<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03806985</url>
  </required_header>
  <id_info>
    <org_study_id>1607018057.B</org_study_id>
    <nct_id>NCT03806985</nct_id>
  </id_info>
  <brief_title>Effects of Psilocybin in Concussion Headache</brief_title>
  <official_title>Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study II</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the effects of oral psilocybin in post-traumatic&#xD;
      headache. Subjects will be randomized to receive placebo, low dose psilocybin, or high dose&#xD;
      psilocybin on two separate test days approximately 14 days apart. Subjects will maintain a&#xD;
      headache diary prior to, during, and after the treatments in order to document headache&#xD;
      frequency and intensity, as well as associated symptoms. Blood samples will be drawn at&#xD;
      various timepoints to measure levels of inflammatory peptides.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Challenging to recruit qualifying subjects&#xD;
  </why_stopped>
  <start_date type="Actual">March 28, 2019</start_date>
  <completion_date type="Actual">June 27, 2023</completion_date>
  <primary_completion_date type="Actual">June 27, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute change in pain intensity</measure>
    <time_frame>Measured at 0, 1, 2, 4, and 24 hours after drug administration</time_frame>
    <description>4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Acute change in nausea/vomiting</measure>
    <time_frame>Measured at 0, 1, 2, 4, and 24 hours after drug administration</time_frame>
    <description>4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Acute change in photophobia</measure>
    <time_frame>Measured at 0, 1, 2, 4, and 24 hours after drug administration</time_frame>
    <description>4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Acute change in phonophobia</measure>
    <time_frame>Measured at 0, 1, 2, 4, and 24 hours after drug administration</time_frame>
    <description>4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Acute change in functional disability</measure>
    <time_frame>Measured at 0, 1, 2, 4, and 24 hours after drug administration</time_frame>
    <description>4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to first headache attack</measure>
    <time_frame>Two weeks following each test session</time_frame>
    <description>Measured in days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to last headache attack</measure>
    <time_frame>Two weeks following each test session</time_frame>
    <description>Measured in days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in headache attack frequency</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>Average number (number per week)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in headache attack duration</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>Average duration (measured in hours)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in pain intensity of headache attacks</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in intensity of nausea/vomiting during headache attacks</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>Average intensity of nausea/vomiting (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in intensity of photophobia during headache attacks</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in intensity of phonophobia during headache attacks</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>Average intensity of phonophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in intensity of functional disability during headache attacks</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>Average intensity of functional disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Use of abortive/rescue medication</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>number of times per week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Headache attack-free time</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>Number of 24 hour days (may be non-consecutive)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>4 questions scored 0 to 30 each; higher numbers indicate worse quality of life.&#xD;
(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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression using Patient Health Questionnaire 9 (PHQ-9)</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>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.&#xD;
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 &gt;20 = Major Depression severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Suicide risk using the Columbia Suicide Severity Rating Scale (CSSRS)</measure>
    <time_frame>From two weeks before first session to two weeks after second session using a headache diary</time_frame>
    <description>A 10-category assessment of suicidal ideation and behavior. 5 categories (scored &quot;yes/no&quot;) relate to the presence of suicidal ideation. 5 categories (scored &quot;yes/no&quot;) relate to the presence of suicidal behavior. A &quot;yes&quot; to any of the suicidal ideation categories indicates the presence of suicidal ideation; a &quot;yes&quot; to any of the suicidal behavior categories indicates the presence of suicidal behavior.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale</measure>
    <time_frame>Taken on each test day approximately 6 hours after drug administration</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood pressure</measure>
    <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)</time_frame>
    <description>Maximum change from baseline during each test day (mmHg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart rate</measure>
    <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)</time_frame>
    <description>Maximum change from baseline during each test day (beats per minute)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peripheral oxygenation</measure>
    <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)</time_frame>
    <description>Maximum change from baseline during each test day (SpO2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peripheral levels of calcitonin gene-related peptide (CGRP)</measure>
    <time_frame>Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration</time_frame>
    <description>Change from baseline during each test day (pg/mg protein)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peripheral levels of pituitary adenylate cyclase-activating peptide (PACAP)</measure>
    <time_frame>Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration</time_frame>
    <description>Change from baseline during each test day (pg/mg protein)</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Post-Traumatic Headache</condition>
  <arm_group>
    <arm_group_label>Placebo/Low Dose Psilocybin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo/High Dose Psilocybin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose Psilocybin/Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose Psilocybin/Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose Psilocybin/Low Dose Psilocybin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose Psilocybin/High Dose Psilocybin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>microcrystalline cellulose capsule</description>
    <arm_group_label>High Dose Psilocybin/Placebo</arm_group_label>
    <arm_group_label>Low Dose Psilocybin/Placebo</arm_group_label>
    <arm_group_label>Placebo/High Dose Psilocybin</arm_group_label>
    <arm_group_label>Placebo/Low Dose Psilocybin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low Dose Psilocybin</intervention_name>
    <description>0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)</description>
    <arm_group_label>High Dose Psilocybin/Low Dose Psilocybin</arm_group_label>
    <arm_group_label>Low Dose Psilocybin/High Dose Psilocybin</arm_group_label>
    <arm_group_label>Low Dose Psilocybin/Placebo</arm_group_label>
    <arm_group_label>Placebo/Low Dose Psilocybin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High Dose Psilocybin</intervention_name>
    <description>0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)</description>
    <arm_group_label>High Dose Psilocybin/Low Dose Psilocybin</arm_group_label>
    <arm_group_label>High Dose Psilocybin/Placebo</arm_group_label>
    <arm_group_label>Low Dose Psilocybin/High Dose Psilocybin</arm_group_label>
    <arm_group_label>Placebo/High Dose Psilocybin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of post-traumatic headache&#xD;
&#xD;
          -  Typical pattern of headache attacks with approximately two attacks or more weekly&#xD;
&#xD;
          -  Attacks are managed by means involving no more than twice weekly triptan use&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Axis I psychotic disorder (e.g. schizophrenia, bipolar I, depression with psychosis)&#xD;
&#xD;
          -  Axis I psychotic disorder in first degree relative&#xD;
&#xD;
          -  Unstable medical condition, severe renal, cardiac or hepatic disease, pacemaker, or&#xD;
             serious central nervous system pathology&#xD;
&#xD;
          -  Pregnant, breastfeeding, lack of adequate birth control&#xD;
&#xD;
          -  History of intolerance to psilocybin, LSD, or related compounds&#xD;
&#xD;
          -  Drug or alcohol abuse within the past 3 months (excluding tobacco)&#xD;
&#xD;
          -  Urine toxicology positive to drugs of abuse&#xD;
&#xD;
          -  Use of vasoconstrictive medications (i.e. sumatriptan, pseudoephedrine, midodrine)&#xD;
             within 5 half-lives of test days&#xD;
&#xD;
          -  Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks&#xD;
&#xD;
          -  Use of antidepressant medication (i.e. TCA, MAOI, SSRI) in the past 6 weeks&#xD;
&#xD;
          -  Use of steroids or certain other immunomodulatory agents (i.e. azathioprine) in the&#xD;
             past 2 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>VA Connecticut Healthcare System</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>psilocybin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Post-Traumatic Headache</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psilocybin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03806985
org study id: 1607018057.B
nct id: NCT03806985
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Acute change in pain intensity
time frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
description: 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
measure: Acute change in nausea/vomiting
time frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
description: 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
measure: Acute change in photophobia
time frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
description: 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
measure: Acute change in phonophobia
time frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
description: 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
measure: Acute change in functional disability
time frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
description: 4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
measure: Time to first headache attack
time frame: Two weeks following each test session
description: Measured in days
measure: Time to last headache attack
time frame: Two weeks following each test session
description: Measured in days
measure: Change in headache attack frequency
time frame: From two weeks before first session to two weeks after second session using a headache diary
description: Average number (number per week)
measure: Change in headache attack duration
time frame: From two weeks before first session to two weeks after second session using a headache diary
description: Average duration (measured in hours)
measure: 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
description: Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
measure: 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
description: Average intensity of nausea/vomiting (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
measure: 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
description: Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
measure: 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
description: Average intensity of phonophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
measure: 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
description: Average intensity of functional disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
measure: Use of abortive/rescue medication
time frame: From two weeks before first session to two weeks after second session using a headache diary
description: number of times per week
measure: Headache attack-free time
time frame: From two weeks before first session to two weeks after second session using a headache diary
description: Number of 24 hour days (may be non-consecutive)
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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)
description: Maximum change from baseline during each test day (mmHg)
measure: 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)
description: Maximum change from baseline during each test day (beats per minute)
measure: 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)
description: Maximum change from baseline during each test day (SpO2)
measure: 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
description: Change from baseline during each test day (pg/mg protein)
measure: 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
description: Change from baseline during each test day (pg/mg protein)
arm group label: Placebo/Low Dose Psilocybin
arm group type: Experimental
description: Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
arm group label: Placebo/High Dose Psilocybin
arm group type: Experimental
description: Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.
arm group label: Low Dose Psilocybin/Placebo
arm group type: Experimental
description: Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
arm group label: High Dose Psilocybin/Placebo
arm group type: Experimental
description: Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.
arm group label: High Dose Psilocybin/Low Dose Psilocybin
arm group type: Experimental
description: Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session.
arm group label: Low Dose Psilocybin/High Dose Psilocybin
arm group type: Experimental
description: Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session.
intervention type: Drug
intervention name: Placebo oral capsule
description: microcrystalline cellulose capsule
arm group label: High Dose Psilocybin/Placebo
arm group label: Low Dose Psilocybin/Placebo
arm group label: Placebo/High Dose Psilocybin
arm group label: Placebo/Low Dose Psilocybin
intervention type: Drug
intervention name: Low Dose Psilocybin
description: 0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
arm group label: High Dose Psilocybin/Low Dose Psilocybin
arm group label: Low Dose Psilocybin/High Dose Psilocybin
arm group label: Low Dose Psilocybin/Placebo
arm group label: Placebo/Low Dose Psilocybin
intervention type: Drug
intervention name: High Dose Psilocybin
description: 0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)
arm group label: High Dose Psilocybin/Low Dose Psilocybin
arm group label: High Dose Psilocybin/Placebo
arm group label: Low Dose Psilocybin/High Dose Psilocybin
arm group label: Placebo/High Dose Psilocybin
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Post-Traumatic Headache
mesh term: Headache
mesh term: Psilocybin