Psilocybin for Depression

(uAspire Trial)

Recruiting at 27 trial locations

Overseen By David Feifel, MD

Age: 18+

Sex: Male

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Usona Institute

Disqualifiers: Cardiovascular conditions, Neurological conditions, Hepatitis, HIV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

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

Compensation: Varies

Number of Visits: 1

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests psilocybin, the active compound in magic mushrooms, to determine its effectiveness in alleviating major depressive disorder (MDD). Participants will receive either a 25 mg or 5 mg dose of psilocybin or a placebo (a pill with no active ingredient) and will be monitored for changes in their depression over time. The trial aims to assess the effectiveness and safety of psilocybin in reducing depression symptoms. Individuals who have experienced moderate to severe depression for at least 60 days and do not have certain heart or neurological conditions might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that psilocybin, a substance found in certain mushrooms, is being studied for its effects on depression. In earlier studies, researchers used psilocybin in controlled environments to help people with various mental health issues. These studies found that most participants generally tolerated psilocybin well.

Some participants might experience mild side effects such as nausea, headaches, or temporary increases in anxiety. However, serious side effects have been rare. Since this study is in a later stage, psilocybin has already been tested in people and found relatively safe for further research.

Researchers create a special setting with trained staff to ensure safety and comfort during the experience. This helps manage any difficult moments that might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for depression, which often involve selective serotonin reuptake inhibitors (SSRIs) or psychotherapy, psilocybin is unique because it uses a psychedelic compound derived from certain mushrooms. Researchers are excited about psilocybin because it targets the brain's serotonin receptors in a novel way, potentially offering rapid and lasting relief from depressive symptoms after just one or two sessions. Additionally, the treatment is accompanied by a "Set and Setting" protocol, which includes supportive and immersive experiences aimed at enhancing the therapeutic effects. This approach could redefine how we understand and treat depression, offering hope for those who haven't found success with traditional therapies.

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

Research has shown that psilocybin may help reduce depression symptoms. In earlier studies, individuals with Major Depressive Disorder (MDD) who received one dose of psilocybin experienced a noticeable reduction in depression symptoms compared to those who received a placebo. In this trial, participants will be randomized to receive either a 25 mg dose of psilocybin, a 5 mg dose, or an inactive placebo. The positive effects of psilocybin can last for several weeks, offering longer relief than some traditional antidepressants. Psilocybin influences serotonin receptors in the brain, which play a crucial role in mood regulation. Early results suggest that a higher dose of 25 mg might be more effective than lower doses. Overall, the evidence supports psilocybin as a potentially effective treatment for depression. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults diagnosed with Major Depressive Disorder as per DSM-5-TR criteria can join this trial. Participants must be at least 18 years old and willing to take a single dose of Psilocybin or placebo.

Inclusion Criteria

If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study

I have been diagnosed with major depression and have been feeling depressed for at least 60 days.

I can swallow pills.

Exclusion Criteria

Are hepatitis or HIV positive

Meet DSM-5-TR criteria for active post-traumatic stress disorder within 6 months prior to Screening

I have severe liver or kidney problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or placebo under the 'Set and Setting' Protocol

6 weeks

1 visit (in-person) for dosing, multiple visits for preparation and integration

Follow-up

Participants are monitored for changes in depressive symptoms, functional disability, and safety measures

1 year

Regular in-clinic visits and bi-weekly telephone visits

Open-label Re-administration (optional)

Eligible participants may receive additional doses of Psilocybin 25 mg under the 'Set and Setting' Protocol

During the 1-year Follow-up Period

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview

The study tests the effectiveness of a single oral dose of Psilocybin (25 mg or 5 mg) compared to an inactive placebo in treating depression symptoms, with follow-up for one year to assess lasting effects.

How Is the Trial Designed?

Group I: Psilocybin 25 mg Experimental Treatment 1 Intervention

During the Double-blind Period, participants randomized to receive Psilocybin 25 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones.

Group II: Long-Term Follow-Up Experimental Treatment 2 Interventions

After the initial 6-week Double-blind Period, all participants will proceed to a 1-year Follow-up Period. Participants will be followed via in-clinic visits and telephone visits during which clinic staff will assess changes in MDD symptom severity and safety measures including concomitant medications, adverse events (AEs), and suicidal ideation and behavior. Participants will also engage in group psychosocial support sessions, including psychoeducation, throughout this period. Participants may also be eligible to receive open-label re-administration(s) of Psilocybin 25 mg under the "Set and Setting" (SaS) Protocol if re-administration eligibility criteria are met.

Group III: Psilocybin 5 mg Active Control 1 Intervention

During the Double-blind Period, participants randomized to receive Psilocybin 5 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones.

Group IV: Inactive Placebo Placebo Group 1 Intervention

During the Double-blind Period, participants randomized to receive inactive placebo will receive a single dose of Microcrystalline Cellulose (MCC) 25 mg administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones.

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?

Usona Institute

Lead Sponsor

Trials

18

Recruited

1,100+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Published Research Related to This Trial

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]

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]

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, 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]

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]

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-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 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]

Citations

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Psilocybin

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

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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 ...

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webbook.nist.gov

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

Psilocybine - the NIST WebBook

Psilocybine's formula is C12H17N2O4P, molecular weight is 284.2481, CAS number is 520-52-5, and also known as Psilocybin.

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ZFIN ChEBI: psilocybin

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

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cancer.gov/publications/dictionaries/cancer-drug/def/psilocybine

Definition of psilocybine - NCI Drug Dictionary

A tryptamine alkaloid, isolated from various genera of fungi including the genus Psilocybe, with hallucinogenic, anxiolytic, and psychoactive activities.

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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.