Investigating the Effects of Cannabidiol on Social Anxiety Disorder

Study Overview
=================
Brief Summary
-----------------
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).

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.

Official Title
-----------------
Investigating the Effects of Cannabidiol on Social Anxiety Disorder

Conditions
-----------------
Phobia, Social

Intervention / Treatment
-----------------
* Drug: Cannabidiol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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. Current diagnosis of social anxiety disorder (QuickSCID-5). 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 beta-blockers or benzodiazepines in past 2 weeks. 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 CYP3A4 or CYP2C19 (as assessed through Lexicomp). History of liver disease. History of hypersensitivity to cannabinoids. History of hypersensitivity to sesame seed oil. Currently breastfeeding (if female).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

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 bottom 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Social Anxiety Disorder, Cannabidiol, fMRI