Mechanistic Studies of Psilocybin in Headache Disorders

Inclusion criteria:

• Age 21 to 70 (inclusive)

• Migraine disease per ICHD-3 criteria (for migraine participants) OR Healthy control patient

Exclusion criterion

• Unstable medical condition or serious nervous system pathology

• Pregnant, breastfeeding, lack of adequate birth control

• Psychotic or manic disorder

• Substance abuse in the prior 3 months

• Use of classic psychedelics (e.g., psilocybin, LSD, mescaline) in the past 6 months

• Use of cannabis or other THC products in the prior 2 weeks

• Urine toxicology positive to drugs of abuse

• The use of triptans (e.g., sumatriptan) or ditans (e.g., lasmiditan) more than twice weekly on average

• Use of serotonergic preventive therapies (i.e., taken chronically; amitriptyline, fluoxetine, imipramine, cyproheptadine) in the past 6 weeks

• Use of preventive or transitional treatments that produce spikes and waning of symptom relief (e.g., botulinum toxin, calcitonin gene-related peptide system targeting antibodies, peripheral nerve or ganglion blocks, chiropractic manipulation)

• History of a bleeding disorder or are currently taking anticoagulants (e.g., warfarin, enoxaparin, dabigatran, apixaban).

• Use of non-steroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen) in the 7 days before PET scan and 7 days after PET scan.