Psilocybin-assisted psychotherapy to help taper long-term opioid pain medicines

Standardized Natural Psilocybin-assisted Psychotherapy for Tapering of Opioid Medication in Patients With Chronic Pain: an Open-label Feasibility Study

This pilot will try psilocybin-assisted psychotherapy to help adults with chronic noncancer pain who are on long-term opioid therapy reduce or stop their opioid medications.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 19 Years to 75 Years
• Sex: All
• Sponsor: University of British Columbia (Academic / other)
• Locations: 1 site (Kelowna, British Columbia)
• Trial ID: NCT05585229 on ClinicalTrials.gov

What this trial studies

This is an open-label, 8-week pilot intervention with one or two supervised psilocybin dosing sessions combined with preparatory and integration psychotherapy using an acceptance and commitment therapy model. The first dosing session (25 mg) is followed by an integration session and a physician-supervised opioid taper, with an optional second dosing (37.5 mg) about one month later. Safety, tolerability, retention, and patient-reported benefits and harms will be tracked, and opioid dose reductions will be measured at 1, 3, and 6 months after the intervention. The study enrolls adults with chronic noncancer pain on stable long-term opioid therapy who have previously been unable to taper and have no contraindications to psilocybin.

Who should consider this trial

Good fit: Adults aged 19–75 with noncancer chronic pain who have been on a stable opioid regimen for at least 90 days, have attempted and failed prior tapers, and have no medical or psychiatric contraindications to psilocybin are ideal candidates.

Not a fit: Patients with significant cardiovascular disease, certain uncontrolled psychiatric disorders, pregnancy or breastfeeding, or those not willing to attempt opioid reduction are unlikely to benefit or may be excluded.

Why it matters

Potential benefit: If successful, the approach could help some patients reduce or stop long-term opioid use while maintaining pain management and improving quality of life.

How similar studies have performed: Psilocybin-assisted psychotherapy has shown promising early results for conditions like depression and some substance use disorders, but direct evidence for facilitating opioid tapering is limited and this application is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Must be 19 - 75 years of age.
2. Have a diagnosed noncancer chronic pain condition including but not limited to neuropathic pain, fibromyalgia, chronic headaches/migraines, back pain, musculoskeletal pain.
3. 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.
4. 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.
5. Able to swallow capsules/tablets.
6. If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study.

Exclusion Criteria:

1. 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.
2. Asthma
3. Have moderate to severe hepatic impairment.
4. Chronic pain is due to cancer.
5. Women who are pregnant, who intend to become pregnant during the study, or who are currently breastfeeding.
6. Have a history of stroke or Transient Ischemic Attack (TIA).
7. Meet DSM-5 criteria for severe alcohol or drug use disorders (other than Opioid use Disorder).
8. Nicotine dependence that would prevent the participant from remaining nicotine free for the duration of dosing sessions (i.e., 6-8 hours).
9. Have Epilepsy.
10. Clinically significant sleep disorders such as sleep apnoea not on appropriate treatment.
11. Have Insulin-dependent diabetes.
12. 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.
13. 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).
14. 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.
15. Have a first degree relative with schizophrenia, Bipolar I or Bipolar II Disorder.
16. Meet DSM-5 criteria for diagnosis of antisocial or borderline personality disorders.
17. Participants with a history of a developmental disorder.
18. Participants diagnosed with serious comorbidities that may or may not influence mental health in the opinion of the qualified investigator.

Where this trial is running

Kelowna, British Columbia

• University of British Columbia - Okanagan Campus — Kelowna, British Columbia, Canada (Recruiting)

Study contacts

• Principal investigator: W. Francois Louw, MD — University of British Columbia
• Study coordinator: W. Francois Louw, MD

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