Psilocybin-facilitated Treatment for Chronic Pain
Randomised, double-blind, parallel-group study (n=30) testing a single oral dose of psilocybin (0.36 mg/kg) versus active placebo (dextromethorphan 2.6 mg/kg) for fibromyalgia.
Detailed Description
Randomised, double-blind, parallel-group trial evaluating psilocybin-assisted treatment for fibromyalgia with 30 female participants, comparing 0.36 mg/kg psilocybin to 2.6 mg/kg dextromethorphan (active placebo).
Participants receive preparatory therapy (minimum two 2-hour sessions), a single 8‑hour supervised dosing session with physiological monitoring, and an integration session the following day; outcomes include pain, fatigue, functioning and quality of life.
Additional measures assess potential mediators such as expectations, pain characteristics, personality and cognitive/emotional factors; participants complete follow-up at ~6 weeks.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
Psilocybin
experimentalSingle oral psilocybin administration (0.36 mg/kg) in treatment-seeking fibromyalgia patients.
Interventions
- Psilocybin0.36 mg/kgvia Oral• single dose
Administered once during an 8-hour dosing session; participants receive preparatory and integration sessions.
Active placebo (DXM)
active comparatorOral dextromethorphan (active placebo) 2.6 mg/kg.
Interventions
- Placebo2.6 mg/kgvia Oral• single dose
Active placebo: dextromethorphan (DXM) 2.6 mg/kg; participants blinded to drug assignment; unblinded at study end.
Participants
Inclusion Criteria
- Inclusion Criteria:
- 1. Female age 25-65;
- 2. Widespread musculoskeletal pain for ≥12 months;
- 3. Symptoms meeting the American College of Rheumatology (ACR) 2016 revisions to the 2010/2011 Fibromyalgia Diagnostic Criteria;
- 4. Participant completes daily report during baseline period (at least 80% completion rate);
- 5. Able to attend UAB for all scheduled appointments;
- 6. Ability to read/write in English;
- 7. No prior hallucinogen use or it will have been at least 3 years since last use of a hallucinogen;
- 8. Availability of a friend or family member into whose care the participant can be released (a key responsibility includes driving participants home) following their drug administration session;
- 9. A current average daily pain score of at least 5 on a 0-10 scale;
- 10. Discontinuation of exclusionary medication occurring at least two weeks and for at least 5 half-lives, whichever is longer, prior to drug administration day.
Exclusion Criteria
- Exclusion Criteria:
- 1. Males;
- 2. Use of opioid medications in the last 60 days;
- 3. Regular use of any anti-inflammatory medication (e.g., aspirin, ibuprofen, naproxen);
- 4. Use of blood thinning medication;
- 5. Use of tricyclic antidepressants, lithium, SSRIs, MAOIs, St. John's Wort, 5-hydroxytryptophan (5-HT), haloperidol, or other antipsychotic medications, mood stabilizers, or medications with serotonin activity;
- 6. Daily consumption of grapefruit juice;
- 7. Febrile illness or use of antibiotics in the 4 weeks before study commencement;
- 8. Planned surgery or procedures during the study period, or operated on in the 4 weeks prior to study commencement;
- 9. Planning to move from the Birmingham area in the next 6 months;
- 10. Planned vaccination during the study period, or vaccinated in the 4 weeks before study commencement;
- 11. Current participation in another treatment trial;
- 12. Pregnant or planning to become pregnant within 6 months, or currently breastfeeding;
- 13. Significant psychological comorbidity that in the discretion of the investigator compromises study integrity (i.e., presence of a current, clinically significant, untreated or unstable psychiatric condition) and/or a baseline HADS depression subscale score of ≥16;
- 14. Current or past history of any psychotic disorders;
- 15. Current or past history of bipolar I or II disorder;
- 16. First or second-degree relatives with any psychotic disorders, or bipolar I or II disorders;
- 17. Current suicidal or homicidal ideation (assessed using Columbia-Suicide Severity Rating Scale at each visit);
- 18. Diagnosed rheumatologic or auto-immune condition;
- 19. Blood or clotting disorder;
- 20. Current hypertension (exceeding 140 systolic or 90 diastolic at resting); resting heart rate >90;
- 21. Acute infection (oral temperature >100°F);
- 22. High-sensitivity c-reactive protein (hs-CRP) ≥ 10mg/L;
- 23. Erythrocyte sedimentation rate (ESR) > 60 mm/hr;
- 24. Positive rheumatoid factor;
- 25. Positive anti-nuclear antibody (ANA);
- 26. Levels of thyroid-stimulating hormone or free thyroxine outside UAB Hospital Labs reference values;
- 27. Use of UGT1A9, UGT1A10 and aldehyde or alcohol dehydrogenase enzyme inhibitors;
- 28. Dependent on any psychoactive drugs other than nicotine and caffeine;
- 29. Use of the antiviral drug efavirenz;
- 30. Use of PDE-5-Inhibitors, soluble guanylate cyclase (sGC) stimulators;
- 31. Severe anemia;
- 32. Phenylketonuria, chronic bronchitis, emphysema, asthma, diabetes, liver disease, and mucus with cough or slowed breathing;
- 33. Use of any medication containing dextromethorphan (e.g., cough suppressants);
- 34. Pain due to other conditions or diseases that would complicate study participation or pain reporting.
- 35. Use of strong or moderate inhibitors of Cytochrome P450 2D6 (CYP2D6)
- 36. Poor metabolizers of CYP2D6 based on genotype
Study Details
- StatusRecruiting
- PhasePhase I
- Typeinterventional
- DesignRandomizedquadruple Blind
- Target Enrollment30 participants
- TimelineStart: 2022-01-01End: 2024-07-01
- Compounds
- Topic