Psilocybin for the Treatment of Migraine Headache

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of oral psilocybin in migraine headache. Subjects will each receive a dose of placebo and a dose of psilocybin approximately 14 days apart. Subjects will be randomized to the order of treatment and they will be randomized to receive either low or high dose psilocybin. Subjects will maintain a headache diary prior to, during, and after the treatments in order to document headache frequency and intensity, as well as associated symptoms. This preliminary study will inform on the basic effects of psilocybin in migraine headache and inform on the design of larger, more definitive studies.

Detailed Description
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The number of arms reflects the design of the enhanced blinding method. The final enrollment number reflects the number of subjects participating in study procedures.

Official Title
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Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study I

Conditions
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Migraine Headache

Intervention / Treatment
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* Drug: High Dose Psilocybin
* Drug: Low Dose Psilocybin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of migraine headache per ICHD-3beta 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 Age 21 to 65 Exclusion Criteria: Axis I psychotic disorder (e.g. schizophrenia, bipolar I, depression with psychosis) Axis I psychotic 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, LSD, or related compounds Drug or alcohol abuse within the past 3 months (excluding tobacco) Urine toxicology positive to drugs of abuse 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo/Low Dose Psilocybin<br>Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session. | Drug: Low Dose Psilocybin<br>* 0.0143 mg/kg psilocybin capsule<br>Drug: Placebo<br>* microcrystalline cellulose capsule<br>|
| Experimental: Placebo/High Dose Psilocybin<br>Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session. | Drug: High Dose Psilocybin<br>* 0.143 mg/kg psilocybin capsule<br>Drug: Placebo<br>* microcrystalline cellulose capsule<br>|
| Experimental: Low Dose Psilocybin/Placebo<br>Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session. | Drug: Low Dose Psilocybin<br>* 0.0143 mg/kg psilocybin capsule<br>Drug: Placebo<br>* microcrystalline cellulose capsule<br>|
| Experimental: High Dose Psilocybin/Placebo<br>Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session. | Drug: High Dose Psilocybin<br>* 0.143 mg/kg psilocybin capsule<br>Drug: Placebo<br>* microcrystalline cellulose capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in migraine headache days | Average days (number of days per week) | From two weeks before first session to two weeks after second session using a headache diary | 
| Change in migraine attack frequency | Average number (number per week) | From two weeks before first session to two weeks after second session using a headache diary | 
| Change in migraine attack duration | Average duration (measured in hours) | From two weeks before first session to two weeks 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) | From two weeks before first session to two weeks after second session using a headache diary | 
| Change in intensity of nausea/vomiting during migraine attacks | Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe) | From two weeks before first session to two weeks after second session using a headache diary | 
| Change in intensity of photophobia | Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe) | From two weeks before first session to two weeks after second session using a headache diary | 
| Change in intensity of phonophobia | Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe) | From two weeks before first session to two weeks after second session using a headache diary | 
| Change in migraine attack-related functional disability | Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe) | From two weeks before first session to two weeks after second session using a headache diary | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the use of abortive/rescue medication | number of days (number of days per week using a migraine abortive) | From two weeks before first session to two weeks after second session using a headache diary | 
| Time to first migraine attack | Measured in days | From the day of each session until two weeks after each test session | 
| Time to second migraine attack | Measured in days | From the day of each session until two weeks after each test session | 
| 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, and (4) lack of sleep Percent change for each measure as well as total score (range 0 to 120) will be calculated. | From two weeks before first session to three 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. | Taken on each test day approximately 6 hours after drug administration | 
| Change in blood pressure | Maximum change in mean arterial blood pressure from baseline during each test day (mmHg) | Measured during each test session prior to drug administration, every 15 minutes in the first hour, every 30 minutes in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects ( 6 hours post drug) | 
| Change in heart rate | Maximum change from baseline during each test day (beats per minute) | Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects ( 6 hours post drug) | 
| Change in peripheral oxygenation | Maximum change from baseline during each test day (SpO2) | Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects ( 6 hours post drug) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psilocybin