A phase IIa open-label dose-finding study with lead-in phase evaluating the safety, pharmacokinetics, and attenuating effects of trazodone on the consciousness-altering effects of psilocybin in individuals with Treatment-Resistant Depression

Condition studied

Treatment-Resistant Depression

Investigational medicinal product(s)

Eligibility

Primary endpoint

Safety and tolerability of trazodone administered prior to psilocybin, evaluated through: -Incidence, severity, and relationship of treatment-emergent adverse events from dosing through Day 30. -Occurrence of dose-limiting toxicities within 24 hours after psilocybin-trazodone co/administration. - Clinically significant changes in vital signs, ECG, and laboratory parameters. -Emergence or worsening of suicidal ideation or behavior assessed using the Columbia–Suicide Severity Rating Scale (C-SSRS)

Endpoint detail

Exploratory assessment of psilocybin-induced subjective effects and preliminary attenuation-related signals, assessed using validated psychometric questionnaires, including the 5D-ASC and EBI. These endpoints will be interpreted as descriptive and hypothesis-generating only., Pharmacokinetic characterization of psilocybin, psilocin, trazodone, and mCPP following co-administration., Identification of a candidate trazodone dose/formulation for further controlled evaluation, based on the integrated assessment of safety, tolerability, PK data, and exploratory subjective pharmacodynamic outcomes.