What side effects are associated with this type of intervention?

Common treatments for depression, such as selective serotonin reuptake inhibitors (SSRIs) and other serotonergic medications, often have side effects that include jitteriness, restlessness, anxiety, agitation, headache, sexual dysfunction, gastrointestinal symptoms (diarrhea and nausea), and insomnia. These side effects are generally dose-related and may subside after the initial days of treatment. Psilocybin, which also interacts with serotonin receptors, particularly 5-HT2A, has shown promise in improving mood and neuroplasticity, but its side effects in clinical settings are still being studied and may include transient anxiety and perceptual changes.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of depression that interact with serotonin receptors. Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and escitalopram are commonly used and work by increasing serotonin levels in the brain. Another class, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine, also targets serotonin but includes norepinephrine. While psilocybin, which interacts with the 5-HT2A receptor, is still under investigation, it shows promise in clinical trials for its potential to improve mood and neuroplasticity. Other serotonergic treatments, such as monoamine oxidase inhibitors (MAOIs) like phenelzine, have also been used but come with dietary restrictions and risk of serotonin syndrome.

What other types of research exist?

Promising novel alternatives to psilocybin for depression treatment include MDMA, which has shown potential in small trials for anxiety and mood disorders, and ergotamine, a mixed 5-HT1A/2A agonist. Additionally, mirtazapine, which has sedative properties and potential mood-improving effects, and buspirone, a 5-HT1A agonist, are also considered potential alternatives.

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Psychedelic

Psilocybin Microdosing for Depression

Phase 2

Recruiting

Research Sponsored by Rotem Petranker

Eligibility Criteria Checklist

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

Must have

Have a preexisting diagnosis of PDD with dysthymic subtype or receive a diagnosis of PDD with dysthymic subtype during screening.

Participants must be 18 to 65 years old

Must not have

The subject has a history of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation

The subject must refrain from starting any new medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up every week until week 14.

Summary

This trial tests if very small doses of psilocybin can safely and effectively improve mood in people with major depression who don't respond to or don't want standard treatments. Psilocybin may help by affecting brain chemicals related to mood. Psilocybin has shown promise as a treatment for major depressive disorder and was designated as a breakthrough therapy by the FDA in 2019.

Who is the study for?

Adults aged 18-65 with Major Depressive Disorder can join this trial. They must speak and read English well, have a high school education, not use psychoactive drugs or alcohol before sessions, and women must test negative for pregnancy and use birth control. Excluded are those with certain medical conditions like uncontrolled blood pressure, seizures, cancer history; those on specific medications; smokers; substance abuse disorders within the last 5 years; unstable health conditions.

What is being tested?

The trial is testing if small doses of psilocybin (2mg) can safely improve mood in people with depression without causing hallucinations. Participants will receive either psilocybin or a placebo first to compare effects.

What are the potential side effects?

Possible side effects may include mild headaches, nausea, dizziness or changes in mood or perception shortly after taking the drug. Since it's microdosing, typical psychedelic experiences like visual changes are unlikely.

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 persistent depressive disorder, dysthymic subtype.

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I am between 18 and 65 years old.

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I am between 18 and 65 years old.

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I have been diagnosed with major depression, including long-term depression.

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I agree not to take any over-the-counter drugs or supplements without approval.

Exclusion Criteria

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

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I have had a stroke, mini-stroke, brain aneurysm, or a blood vessel malformation.

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I will not start any new medications during the trial.

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I have diabetes that requires insulin and I haven't had low blood sugar with oral medications.

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I am currently taking daily medication for mental health or pain.

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I do not have an ongoing major depressive episode.

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I have epilepsy and a history of seizures.

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I am currently taking medication such as ergot alkaloids or simvastatin.

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I do not have severe kidney, liver disease, or serious brain conditions.

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I am pregnant, nursing, or not using effective birth control.

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I am not currently using any strong medication that affects how drugs are processed in my body.

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I will not start any new health practices like diet changes or meditation.

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I have heart or blood vessel conditions but no recent severe symptoms.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ every week until week 14.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~every week until week 14.

This trial's timeline: 3 weeks for screening, Varies for treatment, and every week until week 14. for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Change in Patient Health Questionnaire Somatic-Anxiety-Depression

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Open LabelExperimental Treatment2 Interventions

In this condition participants will receive psilocybin once weekly for 4 weeks, and will be told that they are receiving psilocybin.

Group II: Blinded PsilocybinExperimental Treatment1 Intervention

In this condition participants will receive psilocybin once weekly for 4 weeks, but they will not know whether they receive placebo or psilocybin.

Group III: Blinded PlaceboPlacebo Group1 Intervention

In this condition participants will receive an inert placebo once weekly for 4 weeks, but they will not know whether they receive placebo or psilocybin.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo first

2008

Completed Phase 2

~20

0 / 17Eligibility 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 often target the serotonin system to improve mood and neuroplasticity. Psilocybin, for example, interacts with serotonin receptors, particularly 5-HT2A, which may enhance mood and promote neuroplasticity. Similarly, Selective Serotonin Reuptake Inhibitors (SSRIs) increase serotonin levels in the brain by inhibiting its reuptake, thereby improving mood. Tricyclic Antidepressants (TCAs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) also increase serotonin and norepinephrine levels, which can alleviate depressive symptoms. Understanding these mechanisms is crucial for depression patients as it helps in selecting the most effective treatment tailored to their specific neurochemical needs.

Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial.