Psilocybin-facilitated Treatment for Chronic Pain

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: 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