Psilocybin for the Treatment of Migraine Headache

NCT03341689 | Completed Phase 1 FDA Drug

• 1 other identifier: 1607018057.A
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine Headache

Keywords

Psilocybin

Outcome Measures

Primary Outcomes (8)

• Change in migraine headache days

  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

  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

  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

  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

  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

  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

  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

  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 Outcomes (8)

• Change in the use of abortive/rescue medication

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

• Time to first migraine attack

  From the day of each session until two weeks after each test session

• Time to second migraine attack

  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

  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

  Taken on each test day approximately 6 hours after drug administration

Study Arms (4)

Placebo/Low Dose Psilocybin

EXPERIMENTAL

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

Drug: Low Dose Psilocybin; Drug: Placebo

Placebo/High Dose Psilocybin

EXPERIMENTAL

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

Drug: High Dose Psilocybin; Drug: Placebo

Low Dose Psilocybin/Placebo

EXPERIMENTAL

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

Drug: Low Dose Psilocybin; Drug: Placebo

High Dose Psilocybin/Placebo

EXPERIMENTAL

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

High Dose Psilocybin DRUG

0.143 mg/kg psilocybin capsule

High Dose Psilocybin/Placebo; Placebo/High Dose Psilocybin

Low Dose Psilocybin DRUG

0.0143 mg/kg psilocybin capsule

Low Dose Psilocybin/Placebo; Placebo/Low Dose Psilocybin

Placebo DRUG

microcrystalline cellulose capsule

High Dose Psilocybin/Placebo; Low Dose Psilocybin/Placebo; Placebo/High Dose Psilocybin; Placebo/Low Dose Psilocybin

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Ceruvia Lifesciences: collaborator

Study Sites (1)

VA Connecticut Healthcare System, West Haven Campus

West Haven, Connecticut, 06516, United States

Location

Related Publications (1)

• 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.

  PMID: 33184743 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 14, 2017
• Study Start: November 1, 2017
• Primary Completion: April 30, 2021
• Study Completion: October 31, 2021
• Last Updated: October 12, 2023

Record last verified: 2023-10

Locations

US (1)