# The neural correlates of the effects of psilocybin in OCD: randomized controlled study

> **NIH NIH K23** · YALE UNIVERSITY · 2024 · $187,921

## Abstract

PROJECT SUMMARY/ABSTRACT
This application for a K23 mentored patient-oriented research career development award will provide the
applicant, a clinical neuroscientist with a broad background in translational neuroscience, with advanced training,
an impactful mentored research experience, and protected research time. My long-term goal is to become an
independent physician-scientist, focused on identifying neurobiological correlates and predictors of the
therapeutic effects of novel treatments, especially those with acute effects. By applying such insights, I aim to
develop individualized treatment strategies for mood and anxiety disorders. In line with these goals, I propose a
training plan to gain expertise in translational clinical investigations and neuroimaging methods. This will be
achieved through an integrated career development plan, overseen by a mentoring team with expertise in drug
development, neuroimaging, and neurobiology.
This proposed study will be the first to examine the neural correlates of the effects of psilocybin in obsessive-
Numerous recent studies have reported acute, and sometimes persisting, clinical
benefit after the administration of a single dose of psilocybin in mood and anxiety disorders, addiction, and OCD.
The persistence of clinical effects long after acute intoxication has worn off implies lasting brain changes, but the
mechanisms underlying these lasting therapeutic effects remain poorly understood. We propose to use
connectivity analysis of resting-state functional magnetic resonance imaging (rs-fMRI) data to probe the neuronal
correlates of clinical change after a single dose of psilocybin in OCD, in the context of an independently funded
randomized, placebo-controlled pilot efficacy and tolerability trial that we have just begun at Yale. Consistent
with the experimental therapeutics framework, we here examine the hypothesized brain effects of psilocybin;
while we predict that these will be associated with symptom improvement, our analyses will be informative
whether or not psilocybin proves to have a beneficial clinical effect in this controlled trial. We focus on the default
mode network (DMN), a network known to be involved in the evaluation of internal states, disrupted in OCD, and
affected by psilocybin in other populations. We hypothesize that psilocybin will result in increased (i.e.
normalized) intra-DMN functional connectivity in OCD, and that this will correlate with any clinical change (Aim
1). Baseline DMN connectivity is anticipated to predict subsequent neural and clinical change (Aim 2). Finally,
we will examine connectivity within the corticostriatal circuitry (Aim 3); while this circuitry has not previously been
investigated in the context of psilocybin, it is robustly implicated in OCD.
This work will shed light on the neurobiological underpinnings of lasting clinical and behavioral effects effects
of psilocybin in neuropsychiatric disease, with potential implications for other rapid-acting p...

## Key facts

- **NIH application ID:** 10927367
- **Project number:** 5K23MH122777-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** BENJAMIN KELMENDI
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $187,921
- **Award type:** 5
- **Project period:** 2021-04-07 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10927367

## Citation

> US National Institutes of Health, RePORTER application 10927367, The neural correlates of the effects of psilocybin in OCD: randomized controlled study (5K23MH122777-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10927367. Licensed CC0.

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