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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how psilocybin, a compound in "magic mushrooms," affects stress responses in the body. Researchers are testing whether different doses of psilocybin, combined with a placebo or metyrapone (a drug that reduces cortisol, a stress hormone), lead to positive outcomes. Suitable candidates for this trial have experienced at least one positive encounter with a mind-altering substance, such as psychedelics or cannabis, and have not used any serotonergic psychedelics in the last six months. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking stress response research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin, the main ingredient in "magic mushrooms," is generally safe in controlled settings. Studies have found that low doses can produce noticeable effects without causing harm, improving mood and reducing negative feelings.

For higher doses, evidence suggests that psilocybin is well-tolerated. In healthy individuals, it does not cause long-term negative side effects. Some studies indicate that the positive effects can last for weeks after just one dose.

When combined with metyrapone, a medication affecting stress hormones, psilocybin remains safe, particularly in controlled environments. Any side effects are usually mild and resolve within a few days.

Overall, studies suggest that psilocybin, whether in low or high doses, is well-tolerated in humans, especially under medical supervision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for stress, which often include talk therapy and medications like SSRIs or benzodiazepines, psilocybin offers a completely different approach. Researchers are excited about psilocybin because it works on serotonin receptors in the brain, potentially altering mood and perception in a way that can quickly reduce stress. Additionally, the trial explores combining psilocybin with metyrapone, which may enhance stress-reducing effects by modulating the body's stress hormone response. This combination could offer faster and more effective relief than current options, which often take weeks to show results.

What evidence suggests that this trial's treatments could be effective for stress response?

Research has shown that psilocybin, the main ingredient in magic mushrooms, can boost mood and lower stress. Studies have found that psilocybin significantly and lastingly reduces symptoms of depression. Even with low doses, mood improvements have been observed up to six months after treatment. Higher doses have provided quick and long-lasting relief from depression. In this trial, some participants will receive psilocybin alone, while others will receive a combination of psilocybin and metyrapone, a medicine that blocks stress hormones. This combination might enhance psilocybin's ability to reduce stress, though more research is needed. Overall, psilocybin appears promising for reducing stress and improving mental health. ^{5 6 7 8 9}

Who Is on the Research Team?

Leah Mayo, PhD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

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

Ability to read/write in English

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10801413/

The development of psilocybin therapy for treatment ... At 12 weeks, 20% of participants who had received 25 mg had sustained their response, compared with 10% in the 1 mg group. It is important to note that this ...

2. nature.com nature.com/articles/s41586-024-07624-5

Psilocybin desynchronizes the human brain In clinical trials, a single high dose of psilocybin (25 mg) has demonstrated rapid and sustained symptom relief in depression1,2,3,11,12,13 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724020494

The role of the psychedelic experience in psilocybin ... To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2808950

Single-Dose Psilocybin Treatment for Major Depressive ... A 25-mg dose of psilocybin was well tolerated and may hold promise as a treatment for major depressive disorder when combined with psychological support.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04670081?tab=table

Efficacy and Safety of Psilocybin in Treatment-Resistant ... The study aims to investigate the safety and efficacy of oral psilocybin administered under supportive conditions in treatment-resistant major depression (TRD).

6. sciencedirect.com sciencedirect.com/science/article/pii/S277240852400125X

Safety pharmacology of acute psilocybin administration in ... These findings suggest that a single administration of psilocybin is safe with regard to acute psychological and physical harm in healthy participants in a ...

7. nature.com nature.com/articles/s41598-020-59282-y

Emotions and brain function are altered up to one month ... Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6007659/

Clinical potential of psilocybin as a treatment for mental health ... The subjects were followed for 8 to 16 months post psilocybin administration and exhibited no long-term negative side effects.

9. webmd.com webmd.com/vitamins/ai/ingredientmono-1654/psilocybin

Psilocybin - Uses, Side Effects, and More When taken by mouth: Psilocybin is possibly safe when used as a single dose under medical supervision. Single doses of psilocybin have been used in controlled ...