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.

The purpose of this pilot study is to establish the safety and tolerability of a therapeutic intervention using psilocybin-assisted psychotherapy as a novel treatment for opioid tapering in a sample of patients with chronic pain. Participants will be patients who have failed previous attempts to reduce their use of opioid medication and who have no medical or psychological contraindications for psilocybin administration.

This pilot study involves an 8-week open-label, non-randomized therapeutic intervention and a 6-month follow-up period. To provide a supportive context for the drug experience, participants will receive preparatory and integrative sessions following an acceptance and commitment therapy model for psychedelic therapy. The physician-supervised opioid taper will begin following the first psilocybin dosing session (25mg) after an integration session with therapists, and a second optional psilocybin dosing session (37.5mg) will be facilitated one month later. Assessments will be completed at baseline, and at follow-up points at 1-month, 3-months and 6-months post-intervention to evaluate both acute and long-term effects of the intervention.

Primary outcomes of interest are rates of adverse events, retention rates, and patient perceptions of intervention tolerability. Preliminary efficacy of the treatment will be evaluated by tracking opioid reduction rates and long-term maintenance of these reductions. Other measures of interest include qualities of the psychedelic experience, opioid cravings and withdrawal, chronic pain symptoms, and psychological mechanisms.

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.