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Repeat Dosing of Psilocybin in Migraine Headache

Primary Purpose

Migraine Headache

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Psilocybin
Placebo
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Migraine Headache focused on measuring psilocybin, inflammation, calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating peptide (PACAP)

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • VA Connecticut Healthcare System

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo/Placebo

Placebo/Psilocybin

Psilocybin/Placebo

Psilocybin/Psilocybin

Arm Description

Subjects will receive a dose of placebo, followed by a dose of placebo approximately 7 days later.

Subjects will receive a dose of placebo, followed by a dose of psilocybin approximately 7 days later.

Subjects will receive a dose of psilocybin, followed by a dose of placebo approximately 7 days later.

Subjects will receive a dose of psilocybin, followed by a dose of psilocybin approximately 7 days later.

Outcomes

Primary Outcome Measures

Change in migraine attack frequency
Average number (number per week)
Change in pain intensity of migraine attacks
Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Change in duration of migraine attacks
Average duration (measured in hours)
Change in intensity of photophobia (light sensitivity)
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Change in intensity of phonophobia (noise sensitivity)
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Average intensity of nausea/vomiting
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Change in functional disability
Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

Secondary Outcome Measures

Use of abortive/rescue medication
number of times per week
Time to first migraine attack
Measured in days
Migraine attack-free time
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
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
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.
Change in blood pressure- Systolic
Maximum change from baseline during each test day (mm Hg)
Change in blood pressure- Diastolic
Maximum change from baseline during each test day (mm Hg)
Change in heart rate
Maximum change from baseline during each test day (beats per minute)
Change in peripheral oxygenation
Maximum change from baseline during each test day (SpO2)
Change in peripheral calcitonin gene-related peptide (CGRP) levels
Change in peripheral neuropeptide levels
Change in pituitary adenylate cyclase-activating peptide (PACAP) levels
Change in peripheral neuropeptide levels

Full Information

First Posted
December 20, 2019
Last Updated
October 11, 2023
Sponsor
Yale University
Collaborators
Wallace Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04218539
Brief Title
Repeat Dosing of Psilocybin in Migraine Headache
Official Title
Repeat Dosing of Psilocybin in Headache Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 10, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
Wallace Research Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine Headache
Keywords
psilocybin, inflammation, calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating peptide (PACAP)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo/Placebo
Arm Type
Experimental
Arm Description
Subjects will receive a dose of placebo, followed by a dose of placebo approximately 7 days later.
Arm Title
Placebo/Psilocybin
Arm Type
Experimental
Arm Description
Subjects will receive a dose of placebo, followed by a dose of psilocybin approximately 7 days later.
Arm Title
Psilocybin/Placebo
Arm Type
Experimental
Arm Description
Subjects will receive a dose of psilocybin, followed by a dose of placebo approximately 7 days later.
Arm Title
Psilocybin/Psilocybin
Arm Type
Experimental
Arm Description
Subjects will receive a dose of psilocybin, followed by a dose of psilocybin approximately 7 days later.
Intervention Type
Drug
Intervention Name(s)
Psilocybin
Intervention Description
10mg Psilocybin
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
25mg Diphenhydramine
Primary Outcome Measure Information:
Title
Change in migraine attack frequency
Description
Average number (number per week)
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Change in pain intensity of migraine attacks
Description
Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Change in duration of migraine attacks
Description
Average duration (measured in hours)
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Change in intensity of photophobia (light sensitivity)
Description
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Change in intensity of phonophobia (noise sensitivity)
Description
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Average intensity of nausea/vomiting
Description
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Change in functional disability
Description
Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Secondary Outcome Measure Information:
Title
Use of abortive/rescue medication
Description
number of times per week
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Time to first migraine attack
Description
Measured in days
Time Frame
From the second session until two months after second session using a headache diary
Title
Migraine attack-free time
Description
Number of 24-hour days (may be non-consecutive)
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module
Description
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
Time Frame
From two weeks before the first session to two months after second session using a headache diary
Title
Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
Description
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.
Time Frame
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
Title
Change in blood pressure- Systolic
Description
Maximum change from baseline during each test day (mm Hg)
Time Frame
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)
Title
Change in blood pressure- Diastolic
Description
Maximum change from baseline during each test day (mm Hg)
Time Frame
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)
Title
Change in heart rate
Description
Maximum change from baseline during each test day (beats per minute)
Time Frame
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)
Title
Change in peripheral oxygenation
Description
Maximum change from baseline during each test day (SpO2)
Time Frame
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)
Title
Change in peripheral calcitonin gene-related peptide (CGRP) levels
Description
Change in peripheral neuropeptide levels
Time Frame
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)
Title
Change in pituitary adenylate cyclase-activating peptide (PACAP) levels
Description
Change in peripheral neuropeptide levels
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
VA Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States

12. IPD Sharing Statement

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Repeat Dosing of Psilocybin in Migraine Headache

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