Cannabidiol to Reduce Anxiety Reactivity

NCT05823753 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 801460
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Social Anxiety; Social Anxiety Disorder

Keywords

Cannabidiol (CBD); Social Anxiety

Outcome Measures

Primary Outcomes (3)

• Anandamide

  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.

  Baseline, day 4

• Change in state anxiety (SUDs) during stress task anticipation phase

  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.

  Baseline, day 4

• Change in state anxiety (SUDs) during stress task performance phase

  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.

  Baseline, day 4

Secondary Outcomes (3)

• Change in state anxiety (STAI) during stress task anticipation phase

  Baseline, day 4

• Change in state anxiety (STAI) following the stress task

  Baseline, day 4

• Change in negative self-statements during the stress task

  Baseline, day 4

Other Outcomes (15)

• Change in anxiety-related behavior during stress task

  Baseline, day 4

• Change in Emotional Attention Bias

  Baseline, day 4

• Change in Emotion Recognition

  Baseline, day 4

Study Arms (3)

Cannabidiol 900 mg/d

ACTIVE COMPARATOR

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).

Drug: Cannabidiol

Cannabidiol 300 mg/d

ACTIVE COMPARATOR

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).

Drug: Cannabidiol

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

Interventions

Cannabidiol DRUG

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).

Also known as: Epidiolex

Cannabidiol 300 mg/d; Cannabidiol 900 mg/d

Placebo DRUG

Placebo solution (excipients only, also by Jazz Pharmaceuticals/Greenwich).

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Current or imminent risk of suicide assessed using the Columbia Suicide Severity Rating Scale (C-SSRS)
• Bipolar or psychotic disorders
• History of major neurological disorder or moderate to severe traumatic brain injury or severe or unstable medical conditions that might be compromised by participation in the study.
• Past 6-month substance use disorder (any severity, with the exception of mild alcohol use disorder)
• Prior history of cannabis use disorder, or allergy or intolerance to cannabinoids
• Current (within past 7 days) cannabinoid use (medicinal or recreational; assessed using patient report and a urine sample). Concurrent cannabinoid use is prohibited during the study.
• Positive urinalysis screen for psychoactive drug use (that is not physician prescribed)
• Abnormal and clinically relevant blood count, liver, renal or EKG findings as determined by physician
• Currently prescribed medications with known CBD-interactions (e.g., amiodarone, fluconazole, metronidazole, miconazole, sulfamethoxazole, clarithromycin, erythromycin, cyclosporine, verapamil, itraconazole, voriconazole, boceprevir, St. John's Wart, and carbamazepine)
• Concurrent empirically supported psychosocial treatments for anxiety or mood disorders (e.g., cognitive behavioral therapy)
• Use of any psychotropic medication (e.g. SSRIs, benzodiazepines) within 14 days before study entry \[except for fluoxetine within 30 days\]. Concurrent use is prohibited during the study.
• Use of beta-adrenergic blocking agents ("beta blockers") within 14 days before study entry. Concurrent use is prohibited during the study.
• Use of any over-the-counter, prescription, or herbal product for treating symptoms of anxiety or social anxiety within 14 days before study entry. Concurrent use is prohibited during the study.
• Inability to complete the assessments or test sessions.
• Clinical conditions assessed by the interviewer that necessitate more imminent clinical care. These criteria are in place so participants with these other, more several symptoms can be referred for appropriate services.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Deigo

San Diego, California, 92093, United States

Location

MeSH Terms

Conditions

Phobia, Social

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Phobic Disorders; Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Murray B Stein, MD, MPH

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Charles Taylor, PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical taste, smell, color and viscosity of liquid provided in identical bottles. Each participant will receive two bottles, with instructions of how many ml to take BID from each of Bottle #1 and Bottle #2. The research pharmacy will label the bottles for each randomized participant so they take the dose to which they were randomized.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: A phase II, 3-arm, sub-acute (4-day) steady state dosing clinical trial.

Study Record Dates

• First Submitted: April 10, 2023
• First Posted: April 21, 2023
• Study Start: April 19, 2023
• Primary Completion: August 20, 2024
• Study Completion: August 20, 2024
• Last Updated: January 8, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)