Understanding and Optimizing Psilocybin for Depression

An Investigation of Strategies to Understand and Optimize the Antidepressant Effects of Psilocybin (The OPTIMIZE Study)

Phase 2 Interventional Vail Health Behavioral Health · NCT06512194

This study is testing if a single dose of psilocybin, along with psychological support and additional treatments, can help adults with depression feel better and improve their social behavior.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment141 (estimated)
Ages18 Years to 70 Years
SexAll
SponsorVail Health Behavioral Health Academic / other
Locations1 site (Edwards, Colorado)
Trial IDNCT06512194 on ClinicalTrials.gov

What this trial studies

This investigation examines the effects of a single dose of psilocybin on symptoms of depression, combined with psychological support. It will assess the impact of post-dosing interventions, including transcutaneous auricular vagus nerve stimulation (taVNS), on psychological and behavioral outcomes. The study aims to evaluate real-world social behavior and identify early behavioral responses that may correlate with long-term treatment outcomes. A total of 141 adults with major depressive episodes will participate, receiving preparatory sessions and ongoing support throughout the process.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a current diagnosis of Major Depressive Disorder experiencing a depressive episode lasting at least 60 days.

Not a fit: Patients with a history of psychiatric disorders such as bipolar disorder or psychosis, or those with active suicidal ideation, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a novel treatment approach for individuals suffering from depression.

How similar studies have performed: Other studies have shown promising results with psilocybin and similar psychedelic approaches, indicating potential for success in this investigation.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

Current diagnosis of Major Depressive Disorder (MDD), with a depressive episode lasting ≥ 60 consecutive days at the time of screening, as confirmed by structured clinical interview

Medically healthy, as determined by the screening physician, with no significant medical conditions that would interfere with participation or affect the safety of the subject.

Exclusion Criteria:

History or presence of any psychiatric or medical condition that, in the opinion of the investigator, could pose a safety risk, interfere with participation, or confound study results (e.g., bipolar disorder, psychosis, seizure disorder, or cardiovascular disease).

Known family history of a psychotic disorder (e.g., schizophrenia or schizoaffective disorder) in a first-degree relative (biological parent, full sibling, or child).

Current active suicidal ideation with a specific plan within the prior 2 weeks, as assessed via clinical interview and validated instrument (e.g., C-SSRS).

Suicide attempt within the prior 6 months, regardless of intent or lethality.

Current diagnosis of a substance use disorder

Abnormal ECG at screening that may increase risk during participation (e.g., prolonged QTc, arrhythmias, or other clinically significant findings as determined by the study physician).

Unwilling or unable to discontinue prescription psychotropic medications (e.g., antidepressants, antipsychotics, anxiolytics, lithium, anticonvulsants, or mood stabilizers) for the duration of study participation, including any necessary washout period as determined by the investigator.

Any condition, finding, or behavior (including suspected deception or noncompliance) that, in the opinion of the investigator, renders the participant unsuitable for the study or likely to interfere with the integrity of the data or safety of the subject.

Where this trial is running

Edwards, Colorado

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Depressiondepressionpsilocybinpsychedelicstranscutaneous auricular vagus nerve stimulationdepressive symptomswell-beingadverse events
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.