Mechanistic Studies of Psilocybin in Headache Disorders

Yale University

Status and phase: Enrolling; Early Phase 1

Conditions: Migraine

Treatments: Drug: Placebo; Drug: Psilocybin

Study type: Interventional

Funder types: Other

Identifiers

NCT06464367

2000034634

ES0006 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 21 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

50 participants in 4 patient groups, including a placebo group

Migraine psilocybin

Experimental group

Description:

Migraine participants randomized to receive 10 mg psilocybin (oral)

Treatment:

Drug: Psilocybin

Migraine placebo

Placebo Comparator group

Description:

Migraine participants randomized to receive 2.5 mg THC (oral)

Treatment:

Drug: Placebo

Healthy control psilocybin

Experimental group

Description:

Healthy control participants randomized to receive 10 mg psilocybin (oral)

Treatment:

Drug: Psilocybin

Healthy control placebo

Placebo Comparator group

Description:

Healthy control participants randomized to receive 2.5 mg THC

Treatment:

Drug: Placebo