Deep Transcranial Magnetic Stimulation for Tobacco Cessation in Adults With Opioid Use Disorder

A Pilot Trial of Deep Transcranial Magnetic Stimulation (Deep TMS) for Tobacco Cessation in Patients With Opioid Use Disorder (OUD) Receiving Medications for Opioid Use Disorder (MOUD)

This pilot study will evaluate the use of deep transcranial magnetic stimulation (Deep TMS) to help adults with opioid use disorder (OUD) who are receiving medications for opioid use disorder (MOUD) such as buprenorphine or methadone and who continue to smoke cigarettes and want to quit.

Deep TMS is a noninvasive form of brain stimulation that uses magnetic pulses. The BrainsWay Deep TMS System is FDA-cleared for smoking cessation. This study will use the H4 coil smoking-cessation protocol in people with OUD receiving MOUD. Approximately 12 participants will take part and all participants will receive active Deep TMS. There is no sham or placebo group and no random assignment.

Participants may receive up to 18 Deep TMS sessions over 6 weeks: five sessions per week during the first 3 weeks, followed by one session per week during Weeks 4 through 6. Participants will return for a follow-up visit at Week 10.

The main purpose of the study is to learn whether this Deep TMS approach is safe, tolerable and feasible for people with OUD receiving MOUD and to estimate how many participants are able to remain smoke-free from Week 6 through Week 10. The study will also look for early changes in tobacco craving, opioid craving, continuation of MOUD, mood and anxiety symptoms, pain, heart rate variability, and participants' experiences with the treatment. The findings will be used to help plan a larger future study.

Inclusion Criteria:

• Male or female participants, 22-70 years old.
• Chronic, heavy smoker (>10 cigarettes/day for >1 year) with no continuous abstinence period >3 months in the past 12 months (self-report), and baseline smoking confirmed by either (a) cotinine-positive urine or (b) clinical documentation of current smoking when cotinine interpretation is not reliable due to nicotine replacement or other nicotine product use reported at baseline.
• Motivated to quit smoking, defined as a Motivation To Stop Scale (MTSS) score ≥6 at baseline (i.e., endorsing intention to quit within the next 3 months or within the next month).
• Meet DSM-5 diagnostic criteria for moderate or severe Opioid Use Disorder (OUD), with diagnosis confirmed by the study investigator through clinical interview study assessment.
• Meet DSM-5 diagnostic criteria for Severe Tobacco Use Disorder, confirmed by the study investigator through clinical interview study assessment.
• Have received buprenorphine or methadone consistently for the last 3 months (≥80% proportion of days covered or equivalent documentation for clinic-administered dosing, such as opioid treatment program dosing records or medication administration records demonstrating consistent dosing over the same 3-month period).
• No self-reported illicit fentanyl use in the past 30 days AND evidence of fentanyl-negative urine toxicology, defined as either (a) a documented fentanyl-negative urine drug screen in the medical record within 7 days prior to consent or (b) a fentanyl-negative urine toxicology obtained at baseline screening.
• Able to communicate fluently in English for accurate administration of assessments and safety monitoring.
• For participants with the potential to become pregnant: pregnancy status must be confirmed after informed consent and HIPAA authorization and before study treatment. Participants must have either (a) a negative urine pregnancy test obtained by the study team at baseline after informed consent or (b) a documented negative serum or urine hCG result from standard clinical care within 7 days prior to consent, reviewed or abstracted by the study team only after informed consent and HIPAA authorization.
• At least one prior quit attempt in the past 12 months, defined as intentionally stopping smoking for ≥24 hours (≥1 day) because they were trying to quit, assessed by self-report at baseline screening.

Exclusion Criteria:

• History of seizure disorder, epilepsy, stroke, significant head trauma, or other clinically significant neurologic condition or structural brain lesion (e.g., tumor, vascular malformation, intracranial aneurysm/aneurysm repair, meningitis/encephalitis with neurologic sequelae).
• Metallic, electronic, magnetically activated, or retained metal implants/devices that may contraindicate TMS exposure, including but not limited to pacemaker/implantable cardioverter-defibrillator, cochlear or otologic implants, implanted hearing-aid anchors, deep brain stimulator, vagus nerve stimulator, aneurysm clip/coil, carotid/cerebral stent, ocular metallic implant/stent, cerebrospinal fluid shunt, intracardiac lines/wires, implanted pump, retained bullet/pellet/shrapnel, staples/sutures or metal hardware in or around the head/neck, skull/cervical fixation plates, titanium skull plates, magnetically activated dental implants, or facial tattoos/permanent makeup with metallic ink, as determined by the investigator.
• Unstable or severe medical condition (e.g., uncontrolled cardiac, hepatic, renal, or metabolic disease) that increases risk from study participation, based on medical history review, medical record review, and investigator clinical judgment.
• Current pregnancy, intention to become pregnant during the study period, or actively breastfeeding. For participants with the potential to become pregnant, a negative pregnancy test is required before initiating study treatment.
• Active psychotic disorder, bipolar mania, or major depressive episode with psychotic features, as determined by the study investigator.
• Severe cognitive impairment or neurocognitive disorder that limits the ability to provide informed consent or complete study procedures. Participants unable to complete consent teach-back will be excluded.
• Acute intoxication or clinically significant opioid withdrawal at baseline screening, defined as a Clinical Opiate Withdrawal Scale (COWS) score ≥12.
• Current or recent (within the past 30 days) use of any medication known to significantly lower the seizure threshold, including but not limited to bupropion, clozapine, olanzapine, clomipramine, amitriptyline, or tramadol, or other clinically significant use determined by the investigator to further lower seizure threshold.
• Any lifetime history of electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS).
• Frequent or severe migraine headaches, defined as ≥8 migraine days per month over the past 30 days, or migraine headaches that, in the investigator's clinical judgment, are expected to interfere with tolerating TMS sessions.
• Significant hearing loss that, in the investigator's judgment, would prevent safe participation despite use of hearing protection.
• Participation in another interventional clinical trial within the last 30 days prior to informed consent.
• First-degree family history of epilepsy or seizure disorder (biological parent, full sibling, or child).
• History of recurrent syncope or unexplained fainting, including any episode with loss of consciousness or convulsive features, that has not been adequately evaluated/cleared or would increase risk with TMS in the investigator's judgment.
• Current prescribed benzodiazepine or anticonvulsant regimen that has not been stable for at least 4 weeks before consent, defined as any new start, discontinuation, dose increase or decrease, route/formulation change, change in scheduled dosing frequency, or, for as-needed medications, a change in prescribed instructions or clinically meaningful increase in frequency or amount used during the 4 weeks before consent, as determined by the investigator.