Psilocybin for the Treatment of Migraine Headache

October 10, 2023 updated by: Deepak C. D'Souza, Yale University

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • VA Connecticut Healthcare System, West Haven Campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in migraine headache days
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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
Time Frame: From the day of each session until two weeks after each test session
Measured in days
From the day of each session until two weeks after each test session
Time to second migraine attack
Time Frame: From the day of each session until two weeks after each test session
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
Time Frame: From two weeks before first session to three 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, 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
Time Frame: Taken on each test day 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.
Taken on each test day approximately 6 hours after drug administration
Change in blood pressure
Time Frame: 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)
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
Time Frame: 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)
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
Time Frame: 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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2017

Primary Completion (Actual)

April 30, 2021

Study Completion (Actual)

October 31, 2021

Study Registration Dates

First Submitted

November 9, 2017

First Submitted That Met QC Criteria

November 9, 2017

First Posted (Actual)

November 14, 2017

Study Record Updates

Last Update Posted (Actual)

October 12, 2023

Last Update Submitted That Met QC Criteria

October 10, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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