Psilocybin for Stress Response

(SEP-1 Trial)

Overseen By Ana Deutsch, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must not be taking: Tricyclics, Lithium, SSRIs, MAOIs

Disqualifiers: Depression, Anxiety, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 3 months

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including tricyclic antidepressants, lithium, SSRIs (a type of antidepressant), MAOIs (a type of antidepressant), haloperidol, and benzodiazepines. If you are on any of these, you would need to stop them to participate.

What data supports the effectiveness of the drug psilocybin for stress response?

Research shows that psilocybin, a component of 'magic mushrooms', has been effective in treating mental health issues like depression and anxiety, with long-term improvements seen after just a few doses. It is well-tolerated and may help reduce psychological distress, especially in people with a history of adverse childhood experiences. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin is generally considered safe when given in controlled settings to screened and supported participants, with very low incidence of risky behavior or lasting psychological distress. However, some people may experience challenging psychological effects, and a small number have reported enduring psychological symptoms or sought medical help after use. ^{5 6 7 8 9}

How does the drug psilocybin differ from other treatments for stress response?

Psilocybin is unique because it may reduce stress by temporarily increasing glucocorticoids (hormones involved in stress response) and has long-lasting effects even after a single dose. Unlike traditional treatments, it works through the serotonin system and alters brain circuits related to mood and perception. ^{10 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

Leah Mayo, PhD

Principal Investigator

University of Calgary

Eligibility Criteria

This trial is for individuals interested in exploring how psilocybin, the active ingredient in 'magic mushrooms,' affects stress. Participants will be given psilocybin with either a placebo or metyrapone on four occasions. Specific eligibility criteria are not provided.

Inclusion Criteria

At least one self-reported positive experience with a mind-altering substance (e.g., psychedelics or cannabis) or experience with altered states of consciousness

Ability to read/write in English

I am between 22 and 65 years old.

Exclusion Criteria

Psychiatric diagnoses: major depressive disorder, generalized anxiety disorder, obsessive compulsive disorder, moderate to severe substance use disorders, personality disorders, or schizophrenia or psychotic disorders

I have a hormone-related disorder.

Any sensitivity or adverse reaction to previous use of a hallucinogen

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants complete baseline measures assessing hormone levels, cognitive flexibility, mood, well-being, personality traits, and anxiety levels

1 week

1 visit (in-person)

Treatment

Participants receive psilocybin in combination with placebo or metyrapone on four different occasions

3 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with outcome measures assessed at 1-week and 1-month after each dosing session

4 months

4 visits (in-person)

Treatment Details

Interventions

• Metyrapone
• Psilocybin

Trial Overview The study tests the effects of 25 mg of psilocybin and 1 mg of psilocybin against a placebo and alongside metyrapone, which inhibits cortisol production. The goal is to understand how these treatments influence acute stress responses.

Participant Groups

Group I: High-dose psilocybin + metyrapone Experimental Treatment 2 Interventions

750mg metyrapone + 25 mg psilocybin (+15 min) + 750mg metyrapone (+180 min)

Group II: High-dose psilocybin + placebo Active Control 2 Interventions

placebo + 25 mg psilocybin (+15 min) + placebo (+180 min)

Group III: Low-dose psilocybin + metyrapone Active Control 2 Interventions

750mg metyrapone + 1 mg psilocybin (+15 min) + 750mg metyrapone (+180 min)

Group IV: Low-dose psilocybin + placebo Placebo Group 2 Interventions

placebo + 1 mg psilocybin (+15 min) + placebo (+180 min)

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

Psilocybin, found in 'magic mushrooms', shows promise as a non-addictive alternative for treating mental health disorders like major depressive disorder and addiction, potentially addressing the urgent need for new therapies amid rising addiction and suicide rates.

Current research indicates that psilocybin may offer therapeutic benefits without the overdose risks associated with traditional mind-altering substances, suggesting a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, RB.[2021]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

Psilocybin, a naturally occurring compound found in certain mushrooms, shows promise as a rapid-acting antidepressant, particularly for individuals with treatment-resistant depression, by acting on serotonin receptors, especially the 5-HT2A receptor.

The antidepressant effects of psilocybin are believed to involve not only serotonin modulation but also changes in neural circuitry and brain regions associated with depression, suggesting a complex mechanism of action that could lead to new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression. Ling, S., Ceban, F., Lui, LMW., et al.[2022]

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

[Psilocybin-Assisted Treatment of Depression, Anxiety and Substance use Disorders: Neurobiological Basis and Clinical Application]. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Psilocybin for Treating Psychological Distress among Survivors of Adverse Childhood Experiences: Evidence on Acceptability and Potential Efficacy of Psilocybin Use. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

8. Ireland pubmed.ncbi.nlm.nih.gov

The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Psychedelic-Induced Serotonin 2A Receptor Downregulation Does Not Predict Swim Stress Coping in Mice. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. [2019]