Repeat Dosing of Psilocybin in Migraine Headache

Change in migraine attack frequency

Time frame · From two weeks before the first session to two months after second session using a headache diary

Average number (number per week)

Change in pain intensity of migraine attacks

Time frame · From two weeks before the first session to two months after second session using a headache diary

Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

Change in duration of migraine attacks

Time frame · From two weeks before the first session to two months after second session using a headache diary

Average duration (measured in hours)

Change in intensity of photophobia (light sensitivity)

Time frame · From two weeks before the first session to two months after second session using a headache diary

Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

Change in intensity of phonophobia (noise sensitivity)

Time frame · From two weeks before the first session to two months after second session using a headache diary

Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

Average intensity of nausea/vomiting

Time frame · From two weeks before the first session to two months after second session using a headache diary

Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

Change in functional disability

Time frame · From two weeks before the first session to two months after second session using a headache diary

Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

Use of abortive/rescue medication

Time frame · From two weeks before the first session to two months after second session using a headache diary

number of times per week

Time to first migraine attack

Time frame · From the second session until two months after second session using a headache diary

Measured in days

Migraine attack-free time

Time frame · From two weeks before the first session to two months after second session using a headache diary

Number of 24-hour days (may be non-consecutive)

Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module

Time frame · From two weeks before the first session to two months after second session using a headache diary

4 questions scored 0 to 30 each; higher numbers indicate worse quality of life. (1) pain-related impairment, (2) mood symptoms, (3) anxiety symptoms, (4) lack of sleep. Percent change for each measure as well as total score (range 0 to 120) will be calculated

Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale

Time frame · Starting on the first test day until the second test day approximately one week later; taken both test days approximately 6 hours after drug administration

94 questions scored 0 to 100 each; higher numbers indicate greater psychedelic effects. Questions address 5 dimensions: (1) Oceanic Boundlessness (score range 0-2700), (2) Dread of Ego Dissolution (score range 0-2100), (3) Visionary Restructuralization (score range 0-1800), (4) Auditory Alterations (score range 0-1600), and (5) Vigilance Reduction (score range 0-1200). Score for each dimension as well as total score (range 0 to 9400) will be measured.

Change in blood pressure- Systolic

Time frame · Starting on the first test day until the second test day approximately one week later; measured both test sessions before drug administration, every 30 min in the first hour, then hourly for 4 hours or until resolution of drug effects (~6hrs after drug)

Maximum change from baseline during each test day (mm Hg)

Change in blood pressure- Diastolic

Time frame · Starting on the first test day until the second test day approximately one week later; measured both test sessions before drug administration, every 30 min in the first hour, then hourly for 4 hours or until resolution of drug effects (~6hrs after drug)

Maximum change from baseline during each test day (mm Hg)

Change in heart rate

Time frame · Starting on the first test day until the second test day approximately one week later; measured both test sessions before drug administration, every 30 min in the first hour, then hourly for 4 hours or until resolution of drug effects (~6hrs after drug)

Maximum change from baseline during each test day (beats per minute)

Change in peripheral oxygenation

Time frame · Starting on the first test day until the second test day approximately one week later; measured both test sessions before drug administration, every 30 min in the first hour, then hourly for 4 hours or until resolution of drug effects (~6hrs after drug)

Maximum change from baseline during each test day (SpO2)

Change in peripheral calcitonin gene-related peptide (CGRP) levels

Time frame · Approximately 3 months; measured at screening, on both test days (0, 2, and 4 hours after drug administration), and follow-up (~2 months after second test day)

Change in peripheral neuropeptide levels