Migraine Headache
Conditions
Keywords
psilocybin, inflammation, calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating peptide (PACAP)
Brief summary
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.
Detailed description
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.
Interventions
DRUGPsilocybin
10mg Psilocybin
DRUGPlacebo
25mg Diphenhydramine
Sponsors
The Wallace Foundation
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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 are still present
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in migraine attack frequency | 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 | 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 | 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) | 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) | 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 | 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 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in blood pressure- Diastolic | 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 | 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) |
| Use of abortive/rescue medication | From two weeks before the first session to two months after second session using a headache diary | number of times per week |
| Change in pituitary adenylate cyclase-activating peptide (PACAP) levels | 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 |
| Change in peripheral oxygenation | 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) |
| Time to first migraine attack | From the second session until two months after second session using a headache diary | Measured in days |
| Migraine attack-free time | 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 | 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 |
| Change in peripheral calcitonin gene-related peptide (CGRP) levels | 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 |
| Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale | 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 | 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) |
Countries
United States
Outcome results
None listed