The purpose of this study is to assess brain activity under Psilocybin in a cohort of people with fibromyalgia.

This mechanistic (Non-CTIMP) study will utilise a within-subjects design to examine a candidate brain biomarker of increased plasticity under Psilocybin. Up to 25mg of Psilocybin will be administered under standardised conditions on two occasions, separated by four weeks with in-dosing EEG recordings.

The primary end-point will take place 8 weeks from the first dosing session after which patients will be remotely monitored monthly for 6 months.

Inclusion Criteria:

• Fibromyalgia lasting for more than 3 months, as diagnosed by an appropriate medical professional using the American College of Rheumatology diagnostic criteria.
• Over 18 years of age
• United Kingdom (UK) resident registered with a primary care medical practice
• Sufficiently competent in English with capacity to provide written informed consent
• Agreement for research team to contact primary and/or secondary care team over the course of the study
• No psychedelic use in the past 6 months

Exclusion Criteria:

• Current or previously diagnosed psychotic disorder or bipolar disorder
• Immediate family member with a diagnosed psychotic disorder
• History of serious suicide attempts or presence of significant suicide/self-harm risk at screening
• Emotionally unstable personality, history of mania, or other psychiatric problem that the screening clinician feels may jeopardise the therapeutic alliance and/or safe exposure to psilocybin
• Currently using medication which could interact with psilocybin including anti-psychotics, mood stabilizers & serotonergic antidepressants including selective serotonin reuptake inhibitors (SSRIs), SNRIs, and tricyclic antidepressants (TCAs)*
• On waiting list for interventional treatment for pain (e.g. surgery or targeted injections)
• Actively enrolled on pain management programme over course of study or awaiting further investigations for pain
• Contraindications to EEG components of the study (e.g., epilepsy, migraine, focal scalp sensitivity)
• MRI contraindications (e.g. claustrophobia, metal implants)
• Physical co-morbidities that are unsuitable for the psychedelic component of the study (e.g., epilepsy, severe cardiovascular disease, insulin-dependent diabetes, hepatic or renal failure e.g., CrCl < 30ml/min etc)
• Blood or needle phobia
• Positive pregnancy test at screening or during the study
• People who are breastfeeding
• Unable to engage with physical demands of dosing session (i.e. attend centre and remain in research facility for an extended period of time)
• Unable to access virtual meetings/phone for remote follow-ups
• Patients consuming more than 35 units of alcohol per week.
• Presence of new or un-investigated 'red flag' symptom indicating need for urgent investigation (e.g. upper motor neuron syndrome, gait ataxia, bladder or bowel dysfunction).
• Limited life expectancy (<18 months) or rapidly deteriorating condition that may inhibit completion of the study (6 month remote follow up).
• Currently prescribed any of the following drugs: Antiepileptics, 5HT3-receptor antagonists, Aspirin, Coumarins, Cyproheptadine, Dabigatran, Dapoxetine, Duloxetine, Lithium, Methylphenidate, Methylthioninium, Metoclopramide, NSAIDs (should be avoided), Naratriptan, Pimozide, Rasagiline, Ritonavir, St John's Wort and Vortioxetine. Tramadol and Fentanyl will be avoided due to their serotonergic action, but all other opioids will not be grounds for exclusion.

Fibromyalgia lasting for more than 3 months, as diagnosed by an appropriate medical professional using the American College of Rheumatology diagnostic criteria.