Standardized Natural Psilocybin-assisted Psychotherapy for Tapering of Opioid Medication

NCT05585229 | Recruiting Phase 2 DMC

• 1 other identifier: PsilOps
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label pilot trial to assess the safety and feasibility of a novel 8-week psilocybin-assisted psychotherapy intervention to facilitate successful tapering/discontinuation of opioid pain medication in adult patients receiving long-term opioid therapy for chronic pain. Participation will last approximately 8 months and includes one or two psilocybin-assisted therapy sessions. The study will evaluate the incidence and severity of adverse events during and after treatment, the number of participants who drop out of the study for intervention-related reasons, and the self-reported benefits and harms of the intervention.

Conditions

Chronic Pain; Opioid Dependence

Keywords

Opioid Tapering; Psilocybin; Psychotherapy; Chronic Pain; Hallucinogens; Opioid Use Disorder

Outcome Measures

Primary Outcomes (3)

• Feasibility of psilocybin administration

  Percentage of participants who provide consent and complete the intervention.

  Week 31

• Acceptability of psilocybin administration

  Participant ratings of benefits and harms of the intervention.

  Week 31

• Safety of psilocybin administration

  Number and type of treatment-related adverse events and serious adverse events reported during the intervention.

  Up to 33 Weeks

Secondary Outcomes (3)

• Change in prescribed opioid dose at the 1-month visit compared to initial dose

  Week 11

• Change in prescribed opioid dose at the 3-month visit compared to initial dose

  Week 19

• Change in prescribed opioid dose at the 6-month visit compared to initial dose

  Week 31

Study Arms (1)

Psilocybin-assisted Psychotherapy

EXPERIMENTAL

Participants will undergo a single-arm, 8-week therapeutic intervention using natural standardized psilocybin-assisted psychotherapy as a treatment for opioid tapering in chronic pain patients. Specifically, they will undergo one or two standardized natural psilocybin (PEX010) dosing sessions; 25mg at week 3 and 37.5mg at week 7.

Drug: Psilocybin-assisted Psychotherapy

Interventions

Psilocybin-assisted Psychotherapy DRUG

Participants will complete a 8-week structured psychotherapeutic intervention involving administration of 25mg and 37.5mg PEX010 on two separate occasions.

Also known as: PEX010

Psilocybin-assisted Psychotherapy

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be 19 - 75 years of age.
• Have a diagnosed noncancer chronic pain condition including but not limited to neuropathic pain, fibromyalgia, chronic headaches/migraines, back pain, musculoskeletal pain.
• Currently on a stable dose of opioid therapy on short-acting, long-acting, or combination of opioid medication types, for a minimum duration of 90 consecutive days.
• History of at least one unsuccessful attempt to taper or discontinue long-term opioid therapy, and has expressed current interest in making another attempt to reduce or discontinue.
• Able to swallow capsules/tablets.
• If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study.

You may not qualify if:

• Have any of the following cardiovascular conditions: uncontrolled hypertension, coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, greater than first degree AV block, cardiac ischemia, congestive heart failure, myocardial infarction, tachycardia, chronic bradycardia, artificial heart valve, a clinically significant screening ECG abnormality, or any other significant cardiovascular condition.
• Asthma
• Have moderate to severe hepatic impairment.
• Chronic pain is due to cancer.
• Women who are pregnant, who intend to become pregnant during the study, or who are currently breastfeeding.
• Have a history of stroke or Transient Ischemic Attack (TIA).
• Meet DSM-5 criteria for severe alcohol or drug use disorders (other than Opioid use Disorder).
• Nicotine dependence that would prevent the participant from remaining nicotine free for the duration of dosing sessions (i.e., 6-8 hours).
• Have Epilepsy.
• Clinically significant sleep disorders such as sleep apnoea not on appropriate treatment.
• Have Insulin-dependent diabetes.
• Participants who are or have been taking mood stabilizers (e.g. lithium), SSRIs/SNRIs (e.g. citalopram, venlafaxine, vortioxetine, duloxetine), herbal remedies with serotonin activity (e.g. 5-HTP, St. John's Wort), dopamine agonists (e.g. bupropion), tricyclic antidepressants (e.g. amitriptyline), antipsychotics (e.g. haloperidol), amphetamines (e.g. amphetamine/dextroamphetamine salts, methylphenidate, dextroamphetamine, lisdexamfetamine), monoamine oxidase inhibitors (e.g. isocarboxazid, phenelzine, selegiline, tranylcypromine), alcohol or aldehyde dehydrogenase inhibitors (e.g. disulfiram), and UDG modulators (i.e. UGT modulators such as phenytoin, regorafenib, eltrombopag) during the study or in the preceding 8 weeks.
• Hallucinogenic or psychedelic drug use within 12 months (i.e. any use of mescaline, 2C-B, psilocybin, LSD, 5-MeO-DMT, ibogaine ayahuasca, MDA, MDMA, ketamine or any related molecules).
• Meet DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features, or Bipolar I or Bipolar II Disorder.
• Have a first degree relative with schizophrenia, Bipolar I or Bipolar II Disorder.

Sponsors & Collaborators

• University of British Columbia: lead
• Etheridge Foundation: collaborator

Study Sites (1)

University of British Columbia - Okanagan Campus

Kelowna, British Columbia, V1V 1V7, Canada

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders; Chronic Pain

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• W. Francois Louw, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

W. Francois Louw, MD

CONTACT

250-860-9754; doclouw@mail.ubc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: October 14, 2022
• First Posted: October 18, 2022
• Study Start: October 27, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)