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

Trial Summary

What is the purpose of this trial?

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 cigarettes, and to determine if the location where cTBS is delivered may help smokers reduce or quit smoking. Participation in the study will take 3-weeks over 4 visits, with a total time commitment of approximately 12 hours.

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 data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for nicotine addiction?

Research shows that rTMS can help people quit smoking by reducing cravings and cigarette consumption. In a large study, 19.4% of smokers who received active rTMS quit smoking for at least four weeks, compared to 8.7% who received a fake treatment. This suggests rTMS can be an effective aid for smoking cessation. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, as it is a non-invasive method used to treat various conditions, including depression and nicotine addiction. Studies have shown that it can be safely administered in clinical settings, with protocols established for its use in smoking cessation. ^{1 2 3 4 6}

How does the treatment rTMS differ from other treatments for nicotine addiction?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it is a non-invasive brain stimulation method that targets specific brain areas involved in addiction, such as the prefrontal cortex, to reduce cravings and cigarette consumption. Unlike traditional treatments like nicotine replacement therapy, rTMS directly influences brain activity and connectivity, offering a novel approach to smoking cessation. ^{1 2 4 7 8}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

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

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

Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial. [2018]

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. United States 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. [2023]

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

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

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. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. [2017]

8. Switzerland 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. [2022]