Clinical trial NCT03341689: Psilocybin for the Treatment of Migraine Headache
Official title: Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study I
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Migraine Headache
Keywords: Psilocybin
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Ceruvia Lifesciences
First posted: 2017-11-14
Enrollment: 14
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in migraine headache days
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in migraine attack frequency
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in migraine attack duration
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in pain intensity of migraine attacks
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in intensity of nausea/vomiting during migraine attacks
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in intensity of photophobia
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in intensity of phonophobia
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in migraine attack-related functional disability
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
Secondary outcomes:
measure: Change in the use of abortive/rescue medication
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Time to first migraine attack
timeFrame: From the day of each session until two weeks after each test session
measure: Time to second migraine attack
timeFrame: From the day of each session until two weeks after each test session
measure: Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module
timeFrame: From two weeks before first session to three months after second session using a headache diary
measure: Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
timeFrame: Taken on each test day approximately 6 hours after drug administration
measure: Change in blood pressure
timeFrame: 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)
measure: Change in heart rate
timeFrame: 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)
measure: Change in peripheral oxygenation
timeFrame: 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)
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System, West Haven Campus
state: Connecticut
Study officials:
References:
citation: Schindler EAD, Sewell RA, Gottschalk CH, Luddy C, Flynn LT, Lindsey H, Pittman BP, Cozzi NV, D'Souza DC. Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin. Neurotherapeutics. 2021 Jan;18(1):534-543. doi: 10.1007/s13311-020-00962-y. Epub 2020 Nov 12.