ACTION: Trial of Adding Buprenorphine, CBT, and TMS to Improve Outcomes of Long-Term Opioid Therapy for Chronic Pain

This study will sequentially evaluate three novel and scalable interventions for at-risk individuals on long term opioid therapy for chronic pain: (1) low-dose transdermal buprenorphine initiation without a period of opioid withdrawal; (2) a brief Cognitive Behavioral Intervention for pain (CBI); and (3) "accelerated" rTMS over the left dorsolateral prefrontal cortex, by examining standardized repeated measures of clinical outcomes at baseline, during treatment, and at 4-, 12-, 24- and 52-week follow-up.

With little evidence available to guide the provision of clinical care for patients on long-term opioid therapy (LTOT) in whom the risks outweigh the benefits, major questions remain about optimizing the risk/benefit profile of LTOT, including: how to best engage patients voluntarily in this process; the safety, tolerability and effectiveness of newer treatment approaches; and optimal treatment selection. The primary objective of the proposed study is to begin to systematically address gaps in this important area to improve pain, reduce risk, and improve quality of life for individuals on LTOT.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18yrs;
* English-speaking;
* On LTOT, defined as taking daily prescription opioid therapy for 90 days or more;
* Past week average morphine equivalent dose (MED) ≥50;
* Willing and able to complete written informed consent;
* Willing and able to use a mobile/cell phone;
* Have at least one additional risk for opioid toxicity or overdose from the following list:
* Taking benzodiazepines with opioids
* Substance Use Disorder diagnosis \[non-tobacco; Opioid Risk Tool\]
* Having ever experienced an overdose
* Current major medical problem \[e.g. mod-severe liver disease, pancreatitis, chronic pulmonary disease, untreated sleep apnea, hospitalized for an acute medical issue in the past 6 months\]
* Response to Brief Pain Iinventory Item 8 \<30%, suggesting less than moderately clinically meaningful response to pain treatment
* Co-morbid psychiatric diagnosis \[Opioid Risk Tool\]
* Signs of opioid misuse \[any score \>0 on the following COMM Items: 3, 4, 5, 9, 10, 11, 14, 15, 16\]
* Opioid Risk Tool \>3 or Current Opioid Misuse Measure ≥ 9
* Struggling with the following side effects from opioids \[self-report\]: Dizziness and/or falls Difficult-to-manage stomach pain, nausea, constipation or GI issues, Fatigue or low energy, Sleepiness or sedation, Trouble with memory or thinking clearly \[COMM Item 1\>0\], Other troublesome side effect \[open answer\]

Exclusion Criteria:

* Known seizure disorder;
* On anti-convulsant medication;
* Known allergy to buprenorphine;
* Active moderate or severe non-opioid substance use disorder (DSMV criteria);
* Active suicidal Ideation;
* Known bipolar disorder;
* Cognitive disorder limiting ability to consent or fully participate in the BCI intervention;
* Severe medical condition (e.g. malignancy), likely to limit life expectancy or study participation;
* Receiving methadone or buprenorphine treatment for OUD or pain;
* On naltrexone;
* Pregnancy;
* Currently Incarcerated;
* Hypokalemia;
* Clinically unstable cardiac or pulmonary disease;
* Taking medications that prolong QTc interval or personal/immediate family history of Long QT Syndrome.