What side effects are associated with this type of intervention?

Common treatments for depression, such as SSRIs (e.g., fluoxetine, sertraline) and TCAs (e.g., amitriptyline), have side effects including nausea, insomnia, sexual dysfunction, increased anxiety, dry mouth, constipation, urinary retention, and sedation. Psilocybin, an experimental treatment being studied for its potential to induce neuroplasticity, can cause transient anxiety, confusion, nausea, and hallucinations. Both traditional and experimental treatments require careful monitoring for adverse effects.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of depression, primarily focusing on selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, sertraline, and escitalopram, which increase serotonin levels in the brain. Additionally, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine have been approved. More recently, the FDA approved esketamine, a nasal spray derived from ketamine, which works through a different mechanism involving NMDA receptors and has shown rapid antidepressant effects. While psilocybin is not yet FDA-approved, it is being studied for its potential to induce neuroplasticity and offer a novel approach to treating depression, particularly in treatment-resistant cases.

What other types of research exist?

Promising novel alternatives to psilocybin for depression treatment in 2024 include: 1) Ayahuasca, which has shown potential antidepressant effects linked to changes in serum BDNF. 2) Ketamine, known for its rapid-acting antidepressant properties. 3) Deep Brain Stimulation (DBS), which has been explored for treatment-resistant depression. 4) Vagus Nerve Stimulation (VNS), which has shown positive outcomes in treatment-resistant depression. 5) Cannabidiol (CBD), which has been studied for its potential mood-stabilizing effects.

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Psilocybin for Depression

Phase 1

Waitlist Available

Led By Deepak D'Souza, MD

Research Sponsored by Yale University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosed with Major Depressive Disorder (MDD), single or recurrent episode, and currently experiencing a Major Depressive Episode (MDE)

Failed to achieve a satisfactory clinical response to at least one adequate antidepressant trial during the current depressive episode

Must not have

Axis I psychotic disorder in first degree relative

Currently taking a conventional antidepressant medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up four weeks before the initiation of testing, the day before and after each experimental session, and one and two weeks after each experimental session.

Summary

This trial tests if psilocybin, a compound from mushrooms, can help people with major depression by making their brains more adaptable and improving their symptoms. Psilocybin has shown promise as a treatment for depression in various studies, indicating its potential to improve depressive symptoms.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

Psilocybin may cause temporary changes in perception, mood swings, dizziness, nausea, and headaches. Some people might experience intense emotional experiences or anxiety during its use.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My current depression treatment hasn't worked.

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I am currently seeing a mental health professional.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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A close family member has a severe mental health condition.

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I am currently on antidepressant medication.

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I do not have any unstable health or brain conditions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ four weeks before the initiation of testing, the day before and after each experimental session, one and two weeks after each experimental session, then monthly for three months after the last experimental session.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~four weeks before the initiation of testing, the day before and after each experimental session, one and two weeks after each experimental session, then monthly for three months after the last experimental session.

This trial's timeline: 3 weeks for screening, Varies for treatment, and four weeks before the initiation of testing, the day before and after each experimental session, one and two weeks after each experimental session, then monthly for three months after the last experimental session. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Changes in electrical brain activity associated with neuroplasticity measured by Electroencephalography (EEG)

Secondary study objectives

Change in mood symptoms using the GRID-Hamilton Depression Rating Scale (GRID-HAM-D)

Change in mood symptoms using the Quick Inventory of Depressive Symptoms (QIDS-SR16)

Changes in verbal memory [ Time Frame: One day and two weeks after each experimental session ]

Trial Design

4Treatment groups

Experimental Treatment

Group I: Placebo/Medium Dose PsilocybinExperimental Treatment2 Interventions

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

Group II: Placebo/Low Dose PsilocybinExperimental Treatment2 Interventions

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

Group III: Medium Dose Psilocybin/PlaceboExperimental Treatment2 Interventions

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

Group IV: Low Dose Psilocybin/PlaceboExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Low Dose Psilocybin

2017

Completed Phase 1

~20

Placebo

1995

Completed Phase 3

~2670

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for depression, such as SSRIs (Selective Serotonin Reuptake Inhibitors) and newer therapies like psilocybin, primarily work by altering brain chemistry and promoting neuroplasticity. SSRIs increase serotonin levels in the brain, which can improve mood and emotional stability. Psilocybin, a psychedelic compound, is believed to induce neuroplasticity, which is the brain's ability to reorganize itself by forming new neural connections. This can lead to significant improvements in depressive symptoms by enhancing cognitive flexibility and emotional processing. Understanding these mechanisms is crucial for depression patients as it highlights the potential for these treatments to not only alleviate symptoms but also promote long-term brain health and resilience.

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals - a proof of concept study.Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders?