Psilocybin for Opioid Use Disorder

(BIPOD-Out Trial)

Recruiting in Baltimore (>99 mi)

Overseen By Sandeep Nayak, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must be taking: Buprenorphine

Must not be taking: Antidepressants, Methadone, Naltrexone, others

Disqualifiers: Hypertension, Epilepsy, Diabetes, Schizophrenia, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

90 Participants Needed

Trial Summary

What is the purpose of this trial?

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 outpatient buprenorphine treatment for Opioid use disorder (OUD). The participants will have previously undergone buprenorphine induction before. Effects of adjunctive psilocybin will be determined for longitudinal outcomes of opioid abstinence, compliance with outpatient buprenorphine maintenance, quality of life, and mood.

Do I need to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial requires that you are not on antidepressants, certain medications affecting serotonin, methadone, naltrexone, or specific enzyme inhibitors. If you take these intermittently, you must wait for a period without them before participating.

What data supports the effectiveness of the drug psilocybin for treating opioid use disorder?

Research shows that psilocybin has been studied for various psychiatric disorders, including substance use disorders, and has shown promising results with marked, long-term improvements in some patients. However, more research is needed to determine its effectiveness specifically for opioid use disorder. ^{1 2 3 4 5}

Is psilocybin safe for human use?

Psilocybin has been studied for its safety in humans, showing that while it can cause challenging experiences or 'bad trips,' the risk of lasting psychological distress is low when used in controlled settings with proper support. In clinical trials, psilocybin has been generally well-tolerated, but it can cause temporary hallucinations and changes in perception. ^{1 6 7 8 9}

How does the drug psilocybin differ from other treatments for opioid use disorder?

Psilocybin is unique because it is a psychedelic compound found in 'magic mushrooms' that works by affecting serotonin receptors in the brain, which is different from traditional opioid treatments that often focus on blocking opioid receptors or reducing withdrawal symptoms. It has shown promise in treating various mental health conditions, suggesting a novel approach to addressing the psychological aspects of addiction. ^{1 2 7 8 10}

Research Team

Sandeep Nayak, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 21-70 with Opioid Use Disorder who are fluent in English, willing to undergo or have recently completed buprenorphine induction, and not at high risk for suicide. Participants must meet DSM-5 criteria for OUD, be off antidepressants for a certain period, have prior buprenorphine maintenance experience, test positive for opioids in urine tests, and have stable housing.

Inclusion Criteria

I haven't taken antidepressants for their full withdrawal period before joining.

I am willing to start or have started buprenorphine treatment in the last 3 weeks.

Has access to stable housing

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

I have heart or blood vessel problems, like high blood pressure, chest pain, or a recent stroke.

I have been on buprenorphine for more than 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Buprenorphine Induction

Participants undergo standard-of-care outpatient buprenorphine induction

3 weeks

Psilocybin Administration

Participants receive either a high dose (30 mg) or a very low dose (1 mg) of psilocybin under double-blind conditions

1 day

1 visit (in-person)

Outpatient Buprenorphine Maintenance

Participants undergo an 8-week outpatient phase with standard-of-care buprenorphine maintenance

8 weeks

6 visits (in-person) at 1, 2, 3, 4, 6, and 8 weeks post-dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 to 6 months

Treatment Details

Interventions

• Psilocybin

Trial Overview The study is testing the effects of a single high dose (30 mg) versus a very low dose (1 mg) of psilocybin therapy as an add-on to standard outpatient buprenorphine treatment. It aims to see how psilocybin affects opioid abstinence rates, adherence to buprenorphine maintenance programs, quality of life improvements, and mood changes over time.

Participant Groups

Group I: High-dose psilocybin + buprenorphine Experimental Treatment 1 Intervention

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

Group II: Very low-dose psilocybin + buprenorphine Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Findings from Research

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[2023]

Psilocybin is primarily a pro-drug that converts to the active compound psilocin in the body, which then interacts with serotonin receptors to produce its hallucinogenic effects.

The metabolism of psilocybin and psilocin varies significantly among individuals, affecting their dose-response and potential toxicity, highlighting the need for personalized approaches in therapeutic settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Dinis-Oliveira, RJ.[2018]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

Psilocybin, a prodrug for psilocin, shows strong agonist activity at the serotonin 5-HT2A receptor, which is responsible for its psychedelic effects, and has been shown to have nanomolar affinity for various serotonin receptor subtypes in both in vitro and in vivo studies.

In mouse experiments, psilocybin and related compounds induced head twitch responses, a sign of psychedelic activity, which were blocked by a 5-HT2A antagonist, confirming the involvement of this receptor in their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. Glatfelter, GC., Pottie, E., Partilla, JS., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]