MigraineEarly Phase 1NCT06464367
Mechanistic Studies of Psilocybin in Headache Disorders
A Early Phase 1 study testing Psilocybin in people with Migraine, run by Yale University at 1 site in United States.
Trial summary
In previous clinical trial work, the investigators observed lasting reductions in headache burden after limited dosing of psilocybin. This purpose of this study is to examine potential sources for this observed effect. Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Migraine
- What is being tested?
- Psilocybin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 19 May 2025to 31 Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 21 to 70 (inclusive)
- Migraine disease per ICHD-3 criteria (for migraine participants) OR Healthy control patient
Who cannot join
- Unstable medical condition or serious nervous system pathology
- Pregnant, breastfeeding, lack of adequate birth control
- Psychotic or manic disorder
- Substance abuse in the prior 3 months
- Use of classic psychedelics (e.g., psilocybin, LSD, mescaline) in the past 6 months
- Use of cannabis or other THC products in the prior 2 weeks
Show all 12Show fewer
- Urine toxicology positive to drugs of abuse
- The use of triptans (e.g., sumatriptan) or ditans (e.g., lasmiditan) more than twice weekly on average
- Use of serotonergic preventive therapies (i.e., taken chronically; amitriptyline, fluoxetine, imipramine, cyproheptadine) in the past 6 weeks
- Use of preventive or transitional treatments that produce spikes and waning of symptom relief (e.g., botulinum toxin, calcitonin gene-related peptide system targeting antibodies, peripheral nerve or ganglion blocks, chiropractic manipulation)
- History of a bleeding disorder or are currently taking anticoagulants (e.g., warfarin, enoxaparin, dabigatran, apixaban).
- Use of non-steroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen) in the 7 days before PET scan and 7 days after PET scan.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
Erik Zorrilla, PhD, 203-932-5711 ext. 14335, erik.zorrilla@yale.edu
Emmanuelle Schindler, MD, PhD, 203-932-5711 ext. 14335, emmanuelle.schindler@yale.edu
About this study
In previous clinical trial work, the investigators observed lasting reductions in headache burden after limited dosing of psilocybin. This purpose of this study is to examine potential sources for this observed effect. This study will measure brain resting state functional connectivity (fMRI), central synaptic density (SV2A PET), peripheral markers of inflammation, circadian rhythm (actigraphy), and sleep (sleep EEG) in both migraine and healthy control participants before and one week after the administration of psilocybin or an active control agent.
- Conditions
- Migraine
- Being tested
- Psilocybin, Placebo
- Keywords
- psilocybin, resting state functional connectivity, synaptic density, synaptic vessel glycoprotein 2A (SV2A), circadian rhythm, sleep, inflammation
- Medical subject headings
- Migraine Disorders, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
synthetic psilocybin 10 mg (oral)
PlaceboDrug
synthetic THC 2.5 mg (oral)
| Study group | Role | What they receive |
|---|---|---|
| Migraine psilocybin | Experimental | Migraine participants randomized to receive 10 mg psilocybin (oral) Receives: Drug: Psilocybin |
| Migraine placebo | Placebo comparator | Migraine participants randomized to receive 2.5 mg THC (oral) Receives: Drug: Placebo |
| Healthy control psilocybin | Experimental | Healthy control participants randomized to receive 10 mg psilocybin (oral) Receives: Drug: Psilocybin |
| Healthy control placebo | Placebo comparator | Healthy control participants randomized to receive 2.5 mg THC Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline SV2A PET
Comparing initial SV2A PET between migraine and HC
Measured: from date of randomization until the date of first PET scan, assessed up to 6 months
Baseline RSFC
Comparing initial RSFC between migraine and HC
Measured: from date of randomization until the date of first MRI, assessed up to 6 months
Change in SV2A PET after drug administration
Comparing change in SV2A PET after drug between psilocybin/THC and migraine/HC
Measured: from date of first PET scan to the date of second PET scan, assessed up to 6 months
Change in resting state functional connectivity (RSFC) after drug administration
Comparing change in RSFC after drug between psilocybin/THC and migraine/HC
Measured: from date of first MRI to the date of second MRI, assessed up to 6 months
Secondary outcomes (13)
Change in TNF-alpha
Comparing change in TNF-alpha levels after drug between psilocybin/THC and migraine/HC
Measured: from screening to 7 days after drug administration
Change in IL-1beta
Comparing change in IL-1beta levels after drug between psilocybin/THC and migraine/HC
Measured: from screening to 7 days after drug administration
Change in IL-6
Comparing change in IL-6 levels after drug between psilocybin/THC and migraine/HC
Measured: from screening to 7 days after drug administration
Change in calcitonin gene-related peptide (CGRP)
Comparing change in CGRP levels after drug between psilocybin/THC and migraine/HC
Measured: from screening to 7 days after drug administration
Change in pituitary adenylate cyclase activating polypeptide (PACAP)
Comparing change in PACAP levels after drug between psilocybin/THC and migraine/HC
Measured: from screening to 7 days after drug administration
Change in bedtime (via actigraphy)
Comparing change in bedtime (time) after drug between psilocybin/THC and migraine/HC
Measured: from screening through 14 days after drug administration
Change in get-up time (via actigraphy)
Comparing change in get-up time (time) after drug between psilocybin/THC and migraine/HC
Measured: from screening through 14 days after drug administration
Change in daily active period (via actigraphy)
Comparing change in daily active period (hours) after drug between psilocybin/THC and migraine/HC
Measured: from screening through 14 days after drug administration
Change in daily rest period (via actigraphy)
Comparing change in daily rest period (hours) after drug between psilocybin/THC and migraine/HC
Measured: from screening through 14 days after drug administration
Change in REM latency (via sleep electroencephalography)
Comparing change in REM latency (minutes) after drug between psilocybin/THC and migraine/HC
Measured: from screening to 7 days after drug administration
Change in percent REM (via sleep electroencephalography)
Comparing change in percent REM (%) after drug between psilocybin/THC and migraine/HC
Measured: from screening to 7 days after drug administration
Change in sleep efficiency (via sleep electroencephalography)
Comparing change in sleep efficiency (%) after drug between psilocybin/THC and migraine/HC
Measured: from screening to 7 days after drug administration
Adverse events
Adverse events from any procedure or drug administration
Measured: from screening through 3 months after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2024
- Study start19 May 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MigraineStudies 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- The Wallace Foundation
- Responsible party
- Principal investigator, Emmanuelle Schindler, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06464367
- Sponsor's protocol ID
- 2000034634
- Other IDs
- ES0006
- Status last verified
- Jul 2026
- First submitted
- 8 Jun 2024
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Studies of Psilocybin in Headache Disorders
- ClinicalTrials.gov ID
- NCT06464367
- Acronym / sponsor ID
- 2000034634
- Conditions
- Migraine
- Keywords
- psilocybin, resting state functional connectivity, synaptic density, synaptic vessel glycoprotein 2A (SV2A), circadian rhythm, sleep, inflammation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- The Wallace Foundation
- Study start
- 19 May 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 18 Jun 2024 (actual)
- 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.
In previous clinical trial work, the investigators observed lasting reductions in headache burden after limited dosing of psilocybin. This purpose of this study is to examine potential sources for this observed effect. This study will measure brain resting state functional connectivity (fMRI), central synaptic density (SV2A PET), peripheral markers of inflammation, circadian rhythm (actigraphy), and sleep (sleep EEG) in both migraine and healthy control participants before and one week after the administration of psilocybin or an active control agent.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Migraine psilocybin | Experimental | Drug: PsilocybinMigraine participants randomized to receive 10 mg psilocybin (oral) |
| Migraine placebo | Placebo comparator | Drug: PlaceboMigraine participants randomized to receive 2.5 mg THC (oral) |
| Healthy control psilocybin | Experimental | Drug: PsilocybinHealthy control participants randomized to receive 10 mg psilocybin (oral) |
| Healthy control placebo | Placebo comparator | Drug: PlaceboHealthy control participants randomized to receive 2.5 mg THC |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 21 to 70 (inclusive)
- Migraine disease per ICHD-3 criteria (for migraine participants) OR Healthy control patient
Key exclusion criteria (12 listed)
- Unstable medical condition or serious nervous system pathology
- Pregnant, breastfeeding, lack of adequate birth control
- Psychotic or manic disorder
- Substance abuse in the prior 3 months
- Use of classic psychedelics (e.g., psilocybin, LSD, mescaline) in the past 6 months
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 |
|---|---|---|
| Psilocybinsynthetic psilocybin 10 mg (oral) | Drug | Healthy control psilocybin, Migraine psilocybin |
| Placebosynthetic THC 2.5 mg (oral) | Drug | Healthy control placebo, Migraine placebo |
Primary outcome
Baseline SV2A PET
Time frame: from date of randomization until the date of first PET scan, assessed up to 6 months
Comparing initial SV2A PET between migraine and HC
Baseline RSFC
Time frame: from date of randomization until the date of first MRI, assessed up to 6 months
Comparing initial RSFC between migraine and HC
Change in SV2A PET after drug administration
Time frame: from date of first PET scan to the date of second PET scan, assessed up to 6 months
Comparing change in SV2A PET after drug between psilocybin/THC and migraine/HC
Change in resting state functional connectivity (RSFC) after drug administration
Time frame: from date of first MRI to the date of second MRI, assessed up to 6 months
Comparing change in RSFC after drug between psilocybin/THC and migraine/HC
13 secondary outcomes
Change in TNF-alpha
Time frame: from screening to 7 days after drug administration
Change in IL-1beta
Time frame: from screening to 7 days after drug administration
Change in IL-6
Time frame: from screening to 7 days after drug administration
Change in calcitonin gene-related peptide (CGRP)
Time frame: from screening to 7 days after drug administration
Change in pituitary adenylate cyclase activating polypeptide (PACAP)
Time frame: from screening to 7 days after drug administration
Change in bedtime (via actigraphy)
Time frame: from screening through 14 days after drug administration
Change in get-up time (via actigraphy)
Time frame: from screening through 14 days after drug administration
Change in daily active period (via actigraphy)
Time frame: from screening through 14 days after drug administration
Change in daily rest period (via actigraphy)
Time frame: from screening through 14 days after drug administration
Change in REM latency (via sleep electroencephalography)
Time frame: from screening to 7 days after drug administration
Change in percent REM (via sleep electroencephalography)
Time frame: from screening to 7 days after drug administration
Change in sleep efficiency (via sleep electroencephalography)
Time frame: from screening to 7 days after drug administration
Adverse events
Time frame: from screening through 3 months after drug administration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Psilocybin in people with Migraine, 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 2 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 13 Jul 2026. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Erik Zorrilla, PhD (203-932-5711 ext. 14335, erik.zorrilla@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline SV2A PET (time frame: from date of randomization until the date of first PET scan, assessed up to 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jul 2026.