Repeat Dosing of Psilocybin in Migraine Headache

NCT04218539 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2000026974000
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine Headache

Keywords

psilocybin; inflammation; calcitonin gene-related peptide (CGRP); pituitary adenylate cyclase-activating peptide (PACAP)

Outcome Measures

Primary Outcomes (7)

• Change in migraine attack frequency

  Average number (number per week)

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

• Change in duration of migraine attacks

  Average duration (measured in hours)

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

• Change in intensity of photophobia (light sensitivity)

  Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

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

• Change in intensity of phonophobia (noise sensitivity)

  Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

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

• Average intensity of nausea/vomiting

  Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

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

• Change in functional disability

  Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

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

Secondary Outcomes (11)

• Use of abortive/rescue medication

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

• Time to first migraine attack

  From the second session until two months after second session using a headache diary

• Migraine attack-free time

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

• Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module

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

• Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale

  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

Study Arms (4)

Placebo/Placebo

EXPERIMENTAL

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

Drug: Placebo

Placebo/Psilocybin

EXPERIMENTAL

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

Drug: Psilocybin; Drug: Placebo

Psilocybin/Placebo

EXPERIMENTAL

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

Drug: Psilocybin; Drug: Placebo

Psilocybin/Psilocybin

EXPERIMENTAL

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

Drug: Psilocybin

Interventions

Psilocybin DRUG

10mg Psilocybin

Placebo/Psilocybin; Psilocybin/Placebo; Psilocybin/Psilocybin

Placebo DRUG

25mg Diphenhydramine

Placebo/Placebo; Placebo/Psilocybin; Psilocybin/Placebo

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-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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• The Wallace Foundation: collaborator

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Migraine Disorders; Inflammation

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: January 6, 2020
• Study Start: August 10, 2021
• Primary Completion: November 5, 2023
• Study Completion: November 5, 2023
• Last Updated: February 9, 2024

Record last verified: 2024-02

Locations

US (1)