Psilocybin for Depression

Overseen By Christina Luddy, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Antidepressants

Disqualifiers: Psychotic disorders, Unstable conditions, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a compound in magic mushrooms, can alter the brain to improve major depression symptoms. Researchers will compare different psilocybin doses to assess their effects on mood and mental health. Participants will be divided into groups, receiving either a placebo (a dummy treatment with no active ingredient) or varying psilocybin doses in different sessions. The trial seeks individuals with major depressive disorder who are currently experiencing a depressive episode and have not found relief from at least one antidepressant. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any conventional antidepressant medications to participate in this trial.

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," has been tested in people with encouraging safety results. Previous studies found that most people tolerate it well. Although serious side effects are rare, some individuals experienced mild to moderate effects, such as temporary changes in mood, perception, and thinking, which are often part of the psychedelic experience.

It is important to note that this research remains in the early stages. While initial results are positive, further studies are necessary to fully understand its safety. Currently, long-term safety data is lacking, so the complete picture is not yet available. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Psilocybin is unique because it represents a novel approach to treating depression, a condition often managed with antidepressants like SSRIs and therapy. Unlike traditional treatments that can take weeks to show benefits, psilocybin has the potential to produce rapid and sustained antidepressant effects after just a single or a few doses. This compound works by targeting serotonin receptors in the brain, which can lead to altered perceptions and potentially breakthrough mental health improvements. Researchers are excited about psilocybin because it could offer a faster, more effective way to alleviate depression symptoms compared to current standards.

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

Research has shown that psilocybin may help treat depression. In earlier studies, participants reported feeling significantly less depressed after taking psilocybin. This trial will explore different dosing strategies, with some participants receiving low or medium doses of psilocybin combined with placebo sessions. This mood improvement might occur because psilocybin helps the brain form new connections, potentially enhancing its function and reducing depression symptoms. Although more research is needed to fully understand this process, early results are promising. ^{1 2 3 4 6}

Who Is on the Research Team?

Deepak D'Souza, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with Major Depressive Disorder who haven't improved after trying at least one antidepressant. Participants must be currently seeing a mental health professional and not have any psychotic disorders, drug abuse issues, or unstable medical conditions. Pregnant or breastfeeding individuals are excluded, as well as those without proper birth control.

Inclusion Criteria

I have been diagnosed with Major Depressive Disorder and am currently experiencing a depressive episode.

My current depression treatment hasn't worked.

I am currently seeing a mental health professional.

Exclusion Criteria

Pregnant, breastfeeding, lack of adequate birth control

A close family member has a severe mental health condition.

Axis I psychotic disorder (e.g. schizophrenia, bipolar I, depression with psychosis)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants undergo two experimental sessions approximately 4 weeks apart, receiving either placebo, low dose psilocybin, or medium dose psilocybin

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in mood symptoms and neuroplasticity using EEG and other assessments

12 weeks

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Psilocybin

Trial Overview The study tests if psilocybin can cause changes in the brain that improve depression symptoms. It compares the effects of two different doses of psilocybin to a placebo (a substance with no active drug).

How Is the Trial Designed?

Group I: Placebo/Medium Dose Psilocybin Experimental Treatment 2 Interventions

Subjects in this arm receive placebo in the first session and medium dose psilocybin in the second session.

Group II: Placebo/Low Dose Psilocybin Experimental Treatment 2 Interventions

Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.

Group III: Medium Dose Psilocybin/Placebo Experimental Treatment 2 Interventions

Subjects in this arm receive medium dose psilocybin in the first session and placebo in the second session.

Group IV: Low Dose Psilocybin/Placebo Experimental Treatment 2 Interventions

Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Heffter Research Institute

Collaborator

Trials

15

Recruited

520+

Published Research Related to This Trial

The PsiDeR trial is testing the feasibility of psilocybin-assisted therapy for major depressive disorder (MDD) in 60 participants who have not responded to at least two standard treatments, focusing on recruitment and dropout rates as primary outcomes.

Participants will receive either 25 mg of psilocybin or a placebo, along with psychological therapy, with the primary measure of depression assessed at 3 weeks, indicating a structured approach to evaluate both safety and efficacy of this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial. Rucker, J., Jafari, H., Mantingh, T., et al.[2022]

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]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

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]

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]

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 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 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]

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-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]

Citations

1. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...

2. zfin.org zfin.org/CHEBI:8614

ZFIN ChEBI: psilocybin A tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic alkaloid isolated ...

3. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Psilocybin

Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH Psilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic ...

4. en.wikipedia.org en.wikipedia.org/wiki/Psilocin

Psilocin Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.

5. webbook.nist.gov webbook.nist.gov/cgi/cbook.cgi?ID=520-52-5

Psilocybine - the NIST WebBook Formula · C12H17N2O4P ; Molecular weight · 284.2481 ; Permanent link for this species. Use this link for bookmarking this species for future reference.

6. consensus.app consensus.app/home/blog/what-is-psilocybin-other-names-psilocibin-psilocybine-psilocin-phosphate-ester/

Psilocibin, Psilocybine, Psilocin Phosphate Ester Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms, commonly referred to as “magic mushrooms.”