Overview

This randomized, double-blind, placebo-controlled clinical trial investigates the use of Food and Drug Administration (FDA)-approved cannabidiol (EPIDIOLEX®) as an adjunct to cognitive behavioral therapy (CBT) in adults with generalized anxiety disorder (GAD). The study aims to evaluate whether cannabidiol-assisted CBT enhances emotion regulation via dorsomedial prefrontal cortex (dmPFC) activation and improves anxiety symptom outcomes compared to CBT with placebo.

Eligibility

Inclusion Criteria:

• Right-handed
• Age 18-45 years at enrollment
• Able to consent to the study
• Agree to adhere to lifestyle considerations throughout study duration
• Generally medically and neurologically healthy, including no evidence of intellectual disability or serious cognitive impairment
• Have a current generalized anxiety disorder (GAD) diagnosis according to the The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and/or total scores ≥ 8 on the 7-Item Generalized Anxiety Disorders Scale (GAD-7)

Exclusion Criteria:

• Clinically significant medical or neurologic condition or neurocognitive dysfunction that would affect function and/or task performance and/or interfere with the study protocol
• Any current (or within past 2 months) medical condition requiring medication that would interact with cannabidiol or interfere with the study protocol
• Risk of harm to self or others that requires immediate intervention
• Presence of contraindications, current or past allergic or adverse reaction, or known sensitivity to cannabinoid-like substances or components of EPIDIOLEX®
• Positive drug screen or alcohol breathalyzer
• Unwilling/unable to sign informed consent document
• Currently pregnant (positive pregnancy test), planning pregnancy, or lactating (women),
• Under 18 or over 45 years of age
• Traumatic brain injury, as defined by The American Congress of Rehabilitation as a person who has had a traumatically induced physiological disruption of brain function (i.e., the head being struck, the head striking an object, and/or the brain undergoing an acceleration/deceleration movement \[i.e., whiplash\] without direct external trauma to the head), as manifested by at least one of the following: any loss of consciousness; any loss of memory for events immediately before or after the injury; any alteration in mental status at the time of the incident; or focal neurological deficits that may or may not be transient)
• Inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia), as determined by self-report and/or a preliminary session in a mock scanner
• Presence of ferrous-containing metals within the body (e.g., aneurysm clips, shrapnel/retained particles)
• Receiving concurrent psychotherapy or have received psychotherapy, including for research purposes, within the past year
• Current moderate or severe alcohol/drug use disorder or in the past 8 weeks
• Current or past diagnosis of bipolar and other related disorders, schizophrenia spectrum, or other psychotic disorders;
• GAD-7 score \< 8
• Use of medications known to have severe drug interactions with cannabidiol or that are strong inducers of cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C19 (CYP2C19)
• Visual impairment
• Baseline labs 3 times outside of normal range
• Use of as needed anti-anxiety medications (e.g., benzodiazepines), unstable dose of other psychoactive drug (i.e., \< 4 weeks), or intention to start new treatment during this trial
• Current or past-month use of cannabis, or a tetrahydrocannabinol (THC) or cannabidiol-containing product (self-report and urine drug screen)
• Current or past-month coronavirus disease 2019 (COVID-19) diagnosis or febrile illness
• Treatment with another investigational drug or intervention within the past month
• Difficulty with or inability to comply with the complete clinical trial.