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Psilocybin for the Treatment of Migraine Headache

Primary Purpose

Migraine Headache

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
High Dose Psilocybin
Low Dose 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

Eligibility Criteria

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

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

Sites / Locations

  • VA Connecticut Healthcare System, West Haven Campus

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo/Low Dose Psilocybin

Placebo/High Dose Psilocybin

Low Dose Psilocybin/Placebo

High Dose Psilocybin/Placebo

Arm Description

Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.

Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.

Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.

Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in the use of abortive/rescue medication
number of days (number of days per week using a migraine abortive)
Time to first migraine attack
Measured in days
Time to second migraine attack
Measured in days
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.
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
Maximum change in mean arterial blood pressure from baseline during each test day (mmHg)
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)

Full Information

First Posted
November 9, 2017
Last Updated
October 10, 2023
Sponsor
Yale University
Collaborators
Ceruvia Lifesciences
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1. Study Identification

Unique Protocol Identification Number
NCT03341689
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
April 30, 2021 (Actual)
Study Completion Date
October 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
Collaborators
Ceruvia Lifesciences

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine Headache
Keywords
Psilocybin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo/Low Dose Psilocybin
Arm Type
Experimental
Arm Description
Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
Arm Title
Placebo/High Dose Psilocybin
Arm Type
Experimental
Arm Description
Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.
Arm Title
Low Dose Psilocybin/Placebo
Arm Type
Experimental
Arm Description
Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
Arm Title
High Dose Psilocybin/Placebo
Arm Type
Experimental
Arm Description
Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.
Intervention Type
Drug
Intervention Name(s)
High Dose Psilocybin
Intervention Description
0.143 mg/kg psilocybin capsule
Intervention Type
Drug
Intervention Name(s)
Low Dose Psilocybin
Intervention Description
0.0143 mg/kg psilocybin capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
microcrystalline cellulose capsule
Primary Outcome Measure Information:
Title
Change in migraine headache days
Description
Average days (number of days per week)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in migraine attack frequency
Description
Average number (number per week)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in migraine attack duration
Description
Average duration (measured in hours)
Time Frame
From two weeks before first session to two weeks 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 first session to two weeks after second session using a headache diary
Title
Change in intensity of nausea/vomiting during migraine attacks
Description
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in intensity of photophobia
Description
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in intensity of phonophobia
Description
Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in migraine attack-related functional disability
Description
Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Secondary Outcome Measure Information:
Title
Change in the use of abortive/rescue medication
Description
number of days (number of days per week using a migraine abortive)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Time to first migraine attack
Description
Measured in days
Time Frame
From the day of each session until two weeks after each test session
Title
Time to second migraine attack
Description
Measured in days
Time Frame
From the day of each session until two weeks after each test session
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, and (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 first session to three 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
Taken on each test day approximately 6 hours after drug administration
Title
Change in blood pressure
Description
Maximum change in mean arterial blood pressure from baseline during each test day (mmHg)
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)
Title
Change in heart rate
Description
Maximum change from baseline during each test day (beats per minute)
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)
Title
Change in peripheral oxygenation
Description
Maximum change from baseline during each test day (SpO2)
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)

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-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
Facility Information:
Facility Name
VA Connecticut Healthcare System, West Haven Campus
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33184743
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.
Results Reference
derived

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Psilocybin for the Treatment of Migraine Headache

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