Effects of Psilocybin in Concussion Headache

October 11, 2023 updated by: Yale University

Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study II

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • VA Connecticut Healthcare System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Placebo/Low Dose Psilocybin
Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
Drug: Placebo oral capsule
microcrystalline cellulose capsule
Drug: Low Dose Psilocybin
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
Experimental: Placebo/High Dose Psilocybin
Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.
Drug: Placebo oral capsule
microcrystalline cellulose capsule
Drug: High Dose Psilocybin
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)
Experimental: Low Dose Psilocybin/Placebo
Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
Drug: Placebo oral capsule
microcrystalline cellulose capsule
Drug: Low Dose Psilocybin
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
Experimental: High Dose Psilocybin/Placebo
Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.
Drug: Placebo oral capsule
microcrystalline cellulose capsule
Drug: High Dose Psilocybin
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)
Experimental: High Dose Psilocybin/Low Dose Psilocybin
Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session.
Drug: Low Dose Psilocybin
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
Drug: High Dose Psilocybin
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)
Experimental: Low Dose Psilocybin/High Dose Psilocybin
Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session.
Drug: Low Dose Psilocybin
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
Drug: High Dose Psilocybin
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Acute change in pain intensity
Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Acute change in nausea/vomiting
Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Acute change in photophobia
Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Acute change in phonophobia
Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Acute change in functional disability
Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Time to first headache attack
Time Frame: Two weeks following each test session
Measured in days
Two weeks following each test session
Time to last headache attack
Time Frame: Two weeks following each test session
Measured in days
Two weeks following each test session
Change in headache attack frequency
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
Average number (number per week)
From two weeks before first session to two weeks after second session using a headache diary
Change in headache attack duration
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
Average duration (measured in hours)
From two weeks before first session to two weeks after second session using a headache diary
Change in pain intensity of headache attacks
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
From two weeks before first session to two weeks after second session using a headache diary
Change in intensity of nausea/vomiting during headache attacks
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
Average intensity of nausea/vomiting (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
From two weeks before first session to two weeks after second session using a headache diary
Change in intensity of photophobia during headache attacks
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
From two weeks before first session to two weeks after second session using a headache diary
Change in intensity of phonophobia during headache attacks
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
Average intensity of phonophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
From two weeks before first session to two weeks after second session using a headache diary
Change in intensity of functional disability during headache attacks
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
Average intensity of functional disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
From two weeks before first session to two weeks after second session using a headache diary

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
Time Frame: Taken on each test day approximately 6 hours after drug administration
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.
Taken on each test day approximately 6 hours after drug administration
Change in heart rate
Time Frame: Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Maximum change from baseline during each test day (beats per minute)
Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Change in peripheral oxygenation
Time Frame: Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Maximum change from baseline during each test day (SpO2)
Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Use of abortive/rescue medication
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
number of times per week
From two weeks before first session to two weeks after second session using a headache diary
Headache attack-free time
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
Number of 24 hour days (may be non-consecutive)
From two weeks before first session to two weeks after second session using a headache diary
Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module
Time Frame: From two weeks before first session to two weeks after second session using a headache diary

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.
From two weeks before first session to two weeks after second session using a headache diary
Depression using Patient Health Questionnaire 9 (PHQ-9)
Time Frame: From two weeks before first session to two weeks after second session using a headache diary

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.
From two weeks before first session to two weeks after second session using a headache diary
Suicide risk using the Columbia Suicide Severity Rating Scale (CSSRS)
Time Frame: From two weeks before first session to two weeks after second session using a headache diary
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.
From two weeks before first session to two weeks after second session using a headache diary
Change in blood pressure
Time Frame: Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Maximum change from baseline during each test day (mmHg)
Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Change in peripheral levels of calcitonin gene-related peptide (CGRP)
Time Frame: Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
Change from baseline during each test day (pg/mg protein)
Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
Change in peripheral levels of pituitary adenylate cyclase-activating peptide (PACAP)
Time Frame: Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
Change from baseline during each test day (pg/mg protein)
Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 28, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 27, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 27, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 14, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 14, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1607018057.B

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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