Stress Experience Following Psilocybin
- Conditions
- Assessing the Importance of Cortisol in Facilitating Positive Outcomes Induced by Psilocybin in Healthy Participants
- Interventions
- Registration Number
- NCT06768944
- Lead Sponsor
- University of Calgary
- Brief Summary
The purpose of this study is to determine the importance in the acute stress response induced by psilocybin (the primary component of "magic mushrooms") in facilitating positive outcomes. Participants in this study will be given psilocybin in combination with a placebo or metyrapone, a cortisol synthesis inhibitor medication, on four different occasions.
- Detailed Description
The overall goal of this double-blind, placebo-controlled clinical trial is to systematically explore the relationship between the stress response, improvements in well-being, and the subjective psychedelic experience following psilocybin administration.
The investigators aim to determine whether blocking the glucocorticoid stress response (via metyrapone-mediated cortisol suppression) 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 36 participants aged 22 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 hormone levels (cortisol, adrenocorticotropin hormone (ACTH), and brain-derived neurotrophic factor (BDNF)), cognitive flexibility, mood, well-being, personality traits, and anxiety levels.
Participants will then complete the following sessions in a randomized order:
i) high dose psilocybin (25mg; "active dose") in combination with placebo treatment ii) high dose psilocybin (25mg; "active dose") in combination with metyrapone treatment (2X 750mg) iii) low dose psilocybin (1mg "active control") in combination with placebo treatment, iv) low dose psilocybin (1mg "active control") in combination with metyrapone treatment (2X 750mg)
Outcome measures will be assessed at 1-week and 1-month after each dosing session.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 36
- Individuals of all sexes, gender identities, and ethnicities
- Ages 22 to 65 years of age at the time of screening
- Ability to read/write in English
- No serotonergic psychedelic use in the past 6 months (e.g. psilocybin, LSD, DMT, mescaline)
- Agree not to consume psychoactive drugs 24 hours before dosing sessions or consume psychedelics during duration of study participation
- At least one self-reported positive experience with a mind-altering substance (e.g., psychedelics or cannabis) or experience with altered states of consciousness
- No serious adverse events following previous psychedelic use
- Any notable abnormality on electrocardiogram, physical examination, or routine medical blood or urinalysis laboratory tests
- Psychiatric diagnoses: major depressive disorder, generalized anxiety disorder, obsessive compulsive disorder, moderate to severe substance use disorders, personality disorders, or schizophrenia or psychotic disorders
- Endocrine disorders or dysfunction
- Family history: a first- or second degree relative with a history of schizophrenia or other psychotic disorders, bipolar I or II
- Medications: tricyclic antidepressants, lithium, SSRIs, MAOIs, haloperidol, benzodiazepines
- Currently pregnancy or nursing, trying to become pregnant, or unwilling to use acceptable method of contraception during the study
- Any sensitivity or adverse reaction to previous use of a hallucinogen
- Suffered a mild traumatic brain injury (TBI) within the last 6 months, or a moderate/severe TBI at least once in lifetime
- Any other circumstances that, in the opinion of the investigators, compromises participant safety
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description High-dose psilocybin + placebo Psilocybin 25 mg placebo + 25 mg psilocybin (+15 min) + placebo (+180 min) High-dose psilocybin + placebo Placebo placebo + 25 mg psilocybin (+15 min) + placebo (+180 min) Low-dose psilocybin + placebo Psilocybin 1 mg placebo + 1 mg psilocybin (+15 min) + placebo (+180 min) Low-dose psilocybin + placebo Placebo placebo + 1 mg psilocybin (+15 min) + placebo (+180 min) High-dose psilocybin + metyrapone Psilocybin 25 mg 750mg metyrapone + 25 mg psilocybin (+15 min) + 750mg metyrapone (+180 min) High-dose psilocybin + metyrapone Metyrapone 750 mg 750mg metyrapone + 25 mg psilocybin (+15 min) + 750mg metyrapone (+180 min) Low-dose psilocybin + metyrapone Psilocybin 1 mg 750mg metyrapone + 1 mg psilocybin (+15 min) + 750mg metyrapone (+180 min) Low-dose psilocybin + metyrapone Metyrapone 750 mg 750mg metyrapone + 1 mg psilocybin (+15 min) + 750mg metyrapone (+180 min)
- Primary Outcome Measures
Name Time Method Positive effects One week 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.
- Secondary Outcome Measures
Name Time Method Stress reactivity From dosing session 1 to dosing session 2 (1-month later) to dosing session 3 (2-months later) to dosing session 4 (3-months later) Stress reactivity will be assessed through heart rate variability
Biomarkers of stress from baseline to medication session 1 (one week post-baseline) to medication session 2 (one month post-session 1) to medication session 3 (one month post-session 2) to medication session 4 (one month post-session 3) cortisol, ACTH, BDNF
Mood from baseline to one week post-dosing 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)
Well-being from baseline to one week post-dosing 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.
Anxiety from baseline to one week post-dosing Anxiety will be measured using the State-Trait Anxiety Inventory. The total score ranges from 20-80; a higher score represents a worse outcome.
Cognitive Flexibility from baseline to one week post-dosing 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).
Spontaneous Thought from baseline to one week post-dosing To measure spontaneous thought, participants will complete a Think Aloud task where they narrate their stream of thought in real time.
Reinforcement Learning from baseline to one week post-dosing 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.
Trial Locations
- Locations (1)
University of Calgary
🇨🇦Calgary, Alberta, Canada