HealthyPhase 1/2NCT05301608
Effects of Psilocybin on Electrophysiology and the Dynamic Content of Thought
A Phase 1/2 study testing Psilocybin in people with Healthy, run by Johns Hopkins University at 1 site in United States.
Trial summary
This research study will use computerized tasks, electroencephalography (EEG), and magnetic resonance imaging (MRI) to look at how the drug psilocybin, a naturally occurring compound contained in hundreds of species of psychoactive mushrooms, changes thoughts and brain activity. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Psilocybin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Mar 2022to 1 Jan 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 to 75 years old
- Have given written informed consent
- Have at least a high-school level of education or equivalent (e.g. GED) and be fluent in English
- Be healthy and psychologically stable as determined by screening for medical and psychiatric problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
- Agree to consume approximately the same amount of caffeine-containing beverage (e.g. coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the morning of the drug session day. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on the session day.
- Agree to refrain from using any psychoactive drugs, including alcoholic beverages and nicotine, within 24 hours of each drug administration. The exception is caffeine.
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- Agree not to take any "as-needed" medications on the mornings of drug sessions
- Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
- Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
- Have used a psychedelic drug (e.g. lysergic acid diethylamide(LSD)/acid, psilocybin mushrooms, ayahuasca) at least five times in their lifetime.
- Proof of COVID-19 vaccination
Who cannot join
- Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control.
- Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g. atrial fibrilation), artificial heart valve, or heart attack in the past year
- Epilepsy with history of seizures
- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
- Currently taking psychoactive prescription medication on a regular (e.g. daily) basis
- Currently taking on a regular (e.g. daily) basis any medications having a primary centrally-acting serotonergic effect, including mono-amine oxidase inhibitors (MAOIs). For individuals who have intermittent or "as needed" use of such medications, psilocybin sessions will not be conducted until at least five half-lives of the agent have elapsed after the last dose.
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- More than 20% outside the upper or lower range of ideal body weight according to Metropolitan Life height and weight table
- Current or past history of meeting Diagnostic and Statistical Manual, version 5 (DSM-5) criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition)
- Current or past history within the last five years of meeting DSM-5 criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine)
- Have a first or second-degree relative with bipolar I disorder, schizophrenia spectrum, or other psychotic disorders (except substance/medication-induced or due to another medical condition)
- Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
- Has history of migraine, tension, or other recurring headaches.
- Head trauma, traumatic brain injury, or concussion with loss of consciousness for >2 minutes
- Contraindications for magnetic resonance imaging (MRI) (e.g. claustrophobia incompatible with MRI scanning, medical device or implant incompatible with MRI, prior history as a metal worker and/or certain metallic objects in the body)
- Left-handedness (assessed by the Edinburgh Handedness Inventory)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins Center for Psychedelic and Consciousness Research
Baltimore, Maryland, 21224
Frederick S Barrett, 410-550-9777, fbarret2@jh.edu
About this study
This research study will use computerized tasks, electroencephalography (EEG), and magnetic resonance imaging (MRI) to look at how the drug psilocybin, a naturally occurring compound contained in hundreds of species of psychoactive mushrooms, changes thoughts and brain activity.
Read the detailed description
In this double-blind, placebo-controlled, within-subject, full cross-over study in healthy volunteers, computerized, electroencephalography (EEG), and magnetic resonance imaging (MRI) measures will be assessed to test the acute effects of a moderate dose of psilocybin (10 mg/70 kg) on creativity, the contents and dynamics of thought, memory, and shared vs individual brain response while viewing naturalistic stimuli. Understanding the acute psychological and neural effects of psychedelic drugs such as psilocybin may allow for future optimization of psychedelic medicine, as well as a deeper and more refined understanding of consciousness itself.
- Conditions
- Healthy
- Being tested
- Psilocybin, Placebo
- Keywords
- psilocybin, electroencephalography (EEG), magnetic resonance imaging (MRI), creativity, cognition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Also called 4-phosphoryloxy-N,N-dimethyltryptamine
The psilocybin used in this study is synthetically manufactured and formulated under current good manufacturing practices (cGMP). The active drug is encapsulated using a size 0 blue gelatin capsule and contains 10 mg of psilocybin.
PlaceboDrug
The placebo used in this study is microcrystalline cellulose, an inert substance, encapsulated using a size 0 blue gelatin capsule.
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin First | Experimental | Psilocybin (10mg) will be administered one time orally as a capsule taken with water. Expected duration of acute effects is approximately 6 hours. After a period of a washout, participants will switch to the placebo intervention. Receives: Drug: Psilocybin; Drug: Placebo |
| Placebo First | Placebo comparator | Participants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water. After a period of a washout, participants will switch to the Psilocybin intervention. Receives: Drug: Psilocybin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference between drug conditions in the frequency of word use during free association tasks
Volunteers are instructed to either describe their interpretation of visual stimuli, verbalize a set of freely associated words, or reflect upon and describe out loud the thoughts that are occurring after presentation of short excerpts of popular music. Audio recordings of verbal responses from volunteers will be recorded, transcribed, and then submitted to automated text analysis and natural language processing analysis to compare the semantic content of responses between those that were provided during placebo and those that were provided during psilocybin conditions. The frequency of words that fall into a series of semantic categories (e.g. pronouns, adjectives, positive vs negative valence words) will be compared between drug conditions.
Measured: 8 weeks
Sensitivity in distinguishing old versus newly presented visual stimuli
During drug administration sessions, volunteers will view a series of visual stimuli (words and images) and will be asked to read and remember each visual stimulus. The next day, volunteers will be presented with stimuli that were as well as stimuli that were not presented the previous day, and they will be asked to indicate the confidence with which they remember seeing the given stimulus before ("old") or not ("new"). Sensitivity in distinguishing between old and new words (d') will be calculated from receiver operator characteristic curve analysis of confidence ratings of "new" vs "old" judgements, and compared between drug conditions.
Measured: 8 weeks
Accuracy in the remote associates task as assessed by total correct number of trials
Participants will be presented with three words that are only remotely related to each other (e.g., falling, actor, dust) and ask them to generate a fourth word (e.g., star) that relates to all three words. Total correct number of trials will be compared between drug conditions.
Measured: 8-week study period
Accuracy in the alternative uses task
The Alternative Uses Task assesses the extent one can generate novel uses for presented stimuli (e.g. a brick, or a paper clip). The total number of responses and the number of uniquely novel uses that were generated will be compared between drug conditions.
Measured: 8-week study period
Alpha band power in EEG record
Continuous EEG recordings will be analyzed using spectral decomposition, and the time course of average power in the alpha frequency band will be compared between drug conditions.
Measured: 8-week study period
Reliability of whole-brain response while watching videos
Volunteers will be presented with videos during scanning in the second two drug administration sessions. These will be otherwise unremarkable 6-15 minute videos of natural scenes, human interactions, or narrative stories. We will calculate correlations in measured brain response across subjects, moment-by-moment, which yields a measure of reliability of response to these videos across the brain. This reliability map will be compared between drug conditions.
Measured: 8-week study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2022
- Study start3 Mar 2022
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Johns Hopkins 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- All participants will receive all interventions, in counter-balanced order.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frederick S Barrett, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05301608
- Sponsor's protocol ID
- IRB00251021
- Status last verified
- Jul 2026
- First submitted
- 18 Mar 2022
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data will be made available in public databases (e.g. OSF).
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Psilocybin on Electrophysiology and the Dynamic Content of Thought
- ClinicalTrials.gov ID
- NCT05301608
- Acronym / sponsor ID
- IRB00251021
- Conditions
- Healthy
- Keywords
- psilocybin, electroencephalography (EEG), magnetic resonance imaging (MRI), creativity, cognition
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 3 Mar 2022 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 29 Mar 2022 (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.
This research study will use computerized tasks, electroencephalography (EEG), and magnetic resonance imaging (MRI) to look at how the drug psilocybin, a naturally occurring compound contained in hundreds of species of psychoactive mushrooms, changes thoughts and brain activity.
Detailed description
In this double-blind, placebo-controlled, within-subject, full cross-over study in healthy volunteers, computerized, electroencephalography (EEG), and magnetic resonance imaging (MRI) measures will be assessed to test the acute effects of a moderate dose of psilocybin (10 mg/70 kg) on creativity, the contents and dynamics of thought, memory, and shared vs individual brain response while viewing naturalistic stimuli. Understanding the acute psychological and neural effects of psychedelic drugs such as psilocybin may allow for future optimization of psychedelic medicine, as well as a deeper and more refined understanding of consciousness itself.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- All participants will receive all interventions, in counter-balanced order.
| Arm | Type | Receives |
|---|---|---|
| Psilocybin First | Experimental | Drug: Psilocybin, Drug: PlaceboPsilocybin (10mg) will be administered one time orally as a capsule taken with water. Expected duration of acute effects is approximately 6 hours. After a period of a washout, participants will switch to the placebo intervention. |
| Placebo First | Placebo comparator | Drug: Psilocybin, Drug: PlaceboParticipants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water. After a period of a washout, participants will switch to the Psilocybin intervention. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 18 to 75 years old
- Have given written informed consent
- Have at least a high-school level of education or equivalent (e.g. GED) and be fluent in English
- Be healthy and psychologically stable as determined by screening for medical and psychiatric problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
- Agree to consume approximately the same amount of caffeine-containing beverage (e.g. coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the morning of the drug session day. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on the session day.
Key exclusion criteria (15 listed)
- Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control.
- Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g. atrial fibrilation), artificial heart valve, or heart attack in the past year
- Epilepsy with history of seizures
- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
- Currently taking psychoactive prescription medication on a regular (e.g. daily) basis
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 |
|---|---|---|
| PsilocybinAlso: 4-phosphoryloxy-N,N-dimethyltryptamineThe psilocybin used in this study is synthetically manufactured and formulated under current good manufacturing practices (cGMP). The active drug is encapsulated using a size 0 blue gelatin capsule and contains 10 mg of psilocybin. | Drug | Placebo First, Psilocybin First |
| PlaceboThe placebo used in this study is microcrystalline cellulose, an inert substance, encapsulated using a size 0 blue gelatin capsule. | Drug | Placebo First, Psilocybin First |
Primary outcome
Difference between drug conditions in the frequency of word use during free association tasks
Time frame: 8 weeks
Volunteers are instructed to either describe their interpretation of visual stimuli, verbalize a set of freely associated words, or reflect upon and describe out loud the thoughts that are occurring after presentation of short excerpts of popular music. Audio recordings of verbal responses from volunteers will be recorded, transcribed, and then submitted to automated text analysis and natural language processing analysis to compare the semantic content of responses between those that were provided during placebo and those that were provided during psilocybin conditions. The frequency of words that fall into a series of semantic categories (e.g. pronouns, adjectives, positive vs negative valence words) will be compared between drug conditions.
Sensitivity in distinguishing old versus newly presented visual stimuli
Time frame: 8 weeks
During drug administration sessions, volunteers will view a series of visual stimuli (words and images) and will be asked to read and remember each visual stimulus. The next day, volunteers will be presented with stimuli that were as well as stimuli that were not presented the previous day, and they will be asked to indicate the confidence with which they remember seeing the given stimulus before ("old") or not ("new"). Sensitivity in distinguishing between old and new words (d') will be calculated from receiver operator characteristic curve analysis of confidence ratings of "new" vs "old" judgements, and compared between drug conditions.
Accuracy in the remote associates task as assessed by total correct number of trials
Time frame: 8-week study period
Participants will be presented with three words that are only remotely related to each other (e.g., falling, actor, dust) and ask them to generate a fourth word (e.g., star) that relates to all three words. Total correct number of trials will be compared between drug conditions.
Accuracy in the alternative uses task
Time frame: 8-week study period
The Alternative Uses Task assesses the extent one can generate novel uses for presented stimuli (e.g. a brick, or a paper clip). The total number of responses and the number of uniquely novel uses that were generated will be compared between drug conditions.
Alpha band power in EEG record
Time frame: 8-week study period
Continuous EEG recordings will be analyzed using spectral decomposition, and the time course of average power in the alpha frequency band will be compared between drug conditions.
Reliability of whole-brain response while watching videos
Time frame: 8-week study period
Volunteers will be presented with videos during scanning in the second two drug administration sessions. These will be otherwise unremarkable 6-15 minute videos of natural scenes, human interactions, or narrative stories. We will calculate correlations in measured brain response across subjects, moment-by-moment, which yields a measure of reliability of response to these videos across the brain. This reliability map will be compared between drug conditions.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data will be made available in public databases (e.g. OSF).
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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.
Frederick S Barrett, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Psilocybin in people with Healthy, run by Johns Hopkins 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 11 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 23 Jul 2026. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gabi Lofland ((410) 550-2253, gloflan1@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference between drug conditions in the frequency of word use during free association tasks (time frame: 8 weeks). The study lists 6 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 23 Jul 2026.