Inpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder

NCT06005662 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: IRB00344281
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the effect of a single high dose of psilocybin therapy (30 mg) versus a very low dose (1 mg) as an adjunctive therapy to individuals undergoing standard-of-care buprenorphine treatment for Opioid use disorder (OUD). Effects of adjunctive psilocybin will be determined for longitudinal outcomes of opioid abstinence, compliance with buprenorphine maintenance, quality of life, and mood.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (4)

• Opioid Abstinence

  Non-buprenorphine opioid abstinence as verified by urine toxicology at each visit and Timeline Follow Back (TLFB). These will be combined to assess opioid abstinence for each participant. These will be assessed at the 8-week timepoint for the previous 3-weeks. Missing values will be presumed positive. Timeline Follow Back (TLFB) for Opioids: This is a self-report of drug use per day. This procedure asks participants to retrospectively quantitate their use of drugs. Greater numbers indicate more days using a substance, smaller numbers or zeros mean less or no days using a substance Urine toxicology: Urine samples will be collected at each study visit and screened broadly for illicit drug use including opioids via an outside medical laboratory. Quantitative buprenorphine levels will also be collected following induction to gauge whether buprenorphine is being taken. These measurements will be combined to report the number of participants who were abstinent from opioids.

  up to 8 weeks

• Treatment Retention

  Treatment retention at 8 weeks, as indicated by participants making all follow-up visits, indicating they are taking buprenorphine and with urine toxicology positive for buprenorphine.

  8 weeks

• Number of Days Illicit Opioids Used

  Number of Days Illicit Opioids Used, as indicated by participant self-report and urine toxicology results

  8 weeks

• Number of Negative Urine Toxicologies

  Number of Negative Urine Toxicologies, as indicated by results from weekly urine toxicologies collected for eight weeks

  weekly up to 8 weeks

Secondary Outcomes (4)

• Quality of Life as assessed by the World Health Organization Quality of Life-BREF (WHOQOL-BREF)

  8 weeks

• Depression as assessed by the Beck Depression Inventory II (BDII)

  8 weeks

• Anxiety as assessed by the State-Trait Anxiety Inventory (STAI)

  8 weeks

• Number of Participants Abstinent from Other Drug Substances

  8 weeks

Study Arms (2)

High-dose psilocybin + buprenorphine

EXPERIMENTAL

High-dose psilocybin (30 mg) session following standard-of-care buprenorphine induction

Drug: Psilocybin

Very low-dose psilocybin + buprenorphine

ACTIVE COMPARATOR

Very low dose psilocybin session (1 mg) following standard-of-care buprenorphine induction

Drug: Psilocybin

Interventions

Psilocybin DRUG

The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis

Also known as: Buprenorphine

High-dose psilocybin + buprenorphine; Very low-dose psilocybin + buprenorphine

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-70 years
• Have given written informed consent
• Meet diagnostic criteria for OUD
• No antidepressant medications for approximately 5 half-lives prior to enrollment
• Not currently taking methadone, buprenorphine or naltrexone
• 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.

You may not qualify if:

• 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 electrocardiogram abnormality (e.g., atrial fibrillation), Transient Ischemic Attack or Stroke in the last 6 months, 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 inhibitors.
• o For individuals who have intermittent or as needed 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 medicines such as phenytoin, regorafenib, eltrombopag.
• Currently taking buprenorphine, methadone, or naltrexone.
• 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, nervous system tumor, movement disorders or any neurodegenerative condition.
• Morbidly obese (\>100 pounds above ideal body weight, or Body Mass Index (BMI) \>=40, or BMI \>=35 with high blood pressure or diabetes)
• Body weight \< 45 kilograms
• Be judged by a study team clinician to be at risk for moderate or severe alcohol or benzodiazepine withdrawal.
• Allergic to buprenorphine or hydromorphone
• Current or past history of meeting diagnostic 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.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Psilocybin; Buprenorphine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Sandeep Nayak, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and study team will be masked/blinded to intervention.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction

Study Record Dates

• First Submitted: August 15, 2023
• First Posted: August 22, 2023
• Study Start (Estimated): April 1, 2027
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)