Psilocybin for the Treatment of Cluster Headache

Phase 1

Completed

• Conditions: Cluster Headache
• Interventions: Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin; Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin; Drug: Placebo

• Registration Number: NCT02981173
• Lead Sponsor: Yale University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-11-11
• Study First Submitted QC: 2016-11-30
• Study Start: 2016-12-05
• Study First Posted: 2016-12-05
• Primary Completion: 2022-06-30
• Study Completion: 2022-10-21
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-08
• Last Update Posted: 2023-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Psilocybin Low Dose	0.0143 mg/kg Psilocybin or 1 mg Psilocybin	-
Psilocybin High Dose	0.143 mg/kg Psilocybin or 10 mg Psilocybin	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Time to last attack after completion of pulse regimen	Six months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)	Measured in days
Change in duration of attacks	Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary	Average duration of attacks (minutes)
Difference in the change in cluster attack intensity between 1st and 2nd round	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
Difference in the change in the duration of attacks between 1st and 2nd round	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
Time to first attack after completion of pulse regimen	Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)	Measured in days
Change in cluster period duration compared to typical cluster period (episodic subjects only)	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)
Change in frequency of attacks	Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary	Average number of attacks (number per week)
Change in intensity of attacks	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)
Difference in the change in cluster attack frequency between 1st and 2nd round	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

Secondary Outcome Measures

Name	Time	Method
Use of abortive/rescue medication	Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary	Number of times per week
Attack-free time	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)
Psychedelic effects	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
Change in blood pressure	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)
Health-Related Quality of life	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
Change in peripheral oxygenation	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)
Change in heart rate	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)

Trial Locations

Locations (1)

VA Connecticut Healthcare System; 🇺🇸 West Haven, Connecticut, United States