Cannabidiol to Reduce Anxiety Reactivity
- Conditions
- Social AnxietySocial Anxiety Disorder
- Interventions
- Drug: Placebo
- Registration Number
- NCT05823753
- Lead Sponsor
- University of California, San Diego
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cannabidiol 900 mg/d Cannabidiol Participants will receive CBD (900 mg/d). Evenly split doses of 450 mg will be taken at morning and evening meals for 3 days, and a 450 mg dose will be taken in the morning of day 4 (before the post-test). Placebo Placebo Participants will receive a CBD matching placebo. Evenly split doses will be taken at morning and evening meals for 3 days, and a dose will be taken in the morning of day 4 (before the post-test). Cannabidiol 300 mg/d Cannabidiol Participants will receive CBD (300 mg/d). Evenly split doses of 150 mg will be taken at morning and evening meals for 3 days, and a 150 mg dose will be taken in the morning of day 4 (before the post-test).
- Primary Outcome Measures
Name Time Method Anandamide Baseline, day 4 Change in blood plasma levels of anandamide collected pre-stress task. A standardized mean difference (SMD) increase of 0.5 or greater in favor of CBD (either 300 mg/d or 900 mg/d) vs. placebo is defined as the primary biological target.
Change in state anxiety (SUDs) during stress task performance phase Baseline, day 4 Self-reported current feelings of anxiety using a 0 to 100 subjective units of distress scale. Higher scores reflect greater levels of anxiety. A standardized mean difference (SMD) decrease of 0.3 or greater in favor of CBD (either 300 mg/d or 900 mg/d) vs. placebo during the performance phase of the stress task is defined as one of two primary biobehavioral targets.
Change in state anxiety (SUDs) during stress task anticipation phase Baseline, day 4 Self-reported current feelings of anxiety using a 0 to 100 subjective units of distress scale. Higher scores reflect greater levels of anxiety. A standardized mean difference (SMD) decrease of 0.3 or greater in favor of CBD (either 300 mg/d or 900 mg/d) vs. placebo during the anticipation phase of the stress task is defined as one of two primary biobehavioral targets.
- Secondary Outcome Measures
Name Time Method Change in state anxiety (STAI) following the stress task Baseline, day 4 The Spielberger State-Trait Anxiety Inventory-State subscale (STAI-State) is a 20-item measure that uses a 4-point (1 to 4) Likert scale to assess current anxiety-related affect. Higher scores indicate greater current anxiety.
Change in negative self-statements during the stress task Baseline, day 4 The Self-Statements during Public Speaking - Negative Self-Perception Scale (SSPS-N) is a 5-item scale that measures negative self-evaluations of one's performance on a 0 to 5 Likert scale. Higher scores reflect greater negative self-evaluations.
Change in state anxiety (STAI) during stress task anticipation phase Baseline, day 4 The Spielberger State-Trait Anxiety Inventory-State subscale (STAI-State) is a 20-item measure that uses a 4-point (1 to 4) Likert scale to assess current anxiety-related affect. Higher scores indicate greater current anxiety.
Trial Locations
- Locations (1)
University of California, San Deigo
🇺🇸San Diego, California, United States