NCT05823753

Cannabidiol to Reduce Anxiety Reactivity

Endocannabinoid System Engagement to Reduce Anxiety Reactivity with Cannabidiol in Social Anxiety Disorder (R61 Project)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 63 (actual)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This study seeks to understand how cannabidiol (CBD) - a non-intoxicating chemical compound obtained from the Cannabis sativa plant - affects biological and stress-related responses that are believed to underlie anxiety disorders. This study will evaluate the effects of different doses of CBD on blood plasma levels of anandamide (a molecule in the brain that has been shown to help regulate stress responses; primary biological signature) and anxiety reactivity to a standardized stress task (secondary target) in an acute (4-day) dosing study (i.e., when steady state CBD levels have been reached). Approximately 60 subjects with social anxiety disorder (SAD), ages 18-70, will participate in this study. They will be assigned by chance to receive one of two doses of CBD (150 mg BID or 450 mg BID administered in two divided doses daily) or placebo (which resembles the study drug but has no active ingredients) BID for 3 days and on the morning of day 4. Knowledge gained from this study will help determine the therapeutic potential of CBD for anxiety.

Detailed description

Background and aims: The proposed two-phase, milestone driven project seeks to understand how cannabidiol (CBD) effects biological and stress-related responses that are believed to underlie anxiety disorders. This knowledge will help advance the therapeutic potential of CBD for anxiety. The R61 phase project will evaluate the dose-dependent effects of CBD on blood plasma levels of anandamide (a molecule in the brain that has been shown to help regulate stress responses; primary biological signature) and anxiety reactivity to a standardized stress task (secondary target) in an acute (4-day) dosing study (i.e., when steady state CBD levels have been reached). Aim 1 will test the hypothesis that CBD increases anandamide levels and decreases anxiety reactivity compared to placebo. Aim 2 will determine which dose (150 mg BID or 450 mg BID) of CBD produces a greater effect on anandamide and anxiety reactivity. To achieve these aims, 60 participants meeting diagnostic criteria for social anxiety disorder (SAD) will be randomized 1:1:1 to one of two doses of CBD (300 mg/day or 900 mg/day) or placebo. They will complete standardized paradigms assessing anxiety reactivity and blood draws for determination of CBD and anandamide levels at baseline and day 4. Research design and procedures: This phase II clinical trial will randomize 60 subjects using a double-blind, parallel group design, 1:1:1 to CBD (300 mg/day or 900 mg/day) or placebo. Randomization will be stratified by sex assigned at birth. Study personnel and subjects will be blinded throughout. Only the study biostatistician and pharmacist will be unblinded. Session 1 (intake session) will involve explanation of study procedures, informed written consent, a clinical evaluation, a series of questionnaires, medical exam and history including current treatments, and urine and blood test. This session will determine eligibility to take part in the study. Session 2 (baseline assessment session) will include vital signs, urine test, blood draw (to assess plasma CBD and endocannabinoid metabolites), state mood assessments, computerized tasks assessing responses to emotional faces, and reactivity to a standardized stress task. At the end of this session, subjects will receive their CBD/placebo dispensation kit and instructions for taking CBD/placebo from the study physician. The CBD product to be used in this study is Epidiolex® (Jazz Pharmaceuticals/Greenwich), a plant-derived, highly purified CBD oral solution that is FDA approved for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older. Participants will receive CBD or placebo oral solution twice daily (evenly split doses at morning and evening meals) for three days (to achieve steady state) following the baseline assessment (day 0). Session 3 (post-test session) will occur on the morning of day 4 (time of day matched to baseline ±1h). Participants will be instructed to take their morning dose with a meal as done in previous days. Post-test assessments will be the same as those taken at baseline, including blood draw, urine test, state mood assessments, computerized tasks assessing responses to emotional faces, and reactivity to a standardized stress task. Frequency of adverse and serious adverse events (AE/SAEs) and medication adherence will be assessed by the study physician. At the end of this session, subjects will be debriefed and referred for additional care as appropriate.

Conditions

• Social Anxiety
• Social Anxiety Disorder

Interventions

Type	Name	Description
DRUG	Cannabidiol	The CBD product to be used in this study is Epidiolex (Jazz Pharmaceuticals/Greenwich), a plant-derived, highly purified CBD oral solution that is FDA approved for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older. Doses will be 300 mg/d or 900 mg/d according to participants' assigned condition. Participants will receive CBD or placebo oral solution twice daily (evenly split doses at morning and evening meals) for three days (to achieve steady state) following the baseline assessment (day 0), and in the morning of day 4 (before the post-test).
DRUG	Placebo	Placebo solution (excipients only, also by Jazz Pharmaceuticals/Greenwich).

Timeline

• Start date: 2023-04-19
• Primary completion: 2024-08-20
• Completion: 2024-08-20
• First posted: 2023-04-21
• Last updated: 2025-01-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study