Using psilocybin to enhance buprenorphine treatment for opioid use disorder

Outpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder: a Randomized Double-blind Trial

This study is testing if a single high dose of psilocybin can help people in outpatient buprenorphine treatment for opioid use disorder feel better and stick to their treatment plan.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 21 Years to 70 Years
• Sex: All
• Sponsor: Johns Hopkins University (Academic / other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT06067737 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of a single high dose of psilocybin (30 mg) compared to a very low dose (1 mg) as an adjunctive therapy for individuals undergoing outpatient buprenorphine treatment for opioid use disorder (OUD). Participants, who have previously been prescribed buprenorphine, will be assessed for outcomes such as opioid abstinence, treatment adherence, quality of life, and mood. The study employs a double-blind, controlled design to evaluate the potential benefits of psilocybin in enhancing the effectiveness of standard buprenorphine therapy. It specifically targets individuals who have recently undergone buprenorphine induction or are interested in starting treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21-70 with a diagnosis of opioid use disorder who have previously tolerated buprenorphine and are seeking recovery.

Not a fit: Patients who are naïve to buprenorphine or have not undergone recent buprenorphine induction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with opioid use disorder by enhancing abstinence and quality of life.

How similar studies have performed: While this specific approach is novel, other studies have explored the use of psychedelics in addiction treatment, showing promising results.

Eligibility criteria

Inclusion Criteria:

* Age 21-70 years
* Have given written informed consent
* Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for OUD
* No antidepressant medications for approximately 5 half-lives prior to enrollment
* Willing to undergo buprenorphine induction or has undergone buprenorphine induction in the past 3 weeks
* Reports previous buprenorphine maintenance
* Urine toxicology positive for an opioid
* Has access to stable housing
* Can read, write, and speak English fluently
* Be judged by study team clinicians to be at low risk for suicidality
* Have limited recent use of classic psychedelics (no use in the past year).
* Expresses a desire for sustained recovery from disordered opioid use.

Exclusion Criteria:

General medical exclusion criteria:

* Women who are pregnant, nursing, or not practicing an effective means of birth control
* Cardiovascular conditions: hypertension with resting blood pressure systolic \>139 or diastolic \>89, angina, heart rate \> 99, a clinically significant ECG abnormality (e.g., atrial fibrillation, QTc \> 450), transient ischemic attack (TIA) in the last 6 months, stroke, peripheral or pulmonary vascular disease, cardiac valvulopathy
* Epilepsy
* Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
* Currently taking on a daily basis any medications (including herbal substances and supplements) with a central nervous system effect on serotonin, including serotonin-reuptake inhibitors and monoamine oxidase (MAO) inhibitors.
* For individuals who have intermittent or as needed (PRN) use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
* Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or UDP-glucuronosyltransferase (UGT)1A9 inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag.
* Currently taking methadone or naltrexone.
* Currently on longstanding buprenorphine maintenance (3+ weeks post-induction)
* Naïve to buprenorphine
* Reports of significant adverse events (severe withdrawal, medical complications, hospitalization) during previous buprenorphine induction(s).
* Unable or unwilling to discontinue acid-reducing agents or major metabolizing enzyme inhibitors for 5-half lives prior to the experimental dosing session.
* Have a seizure disorder, multiple sclerosis, history of significant head trauma, central nervous system (CNS) tumor, movement disorders or any neurodegenerative condition.
* Morbidly obese (\>100 lbs above ideal body weight, or Body Mass Index (BMI) \>=40, or BMI \>=35 with high blood pressure or diabetes)
* Body weight \< 45 kg
* Be judged by a study team clinician to be at risk for moderate or severe alcohol or benzodiazepine withdrawal.
* Allergic to buprenorphine
* For blood samples, the following lab values will be exclusionary: transaminases greater than x2 the upper limit of normal lab reference range, hemoglobin less than 11 g/d, and creatinine clearance \< 40 ml/min using the Cockraft and Gault equation.

Psychiatric Exclusion Criteria:

* Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder or Major Depression with psychotic features.
* Have a first or second degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I or II disorder.

Where this trial is running

Baltimore, Maryland

• Johns Hopkins Center for Psychedelic and Consciousness Research — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Sandeep Nayak, MD — Johns Hopkins University
• Study coordinator: Andrew L Gaddis, MD

Conditions Opioid Use Disorder