Repeat Dosing of Psilocybin in Migraine Headache

Inclusion Criteria: * Diagnosis of migraine headache per ICHD-3 criteria * Typical pattern of migraine attacks with approximately two migraines or more weekly * Attacks are managed by means involving no more than twice weekly triptan use Exclusion Criteria: * Axis I psychotic or manic disorder (e.g., schizophrenia, bipolar I, depression with psychosis) * Axis I psychotic or manic disorder in first degree relative * Unstable medical condition; severe renal, cardiac, or hepatic disease; pacemaker; or serious central nervous system pathology * Pregnant, breastfeeding, lack of adequate birth control * History of intolerance to psilocybin, lysergic acid diethylamide (LSD), or related compounds * Drug abuse within the past 3 months (excluding tobacco) * Urine toxicology positive to drugs of abuse * Alcohol use of \>21 drinks per week (males); \>14 drinks per week (females; NIAAA guidelines) * Use of alcohol in the week prior to the first test day * Use of vasoconstrictive medications (i.e., sumatriptan, pseudoephedrine, midodrine) within 5 half-lives of test days * Use of serotonergic antiemetics (i.e., ondansetron) in the past 2 weeks * Use of antidepressant medication (i.e., TCA, MAOI, SSRI) in the past 6 weeks * Use of steroids or certain other immunomodulatory agents (i.e., azathioprine) in the past 2 weeks * Use of migraine onabotulinum toxin (i.e., Botox) or monoclonal antibodies against CGRP or its receptor (i.e., erenumab) in the past month or while therapeutic effects a…