Repeat Dosing of Psilocybin in Migraine Headache

Migraine Headache Clinical Trial

Official title:

Repeat Dosing of Psilocybin in Headache Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04218539
• Other study ID #: 2000026974
• Secondary ID: 000
• Status: Completed
• Phase: Phase 1
• Start date: August 10, 2021
• Est. completion date: November 5, 2023

Study information

• Verified date: February 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 5, 2023
• Est. primary completion date: November 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Headache
• Migraine Disorders
• Migraine Headache

Intervention

Drug:
• Psilocybin
10mg Psilocybin
• Placebo
25mg Diphenhydramine

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Wallace Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in migraine attack frequency	Average number (number per week)	From two weeks before the first session to two months after second session using a headache diary
Primary	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 the first session to two months after second session using a headache diary
Primary	Change in duration of migraine attacks	Average duration (measured in hours)	From two weeks before the first session to two months after second session using a headache diary
Primary	Change in intensity of photophobia (light sensitivity)	Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before the first session to two months after second session using a headache diary
Primary	Change in intensity of phonophobia (noise sensitivity)	Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before the first session to two months after second session using a headache diary
Primary	Average intensity of nausea/vomiting	Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before the first session to two months after second session using a headache diary
Primary	Change in functional disability	Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before the first session to two months after second session using a headache diary
Secondary	Use of abortive/rescue medication	number of times per week	From two weeks before the first session to two months after second session using a headache diary
Secondary	Time to first migraine attack	Measured in days	From the second session until two months after second session using a headache diary
Secondary	Migraine attack-free time	Number of 24-hour days (may be non-consecutive)	From two weeks before the first session to two months after second session using a headache diary
Secondary	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	From two weeks before the first session to two months after second session using a headache diary
Secondary	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.	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
Secondary	Change in blood pressure- Systolic	Maximum change from baseline during each test day (mm Hg)	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)
Secondary	Change in blood pressure- Diastolic	Maximum change from baseline during each test day (mm Hg)	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)
Secondary	Change in heart rate	Maximum change from baseline during each test day (beats per minute)	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)
Secondary	Change in peripheral oxygenation	Maximum change from baseline during each test day (SpO2)	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)
Secondary	Change in peripheral calcitonin gene-related peptide (CGRP) levels	Change in peripheral neuropeptide 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)
Secondary	Change in pituitary adenylate cyclase-activating peptide (PACAP) levels	Change in peripheral neuropeptide 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)