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CompletedNCT03341689Updated Oct 12, 2023

Psilocybin for the Treatment of Migraine Headache

A Phase 1 interventional study of High Dose Psilocybin and Low Dose Psilocybin in Migraine Headache, sponsored by Yale University. Completed at 1 site in United States. Open to participants aged 21 Years to 65 Years. Per ClinicalTrials.gov, last updated 2023-10-12.

Sponsored by Yale University · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
14
Allocation
Randomized
Ages
21 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Migraine Headache

Keywords

  • Psilocybin
03

Who can participate

Ages eligible
21 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Care provider)
Enrollment
14 participants (actual)

Study arms

  • Experimental
    Placebo/Low Dose Psilocybin

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

    Drug: Low Dose Psilocybin · Drug: Placebo

  • Experimental
    Placebo/High Dose Psilocybin

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

    Drug: High Dose Psilocybin · Drug: Placebo

  • Experimental
    Low Dose Psilocybin/Placebo

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

    Drug: Low Dose Psilocybin · Drug: Placebo

  • Experimental
    High Dose Psilocybin/Placebo

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

    Drug: High Dose Psilocybin · Drug: Placebo

Interventions

  • DrugHigh Dose Psilocybin

    0.143 mg/kg psilocybin capsule

  • DrugLow Dose Psilocybin

    0.0143 mg/kg psilocybin capsule

  • DrugPlacebo

    microcrystalline cellulose capsule

05

What researchers measure

Primary outcomes

  1. Change in migraine headache days

    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

  2. Change in migraine attack frequency

    Average number (number per week)

    Time frame: From two weeks before first session to two weeks after second session using a headache diary

  3. Change in migraine attack duration

    Average duration (measured in hours)

    Time frame: From two weeks before first session to two weeks after second session using a headache diary

  4. Change in pain intensity of migraine attacks

    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

  5. Change in intensity of nausea/vomiting during migraine attacks

    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

  6. Change in intensity of photophobia

    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

  7. Change in intensity of phonophobia

    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

  8. Change in migraine attack-related functional disability

    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 outcomes

  1. Change in the use of abortive/rescue medication

    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

  2. Time to first migraine attack

    Measured in days

    Time frame: From the day of each session until two weeks after each test session

  3. Time to second migraine attack

    Measured in days

    Time frame: From the day of each session until two weeks after each test session

  4. 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.

    Time frame: From two weeks before first session to three months after second session using a headache diary

  5. 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.

    Time frame: Taken on each test day approximately 6 hours after drug administration

  6. Change in blood pressure

    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)

  7. Change in heart rate

    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)

  8. Change in peripheral oxygenation

    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)

06

Study locations

1 site
  • VA Connecticut Healthcare System, West Haven Campus
    West Haven, Connecticut 06516, United States
07

References and documents

Publications

  • 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. PubMed 33184743 ↗
08

Registry details

Key details

Study ID
NCT03341689
Lead sponsor
Yale University
Collaborators
Ceruvia Lifesciences
Responsible party
Deepak C. D'Souza (Professor, Yale University) — Principal investigator
First posted
Nov 14, 2017
Start date
Nov 1, 2017
Primary completion
Apr 30, 2021
Completion
Oct 31, 2021
Last update
Oct 12, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
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