What side effects are associated with this type of intervention?

Common treatments for depression, such as SSRIs (e.g., fluoxetine, sertraline) and SNRIs (e.g., duloxetine), often have side effects including nausea, headache, sexual dysfunction, weight gain, and insomnia. Tricyclic antidepressants (TCAs) may cause sedation, dry mouth, and dizziness. Newer treatments like psilocybin analogs, such as CYB003, are being studied for their safety and tolerability, but potential side effects could include transient anxiety, nausea, and perceptual changes. It is important to discuss these with a healthcare provider to tailor treatment to individual needs and tolerances.

What prior FDA approvals exist?

The FDA has approved several classes of drugs for the treatment of major depressive disorder (MDD), including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine, and atypical antidepressants like bupropion. More recently, the FDA has approved esketamine, a nasal spray derived from ketamine, for treatment-resistant depression. While traditional antidepressants primarily target monoamine neurotransmitters, newer treatments like esketamine and investigational drugs such as psilocybin analogs (e.g., CYB003) are being explored for their rapid-acting and potentially transformative effects on depressive symptoms.

What other types of research exist?

Promising novel alternatives to CYB003 for treating major depressive disorder in 2024 include: 1) Psilocybin, which has shown efficacy in treatment-resistant depression and psychiatric distress in cancer patients. 2) Ketamine, known for its rapid-acting antidepressant effects and supported by various clinical trials. 3) MDMA-assisted psychotherapy, particularly for PTSD, which may have implications for MDD. 4) Direct acid sphingomyelinase (ASM) inhibitors, which have demonstrated antidepressant activity in preclinical models. 5) WY14643, which has shown antidepressant-like effects via the BDNF signaling pathway in animal studies.

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Psychedelic

CYB003 for Major Depressive Disorder

Phase 1 & 2

Waitlist Available

Research Sponsored by Cybin IRL Limited

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day -1, day 2, day 10, day 17, day 21, day 23, day 31, day 38, day 42, and day 56

Summary

This trial is testing a new medication called CYB003 to see if it is safe and well-tolerated when taken by mouth. The study includes both healthy people and those with major depressive disorder. The main goal is to ensure the medication can be safely used by these groups.

Who is the study for?

This trial is for adults aged 21-55 with moderate to severe Major Depressive Disorder (MDD), who are generally healthy but have had an inadequate response to antidepressants. Participants must weigh at least 60 kg, not smoke, and have a BMI of 18-30 kg/m2. They cannot have treatment-resistant MDD or other major psychiatric conditions, be on certain medications, or pose any suicide risk.

What is being tested?

The study tests the safety and tolerability of CYB003, a psilocybin analog given in ascending oral doses to healthy participants with and without MDD. It includes psychological support and psychotherapy sessions. Some participants will receive a placebo instead of CYB003 for comparison.

What are the potential side effects?

While specific side effects aren't listed here, typical ones from similar substances include nausea, headache, dizziness, altered sensory experiences and mood changes. The study aims to identify any potential side effects from CYB003.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ screening

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~screening

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

Treatment Details

Study Objectives

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

Primary study objectives

Adverse Events (All Arms)

Columbia Suicide Severity Rating Scale (CSSRS) Lifetime version (All Arms)

Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arm E)

+20 more

Secondary study objectives

5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arm E)

5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms A & B)

5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms C & D)

+18 more

Trial Design

5Treatment groups

Experimental Treatment

Placebo Group

Group I: E: Healthy Volunteers - CYB003 in 3 of 3 Medicine SessionsExperimental Treatment2 Interventions

Arm E healthy volunteers will receive CYB003 in 3 of 3 medicine sessions, approximately one week apart from each other, to assess bioavailability and food effect. The CYB003 dose received will depend on the safety review committee selection/time of enrollment. All healthy volunteers will receive psychological support throughout the study.

Group II: C: Healthy Volunteers - CYB003 in 2 of 2 Medicine SessionsExperimental Treatment2 Interventions

Arm C healthy volunteers will receive CYB003 in 2 of 2 medicine sessions, approximately one to two weeks apart. The CYB003 dose received will depend on the cohort/time of enrollment. All healthy volunteers will receive psychological support throughout the study.

Group III: A: MDD Participants - CYB003 in 2 of 2 Medicine SessionsExperimental Treatment2 Interventions

Arm A MDD participants will receive CYB003 in 2 of 2 medicine sessions, approximately three weeks apart. The CYB003 dose received will depend on the cohort/time of enrollment. All MDD participants will receive supportive EMBARK psychotherapy throughout the study.

Group IV: B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2Placebo Group3 Interventions

Arm B MDD participants will receive placebo in Medicine Session 1, and approximately three weeks later will receive CYB003 in Medicine Session 2. The CYB003 dose received will depend on the cohort/time of enrollment. All MDD participants will receive supportive EMBARK psychotherapy throughout the study.

Group V: D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2Placebo Group3 Interventions

Arm D healthy volunteers will receive placebo in Medicine Session 1, and approximately one to two weeks later will receive CYB003 in Medicine Session 2. The CYB003 dose received will depend on the cohort/time of enrollment. All healthy volunteers will receive psychological support throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CYB003

2022

Completed Phase 2

~60

Psychotherapy

2014

Completed Phase 3

~3440

Psychological Support

2022

Completed Phase 2

~60

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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 include SSRIs and SNRIs, which work by increasing the levels of serotonin and norepinephrine in the brain, respectively, to improve mood and emotional stability. Novel treatments like ketamine and psilocybin analogs (such as CYB003) act on the glutamatergic system, providing rapid antidepressant effects by modulating synaptic plasticity and connectivity. These mechanisms are crucial for depression patients as they offer different pathways to alleviate symptoms, especially for those who do not respond to traditional therapies. Understanding these mechanisms helps in tailoring personalized treatment plans and exploring new therapeutic options.

Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond.Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders?microRNAs as novel antidepressant targets: converging effects of ketamine and electroconvulsive shock therapy in the rat hippocampus.