# Randomized placebo controlled trial to determine the biological signature of cannabidiol as a treatment for social anxiety disorder

> **NIH NIH R61** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $591,682

## Abstract

PROJECT SUMMARY/ABSTRACT
Social anxiety disorder (SAD) SAD is a common, early onset disorder that untreated, results in high chronicity,
comorbidity, health care utilization, and functional and quality of life impairment. Novel treatments for SAD are
needed, as many patients do not access, tolerate or respond to available treatments. Cannabidiol (CBD) is a
natural compound from the cannabis plant that lacks the mind-altering effects of THC. With a recent surge in
use of unregulated forms of CBD sold online or over the counter, patients are attempting to self-medicate without
regulated formulations or evidenced based dose guidelines of CBD for anxiety disorders including SAD, creating
an urgent need for rigorous biologically informed study. Together there exist strong preclinical and well-replicated
human laboratory evidence for CBD’s acute anxiolytic effects, making it one of the most promising novel drug
candidates for the treatment of anxiety, and social anxiety in particular. This proposal aims to build on promising
preliminary scientific support for potential engagement with SAD-relevant neural and behavioral targets and
clinical effects of CBD to help fill this gap. The goal of these studies is to establish a biological signature of CBD’s
putative therapeutic effects in SAD and its link to core SAD symptoms, and to provide clinical effect sizes, safety,
and feasibility data to guide a future definitive RCT of CBD for SAD. Our overarching hypothesis is that CBD will
improve well-established abnormalities present in fear neurocircuitry and performance stress responding in
adults with SAD, and that this SAD target engagement will be associated with symptom improvement. First in
the R61, we will study two dose levels of a Phase 3 trial suitable hemp-derived (legal) oral CBD formulation with
enhanced bioavailability versus placebo (PBO) in a 3 week double-blind RCT. Participants will undergo a
modified Trier Social Stress Test (TSST) at week 2, and a standardized 2-day fear learning and extinction
protocol at week 3, with fMRI brain activation accompanying fear extinction recall and fearful faces tasks on the
second day. These methods will enable measurement of CBD vs PBO target engagement with three evidence-
based targets: 1) Ventromedial prefrontal cortex (vmPFC) activation during fear extinction recall, 2) Amygdala
activation in response to fearful faces, and 3) Visual analogue mood scale (VAMS) anxiety rating in response to
the TSST speech. The GO criterion for progression from R61 to R33 will be met if target engagement is observed
for at least one target, ordered as above, for at least one of the two CBD doses in the absence of clinically
significant adverse effects. Next, the R33 will replicate CBD vs PBO R61 target(s) engagement using identical
methods and timing of assessment, except with one (optimal) CBD dose vs. PBO continued over 8 weeks to
enable association of target engagement with SAD symptom change. A pharmacokinetic study of p...

## Key facts

- **NIH application ID:** 10499785
- **Project number:** 1R61AT012026-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Esther Marian Blessing
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $591,682
- **Award type:** 1
- **Project period:** 2022-09-19 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499785

## Citation

> US National Institutes of Health, RePORTER application 10499785, Randomized placebo controlled trial to determine the biological signature of cannabidiol as a treatment for social anxiety disorder (1R61AT012026-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10499785. Licensed CC0.

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