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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.
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:
i) 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-dose psilocybin + placebo | Active Comparator | placebo + psilocybin (+60 min) |
|
| Low-dose psilocybin + placebo | Active Comparator | placebo + psilocybin (+60 min) |
|
| High-dose psilocybin + risperidone | Experimental | risperidone + psilocybin (+60 min) |
|
| Low-dose psilocybin + risperidone | Active Comparator | risperidone + psilocybin (+60 min) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Psilocybin high-dose | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | One week and one month post-dosing |
| Measure | Description | Time Frame |
|---|---|---|
| Stress reactivity | Stress reactivity will be assessed through heart rate variability | From start of dosing session to end of dosing session |
| Biomarkers of stress and plasticity | cortisol, ACTH, BDNF |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ana Deutsch, MSc | Contact | 587-893-0257 | ana.deutsch@ucalgary.ca |
| Name | Affiliation | Role |
|---|---|---|
| Leah Mayo, PhD | University of Calgary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Calgary | Recruiting | Calgary | Alberta | T2N 4N1 | Canada |
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| ID | Term |
|---|---|
| D015775 | Fractures, Stress |
| ID | Term |
|---|---|
| D050723 | Fractures, Bone |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D011562 | Psilocybin |
| D018967 | Risperidone |
| ID | Term |
|---|---|
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
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|
| Psilocybin low-dose | Drug | 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 MG | Drug | risperidone 1mg capsules |
|
|
| Placebo | Drug | inactive placebo |
|
| 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) | 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. | 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. | 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). | 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. | 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. | from baseline to one week and one month post-dosing |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014363 | Tryptamines |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |