Psilocybin – Induced Neuroplasticity in the Treatment of Major Depressive Disorder

The primary goal of this pilot study is to investigate whether psilocybin alters neuroplasticity in people with major depressive disorder. The primary hypothesis is that psilocybin will result in neuroplastic changes that parallel improvement in symptoms of depression.

Status Completed
Results Published No
Start date 30 June 2018
End date 04 January 2023
Chance of happening 100%
Phase Phase I
Design Blinded
Type Interventional
Generation First
Participants 18
Sex All
Age 18- 65
Therapy No

Trial Details

In this placebo-controlled, blinded study, individuals with depression will participate in 2 experimental sessions approximately 4 weeks apart during which they will receive two of the following three interventions: 1) placebo, 2) low dose psilocybin (0.1 mg/kg), and 3) medium dose psilocybin (0.3 mg/kg).

NCT Number NCT03554174

Sponsors & Collaborators

Yale University
The Yale Psychedelic Science Group was established in 2016.

Heffter Research Institute
The Heffter Research Institute has been advancing psychedelics (psilocybin) as medicines since 1993.


Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms
This double-blind, placebo-controlled, within-subject study (n=19) involved individuals with major depressive disorder (MDD). It investigated the effects of a single dose of psilocybin on electroencephalographic (EEG) correlates of neuroplasticity and depression symptoms. The results showed that EEG theta power doubled in amplitude two weeks after psilocybin administration. This increase was correlated with improvements in depression symptoms, suggesting that psilocybin may produce sustained changes in brain neuroplasticity and have antidepressant effects. Note that the improvement in depression scores was not significant vs placebo.

Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial
This single-blind, placebo-controlled study (n=19) of psilocybin (21mg/70kg) in combination with therapy (ACT, 8x) finds an improvement in depression scores. However, the difference between the psilocybin and placebo groups was insignificant. Though the study tried to control for expectancy (placebo) effects, participants (80%) correctly guessed if they received psilocybin.

Measures Used

Hamilton Depression Rating Scale
The Hamilton Depression Rating Scale (HDRS) is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluating recovery. The scale consists of 17 items which each item being scoring on a 3 or 5 point scale. The higher the score, the more likely a person is depressed.

Quick Inventory of Depressive Symptomatology
The Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR16) is a self-report tool designed to screen for depression and measure changes in the severity of symptoms.

Data attribution

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