Psilocybin for Opioid Use Disorder

Overseen By Megan Ivey, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Anna Rose Childress, Ph.D.

Must be taking: MAT for OUD

Must not be taking: Psychoactive medications

Disqualifiers: Schizophrenia, Bipolar, Severe MDD, others

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

Compensation: Varies

Number of Visits: 16

Duration: 1 day

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a compound in certain mushrooms, can aid individuals with opioid use disorder (OUD) who are already receiving medication-assisted treatment (MAT) like buprenorphine or methadone. Researchers are testing two different doses of psilocybin to determine if it improves brain function and clinical outcomes, such as reducing drug use and increasing adherence to MAT. The trial includes brain and behavior tests, with follow-ups for a year to monitor progress. It suits individuals voluntarily in a residential addiction treatment facility, currently undergoing MAT, and seeking additional support for OUD. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to continue taking their current medication for opioid use disorder, such as buprenorphine or methadone, as part of the study. However, you may need to avoid other psychoactive medications, like antidepressants, unless approved by the study's medical director.

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

In earlier studies, psilocybin has shown potential in treating substance use problems, such as opioid addiction. Research indicates that psilocybin is generally safe for people. For example, one study found that a 25 mg dose posed no major safety issues. Another study found a 50 mg dose was safe, but researchers reduced it to 40 mg for added caution.

For the smaller 1 mg dose, specific safety information is limited, but overall research suggests psilocybin is generally safe. These studies indicate that both low and high doses of psilocybin are likely safe for participants, with more detailed safety data available for the higher dose. ^{1 2 3 4 5}

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

Researchers are excited about psilocybin for opioid use disorder because it offers a new approach compared to traditional treatments like methadone, buprenorphine, and naltrexone. Unlike these treatments, which mainly focus on managing withdrawal symptoms and cravings, psilocybin is a psychedelic compound that may help address the underlying psychological and behavioral aspects of addiction. Psilocybin works by targeting serotonin receptors in the brain, potentially leading to transformative experiences and shifts in perspective that can aid in breaking the cycle of addiction. Moreover, psilocybin's effects could last after just a single dose, offering a promising alternative to daily medication regimens.

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

This trial will compare the effects of different doses of psilocybin on opioid use disorder. Studies have shown that psilocybin might help reduce symptoms of substance use problems, including opioid use. Early findings suggest that psilocybin can lower the use of opioids and nicotine, although results vary for other substance use issues. Research indicates that psilocybin-assisted treatment also has strong antidepressant effects, which could help people with opioid use problems. Trials have used psilocybin to help decrease the misuse of opioids and other drugs. While more research is needed, these studies provide hope that psilocybin might be effective in treating opioid use problems. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals on Medication-Assisted Treatment (MAT) for Opioid Use Disorder. Participants must be willing to undergo brain and behavioral testing, submit urine screens twice a week, and complete surveys regularly. The study excludes those who don't meet these requirements.

Inclusion Criteria

Voluntary enrollment in the residential addiction treatment facility

Intention on residing within residential addiction treatment facility for the duration of the Pre/Post PSI dosing period

Meet criteria for opioid use disorder (based on DSM-5 criteria) as primary diagnosis and voluntarily seeking treatment

Exclusion Criteria

Meets DSM-5 criteria for moderate to severe substance use disorder for substances other than cocaine, alcohol, marijuana, or nicotine

Participation in clinical trial and receipt of investigational drug(s) during 30 days prior to the research study, except as explicitly approved by the Principal Investigator

History of serious head trauma, seizures not related to withdrawal, or presence of certain prosthetics in the body

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Testing

Brain and behavioral testing sessions conducted 24-48 hours before Psilocybin dosing

1 week

Treatment

Participants receive a single dose of either 25 mg or 1 mg PEX010

1 day

Post-Treatment Testing

Brain and behavioral testing sessions conducted 1 week after Psilocybin dosing

1 week

Outcomes Phase

Participants submit urine screens twice a week and complete surveys to collect data on drug use, MAT adherence, and mental health symptoms

8 weeks

16 visits (in-person)

Follow-up

Research follow-ups every three months to monitor long-term outcomes

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview

The trial tests the efficacy of PEX010 (Psilocybin), comparing two doses: 25-mg and 1-mg. It's double-blind, meaning neither participants nor researchers know who gets which dose. The goal is to see if Psilocybin improves neurocognition and clinical outcomes in OUD patients.

How Is the Trial Designed?

Group I: High Dose Psilocybin Experimental Treatment 1 Intervention

25 mg PEX010 capsule, single dose

Group II: Low Dose Psilocybin Active Control 1 Intervention

1 mg PEX010 capsule, single dose

Who Is Running the Clinical Trial?

Anna Rose Childress, Ph.D.

Lead Sponsor

Trials

3

Recruited

70+

Published Research Related to This Trial

A systematic review of 16 studies found that psilocybin is generally well-tolerated, with the most common side effects being transient nausea and headache, and no reports of severe long-term issues like psychosis.

Psilocybin shows promise as a safe treatment option for psychiatric and substance-dependence conditions, particularly for patients who do not respond to standard therapies, as it has demonstrated both acute and long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review. Kaminski, D., Reinert, JP.[2023]

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]

Methamphetamine use disorder is a serious condition with high relapse rates and limited effectiveness of current treatments, highlighting the need for new therapeutic options.

Psilocybin-assisted psychotherapy shows promise as a potential treatment for methamphetamine use disorder, based on early experiences from four clinical trials, although no published studies currently exist on this specific application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. Brett, J., Knock, E., Korthuis, PT., et al.[2023]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

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]

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]

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, 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]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

In a proof-of-concept study involving 10 alcohol-dependent participants, psilocybin administration led to a significant increase in abstinence rates after treatment, with effects maintained for up to 36 weeks.

Participants experienced no significant adverse events, suggesting that psilocybin is safe for use in this context, and the intensity of the psilocybin effects predicted positive changes in drinking behavior and cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Bogenschutz, MP., Forcehimes, AA., Pommy, JA., et al.[2022]

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]

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.

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 ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0149763425001630

Efficacy and safety of psilocybin for the treatment ...

Early findings suggest psilocybin's potential in reducing opioid and nicotine use, though results remain mixed for other SUDs.

4.

pharmacy.wisc.edu

pharmacy.wisc.edu/2022/12/08/two-first-in-kind-clinical-trials-explore-psilocybin-for-substance-misuse/

Two First-in-Kind Clinical Trials Explore Psilocybin for ...

A UW–Madison research team is investigating the use of psilocybin to aid in decreasing opioid and methamphetamine misuse.

5.

withpower.com

withpower.com/trial/psilocybin-for-opioid-use-disorder-5f994

Psilocybin for Opioid Use Disorder · Info for Participants

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11661506/

Psilocybin for Opioid Use Disorder in Two Adults Stabilized ...

This technical report presents methodological considerations and preliminary data from a safety-feasibility trial examining the interaction between psilocybin ...

7.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00081-1/fulltext

Psilocybin-assisted therapy for relapse prevention in ...

Safety outcomes are reported in Supplementary Table S11. The psilocybin dose (25 mg) administered in our study was well-tolerated.