Psilocybin for Depression

Overseen By Geena Fram

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: MAOIs, Lithium, Methadone, others

Disqualifiers: Psychotic disorders, Hypertension, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1 day

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to investigate the safety, feasibility, and tolerability of psilocybin treatment in individuals with functional impairment due to psychiatric symptoms. The secondary objective of this study is to determine whether individuals with functional impairments due to psychiatric symptoms will experience statistically significant symptom reduction and functional improvement from baseline symptom measurements (Visit 3) to 1-week (Visit 7), 4-weeks (Visit 8), and 6-weeks (Visit 9) post dosing. The investigators will recruit individuals with mood, anxiety, trauma, addictive, or related symptomatology, and who have functional impairment associated with these symptoms. A DSM-5 diagnosis is not required (nor is it an exclusion). The investigators will allow for comorbidity and only exclude based on psychological and physiological safety considerations. Critically, this approach will allow us to assess the tolerability of our interventions in individuals who would typically be excluded from efficacy studies due to various comorbid DSM-5 conditions. The investigators will employ an open-label study where participants will be given one dose of oral psilocybin 25mg. The investigators will also have follow-up visits at 1, 4, and 6 weeks and an optional long-term follow-up at 3, 6, and 12 months.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that changes to psychotropic medication and/or dosages within the past 3 months are not allowed. Additionally, certain medications like MAOIs, Lithium, and methadone should not be used recently before enrollment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug psilocybin for depression?

Several clinical trials have shown that psilocybin can reduce symptoms of depression, and it has been well tolerated with limited side effects. Some patients with treatment-resistant depression have experienced significant, long-term improvements after just one or a few sessions. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin has been studied for its safety in humans, and research suggests that it can be used safely under controlled conditions. In a study with healthy adults, escalating doses of psilocybin were administered without serious adverse effects. However, caution is advised, especially for individuals with cardiovascular conditions, as the safety in these cases is not fully known. ^{2 5 6 7 8}

How is the drug psilocybin different from other depression treatments?

Psilocybin is unique because it is a natural compound found in certain mushrooms and works quickly to reduce depression symptoms by affecting serotonin receptors in the brain. Unlike traditional antidepressants that require long-term use, psilocybin can have significant effects after just one or two doses, often combined with therapy. ^{1 2 4 9 10}

Research Team

Benjamin Kelmendi, MD

Principal Investigator

Yale University

Gabrielle Agin-Liebes, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for individuals with psychiatric symptoms causing functional impairment, such as mood, anxiety, trauma-related or addictive behaviors. Participants must be able to take oral pills, refrain from certain medications on dosing day, and have reliable transportation post-dosing. They should not be starting new psychiatric meds within 4 weeks after dosing.

Inclusion Criteria

I can swallow pills by mouth.

I have been diagnosed with a psychiatric condition that affects my daily life.

I can speak and understand English well enough to make informed decisions about my care.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive one dose of oral psilocybin (25 mg) with non-directive support before, during, and after treatment sessions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at 1, 4, and 6 weeks post dosing

6 weeks

3 visits (in-person)

Long-term Follow-up (optional)

Participants may opt into long-term follow-up with reassessments at 3, 6, and 12 months post dosing

12 months

3 visits (in-person)

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests the safety and impact of a single dose of psilocybin (25mg) on various psychiatric symptoms and functional impairments. It's an open-label trial where participants know they're receiving psilocybin, followed by assessments at 1 week, 4 weeks, and 6 weeks post-dose.

Participant Groups

Group I: Open-label Experimental Treatment 1 Intervention

Psilocybin will be administered in an opaque, size 2 gelatin capsule with approximately 180 ml of water to be orally ingested at Visit 5. The dose of psilocybin will be 25 mg.

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Usona Institute

Collaborator

Trials

18

Recruited

1,100+

Findings from Research

Psilocybin has shown promise in clinical trials for reducing symptoms of depression, indicating its potential as a novel treatment option.

Patients with treatment-resistant depression (TRD) may benefit the most from psilocybin therapy, although the risks associated with its use are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. Kozak, Z., Johnson, MW., Aaronson, ST.[2023]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

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]

A single, moderate dose of psilocybin significantly reduced depressive symptoms in 52 participants with major depressive disorder, showing a decrease of 13.0 points on the MADRS scale compared to baseline, which was significantly greater than the placebo group.

54% of participants in the psilocybin group met the criteria for remission of depression 14 days after treatment, and no serious adverse events were reported, indicating a favorable safety profile for this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. von Rotz, R., Schindowski, EM., Jungwirth, J., et al.[2023]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

In a study examining the effects of Psilocybe cubensis and Panaeolus cyanescens mushrooms on heart cells, the extracts did not worsen hypertrophy caused by endothelin-1 and provided protection against TNF-α-induced cell injury.

The findings suggest that these mushroom extracts can be safely used in controlled conditions for potential therapeutic benefits in heart disease, although caution is advised with higher concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. Nkadimeng, SM., Steinmann, CML., Eloff, JN.[2021]

Psilocybin, derived from Psilocybe cubensis mushrooms, is being investigated as a novel treatment for major depression, with a focus on its safety and efficacy compared to traditional antidepressants.

The proposed study will include both preclinical toxicity evaluations in mice and a clinical trial assessing the safety and pharmacokinetics of psilocybin in healthy adults, followed by an open trial in patients with major depressive disorder, aiming to provide comprehensive data on its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. Escamilla, R., González-Trujano, ME., González Mariscal, JM., et al.[2023]

Psilocybin, a prodrug for psilocin, shows strong agonist activity at the serotonin 5-HT2A receptor, which is responsible for its psychedelic effects, and has been shown to have nanomolar affinity for various serotonin receptor subtypes in both in vitro and in vivo studies.

In mouse experiments, psilocybin and related compounds induced head twitch responses, a sign of psychedelic activity, which were blocked by a 5-HT2A antagonist, confirming the involvement of this receptor in their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. Glatfelter, GC., Pottie, E., Partilla, JS., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

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

The pharmacology of psilocybin. [2016]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

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

Intravenous mushroom poisoning. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. [2021]

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

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. [2023]

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

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]