In seeking to understand the capacity for psilocybin to reduce migraine headache burden, this study will investigate single and repeated dosing of psilocybin up to two doses. In seeking to identify an underlying mechanism in psilocybin's effects, neuroinflammatory markers for migraine headache will be measured.
Migraine headache is a common medical condition and a top cause of disability worldwide. Treatment options for migraine headache are many and varied, though an approximated 10% of migraineurs is refractory to medication and thus, there is a need to develop alternative treatments. There is anecdotal evidence supporting lasting therapeutic effects after limited dosing of psilocybin and related compounds in headache disorders. The cause of this unique effect remains unknown, though the drug class has demonstrable anti-inflammatory activity, a biological process relevant to migraine and other headache disorders. In seeking to understand the capacity for psilocybin to reduce migraine headache burden, this study will investigate single and repeated dosing of psilocybin up to two doses. In seeking to identify an underlying mechanism in psilocybin's effects, neuroinflammatory markers for migraine headache will be measured. The results from this study will serve in the development of larger investigations seeking to understand the effects of psilocybin and related compounds in headache disorders.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
18
10mg Psilocybin
25mg Diphenhydramine
VA Connecticut Healthcare System
West Haven, Connecticut, United States
Change in migraine attack frequency
Average number (number per week)
Time frame: From two weeks before the first session to two months after second session using a headache diary
Change in pain intensity of migraine attacks
Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time frame: From two weeks before the first session to two months after second session using a headache diary
Change in duration of migraine attacks
Average duration (measured in hours)
Time frame: From two weeks before the first session to two months after second session using a headache diary
Change in intensity of photophobia (light sensitivity)
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time frame: From two weeks before the first session to two months after second session using a headache diary
Change in intensity of phonophobia (noise sensitivity)
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time frame: From two weeks before the first session to two months after second session using a headache diary
Average intensity of nausea/vomiting
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time frame: From two weeks before the first session to two months after second session using a headache diary
Change in functional disability
Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time frame: From two weeks before the first session to two months after second session using a headache diary
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Use of abortive/rescue medication
number of times per week
Time frame: From two weeks before the first session to two months after second session using a headache diary
Time to first migraine attack
Measured in days
Time frame: From the second session until two months after second session using a headache diary
Migraine attack-free time
Number of 24-hour days (may be non-consecutive)
Time frame: From two weeks before the first session to two months after second session using a headache diary
Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module
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
Time frame: From two weeks before the first session to two months after second session using a headache diary
Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
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.
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
Change in blood pressure- Systolic
Maximum change from baseline during each test day (mm Hg)
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)
Change in blood pressure- Diastolic
Maximum change from baseline during each test day (mm Hg)
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)
Change in heart rate
Maximum change from baseline during each test day (beats per minute)
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)
Change in peripheral oxygenation
Maximum change from baseline during each test day (SpO2)
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)
Change in peripheral calcitonin gene-related peptide (CGRP) levels
Change in peripheral neuropeptide 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 pituitary adenylate cyclase-activating peptide (PACAP) levels
Change in peripheral neuropeptide 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)