Double-blind, randomised, placebo-controlled crossover Phase I study (n=18) with two dosing sessions ~4 weeks apart comparing placebo, low-dose psilocybin (0.1 mg/kg) and medium-dose psilocybin (0.3 mg/kg) in people with major depressive disorder to assess neuroplasticity and symptom change.
This randomised, double-blind crossover study enrolls 18 participants with Major Depressive Disorder to receive two of three interventions across two sessions (~4 weeks apart): placebo, low-dose psilocybin (0.1 mg/kg) or medium-dose psilocybin (0.3 mg/kg). The primary purpose is treatment and to evaluate psilocybin-induced neuroplasticity alongside clinical response.
Outcomes include neuroimaging and biomarkers of plasticity and clinical measures of depression; standard safety monitoring and urine toxicology are used. Participants must have failed at least one adequate antidepressant trial and be engaged with a mental health clinician.
0.1 mg/kg psilocybin capsule in crossover session.
0.1 mg/kg oral capsule
0.3 mg/kg psilocybin capsule in crossover session.
0.3 mg/kg oral capsule
Microcrystalline cellulose capsule used as placebo control in crossover.
Microcrystalline cellulose capsule (placebo)
In a double‑blind, placebo‑controlled within‑subject study of 19 individuals with major depression, a single 0.3 mg/kg dose of psilocybin produced a twofold increase in auditory‑evoked theta (4–8 Hz) power at two weeks that correlated with reductions in GRID‑HAM‑D‑17 scores, whereas placebo produced no change. This sustained theta enhancement—interpreted as an EEG correlate of long‑term potentiation—may serve as a biomarker of psilocybin‑induced neuroplasticity underlying its antidepressant effects.