Psilocybin for the Treatment of Cluster Headache

Study Overview
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Brief Summary
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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.

Official Title
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Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders

Conditions
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Cluster Headache

Intervention / Treatment
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* Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin
* Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Psilocybin High Dose<br> | Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin<br>* 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)<br>|
| Active Comparator: Psilocybin Low Dose<br> | Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin<br>* 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)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first attack after completion of pulse regimen | 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 | 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 | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) |