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Completed

NCT Number: NCT02981173

Psilocybin for the Treatment of Cluster Headache

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.

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Key information

Conditions

Cluster Headache Brain Diseases Central Nervous System Diseases Headache Disorders Headache Disorders, Primary Nervous System Diseases Trigeminal Autonomic Cephalalgias

Age range

21 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

0.143 mg/kg Psilocybin or 10 mg Psilocybin

Drug

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)

0.0143 mg/kg Psilocybin or 1 mg Psilocybin

Drug

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)

Placebo

Drug

Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)

Primary outcomes

  1. 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

  2. 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

  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)

  4. 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)

  5. 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)

  6. 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)

  7. 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

  8. 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

  9. 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

Secondary outcomes

  1. 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

  2. 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)

  3. 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

  4. 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

  5. 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)

  6. 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)

  7. 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)

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • CH TAC LLC
  • Ceruvia Lifesciences
  • Heffter Research Institute

Registry information

Official study title

Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders

Important dates

Study start
2016
Primary completion
2022
Study completion
2022
First posted
Dec 5, 2016
Registry last updated
Dec 15, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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