Post-Traumatic HeadachePhase 1NCT03806985
Effects of Psilocybin in Concussion Headache
A Phase 1 study testing Low Dose Psilocybin and High Dose Psilocybin in people with Post-Traumatic Headache, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Post-Traumatic Headache
- What is being tested?
- Low Dose Psilocybin and High Dose Psilocybin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2019to 27 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
About this study
Official title: 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.
- Conditions
- Post-Traumatic Headache
- Being tested
- Placebo oral capsule, Low Dose Psilocybin, High Dose Psilocybin
- Keywords
- psilocybin
- Medical subject headings
- Post-Traumatic Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo oral capsuleDrug
microcrystalline cellulose capsule
Low Dose PsilocybinDrug
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
High Dose PsilocybinDrug
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)
| Study group | Role | What they receive |
|---|---|---|
| Placebo/Low Dose Psilocybin | Experimental | Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session. Receives: Drug: Placebo oral capsule; Drug: Low Dose Psilocybin |
| Placebo/High Dose Psilocybin | Experimental | Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session. Receives: Drug: Placebo oral capsule; Drug: High Dose Psilocybin |
| Low Dose Psilocybin/Placebo | Experimental | Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session. Receives: Drug: Placebo oral capsule; Drug: Low Dose Psilocybin |
| High Dose Psilocybin/Placebo | Experimental | Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session. Receives: Drug: Placebo oral capsule; Drug: High Dose Psilocybin |
| High Dose Psilocybin/Low Dose Psilocybin | Experimental | Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session. Receives: Drug: Low Dose Psilocybin; Drug: High Dose Psilocybin |
| Low Dose Psilocybin/High Dose Psilocybin | Experimental | Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session. Receives: Drug: Low Dose Psilocybin; Drug: High Dose Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute change in pain intensity
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured: Measured at 0, 1, 2, 4, and 24 hours after drug administration
Acute change in nausea/vomiting
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured: Measured at 0, 1, 2, 4, and 24 hours after drug administration
Acute change in photophobia
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured: Measured at 0, 1, 2, 4, and 24 hours after drug administration
Acute change in phonophobia
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured: Measured at 0, 1, 2, 4, and 24 hours after drug administration
Acute change in functional disability
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Measured: Measured at 0, 1, 2, 4, and 24 hours after drug administration
Time to first headache attack
Measured in days
Measured: Two weeks following each test session
Time to last headache attack
Measured in days
Measured: Two weeks following each test session
Change in headache attack frequency
Average number (number per week)
Measured: From two weeks before first session to two weeks after second session using a headache diary
Change in headache attack duration
Average duration (measured in hours)
Measured: From two weeks before first session to two weeks after second session using a headache diary
Change in pain intensity of headache attacks
Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Measured: 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
Average intensity of nausea/vomiting (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Measured: From two weeks before first session to two weeks after second session using a headache diary
Change in intensity of photophobia during headache attacks
Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Measured: From two weeks before first session to two weeks after second session using a headache diary
Change in intensity of phonophobia during headache attacks
Average intensity of phonophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Measured: 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
Average intensity of functional disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Measured: From two weeks before first session to two weeks after second session using a headache diary
Secondary outcomes (11)
Use of abortive/rescue medication
number of times per week
Measured: From two weeks before first session to two weeks after second session using a headache diary
Headache attack-free time
Number of 24 hour days (may be non-consecutive)
Measured: 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
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.
Measured: From two weeks before first session to two weeks after second session using a headache diary
Depression using Patient Health Questionnaire 9 (PHQ-9)
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.
Measured: 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)
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.
Measured: From two weeks before first session to two weeks after second session using a headache diary
Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
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.
Measured: Taken on each test day approximately 6 hours after drug administration
Change in blood pressure
Maximum change from baseline during each test day (mmHg)
Measured: 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 heart rate
Maximum change from baseline during each test day (beats per minute)
Measured: 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
Maximum change from baseline during each test day (SpO2)
Measured: 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)
Change from baseline during each test day (pg/mg protein)
Measured: 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)
Change from baseline during each test day (pg/mg protein)
Measured: Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2019
- Study start28 Mar 2019
- Primary completion27 Jun 2023
- Study completion27 Jun 2023
Why it stopped: Challenging to recruit qualifying subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-Traumatic HeadacheStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03806985
- Sponsor's protocol ID
- 1607018057.B
- Status last verified
- Oct 2023
- First submitted
- 14 Jan 2019
- Last updated
- 12 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study II
- ClinicalTrials.gov ID
- NCT03806985
- Acronym / sponsor ID
- 1607018057.B
- Conditions
- Post-Traumatic Headache
- Keywords
- psilocybin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Challenging to recruit qualifying subjects
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 28 Mar 2019 (actual)
- Primary completion
- 27 Jun 2023 (actual)
- Study completion
- 27 Jun 2023 (actual)
- First posted
- 16 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Placebo/Low Dose Psilocybin | Experimental | Drug: Placebo oral capsule, Drug: Low Dose PsilocybinSubjects in this arm receive placebo in the first session and low dose psilocybin in the second session. |
| Placebo/High Dose Psilocybin | Experimental | Drug: Placebo oral capsule, Drug: High Dose PsilocybinSubjects in this arm receive placebo in the first session and high dose psilocybin in the second session. |
| Low Dose Psilocybin/Placebo | Experimental | Drug: Placebo oral capsule, Drug: Low Dose PsilocybinSubjects in this arm receive low dose psilocybin in the first session and placebo in the second session. |
| High Dose Psilocybin/Placebo | Experimental | Drug: Placebo oral capsule, Drug: High Dose PsilocybinSubjects in this arm receive high dose psilocybin in the first session and placebo in the second session. |
| High Dose Psilocybin/Low Dose Psilocybin | Experimental | Drug: Low Dose Psilocybin, Drug: High Dose PsilocybinSubjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session. |
| Low Dose Psilocybin/High Dose Psilocybin | Experimental | Drug: Low Dose Psilocybin, Drug: High Dose PsilocybinSubjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo oral capsulemicrocrystalline cellulose capsule | Drug | High Dose Psilocybin/Placebo, Low Dose Psilocybin/Placebo, Placebo/High Dose Psilocybin, Placebo/Low Dose Psilocybin |
| Low Dose Psilocybin0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option) | Drug | High Dose Psilocybin/Low Dose Psilocybin, Low Dose Psilocybin/High Dose Psilocybin, Low Dose Psilocybin/Placebo, Placebo/Low Dose Psilocybin |
| High Dose Psilocybin0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option) | Drug | High Dose Psilocybin/Low Dose Psilocybin, High Dose Psilocybin/Placebo, Low Dose Psilocybin/High Dose Psilocybin, Placebo/High Dose Psilocybin |
Primary outcome
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)
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)
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)
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)
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)
Time to first headache attack
Time frame: Two weeks following each test session
Measured in days
Time to last headache attack
Time frame: Two weeks following each test session
Measured in days
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)
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)
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)
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)
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)
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)
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)
11 secondary outcomes
Use of abortive/rescue medication
Time frame: 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
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
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
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
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
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)
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)
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)
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 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
Results and safety
The study was stopped early (reason given: Challenging to recruit qualifying subjects). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Low Dose Psilocybin and High Dose Psilocybin in people with Post-Traumatic Headache, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Challenging to recruit qualifying subjects). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute change in pain intensity (time frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2023.