Effects of Psilocybin in Concussion Headache

Psilocybin

Brief Summary

The purpose of this study is to investigate the effects of oral psilocybin in post-traumatic headache. Subjects will be randomized to receive placebo, low dose psilocybin, or high dose psilocybin on two separate test days approximately 14 days apart. Subjects will maintain a headache diary prior to, during, and after the treatments in order to document headache frequency and intensity, as well as associated symptoms. Blood samples will be drawn at various timepoints to measure levels of inflammatory peptides.

Intervention / Treatment

  • Placebo oral capsule (DRUG)
    microcrystalline cellulose capsule
  • Low Dose Psilocybin (DRUG)
    0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
  • High Dose Psilocybin (DRUG)
    0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)

Condition or Disease

  • Post-Traumatic Headache

Phase

  • Phase 1

    • Study Design

    Study type: INTERVENTIONAL
    Status: Terminated
    Study results: No Results Available
    Age: 21 Years to 65 Years
    Enrollment: 12 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    DOUBLE:
    • Participant
    • Care Provider

    Clinical Trial Dates

    Start date: Mar 28, 2019 ACTUAL
    Primary Completion: Jun 27, 2023 ACTUAL
    Completion Date: Jun 27, 2023 ACTUAL
    Study First Posted: Jan 16, 2019 ACTUAL
    Results First Posted: Aug 30, 2020
    Last Updated: Jul 19, 2023

    Sponsors / Collaborators

    Lead Sponsor: Yale University
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    West Haven, Connecticut, USA

    Participant Groups

    • Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.

    • Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.

    • Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.

    • Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.

    • Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session.

    • Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session.

    Eligibility Criteria

    Sex: All
    Minimum Age: 21
    Maximum Age: 65
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * Diagnosis of post-traumatic headache
    * Typical pattern of headache attacks with approximately two attacks or more weekly
    * Attacks are managed by means involving no more than twice weekly triptan use

    Exclusion Criteria:

    * 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, LSD, or related compounds
    * Drug or alcohol abuse within the past 3 months (excluding tobacco)
    * Urine toxicology positive to drugs of abuse
    * Use of vasoconstrictive medications (i.e. sumatriptan, pseudoephedrine, midodrine) within 5 half-lives of test days
    * Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks
    * Use of antidepressant medication (i.e. TCA, MAOI, SSRI) in the past 6 weeks
    * Use of steroids or certain other immunomodulatory agents (i.e. azathioprine) in the past 2 weeks

    Primary Outcomes

    • 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)

    • 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)

    • 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)

    • 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)

    • 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)

    • Measured in days

    • Measured in days

    • Average number (number per week)

    • Average duration (measured in hours)

    • Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

    • Average intensity of nausea/vomiting (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

    • Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

    • Average intensity of phonophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

    • Average intensity of functional disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

    Secondary Outcomes

    • number of times per week

    • Number of 24 hour days (may be non-consecutive)

    • 4 questions scored 0 to 30 each; higher numbers indicate worse quality of life. (1) pain-related impairment, (2) mood symptoms, (3) anxiety symptoms, and (4) lack of sleep Percent change for each measure as well as total score (range 0 to 120) will be calculated.

    • 9 question self-report questionnaire to assess the presence of depression-related symptoms. Each question is rated on a scale of 0-3 (0 = Not at all; 1 = Several days; 2 = More than half the days; 3 = Nearly every day). Higher scores indicate greater presence of depression-related symptoms. Total score is calculated. Total score 5-9 = minimal symptoms; total score 10-14 = Major Depression, mild; total score 15-19 = Major Depression, moderately severe; total score \>20 = Major Depression severe.

    • A 10-category assessment of suicidal ideation and behavior. 5 categories (scored "yes/no") relate to the presence of suicidal ideation. 5 categories (scored "yes/no") relate to the presence of suicidal behavior. A "yes" to any of the suicidal ideation categories indicates the presence of suicidal ideation; a "yes" to any of the suicidal behavior categories indicates the presence of suicidal behavior.

    • 94 questions scored 0 to 100 each; higher numbers indicate greater psychedelic effects Questions address 5 dimensions: (1) Oceanic boundlessness (score range 0-2700), (2) Dread of Ego Dissolution (score range 0-2100), (3) Visionary Restructuralization (score range 0-1800), (4) Auditory Alterations (score range 0-1600), and (5) Vigilance reduction (score range 0-1200) Score for each dimension as well as total score (range 0 to 9400) will be measured.

    • Maximum change from baseline during each test day (mmHg)

    • Maximum change from baseline during each test day (beats per minute)

    • Maximum change from baseline during each test day (SpO2)

    • Change from baseline during each test day (pg/mg protein)

    • Change from baseline during each test day (pg/mg protein)

    More Details

    NCT Number: NCT03806985
    Other IDs: 1607018057.B
    Study URL: https://clinicaltrials.gov/study/NCT03806985
    Last updated: Sep 29, 2023