Brain Stimulation for Nicotine Addiction in Schizophrenia

Overseen By Hilary A Tindle, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must not be taking: CNS active drugs

Disqualifiers: Intellectual disability, Substance use disorder, Neurologic disorder, 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: 5

Duration: 5 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two types of brain stimulation might reduce nicotine cravings, especially in individuals with schizophrenia or related disorders. The researchers aim to determine if these treatments can alter brain connections linked to craving and whether these changes differ between those with and without psychosis. Participants will receive one type of treatment for a few days, take a break, and then try the other. This trial may suit individuals who use nicotine and either have schizophrenia or do not have any psychotic disorders. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments for nicotine cravings.

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

The trial protocol does not specify if you need to stop your current medications. However, your medications will be reviewed by a physician, and a decision will be made based on your medical history and medication details.

What prior data suggests that this brain stimulation technique is safe for nicotine-using individuals with and without psychosis?

Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) helps people with schizophrenia reduce cigarette use. This is significant because individuals with schizophrenia often struggle more to quit smoking. Research also indicates that this type of brain stimulation is generally well-tolerated.

In this trial, researchers are using specific techniques called intermittent theta burst stimulation (iTBS) and continuous theta burst stimulation (cTBS). These methods use magnetic pulses to stimulate the brain, and past research suggests they are generally safe, with no significant harmful effects reported.

Studies have not linked the treatment to major side effects, meaning no serious issues have been widely reported. Based on these findings, the treatment appears safe for humans so far. However, as with any medical procedure, individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the brain stimulation techniques being studied for nicotine addiction in individuals with schizophrenia because they offer a novel approach compared to standard treatments like nicotine replacement therapies or medications such as bupropion and varenicline. These techniques, involving network-targeted neuromodulation, use theta burst stimulation (TBS) to specifically target brain networks associated with addiction and self-control. The treatments focus on the left dorsolateral prefrontal cortex and the default mode network, aiming to directly modulate brain activity linked to craving and impulse control. This targeted approach might provide more immediate and lasting effects, offering a promising alternative for individuals who struggle with traditional methods.

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

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can reduce tobacco cravings and cigarette use in people with schizophrenia. In this trial, participants will receive different sequences of brain stimulation. One group will first receive intermittent theta burst stimulation (iTBS) targeted to the left dorsolateral prefrontal cortex (L DLPFC), followed by continuous theta burst stimulation (cTBS) targeted to the default mode network (DMN). Another group will receive the treatments in the reverse order. Studies have found that focusing on the DMN with cTBS may decrease cravings by altering brain connections related to addiction. Additionally, stimulating the L DLPFC with iTBS can affect brain circuits linked to nicotine use. This approach is under study because traditional methods for quitting smoking are often less effective for people with schizophrenia. These findings suggest that these brain stimulation techniques may offer new hope for managing nicotine addiction, especially in those with psychotic disorders. ^{1 2 4 5 6}

Who Is on the Research Team?

Heather B Ward, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals who use nicotine and have schizophrenia, as well as those without a psychotic disorder. Participants should be interested in how brain stimulation might help with nicotine cravings.

Inclusion Criteria

Diagnosis of either schizophrenia or schizoaffective disorder according to Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and confirmed by Structured Clinical Interview for the DSM (SCID) (First et al. 2015)

Current nicotine use (confirmed by expired carbon monoxide or urine cotinine)

Must be able to read, speak and understand English

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rTMS treatment targeting either the DMN or L DLPFC for five consecutive days, followed by a washout period and crossover to the other treatment.

5 weeks

5 visits (in-person) per treatment phase

Follow-up

Participants are monitored for changes in functional connectivity and craving after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Network-Targeted Neuromodulation

Trial Overview

The study tests two types of transcranial magnetic stimulation (rTMS) to see if they can alter brain activity related to nicotine use and reduce cravings. It compares the effects on people with and without psychosis.

How Is the Trial Designed?

Group I: L DLPFC-Targeted iTBS, Then DMN-Targeted cTBS Active Control 1 Intervention

Participants will first receive intermittent theta burst stimulation (iTBS) at 100% active motor threshold (AMT) anatomically targeted to the left dorsolateral prefrontal cortex for five consecutive days. iTBS will be administered in a pattern consisting of 2s trains of 3 pulses at 50Hz, repeated at 5Hz, every 10s for a total of 600 pulses. There will then be a washout period of at least two weeks before starting the DMN-Targeted cTBS. Participants will then receive continuous theta burst stimulation (cTBS) at 100% AMT targeted to an individual-specific map of the left parietal node of the default mode network for five consecutive days. cTBS will be administered in a pattern consisting of 1 60s train of 3 pulses at 50Hz, repeated at 5Hz, for a total of 600 pulses.

Group II: DMN-Targeted cTBS, Then L DLPFC-Targeted iTBS Active Control 1 Intervention

Participants will first receive continuous theta burst stimulation (cTBS) at 100% AMT targeted to an individual-specific map of the left parietal node of the default mode network for five consecutive days. cTBS will be administered in a pattern consisting of 1 60s train of 3 pulses at 50Hz, repeated at 5Hz, for a total of 600 pulses. There will then be a washout period of at least two weeks before starting the L DLPFC-Targeted iTBS. Participants will receive intermittent theta burst stimulation (iTBS) at 100% active motor threshold (AMT) anatomically targeted to the left dorsolateral prefrontal cortex for five consecutive days. iTBS will be administered in a pattern consisting of 2s trains of 3 pulses at 50Hz, repeated at 5Hz, every 10s for a total of 600 pulses.

Network-Targeted Neuromodulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Smoking cessation
• Major depressive disorder
• Obsessive-compulsive disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Smoking cessation

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Smoking cessation

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

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 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]

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]

Individuals with schizophrenia have a significantly higher prevalence of tobacco use disorder, with up to 80% smoking regularly, highlighting the need for tailored treatment approaches.

Current noninvasive brain stimulation (NIBS) methods, while effective in neurotypical smokers, have shown mixed results in treating nicotine dependence in schizophrenia, suggesting that nicotine may have unique effects in this population that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Brain Stimulation for Nicotine Dependence in Schizophrenia: A Mini Review. Ward, HB., Brady, RO., Halko, MA., 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 preliminary study involving 24 outpatients with schizophrenia and cannabis use disorder, high-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex was found to be safe and well-tolerated, with a high retention rate of about 90%.

The active rTMS group showed a trend towards reduced cannabis use and craving, along with significant improvements in psychiatric symptoms and attention, suggesting that rTMS may be an effective treatment option for cannabis use disorder in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia. Bidzinski, KK., Lowe, DJE., Sanches, M., et al.[2022]

High dose transcranial magnetic stimulation (rTMS) at 10 Hz significantly reduced negative symptoms in schizophrenia patients, particularly blunted affect, emotional withdrawal, and passive/apathetic social withdrawal, with an effective rate of 43.75% compared to 11.43% in the control group.

While rTMS was found to be effective, it was associated with a higher incidence of headaches (37.50% in the study group) compared to the control group, indicating a need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. Gan, J., Duan, H., Chen, Z., et al.[2018]

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]

Citations

1.

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 ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06389266

Study Details | NCT06389266 | Network-Targeted ...

By applying cTBS to the DMN, a target that modulates craving in schizophrenia, the investigators expect DMN connectivity to decrease, thereby decreasing craving ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12259921/

Comparing neuromodulation targets to reduce cigarette ...

Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. Prog Neuro Psychopharmacol Biol Psychiatry. 2014;49:30 ...

4.

withpower.com

withpower.com/trial/phase-tobacco-use-disorder-5-2023-e0428

Brain Stimulation for Nicotine Addiction in Schizophrenia

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce tobacco cravings and consumption in people with schizophrenia, although ...

5.

sciencedirect.com

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

Repetitive transcranial magnetic stimulation for smoking ...

Prikryl et al. Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. Prog Neuropsychopharmacol. Biol ...

6.

nature.com

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

Comparing neuromodulation targets to reduce cigarette ...

Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. Prog Neuro Psychopharmacol Biol ...