Psilocybin + Counseling for Opioid Use Disorder

Overseen By PROTEA Research

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Must be taking: Buprenorphine-naloxone

Must not be taking: Methadone

Disqualifiers: Hypertension, Heart disease, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

Duration: 5 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding psilocybin (a compound found in certain mushrooms) to a stable buprenorphine-naloxone treatment can aid individuals with opioid use disorder. Researchers aim to determine if this combination is safe and enhances the current treatment's effectiveness. Participants will take two doses of psilocybin, combined with counseling, to assess changes in self-confidence, life quality, and pain levels. This trial may suit someone with moderate or severe opioid use disorder, currently misusing opioids, and on a stable dose of buprenorphine-naloxone to manage withdrawal symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of buprenorphine-naloxone. If you are currently on methadone or have been on buprenorphine for over four weeks before the study, you cannot participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that psilocybin, the treatment tested in this trial, is generally safe when used properly. It has been studied in various contexts, such as aiding cancer survivors, and is usually well-tolerated. Although specific studies on psilocybin for treating opioid addiction are lacking, its use in other conditions suggests general safety.

This trial is in its early stages (Phase 1), focusing primarily on safety and side effects. Researchers closely monitor participants to ensure the treatment's safety. In past research, serious side effects have been rare, but like any treatment, psilocybin can cause side effects. These might include temporary changes in mood or perception, but studies suggest these are usually manageable.

In this trial, participants take psilocybin in capsule form along with counseling. They receive two doses, about four weeks apart, allowing researchers to observe any side effects over time. This careful approach aims to ensure participant safety while exploring psilocybin's potential benefits. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for opioid use disorder?

Researchers are excited about psilocybin with counseling for opioid use disorder because it offers a novel approach compared to traditional treatments like methadone or buprenorphine alone. Unlike these standard options, psilocybin works by potentially resetting neural pathways in the brain, which could alter the way individuals perceive cravings and dependency. This psychedelic compound, combined with facilitated counseling, might offer a more holistic and long-lasting change in behavior, providing hope for those who have not found success with existing therapies. Additionally, psilocybin is administered in just two doses, which may reduce the need for continuous medication, a significant advantage over daily treatments.

What evidence suggests that psilocybin might be an effective treatment for opioid use disorder?

Research has shown that psilocybin, a substance found in certain mushrooms, may help treat mental health issues. Evidence indicates that psilocybin can significantly reduce symptoms of depression and anxiety, which often accompany substance use problems like opioid addiction. In this trial, participants will receive psilocybin with facilitated counseling. Studies suggest that psilocybin can alter brain activity, possibly helping to break addiction habits. When combined with counseling, psilocybin might enhance the effectiveness of standard opioid treatments like buprenorphine-naloxone. Although more research is needed specifically for opioid use disorder, early results in other areas suggest potential benefits. ^{6 7 8 9 10}

Who Is on the Research Team?

Randall Brown, MD PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

Adults aged 21-65 with opioid use disorder (OUD) who are on a stable buprenorphine-naloxone treatment. Participants must have healthy kidneys, be able to understand English, and agree to use effective contraception. They should not be on methadone, under legal supervision that prohibits study participation, or have certain heart conditions or insulin-dependent diabetes.

Inclusion Criteria

I am between 21 and 65 years old.

I can provide a contact for someone who will support me during and after my treatment.

My kidneys are functioning well.

Exclusion Criteria

I am currently experiencing heart-related chest pain.

Urine drug test containing non-prescribed drugs of abuse

Any finding(s), based on the screening process, that the PI feels makes the study unsuitable for the participant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preparatory Counseling

Participants undergo at least 6 hours of preparatory counseling and preparation for psilocybin dosing

1 week

Multiple sessions (in-person)

Treatment

Participants receive two oral doses of psilocybin, approximately 4 weeks apart, with observation and integration sessions

5 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and changes in opioid craving

4 weeks

1 visit (in-person), ongoing monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine
• Psilocybin

Trial Overview

The trial is testing the safety and effects of adding two doses of psilocybin to ongoing buprenorphine-naloxone therapy for OUD. It aims to see if psilocybin can improve self-efficacy, quality of life, and pain while maintaining the effectiveness of buprenorphine-naloxone.

How Is the Trial Designed?

Group I: Open-label Experimental Treatment 1 Intervention

Psilocybin with facilitated counseling: Psilocybin will be administered in the form of capsules, taken orally with water. Each participant will receive 2 doses, approximately 4 weeks apart.

Buprenorphine is already approved in United States, European Union for the following indications:

Approved in United States as Buprenorphine for:

• Moderate to severe opioid addiction (dependence)

Approved in European Union as Buprenorphine for:

• Opioid dependence

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Heffter Research Institute

Collaborator

Trials

15

Recruited

520+

Etheridge Foundation

Collaborator

Trials

3

Recruited

50+

Published Research Related to This Trial

The study will involve 280 adults with opioid use disorder and aims to improve adherence to buprenorphine-naloxone treatment through two psychological interventions: contingency management (CM) and brief motivational interviewing plus substance-free activities and mindfulness (BSM).

The primary goal is to assess which intervention is more effective in promoting medication adherence, measured by attendance at physician appointments and the presence of buprenorphine in urine toxicology, with follow-up occurring 8 months after randomization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder. Peter, SC., Murphy, JG., Witkiewitz, K., et al.[2023]

Buprenorphine is a safe and effective medication for treating opioid use disorder (OUD) in individuals with HIV, helping to reduce cravings and overdose risks while improving HIV care outcomes.

Despite its proven benefits, there is a significant gap in the implementation of buprenorphine prescribing in HIV care settings, highlighting the need for HIV clinicians to obtain waivers and integrate OUD education into their training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Call to Action: Integration of Buprenorphine Prescribing Into the Care of Persons With Human Immunodeficiency Virus and Opioid Use Disorder. Fujita, AW., Wilson, JD., Kennedy, AJ.[2022]

A survey of intravenous drug users in Helsinki revealed that 73% used buprenorphine as their primary drug, primarily for self-treating addiction or withdrawal symptoms.

The combination of buprenorphine and naloxone (Suboxone) was tried by 68% of respondents, but 80% reported negative experiences, suggesting that while it may help reduce buprenorphine abuse, its acceptance among users is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Alho, H., Sinclair, D., Vuori, E., et al.[2015]

In a pilot study involving 15 participants, those who underwent psilocybin-facilitated smoking cessation reported significant insights into their self-identity and reasons for smoking, which contributed to their ability to quit smoking.

Participants experienced lasting positive changes beyond smoking cessation, such as increased altruism and pro-social behavior, suggesting that the therapeutic effects of psilocybin may extend beyond the immediate treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. Noorani, T., Garcia-Romeu, A., Swift, TC., et al.[2019]

Lifetime use of psilocybin is associated with significantly lower odds of developing opioid use disorder (OUD), with an adjusted odds ratio of 0.70 based on a large sample of 214,505 participants from the National Survey on Drug Use and Health.

Psilocybin use was linked to reduced odds of meeting seven out of eleven DSM-IV criteria for OUD, suggesting its potential as a therapeutic option, although further clinical trials are necessary to establish a causal relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample. Jones, G., Ricard, JA., Lipson, J., et al.[2022]

Over 400 clinicians participated in free buprenorphine training, but only 30 out of 101 attending physicians applied for the necessary x-waiver to prescribe it, highlighting a significant gap between training and actual prescribing.

Despite the removal of training requirements for prescribing buprenorphine, the low number of physicians who went on to prescribe it suggests that additional cultural and systemic changes are needed to improve access to treatment for opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing Access to Medications for Opioid Use Disorder in Primary Care: Removing the Training Requirement May Not Be Enough. Russell, HA., Sanders, M., Meyer, JKV., et al.[2021]

Buprenorphine is a safe and effective treatment for opioid dependence, particularly when combined with naloxone, which reduces its potential for abuse.

New regulations enable certified physicians to prescribe buprenorphine in their offices, significantly improving patient access to this important treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance: a new treatment for opioid dependence. Collins, GB., McAllister, MS.[2019]

Increasing access to buprenorphine, a treatment for opioid use disorder, is crucial for reducing overdose deaths, but limited availability of buprenorphine monoproduct is a significant barrier.

The requirement to prescribe buprenorphine as a combination product with naloxone may lead to adverse effects that are more serious than previously thought, potentially harming the patient-provider relationship and increasing stigma, which can hinder access to care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Naloxone Component of Buprenorphine/Naloxone: Discouraging Misuse, but at What Cost? Gregg, J., Hartley, J., Lawrence, D., et al.[2023]

Psychedelic treatments, including psilocybin, ibogaine, and ayahuasca, show promise for improving psychological and psychosocial outcomes in individuals with substance use disorder (SUD) and substance misuse, but the evidence is limited and varied across different substances.

Currently, there is insufficient research to definitively establish the effectiveness of psychedelics for specific SUDs, highlighting the need for more rigorous studies with larger sample sizes and longer follow-up periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychedelic Treatments for Substance Use Disorder and Substance Misuse: A Mixed Methods Systematic Review. Sharma, R., Batchelor, R., Sin, J.[2023]

Buprenorphine (Subutex) is recognized for its improved safety profile in treating opioid dependence, particularly by reducing the risk of overdose compared to other opioids.

Despite its safety advantages, there are still risks associated with the diversion of buprenorphine for misuse, as evidenced by cases of attempted intravenous injection, highlighting the need for strict dispensing protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Groin tissue necrosis requiring skin graft following parenteral abuse of buprenorphine tablets. Feeney, GF., Fairweather, P.[2013]

A study involving 28 Black individuals with Opioid Use Disorder revealed that while most had heard of psilocybin, only a small number had actually used it, indicating limited exposure to this potential treatment.

Despite a willingness to consider psilocybin therapy, over 80% of participants perceived significant risks associated with its use, highlighting the need for culturally informed education and outreach to improve understanding and acceptance of psilocybin as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin use patterns and perception of risk among a cohort of Black individuals with Opioid Use Disorder. Clifton, JM., Belcher, AM., Greenblatt, AD., et al.[2023]

Psilocybin, found in 'magic mushrooms', shows promise as a non-addictive alternative for treating mental health disorders like major depressive disorder and addiction, potentially addressing the urgent need for new therapies amid rising addiction and suicide rates.

Current research indicates that psilocybin may offer therapeutic benefits without the overdose risks associated with traditional mind-altering substances, suggesting a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, RB.[2021]

A study involving 158 opioid users in New York City found that while 70% were aware of buprenorphine treatment, only 12% had actually been prescribed it, indicating a significant gap in treatment utilization.

Indirect exposure to buprenorphine, such as knowing someone who has used it, was linked to a higher interest in treatment (adjusted odds ratio of 2.65), suggesting that peer mentorship could be an effective strategy to increase buprenorphine uptake among opioid users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

I heard about it from a friend: assessing interest in buprenorphine treatment. Fox, AD., Shah, PA., Sohler, NL., et al.[2021]

A survey of 476 residency program directors revealed that while 76.9% of residents frequently manage patients with opioid use disorder (OUD), only 23.5% of programs dedicate significant curricular time (12+ hours) to addiction medicine, and only 35.9% encourage training in office-based opioid treatment (OBOT).

Despite the majority of program directors believing that increased training in OBOT would improve access to treatment for OUD, barriers such as a lack of qualified preceptors and competing curricular priorities hinder the implementation of OBOT training in residency programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training in office-based opioid treatment with buprenorphine in US residency programs: A national survey of residency program directors. Tesema, L., Marshall, J., Hathaway, R., et al.[2019]

Integrating buprenorphine treatment for opioid dependence with HIV primary care can optimize health outcomes for patients dealing with both issues, as supported by the CDC's strategic plan.

The review outlines four effective models for this integration: on-site addiction/HIV specialist treatment, HIV primary care physician model, nonphysician health professional model, and community outreach model, which can help facilitate better care for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial strategies for integrating buprenorphine into HIV care settings in the United States. Sullivan, LE., Bruce, RD., Haltiwanger, D., et al.[2019]

Citations

1.

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 ...

2.

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 ...

3.

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.

4.

webbook.nist.gov

webbook.nist.gov/cgi/cbook.cgi?ID=520-52-5

Psilocybine - the NIST WebBook

Formula · C12H17N2O4P ; Molecular weight · 284.2481 ; Permanent link for this species. Use this link for bookmarking this species for future reference.

5.

zfin.org

zfin.org/CHEBI:8614

ZFIN ChEBI: psilocybin

A tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic alkaloid isolated ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05506982?term=psychedelic&cond=cancer&viewType=Table&rank=7

Study Details | NCT05506982 | Psilocybin Combined With ...

This phase I trial evaluates the side effects of psilocybin and how well it works under supportive care conditions in cancer survivors living with ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12001667/

A Modern Overview of the Potential Therapeutic Effects ...

Although more research is needed, early findings suggest that psilocybin has a favorable safety profile when used appropriately. While ...

8.

pmc.ncbi.nlm.nih.gov

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

Therapeutic effect of psilocybin in addiction: A systematic ...

Opioids. No studies were identified that evaluated the efficacy of psilocybin in patients with opioid use disorder.

9.

psychiatrictimes.com

psychiatrictimes.com/view/comp360-psilocybin-for-treatment-resistant-depression-positive-phase-3-efficacy-data

COMP360 Psilocybin for Treatment-Resistant Depression

This study aims to compare the safety and efficacy of 2 fixed doses, taken 3 weeks apart, of 25 mg COMP360 to 10 mg COMP360 and 1 mg COMP360. “ ...

10.

psychedelicalpha.com

psychedelicalpha.com/data/psychedelic-drug-development-tracker

Psychedelics Drug Development Tracker

This overview seeks to map out drug discovery & development activity in psychedelics. Candidates currently undergoing clinical trials are presented first.