Investigating the Effects of Cannabidiol on Social Anxiety Disorder (CAN-SAD)

The purpose of this study is to test whether a single-dose of Epidiolex (cannabidiol) is associated with reduced psychological, physiological, and neuroimaging measures of anxiety in people diagnosed with social anxiety disorder (SAD).

Study Overview

• Status: Recruiting
• Conditions: Phobia, Social
• Intervention / Treatment: Drug: Cannabidiol; Drug: Placebo

Detailed Description

Using a randomized, double-blind, placebo-controlled, parallel-group study design, this scientific investigation will examine the effect of 3 milliliters (mL) of Epidiolex (100mg cannabidiol/mL) on behavioral, physiological, and neuroimaging measures of anxiety in subjects diagnosed with SAD. The study will enroll 50 subjects with SAD who will be randomized in a double-blind manner to receive either Epidiolex or placebo before experiencing the Trier Social Stress Test (TSST), the gold-standard for ethically inducing stress in a controlled laboratory setting. Following the TSST, neuroimaging measures of emotional processing and self-referential processing will be acquired using functional magnetic resonance imaging (fMRI).

This study will be conducted primarily at Massachusetts Institute of Technology with research and clinical support from Massachusetts General Hospital.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Omar Rutledge, MS; Phone Number: 617-324-2898; Email: orutledge@mit.edu

Study Locations

• United States
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02139
      • Recruiting
      • Massachusetts Institute of Technology
      • Contact: Omar Rutledge, MS; Phone Number: 617-324-2898; Email: orutledge@mit.edu
      • Principal Investigator: John Gabrieli, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability and willingness to provide written informed consent.
• Sufficiently fluent in English to participate in the trial.
• Between 18-55 years of age (inclusive).
• Right-hand dominant.
• Current medications are stable for past 30 days (no changes to dose or frequency).
• Negative result on pregnancy test (if female).
• Negative result on urine drug screening.
• Liebowitz Social Anxiety Scale (LSAS ≥ 60).

Exclusion Criteria:

• History of bipolar disorder, schizophrenia, psychosis, delusional disorders.
• History of eating disorder within past 6 months.
• History of any traumatic brain injury.
• Currently diagnosed with diabetes mellitus.
• Presence of severe medical illness that would prevent completion of study procedures.
• Presence of significant neurological illness or cognitive dysfunction (e.g.; seizures, dementia).
• History of substance use disorder within past 6 months (other than nicotine and caffeine).
• Use of any cannabis-containing products in past 30 days (CBD or THC).
• Use of benzodiazepines in past 2 weeks.
• Use of alpha- or beta-blockers in past week.
• History of claustrophobia.
• Contraindications for MRI (e.g.; shrapnel).
• Presence of any other medical condition that, in the investigator's opinion, may interfere with the study procedures.
• Use of concomitant medication that has a strong interaction with CBD.
• History of liver disease.
• History of hypersensitivity to cannabinoids.
• History of hypersensitivity to sesame seed oil.
• Currently breastfeeding (if female).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cannabidiol; 300mg Cannabidiol (3mL Epidiolex), oral, single-dose	Drug: Cannabidiol; Participants randomized to the cannabidiol arm will receive 3mL of Epidiolex (100mg cannabidiol/mL) in a single-dose.; Other Names: Epidiolex
Placebo Comparator: Placebo; Placebo (3mL sesame seed oil), oral, single-dose	Drug: Placebo; Participants randomized to the placebo arm will receive 3mL of placebo (sesame seed oil) in a single dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Acute Subjective Anxiety	Subjective anxiety will be assessed with a modified Visual Analog Mood Scale (VAMS) which utilizes a vertical 100 millimeter (mm) bipolar visual scale between two opposing moods consisting of the following word pairs: calm-excited, relaxed-tense, and tranquil-troubled. Total subjective anxiety for each timepoint will be the average distance from the top for the three-question battery. VAMS will be assessed 15 minutes before drug administration (-180 minutes before start of TSST), 150 minutes after drug administration (-15 minutes before start of TSST), after the Anticipation Phase (-5 minutes before start of TSST), after the Stress Procedures (+10 minutes after start of TSST), after 5 minutes in the Recovery Phase (+20 minutes after start of TSST), and 15 minutes after start of the Recovery Phase (+30 minutes after start of TSST).	-180 minutes, -15 minutes, -5 minutes, +10 minutes, +20 minutes, +30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in Salivary Alpha Amylase	Physiological stress will be assessed indirectly with salivary alpha amylase (sAA) activity which is regulated by the sympathetic branch of the autonomic nervous system. Samples will be collected using the SalivaBio Oral Swab (SOS) from Salimetrics. Participants will place the SOS in their mouth for 1-2 minutes at each timepoint to collect saliva. sAA will be assessed 15 minutes before drug administration (-180 minutes before start of TSST), 150 minutes after drug administration (-15 minutes before start of TSST), after the Anticipation Phase (-5 minutes before start of TSST), after the Stress Procedures (+10 minutes after start of TSST), after 5 minutes in the Recovery Phase (+20 minutes after start of TSST), and 15 minutes after start of the Recovery Phase (+30 minutes after start of TSST).	-180 minutes, -15 minutes, -5 minutes, +10 minutes, +20 minutes, +30 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in fMRI BOLD Response	Patterns of brain activation measured as blood-oxygenation-level dependent (BOLD) signals will be assessed using 3.0 Tesla (3T) functional magnetic resonance imaging (fMRI). Several exploratory imaging paradigms, including the emotional face-matching task (EFMT) and the self-referential comment task (SRCT), will be used to examine differences between participants who receive Epidiolex (cannabidiol) and those that receive placebo. Neuroimaging will begin approximately 210 minutes after drug administration (+45 minutes after the TSST).	+45 minutes

Collaborators and Investigators

• Sponsor: Massachusetts Institute of Technology
• Collaborators: Massachusetts General Hospital
• Investigators: Principal Investigator: John Gabrieli, PhD, Massachusetts Institute of Technology

Publications and helpful links

Helpful Links

• CAN-SAD Recruitment Site

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 13, 2022

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: fMRI; Social Anxiety Disorder; Cannabidiol
• Additional Relevant MeSH Terms: Mental Disorders; Phobic Disorders; Anxiety Disorders; Phobia, Social; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Cannabidiol
• Other Study ID Numbers: 2206000688

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data, code, and materials used in the analyses will be made available upon request by John Gabrieli and Massachusetts Institute of Technology after scientific review and a completed data use agreement/material transfer agreement beginning one year after publication of the results. Any requests should be submitted to John Gabrieli at gabrieli@mit.edu.
• IPD Sharing Time Frame: Data will become available beginning one year after publication of the results.
• IPD Sharing Access Criteria: Data will be provided pending a scientific review and a completed data use agreement/material transfer agreement. Requests should be submitted to John Gabrieli at gabrieli@mit.edu.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No