Psilocybin for the Treatment of Cluster Headache

July 27, 2022 updated by: Deepak C. D'Souza, Yale University

Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders

The purpose of this study is to investigate the effects of an oral psilocybin pulse regimen in cluster headache. Subjects will be randomized to receive oral placebo, low dose psilocybin, or high dose psilocybin in three experimental sessions, each separated by 5 days. Subjects will maintain a headache diary prior to, during, and after the pulse regimen in order to document headache frequency and intensity before, during, and after the pulse regimen. After at least 6 months from the last experimental session, subjects may be invited for a second round, in which they will be randomized to receive either low dose or high dose psilocybin.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • VA Connecticut Healthcare System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chronic cluster headache with at least one attack daily
  • Episodic cluster headache with periods that are predictable and have a duration of approximately 2 months
  • Attacks are managed by means involving no more than twice weekly triptan use (e.g., high-flow oxygen, heat/cold pack)

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, lysergic acid diethylamide (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 five half-lives of test days
  • Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks
  • Use of antidepressant medications (i.e. amitriptyline, isocarboxazid, fluoxetine, citalopram) in the past 6 weeks
  • Use of steroids or certain other immunomodulatory agents (i.e. azathioprine) in the past 2 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)
Active Comparator: Psilocybin High Dose
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option) ingested on each of three test days (5 days apart +/- 1-2 days)
Active Comparator: Psilocybin Low Dose
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin (fixed-dose option) ingested on each of three test days (5 days apart +/- 1-2 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first attack after completion of pulse regimen
Time Frame: Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)
Measured in days
Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)
Time to last attack after completion of pulse regimen
Time Frame: Six months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)
Measured in days
Six months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)
Change in frequency of attacks
Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Average number of attacks (number per week)
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Change in intensity of attacks
Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Average intensity of attacks (1-10 on visual analog scale)
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Change in duration of attacks
Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Average duration of attacks (minutes)
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Change in cluster period duration compared to typical cluster period (episodic subjects only)
Time Frame: Measured from 2 weeks before pulse regimen to 6 months following the completion of pulse regimen, then comparing to historical average duration of cluster periods
Duration of cluster period after intervention (days)
Measured from 2 weeks before pulse regimen to 6 months following the completion of pulse regimen, then comparing to historical average duration of cluster periods
Difference in the change in cluster attack frequency between 1st and 2nd round
Time Frame: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Average number of attacks (number per week); only in those subjects who return for 2nd round
Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Difference in the change in cluster attack intensity between 1st and 2nd round
Time Frame: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Average intensity of attacks (1-10 on visual analog scale); only in those subjects who return for 2nd round
Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Difference in the change in the duration of attacks between 1st and 2nd round
Time Frame: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Average duration of attacks (minutes); only in those subjects who return for 2nd round
Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Use of abortive/rescue medication
Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Number of times per week
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Attack-free time
Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Number of 24 hour days (may be nonconsecutive)
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Health-Related Quality of life
Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Using the CDC's Health-Related Quality of Life (HRQOL) scale
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Psychedelic effects
Time Frame: Taken daily on each experimental day after the resolution of psychedelic effects, approximately 6 hours after drug administration
Using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
Taken daily on each experimental day after the resolution of psychedelic effects, approximately 6 hours after drug administration
Change in blood pressure
Time Frame: Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Maximum change from baseline during each experimental session (mmHg)
Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Change in heart rate
Time Frame: Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Maximum change from baseline during each experimental session (beats per minute)
Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Change in peripheral oxygenation
Time Frame: Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Maximum change from baseline during each experimental session (SpO2)
Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (Anticipated)

June 1, 2023

Study Completion (Anticipated)

June 1, 2023

Study Registration Dates

First Submitted

November 11, 2016

First Submitted That Met QC Criteria

November 30, 2016

First Posted (Estimate)

December 5, 2016

Study Record Updates

Last Update Posted (Actual)

July 28, 2022

Last Update Submitted That Met QC Criteria

July 27, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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