Cluster HeadachePhase 1NCT02981173
Psilocybin for the Treatment of Cluster Headache
A Phase 1 study testing 0.143 mg/kg Psilocybin or 10 mg Psilocybin and 0.0143 mg/kg Psilocybin or 1 mg Psilocybin in people with Cluster Headache, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Cluster Headache
- What is being tested?
- 0.143 mg/kg Psilocybin or 10 mg Psilocybin and 0.0143 mg/kg Psilocybin or 1 mg Psilocybin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2016to 21 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
About this study
Official title: 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.
- Conditions
- Cluster Headache
- Being tested
- 0.143 mg/kg Psilocybin or 10 mg Psilocybin, 0.0143 mg/kg Psilocybin or 1 mg Psilocybin, Placebo
- Medical subject headings
- Cluster Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0.143 mg/kg Psilocybin or 10 mg PsilocybinDrug
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 PsilocybinDrug
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)
PlaceboDrug
Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin High Dose | Active comparator | Not described Receives: Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin |
| Psilocybin Low Dose | Active comparator | Not described Receives: Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first attack after completion of pulse regimen
Measured in days
Measured: 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
Measured: 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: 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: 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: 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: 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: 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: 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: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Secondary outcomes (7)
Use of abortive/rescue medication
Number of times per week
Measured: 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: 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: 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
Measured: 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: 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: 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: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2016 (estimated)
- Study start5 Dec 2016
- Primary completion30 Jun 2022
- Study completion21 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cluster HeadacheStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Heffter Research Institute, Ceruvia Lifesciences, CH TAC LLC
- Responsible party
- Principal investigator, Deepak C. D'Souza, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02981173
- Sponsor's protocol ID
- 1607018057
- Status last verified
- Dec 2023
- First submitted
- 11 Nov 2016
- Last updated
- 15 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Schindler EAD, Sewell RA, Gottschalk CH, Flynn LT, Zhu Y, Pittman BP, Cozzi NV, D'Souza DC. Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial. J Neurol Sci. 2024 May 15;460:122993. doi: 10.1016/j.jns.2024.122993. Epub 2024 Apr 2.
PubMed 38581739
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders
- ClinicalTrials.gov ID
- NCT02981173
- Acronym / sponsor ID
- 1607018057
- Conditions
- Cluster Headache
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Heffter Research Institute, Ceruvia Lifesciences, CH TAC LLC
- Study start
- 5 Dec 2016 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 21 Oct 2022 (actual)
- First posted
- 5 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Psilocybin High Dose | Active comparator | Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin |
| Psilocybin Low Dose | Active comparator | Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 0.143 mg/kg Psilocybin or 10 mg Psilocybin0.143 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) | Drug | Psilocybin High Dose |
| 0.0143 mg/kg Psilocybin or 1 mg Psilocybin0.0143 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) | Drug | Psilocybin Low Dose |
| PlaceboMicrocrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days) | Drug | Placebo |
Primary outcome
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
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
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)
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)
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)
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)
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
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
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
7 secondary outcomes
Use of abortive/rescue medication
Time frame: 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
Health-Related Quality of life
Time frame: 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
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)
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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2023.
- Derived from this study: PubMed 38581739Schindler EAD, Sewell RA, Gottschalk CH, Flynn LT, Zhu Y, Pittman BP, Cozzi NV, D'Souza DC. Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial. J Neurol Sci. 2024 May 15;460:122993. doi: 10.1016/j.jns.2024.122993. Epub 2024 Apr 2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 0.143 mg/kg Psilocybin or 10 mg Psilocybin and 0.0143 mg/kg Psilocybin or 1 mg Psilocybin in people with Cluster Headache, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02981173, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.