Migraine
Conditions
Keywords
psilocybin, resting state functional connectivity, synaptic density, synaptic vessel glycoprotein 2A (SV2A), circadian rhythm, sleep, inflammation
Brief 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. 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.
Interventions
DRUGPsilocybin
synthetic psilocybin 10 mg (oral)
DRUGPlacebo
synthetic THC 2.5 mg (oral)
Sponsors
Yale University
The Wallace Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 21 to 70 (inclusive) * Migraine disease per ICHD-3 criteria (for migraine participants) OR Healthy control patient Exclusion criterion * 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 * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline SV2A PET | 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 | 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 | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in TNF-alpha | from screening to 7 days after drug administration | Comparing change in TNF-alpha levels after drug between psilocybin/THC and migraine/HC |
| Change in IL-1beta | from screening to 7 days after drug administration | Comparing change in IL-1beta levels after drug between psilocybin/THC and migraine/HC |
| Change in IL-6 | from screening to 7 days after drug administration | Comparing change in IL-6 levels after drug between psilocybin/THC and migraine/HC |
| Change in calcitonin gene-related peptide (CGRP) | from screening to 7 days after drug administration | Comparing change in CGRP levels after drug between psilocybin/THC and migraine/HC |
| Change in pituitary adenylate cyclase activating polypeptide (PACAP) | from screening to 7 days after drug administration | Comparing change in PACAP levels after drug between psilocybin/THC and migraine/HC |
| Change in bedtime (via actigraphy) | from screening through 14 days after drug administration | Comparing change in bedtime (time) after drug between psilocybin/THC and migraine/HC |
| Change in get-up time (via actigraphy) | from screening through 14 days after drug administration | Comparing change in get-up time (time) after drug between psilocybin/THC and migraine/HC |
| Change in daily active period (via actigraphy) | from screening through 14 days after drug administration | Comparing change in daily active period (hours) after drug between psilocybin/THC and migraine/HC |
| Change in daily rest period (via actigraphy) | from screening through 14 days after drug administration | Comparing change in daily rest period (hours) after drug between psilocybin/THC and migraine/HC |
| Change in REM latency (via sleep electroencephalography) | from screening to 7 days after drug administration | Comparing change in REM latency (minutes) after drug between psilocybin/THC and migraine/HC |
| Change in percent REM (via sleep electroencephalography) | from screening to 7 days after drug administration | Comparing change in percent REM (%) after drug between psilocybin/THC and migraine/HC |
| Change in sleep efficiency (via sleep electroencephalography) | from screening to 7 days after drug administration | Comparing change in sleep efficiency (%) after drug between psilocybin/THC and migraine/HC |
| Adverse events | from screening through 3 months after drug administration | Adverse events from any procedure or drug administration |
Countries
United States
Contacts
CONTACTErik Zorrilla, PhD
CONTACTEmmanuelle Schindler, MD, PhD
Outcome results
None listed