, 11, 13, 14], and improved smoking cessation outcomes [8, 15,16,17] ...

5. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20221022

Converging Evidence for Frontopolar Cortex as a Target ... Mechanistic studies and clinical trials have provided increasing evidence for the effectiveness of noninvasive neuromodulation with transcranial ...

6. reporter.nih.gov reporter.nih.gov/search/3_Z7kzD1RkSoQdTKvkQGpA/project-details/11014359

Network-Targeted Neuromodulation for Nicotine ... Current smoking cessation treatments are derived from people without psychosis and are significantly less effective for people with schizophrenia. We used a ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178123002901

Repetitive transcranial magnetic stimulation for smoking ... Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Addiction. (2009).

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

Transcranial Magnetic Stimulation Treatment for Smoking ... This article aims to introduce TMS, to provide an overview of the evidence of TMS for smoking cessation, and to outline the procedures for implementing TMS in ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2451902223001969

Effects of Hyperdirect Pathway Theta Burst Transcranial ... Despite the extant literature linking HDP-mediated IC and addictive behaviors, there are currently no evidence-based treatments that have been ...

10. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.892075/full

Accelerated Intermittent Theta Burst Stimulation in Smoking ... Our results suggest that aiTBS is a tolerable treatment. All treatment groups equally reduced cigarette consumption, nicotine dependence, craving and perceived ...