Sex Differences in Neural Response to Cannabidiol

This is a randomized, double-blind, within-subjects, cross-over design to assess neural changes following a single dose of cannabidiol (CBD) (600mg) versus placebo among healthy female volunteers.

Study Overview

• Status: Completed
• Conditions: CBD; Neural Responses
• Intervention / Treatment: Drug: Cannabidiol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Sarah D. Lichenstein, PhD; Phone Number: (646) 345-6934; Email: sarah.lichenstein@yale.edu
• Study Contact Backup: Name: Sarah W Yip, PhD; Phone Number: (203) 737-4358; Email: sarah.yip@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Female, aged 18-65
4. In good general health as evidenced by medical history and medically eligible to receive CBD, as determined by the licensed physician, Dr. Ayana Jordan
5. Body Mass Index between 18.5 and 30
6. For females of reproductive potential: agreement to use highly effective contraception during study participation and/or negative pregnancy test prior to fMRI scanning

Exclusion Criteria:

1. Recent use of cannabis (any past month use)
2. Lifetime history of cannabis use disorder
3. Lifetime history of chronic pain disorder
4. Current DSM-5 disorder, as determined via Structured Clinical Interview (SCID-5)
5. Presence of any contraindication to MRI scanning
6. Known allergic reactions to cannabidiol
7. Lifetime use of Epidiolex
8. Currently taking any medications that could interact with cannabidiol
9. Current smoker or tobacco use >1x/week
10. Not fluent in English
11. Less than 6th grade reading level

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cannabidiol; Participants will receive a single 600mg oral dose of Epidiolex (cannabidiol) 2 hours prior to fMRI scanning.	Drug: Cannabidiol; Participants will receive a single 600mg oral dose of Epidiolex (cannabidiol) 2 hours prior to fMRI scanning.
Placebo Comparator: Placebo; Participants will receive a single oral dose of placebo 2 hours prior to fMRI scanning.	Other: Placebo; Participants will receive a single oral dose of placebo 2 hours prior to fMRI scanning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amygdala activation during stress	Participants will complete 1 fMRI scan following CBD administration and another fMRI scan following placebo administration. During each scan, participants will complete the Emotion Regulation Task (ERT). The first primary outcome measure will be amygdala response during the negative emotionality contrast of the ERT during their CBD relative to their placebo scan.	fMRI will begin 2 hours post-drug administration and will last no more than 1 hour.
Insula activation during social exclusion	Participants will complete 1 fMRI scan following CBD administration and another fMRI scan following placebo administration. During each scan, participants will complete the Cyberball Task. The second primary outcome measure will be insula response during the exclusion versus inclusion contrast of the Cyberball Task during their CBD relative to their placebo scan.	fMRI will begin 2 hours post-drug administration and will last no more than 1 hour.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patterns of amygdala functional connectivity during stress	Participants will complete 1 fMRI scan following CBD administration and another fMRI scan following placebo administration. During each scan, participants will complete the Emotion Regulation Task (ERT). The first secondary outcome measure will be participants' pattern of seed-based functional connectivity with the amygdala during the negative emotionality contrast of the ERT during their CBD relative to their placebo scan.	fMRI will begin 2 hours post-drug administration and will last no more than 1 hour.
Patterns of insula functional connectivity during social exclusion	Participants will complete 1 fMRI scan following CBD administration and another fMRI scan following placebo administration. During each scan, participants will complete the Cyberball Task. The second secondary outcome measure will be participants' pattern of seed-based functional connectivity with the insula during the exclusion versus inclusion contrast of the Cyberball Task during their CBD relative to their placebo scan.	fMRI will begin 2 hours post-drug administration and will last no more than 1 hour.

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Sarah D. Lichenstein, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): April 27, 2023
• Study Completion (Actual): April 27, 2023

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 2, 2021

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anticonvulsants; Cannabidiol
• Other Study ID Numbers: 2000029579

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Because this is a pilot project, we do not plan to share to data. Pending the results of the pilot project, we hope to pursue funding for a larger study to examine sex differences in neural response to CBD more directly (including both male and female participants) and on a larger scale (larger sample than pilot project), and we will plan to make these data available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No