Investigating the Importance of the Subjective Psychedelic ExperiencePhase 2SEP-1NCT06768944
Subjective Experience Following Psilocybin
A Phase 2 study testing Psilocybin high-dose, Psilocybin low-dose and Risperidone 1 MG in people with Investigating the Importance of the Subjective Psychedelic Experience, run by University of Calgary at 1 site in Canada.
Trial summary
The purpose of this study is to determine the importance of the acute subjective experience induced by psilocybin (the primary component of "magic mushrooms") in facilitating positive outcomes. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Investigating the Importance of the Subjective Psychedelic Experience
- What is being tested?
- Psilocybin high-dose, Psilocybin low-dose and Risperidone 1 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 1 siteCanada
- Study dates
- 15 May 2026to Jan 2028
- Phase
- Phase 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Individuals of all sexes, gender identities, and ethnicities
- Ages 18 to 65 years of age at the time of screening
- Ability to read/write in English
- Agree not to consume psychoactive drugs 24 hours before dosing sessions or consume psychedelics during duration of study participation
Who cannot join
- Any notable abnormality on electrocardiogram or routine medical blood or urinalysis laboratory tests
- Current psychiatric diagnoses, such as: major depressive disorder, generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive compulsive disorder, moderate to severe substance use disorders, eating disorders, personality disorders, post-traumatic stress disorder
- Lifetime or current psychiatric diagnoses of: psychosis, schizophrenia, bipolar disorder
- Family history: a first- or second degree relative with a history of schizophrenia or other psychotic disorders, bipolar I or II
- Medication: Any medication with the potential to interact with the investigational medicinal products, especially those with serotonergic mechanisms of actions like SSRIs, SNRIs or MAO-Inhibitors as well as other antipsychotics
- Currently pregnancy or nursing, trying to become pregnant, or unwilling to use acceptable method of contraception during the study
Show all 11Show fewer
- Current or recent (within 12 weeks) participation in a clinical trial involving medication administration
- Cognitive impairment (Folsetin Mini Mental State Exam score < 24)
- A disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
- Suffered a traumatic brain injury with one of the following symptoms Loss of consciousness >30min Alteration of consciousness/mental state >24h Post-traumatic amnesia >1 day Glasgow Coma Scale (best available score in first 24 hours) <13
- Any other circumstances that, in the opinion of the investigators, compromises participant safety
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University of Calgary
Calgary, Alberta, T2N 4N1
Ana Deutsch, MSc, 587-893-0257, septrial@ucalgary.ca
Leah Mayo, PhD
About this study
Official title: The Role of the Subjective Experience in Supporting Positive Effects Following Psilocybin: a Randomized, Controlled Clinical Trial Using Risperidone in Healthy Adults
The purpose of this study is to determine the importance of the acute subjective experience induced by psilocybin (the primary component of "magic mushrooms") in facilitating positive outcomes. Participants in this study will be given psilocybin in combination with either a placebo or risperidone, an atypical antipsychotic that block the subjective effects of psilocybin.
Read the detailed description
The overall goal of this clinical trial is to systematically explore the relationship between the subjective psychedelic experience, improvements in well-being, and the stress response following psilocybin administration.
The investigators aim to determine whether blocking the acute subjective effects (via risperidone) will influence the acute or protracted effects of psilocybin as measured via self-report, biochemical, or psychophysiological measures. The study also aims to determine if individual variability in stress reactivity or regulation predicts acute (day of dosing) or protracted (1-week later) effects of psilocybin.
A single site will recruit 128 participants aged 18 to 65 who do not meet criteria for any psychiatric diagnoses. A series of questionnaires, blood labs, and medical exams including electrocardiogram will determine inclusion into the study. Once accepted into the study, participants will complete baseline measures assessing biomarkers such as cortisol and brain-derived neurotrophic factor (BDNF) levels, cognitive flexibility, mood, well-being, personality traits, and anxiety levels.
Participants will then be randomly assigned into one of the following groups:
- high dose psilocybin in combination with placebo pretreatment ii) high dose psilocybin in combination with risperidone pretreatment iii) low dose psilocybin in combination with placebo pretreatment iv) low dose psilocybin in combination with risperidone pretreatment
Outcome measures will be assessed at 1-week and 1-month after each dosing session.
- Being tested
- Psilocybin high-dose, Psilocybin low-dose, Risperidone 1 MG, Placebo
- Keywords
- psychedelics, psilocybin, stress response, cortisol, healthy participants, risperidone, subjective effects
- Medical subject headings
- Fractures, Stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin high-doseDrug
Also called PEX010, high-dose psilocybin
The drug product (DP) PEX010 is a capsule for oral administration and is manufactured with DS PYEX (12.5-14.0% psilocybin), excipients, and HPMC capsules. The product is manufactured in two product strengths, and this represents the high-dose
Psilocybin low-doseDrug
Also called PEX010, low-dose psilocybin
The drug product (DP) PEX010 is a capsule for oral administration and is manufactured with DS PYEX (12.5-14.0% psilocybin), excipients, and HPMC capsules. The product is manufactured in two product strengths, and this represents the low-dose.
Risperidone 1 MGDrug
Also called Risperdal
risperidone 1mg capsules
PlaceboDrug
inactive placebo
| Study group | Role | What they receive |
|---|---|---|
| High-dose psilocybin + placebo | Active comparator | placebo + psilocybin (+60 min) Receives: Drug: Psilocybin high-dose; Drug: Placebo |
| Low-dose psilocybin + placebo | Active comparator | placebo + psilocybin (+60 min) Receives: Drug: Psilocybin low-dose; Drug: Placebo |
| High-dose psilocybin + risperidone | Experimental | risperidone + psilocybin (+60 min) Receives: Drug: Psilocybin high-dose; Drug: Risperidone 1 MG |
| Low-dose psilocybin + risperidone | Active comparator | risperidone + psilocybin (+60 min) Receives: Drug: Psilocybin low-dose; Drug: Risperidone 1 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive effects
Persisting Effects Questionnaire (PEQ) - 145 questions rated using a 6-point Likert scale from 0 to 6. There are 12 sub-scale themes assessing positive and negative changes in Attitudes About Life, Attitudes About Self, Mood Changes, Social Effects, Behavioural Changes, and Spirituality. Higher scores in the positive sub-scales indicate a better outcome, while higher scores in the negative sub-scales indicate a worse outcome.
Measured: One week and one month post-dosing
Secondary outcomes (8)
Stress reactivity
Stress reactivity will be assessed through heart rate variability
Measured: From start of dosing session to end of dosing session
Biomarkers of stress and plasticity
cortisol, ACTH, BDNF
Measured: from baseline to dosing session (one week post-baseline) to follow-up 1 (one week post doing session) to follow-up 2 (one month post dosing session)
Mood
Mood will be assessed using the Positive and Negative Affect Schedule. The questionnaire has two sub-scales: the positive affect score (scores range from 10-50, higher scores represent better outcome) and the negative affect score (scores range from 10-50, higher scores represent worse outcome)
Measured: from baseline to one week and one month post-dosing
Well-being
Well-being will be assessed using the Warwick-Edinburgh Mental Wellbeing Scale. The total score ranges from 14-70; a higher score represents a better outcome.
Measured: from baseline to one week and one month post-dosing
Anxiety
Anxiety will be measured using the State-Trait Anxiety Inventory. The total score ranges from 20-80; a higher score represents a worse outcome.
Measured: from baseline to one week and one month post-dosing
Cognitive Flexibility
The Berg Card Sorting Task is a set-shifting measure of cognitive flexibility modeled after the Wisconsin Card Sorting task. Participants must select the stimulus that is different from others based on feedback and adapt their responses once the criteria for correct choice switches. Perseverative errors are defined as the number of instances in which three incorrect responses are made based on a previous rule, and they are thought to reflect less cognitive flexibility (or cognitive rigidity).
Measured: from baseline to one week and one month post-dosing
Spontaneous Thought
To measure spontaneous thought, participants will complete a Think Aloud task where they narrate their stream of thought in real time.
Measured: from baseline to one week and one month post-dosing
Reinforcement Learning
Reinforcement learning will be assessed using a three-armed bandit task. This is a decision-making task in which participants must choose between three alternative targets whose values (probability of reward) changes over the trials.
Measured: from baseline to one week and one month post-dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2025
- Study start15 May 2026
- Primary completionDec 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Investigating the Importance of the Subjective Psychedelic ExperienceStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Leah Mayo, PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06768944
- Sponsor's protocol ID
- REB24-1121
- Acronym
- SEP-1
- Status last verified
- May 2026
- First submitted
- 16 Dec 2024
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of the Subjective Experience in Supporting Positive Effects Following Psilocybin: a Randomized, Controlled Clinical Trial Using Risperidone in Healthy Adults
- ClinicalTrials.gov ID
- NCT06768944
- Acronym / sponsor ID
- SEP-1 / REB24-1121
- Keywords
- psychedelics, psilocybin, stress response, cortisol, healthy participants, risperidone, subjective effects
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 128 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 15 May 2026 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 10 Jan 2025 (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 determine the importance of the acute subjective experience induced by psilocybin (the primary component of "magic mushrooms") in facilitating positive outcomes. Participants in this study will be given psilocybin in combination with either a placebo or risperidone, an atypical antipsychotic that block the subjective effects of psilocybin.
Detailed description
The overall goal of this clinical trial is to systematically explore the relationship between the subjective psychedelic experience, improvements in well-being, and the stress response following psilocybin administration.
The investigators aim to determine whether blocking the acute subjective effects (via risperidone) will influence the acute or protracted effects of psilocybin as measured via self-report, biochemical, or psychophysiological measures. The study also aims to determine if individual variability in stress reactivity or regulation predicts acute (day of dosing) or protracted (1-week later) effects of psilocybin.
A single site will recruit 128 participants aged 18 to 65 who do not meet criteria for any psychiatric diagnoses. A series of questionnaires, blood labs, and medical exams including electrocardiogram will determine inclusion into the study. Once accepted into the study, participants will complete baseline measures assessing biomarkers such as cortisol and brain-derived neurotrophic factor (BDNF) levels, cognitive flexibility, mood, well-being, personality traits, and anxiety levels.
Participants will then be randomly assigned into one of the following groups:
- high dose psilocybin in combination with placebo pretreatment ii) high dose psilocybin in combination with risperidone pretreatment iii) low dose psilocybin in combination with placebo pretreatment iv) low dose psilocybin in combination with risperidone pretreatment
Outcome measures will be assessed at 1-week and 1-month after each dosing session.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| High-dose psilocybin + placebo | Active comparator | Drug: Psilocybin high-dose, Drug: Placeboplacebo + psilocybin (+60 min) |
| Low-dose psilocybin + placebo | Active comparator | Drug: Psilocybin low-dose, Drug: Placeboplacebo + psilocybin (+60 min) |
| High-dose psilocybin + risperidone | Experimental | Drug: Psilocybin high-dose, Drug: Risperidone 1 MGrisperidone + psilocybin (+60 min) |
| Low-dose psilocybin + risperidone | Active comparator | Drug: Psilocybin low-dose, Drug: Risperidone 1 MGrisperidone + psilocybin (+60 min) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Individuals of all sexes, gender identities, and ethnicities
- Ages 18 to 65 years of age at the time of screening
- Ability to read/write in English
- Agree not to consume psychoactive drugs 24 hours before dosing sessions or consume psychedelics during duration of study participation
Key exclusion criteria (11 listed)
- Any notable abnormality on electrocardiogram or routine medical blood or urinalysis laboratory tests
- Current psychiatric diagnoses, such as: major depressive disorder, generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive compulsive disorder, moderate to severe substance use disorders, eating disorders, personality disorders, post-traumatic stress disorder
- Lifetime or current psychiatric diagnoses of: psychosis, schizophrenia, bipolar disorder
- Family history: a first- or second degree relative with a history of schizophrenia or other psychotic disorders, bipolar I or II
- Medication: Any medication with the potential to interact with the investigational medicinal products, especially those with serotonergic mechanisms of actions like SSRIs, SNRIs or MAO-Inhibitors as well as other antipsychotics
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 |
|---|---|---|
| Psilocybin high-doseAlso: PEX010, high-dose psilocybinThe drug product (DP) PEX010 is a capsule for oral administration and is manufactured with DS PYEX (12.5-14.0% psilocybin), excipients, and HPMC capsules. The product is manufactured in two product strengths, and this represents the high-dose | Drug | High-dose psilocybin + placebo, High-dose psilocybin + risperidone |
| Psilocybin low-doseAlso: PEX010, low-dose psilocybinThe drug product (DP) PEX010 is a capsule for oral administration and is manufactured with DS PYEX (12.5-14.0% psilocybin), excipients, and HPMC capsules. The product is manufactured in two product strengths, and this represents the low-dose. | Drug | Low-dose psilocybin + placebo, Low-dose psilocybin + risperidone |
| Risperidone 1 MGAlso: Risperdalrisperidone 1mg capsules | Drug | High-dose psilocybin + risperidone, Low-dose psilocybin + risperidone |
| Placeboinactive placebo | Drug | High-dose psilocybin + placebo, Low-dose psilocybin + placebo |
Primary outcome
Positive effects
Time frame: One week and one month post-dosing
Persisting Effects Questionnaire (PEQ) - 145 questions rated using a 6-point Likert scale from 0 to 6. There are 12 sub-scale themes assessing positive and negative changes in Attitudes About Life, Attitudes About Self, Mood Changes, Social Effects, Behavioural Changes, and Spirituality. Higher scores in the positive sub-scales indicate a better outcome, while higher scores in the negative sub-scales indicate a worse outcome.
8 secondary outcomes
Stress reactivity
Time frame: From start of dosing session to end of dosing session
Biomarkers of stress and plasticity
Time frame: from baseline to dosing session (one week post-baseline) to follow-up 1 (one week post doing session) to follow-up 2 (one month post dosing session)
Mood
Time frame: from baseline to one week and one month post-dosing
Well-being
Time frame: from baseline to one week and one month post-dosing
Anxiety
Time frame: from baseline to one week and one month post-dosing
Cognitive Flexibility
Time frame: from baseline to one week and one month post-dosing
Spontaneous Thought
Time frame: from baseline to one week and one month post-dosing
Reinforcement Learning
Time frame: from baseline to one week and one month post-dosing
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 2 Sep 2026.
- Individual participant dataSharing planned: No
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.
Leah Mayo, PhD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin high-dose, Psilocybin low-dose and Risperidone 1 MG in people with Investigating the Importance of the Subjective Psychedelic Experience, run by University of Calgary at 1 site in Canada.
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 4 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: looking for participants now, as of the sponsor's last update on 2 Sep 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 Canada. 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 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 Ana Deutsch, MSc (587-893-0257, septrial@ucalgary.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Positive effects (time frame: One week and one month post-dosing). 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 2 Sep 2026.