Psilocybin for Opioid Use Disorder

(BIPOD-Out Trial)

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a single high dose of psilocybin, a psychedelic compound, can help individuals with Opioid Use Disorder (OUD) adhere to their treatment plans and improve their overall quality of life. Participants will receive either a high dose or a very low dose of psilocybin alongside their regular buprenorphine treatment. The trial aims to determine if psilocybin can maintain opioid abstinence and enhance mood. Individuals who have recently used buprenorphine and seek recovery from opioid use may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin, the active ingredient in "magic mushrooms," has undergone testing in various studies for its safety in humans. At high doses, psilocybin can cause hallucinations and other effects lasting up to six hours, including changes in perception and mood. Some individuals might feel anxious or confused during this time.

In studies with very low doses, such as 1 mg, the effects are much milder and often not noticeable, suggesting that low doses are generally safe with fewer side effects. However, since this trial combines psilocybin with buprenorphine, a medication for opioid addiction, monitoring for any unique reactions is important.

Overall, while psilocybin can cause some short-term side effects, research has used it without causing significant long-term harm. Participants should be aware of possible temporary effects like changes in perception and mood. Always discuss potential risks with the study team to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using psilocybin to treat opioid use disorder because it takes a novel approach by targeting the brain's serotonin receptors, potentially offering a new way to combat addiction. Unlike traditional treatments like methadone or buprenorphine, which primarily work on opioid receptors to reduce withdrawal symptoms, psilocybin's action on serotonin might help patients break the cycle of addiction by altering perception and thought patterns associated with substance use. Additionally, psilocybin could offer rapid effects after just a few sessions, contrasting with the long-term commitment often required by current therapies.

What evidence suggests that this trial's treatments could be effective for opioid use disorder?

Research suggests that psilocybin may help treat Opioid Use Disorder (OUD). Studies have found that psilocybin therapy can lessen withdrawal symptoms and improve the quality of life for individuals with substance use issues. In this trial, participants will receive either a high dose or a very low dose of psilocybin, both combined with buprenorphine. Previous studies have shown that a high dose of psilocybin effectively reduces opioid use and withdrawal symptoms. However, less information is available for the very low dose, and its effectiveness remains under study. Overall, psilocybin shows potential as an additional therapy for those dealing with opioid addiction. ^{6 7 8 9 10}

Who Is on the Research Team?

Sandeep Nayak, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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-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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06796062

NCT06796062 | Psilocybin for Opioid Use Disorder (OUD) This is a double-blind, adaptive, 2-stage, multi-site, phase 2 randomized controlled clinical trial designed to evaluate effects of moderate and high dose ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05242029

Psilocybin for Opioid Use Disorder in Patients on ... This study will investigate whether psilocybin administered under supportive conditions can reduce illicit opioid use and improve quality of life.

3. reporter.nih.gov reporter.nih.gov/project-details/11044441

Psilocybin - NIH RePORTER This study investigates whether psilocybin can help patients in opioid use disorder treatment stop using illicit opioids.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178125000952

The therapeutic effects of psychedelics for opioid use ... Most of these studies showed the effectiveness of psychedelics in reducing opioid withdrawal signs (in some cases naloxone/naltrexone-induced withdrawal) ( ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9947277/

Therapeutic effect of psilocybin in addiction: A systematic ... All four clinical trials indicated a beneficial effect of psilocybin-assisted therapy on SUD symptoms. Larger RCTs in patients with SUDs need to evaluate ...

6. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...

7. en.wikipedia.org en.wikipedia.org/wiki/Psilocin

Psilocin Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.

8. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Psilocybin

Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH Psilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic ...

9. sciencedirect.com sciencedirect.com/topics/immunology-and-microbiology/psilocybin

Psilocybin - an overview At high doses (5.0 g), psilocybin causes open eye hallucinations. The hallucinogenic and sympathomimetic properties of this agent can last for up to 6 hours. At ...

10. consensus.app consensus.app/home/blog/what-is-psilocybin-other-names-psilocibin-psilocybine-psilocin-phosphate-ester/

Psilocibin, Psilocybine, Psilocin Phosphate Ester Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms, commonly referred to as “magic mushrooms.”