Mechanistic Studies of Psilocybin in Headache Disorders

Migraine Clinical Trial

Official title:

Mechanistic Studies of Psilocybin in Headache Disorders

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06464367
• Other study ID #: 2000034634
• Secondary ID: ES0006
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: September 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: Yale University
• Contact: Heather Garrett, BS
• Phone: 203-937-5711
• Email: heather.garrett[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 31, 2026
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Headache
• Headache Disorders
• Migraine

Intervention

Drug:
• Psilocybin
synthetic psilocybin 10 mg (oral)
• Placebo
synthetic THC 2.5 mg (oral)

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Wallace Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Acute change in TNF-alpha during drug administration	Comparing change in TNF-alpha between psilocybin/THC and migraine/HC	0, 120, and 240 minutes after drug administration
Other	Acute change in IL-1beta during drug administration	Comparing change in IL-1beta between psilocybin/THC and migraine/HC	0, 120, and 240 minutes after drug administration
Other	Acute change in IL-6 during drug administration	Comparing change in IL-6 between psilocybin/THC and migraine/HC	0, 120, and 240 minutes after drug administration
Other	Acute change in calcitonin gene related peptide (CGRP) during drug administration	Comparing change in CGRP between psilocybin/THC and migraine/HC	0, 120, and 240 minutes after drug administration
Other	Acute change in pituitary adenylate cyclase activating polypeptide (PACAP) during drug administration	Comparing change in PACAP between psilocybin/THC and migraine/HC	0, 120, and 240 minutes after drug administration
Other	Acute change in mean arterial pressure (MAP) during drug administration	Comparing change in MAP (mmHg) between psilocybin/THC and migraine/HC	0, 30, 60, 120, 180, 240, 300, and 360 minutes after drug administration
Other	Acute change in heart rate during drug administration	Comparing change in heart rate (beats per minute) between psilocybin/THC and migraine/HC	0, 30, 60, 120, 180, 240, 300, and 360 minutes after drug administration
Other	Acute change in SpO2 during drug administration	Comparing change in SpO2 (%) between psilocybin/THC and migraine/HC	0, 30, 60, 120, 180, 240, 300, and 360 minutes after drug administration
Other	Acute change in general drug effects during drug administration	Comparing "overall," "anxiety/fear," "sleepiness/sedation," "nausea," "joy/intense happiness,""peace/harmony" between psilocybin/THC and migraine/HC	0, 30, 60, 120, 180, 240, 300, and 360 minutes after drug administration
Other	Acute psychedelic effects during drug administration	Comparing 5-Dimensional Altered States of Consciousness scale scores (0-100; higher score being more psychedelic) between psilocybin/THC and migraine/HC	up to 8 hours after drug administration
Primary	Baseline SV2A PET	Comparing initial SV2A PET between migraine and HC	from date of randomization until the date of first PET scan, assessed up to 6 months
Primary	Baseline RSFC	Comparing initial RSFC between migraine and HC	from date of randomization until the date of first MRI, assessed up to 6 months
Primary	Change in SV2A PET after drug administration	Comparing change in SV2A PET after drug between psilocybin/THC and migraine/HC	from date of first PET scan to the date of second PET scan, assessed up to 6 months
Primary	Change in resting state functional connectivity (RSFC) after drug administration	Comparing change in RSFC after drug between psilocybin/THC and migraine/HC	from date of first MRI to the date of second MRI, assessed up to 6 months
Secondary	Change in TNF-alpha	Comparing change in TNF-alpha levels after drug between psilocybin/THC and migraine/HC	from screening to 7 days after drug administration
Secondary	Change in IL-1beta	Comparing change in IL-1beta levels after drug between psilocybin/THC and migraine/HC	from screening to 7 days after drug administration
Secondary	Change in IL-6	Comparing change in IL-6 levels after drug between psilocybin/THC and migraine/HC	from screening to 7 days after drug administration
Secondary	Change in calcitonin gene-related peptide (CGRP)	Comparing change in CGRP levels after drug between psilocybin/THC and migraine/HC	from screening to 7 days after drug administration
Secondary	Change in pituitary adenylate cyclase activating polypeptide (PACAP)	Comparing change in PACAP levels after drug between psilocybin/THC and migraine/HC	from screening to 7 days after drug administration
Secondary	Change in bedtime (via actigraphy)	Comparing change in bedtime (time) after drug between psilocybin/THC and migraine/HC	from screening through 14 days after drug administration
Secondary	Change in get-up time (via actigraphy)	Comparing change in get-up time (time) after drug between psilocybin/THC and migraine/HC	from screening through 14 days after drug administration
Secondary	Change in daily active period (via actigraphy)	Comparing change in daily active period (hours) after drug between psilocybin/THC and migraine/HC	from screening through 14 days after drug administration
Secondary	Change in daily rest period (via actigraphy)	Comparing change in daily rest period (hours) after drug between psilocybin/THC and migraine/HC	from screening through 14 days after drug administration
Secondary	Change in REM latency (via sleep electroencephalography)	Comparing change in REM latency (minutes) after drug between psilocybin/THC and migraine/HC	from screening to 7 days after drug administration
Secondary	Change in percent REM (via sleep electroencephalography)	Comparing change in percent REM (%) after drug between psilocybin/THC and migraine/HC	from screening to 7 days after drug administration
Secondary	Change in sleep efficiency (via sleep electroencephalography)	Comparing change in sleep efficiency (%) after drug between psilocybin/THC and migraine/HC	from screening to 7 days after drug administration
Secondary	Adverse events	Adverse events from any procedure or drug administration	from screening through 3 months after drug administration