tDCS + Varenicline for Smoking Cessation

Overseen By Laurie A Zawertailo, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Centre for Addiction and Mental Health

Must be taking: Varenicline

Must not be taking: Buproprion, NRT, Cytisine

Disqualifiers: Unstable psychiatric illness, Seizures, Pregnancy, Pacemakers, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining brain stimulation (a non-invasive electrical treatment) with varenicline (a medication that aids smoking cessation) helps people quit smoking more effectively than the medication alone. The researchers aim to determine if this combination improves quitting rates in both the short and long term and to assess its safety. Individuals who smoke at least 8 cigarettes a day and wish to quit may be suitable for this study. Participants must attend regular sessions over a period to receive treatment and monitor their progress. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand its benefits for more patients, offering a chance to contribute to valuable research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used smoking cessation medications in the past 3 months.

What is the safety track record for active tDCS plus varenicline?

Research has shown that using transcranial direct current stimulation (tDCS) with varenicline is generally safe. Studies have found that tDCS can help people smoke fewer cigarettes without causing serious side effects. Varenicline, approved by the FDA to help people quit smoking, has a well-known safety record. Some individuals might experience mild side effects like nausea or vivid dreams with varenicline, but these are usually manageable.

Previous research combining tDCS with varenicline did not reveal any new or unexpected side effects compared to using each treatment alone. Since this study is in a later phase, earlier research has reviewed and confirmed the combination's safety. While some mild side effects might occur, the treatment is expected to be safe for most participants. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this treatment because it combines two innovative approaches to help people quit smoking. Unlike most treatments that primarily rely on medications like nicotine replacement therapy or bupropion, this approach uses transcranial direct current stimulation (tDCS) and varenicline. tDCS is a non-invasive brain stimulation technique that may help reduce cravings by altering brain activity, while varenicline targets nicotine receptors to reduce withdrawal symptoms. This dual-action strategy could enhance the effectiveness of smoking cessation efforts by addressing both the behavioral and biochemical aspects of addiction.

What evidence suggests that this trial's treatments could be effective for smoking cessation?

Research has shown that varenicline, a medication often used to help people quit smoking, effectively increases the number of successful quitters. One study found that 40% of people using varenicline quit smoking after 12 weeks. Another study showed that varenicline users had more success than those using bupropion.

Regarding brain stimulation, studies have found that transcranial direct current stimulation (tDCS) can help reduce cigarette cravings. One study found that people who received tDCS for 12 weeks achieved good results in quitting smoking. In this trial, participants in the experimental group will receive active tDCS along with varenicline. Additionally, a small study suggested that combining tDCS with varenicline could double varenicline's effectiveness. These findings suggest that this combination might be a promising way to quit smoking. ^{1 6 7 8 9}

Who Is on the Research Team?

Laurie A Zawertailo, PhD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for individuals seeking to quit smoking and are struggling with tobacco use disorder. Participants should be willing to undergo daily sessions of tDCS and take varenicline as prescribed. Specific eligibility details were not provided, so interested individuals should inquire further.

Inclusion Criteria

Is seeking treatment for tobacco dependence

Be able to provide informed written consent

Smoke ≥ 8 cigarettes per day (CPD)

Exclusion Criteria

Current regular use of nicotine-containing products besides cigarettes (e.g. electronic cigarettes, etc.)

Current pacemakers or implanted electrical devices

I have used smoking cessation aids in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active tDCS sessions plus 12 weeks of varenicline. The tDCS treatment includes 10 daily sessions for the first 2 weeks, followed by 5 bi-weekly booster sessions.

12 weeks

10 visits (2 in-person, 8 virtual) for initial sessions, 5 in-person booster sessions

Follow-up

Participants are monitored for smoking behavior at 6- and 12-months post-treatment.

12 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active Transcranial Direct Current Stimulation (tDCS)
• Sham Transcranial Direct Current Stimulation (tDCS)
• Varenicline

Trial Overview The study tests if active tDCS combined with the medication varenicline helps people stop smoking better than a sham (fake) tDCS plus varenicline. It includes daily sessions for two weeks, bi-weekly boosters thereafter, and follow-ups at 6 and 12 months.

How Is the Trial Designed?

Group I: Experimental Group (Active tDCS plus Varenicline) Active Control 2 Interventions

The experimental group will receive active tDCS sessions plus 12 weeks of 1 mg varenicline bid. Participants will start varenicline treatment on the same day as the first tDCS session, and will follow a standard dose escalation schedule. The tDCS treatment schedule includes 10 daily sessions for the first 2 weeks (M to F), followed by 5 single bi-weekly booster sessions for the remainder of the treatment period. Participants will come in-person for two follow-up sessions to assess smoking behaviour at 6- and 12-months post-treatment.

Group II: Control Group Placebo Group 2 Interventions

The control group will receive sham (fake) tDCS sessions plus 12 weeks of 1 mg varenicline bid. Participants will start varenicline treatment on the same day as the first tDCS session, and will follow a standard dose escalation schedule. The tDCS treatment schedule includes 10 daily sessions for the first 2 weeks (M to F), followed by 5 single bi-weekly booster sessions for the remainder of the treatment period. Participants will come in-person for two follow-up sessions to assess smoking behaviour at 6- and 12-months post-treatment.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

This study investigates the effectiveness of transcranial Direct Current Stimulation (tDCS) combined with varenicline for smoking cessation in a double-blind, sham-controlled trial involving 50 healthy smokers over a 12-week treatment period.

The primary goal is to determine if active tDCS can improve 30-day continuous abstinence rates compared to sham tDCS, while also using MRI scans to explore potential changes in brain structure and function related to addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: Study protocol for a double-blind single dummy randomized controlled trial. Zawertailo, L., Zhang, H., Rahmani, N., et al.[2023]

In a randomized sham-controlled trial involving 44 participants, both active and sham tDCS groups showed a significant decrease in daily cigarette consumption and craving, but there were no improvements in executive functions, indicating that the effects may not be due to the stimulation itself.

The study suggests that high perceived stress and low self-control may predict successful reductions in cigarette consumption, highlighting the potential influence of psychological factors over the effects of tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of perceived stress and self-control on efficacy of repeated transcranial direct current stimulation in non-treatment-seeking smokers. Müller, T., Shevchenko, Y., Gerhardt, S., et al.[2021]

In a study involving 30 patients with heroin dependency, transcranial direct current stimulation (tDCS) effectively reduced the objective measure of cigarette smoking, as indicated by lower expired CO concentrations after 5 days of treatment.

Both the active tDCS and sham control groups reported a decrease in the number of cigarettes smoked, but there was no significant difference in craving levels between the two groups, suggesting that while tDCS may help reduce smoking behavior, it does not significantly impact the desire to smoke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) may reduce the expired CO concentration among opioid users who smoke cigarettes: a randomized sham-controlled study. Lin, SH., Chen, PS., Chen, KC., et al.[2022]

Transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) significantly reduced cigarette craving by about 50% in a study of 20 smokers, indicating its potential as a treatment for smoking addiction.

While the number of cigarettes smoked did not change, the study suggests that tDCS may be more effective for smokers with higher nicotine dependence and motivation to quit, highlighting the need for further research in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation of the prefrontal cortex reduces cigarette craving in not motivated to quit smokers: A randomized, sham-controlled study. Perri, RL., Perrotta, D.[2021]

In a study involving 210 tobacco-dependent male participants, transcranial Direct Current Stimulation (tDCS) for 12 weeks showed a 25.7% abstinence rate, comparable to the 20% rate achieved with bupropion, suggesting tDCS could be an effective alternative for smoking cessation.

Participants receiving tDCS had lower nicotine dependency scores compared to those treated with bupropion, indicating that tDCS may not only help with quitting smoking but also reduce the level of addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of transcranial direct current stimulation compared to standard bupropion for the treatment of tobacco dependence: A randomized sham-controlled trial. Ghorbani Behnam, S., Mousavi, SA., Emamian, MH.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6375608/

Effect of transcranial direct current stimulation on the number ... We found that 3 tDCS sessions significantly reduced cigarette smoking in a short period following stimulation in the active as well as in the sham groups. The ...

2. nature.com nature.com/articles/s41598-025-85877-4

Transcranial direct current stimulation associated with ... The results of the present study demonstrated that tDCS associated with AE (G3) significantly reduced cigarette consumption and craving, in ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924933819300793

The effects of transcranial direct current stimulation ... The 12-week tDCS had a clinically good therapeutic effect on smoking cessation and its dependency. It may be a substitute for bupropion treatment.

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0277408

Active versus sham transcranial direct current stimulation ... This study aims to investigate the effectiveness of tDCS in combination with varenicline for smoking cessation.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06798324

tDCS Plus Varenicline for Smoking Cessation A prior pilot study in our lab found that adjunct active tDCS doubled varenicline's effectiveness at end of treatment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9731486/

Active versus sham transcranial direct current stimulation ... This study aims to investigate the effectiveness of tDCS in combination with varenicline for smoking cessation.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X15012140

Transcranial Direct Current Brain Stimulation Increases ... Active tDCS (vs. sham) decreased the total number of cigarettes smoked. •. Acute tDCS over the left DLPFC shows promise for smoking cessation treatment.

8. withpower.com withpower.com/trial/phase-4-substance-related-disorders-2025-c1147

tDCS + Varenicline for Smoking Cessation ... Active Transcranial Direct Current Stimulation (tDCS) and Varenicline will have tolerable side effects & efficacy for patients with Smoking Cessation, Smoking ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03841292

Using Non-invasive Brain Stimulation (tDCS) With ... The primary objective of this research is to provide preliminary evidence of the effectiveness of tDCS as an adjunct treatment to pharmacotherapy for smoking ...