Recruiting

Phase 3

Cannabidiol with CBTCannabidiol-Assisted Learning for Managing Generalized Anxiety Disorder

Sponsor:

Wayne State University

Code:

NCT07123467

Conditions

Generalized Anxiety Disorder (GAD)

Anxiety Disorders

Eligibility Criteria

Sex: All

Age: 18 - 45

Healthy Volunteers: Not accepted

Interventions

Low-Dose Cannabidiol

Placebo Matched to Moderate-Dose Cannabidiol

Moderate-Dose Cannabidiol

Placebo Matched to Low-Dose Cannabidiol

Study Details

Brief summary:

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.

Conditions

Generalized Anxiety Disorder (GAD)

Anxiety Disorders

Study ID

NCT07123467

Start date

Nov 3, 2025

Status verified date

Mar, 2026

Completion date

Aug 31, 2027

Anticipated

Primary completion date

Aug 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 45

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

90 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Brief Cognitive Behavioral Therapy + Moderate-Dose Cannabidiol

Participants will receive a 5-week course of brief cognitive behavioral therapy (CBT) combined with oral cannabidiol (EPIDIOLEX®) at a moderate dose. Dosing starts at 5 milligram/kilogram/day and titrates to 10 milligram/kilogram/day (divided twice a day) after 6 days. Cannabidiol is administered chronically throughout CBT to examine target engagement and symptom outcomes.

experimental: Brief Cognitive Behavioral Therapy + Low-Dose Cannabidiol

Participants will receive a 5-week course of brief cognitive behavioral therapy (CBT) combined with a lower dose of oral cannabidiol (EPIDIOLEX®), maintained at 5 milligram/kilogram/day (divided twice a day) throughout the treatment period. No titration is required.

placebo comparator: Brief Cognitive Behavioral Therapy + Placebo Titrated to Match Moderate-Dose Cannabidiol

Participants will receive a 5-week course of brief cognitive behavioral therapy (CBT) combined with a matched placebo oral solution. The placebo mimics the appearance, smell, and taste of EPIDIOLEX®. For blinding the moderate dose cannabidiol arm, dosing starts at 5 milligram/kilogram/day and titrates to 10 milligram/kilogram/day (divided twice a day) after 6 days.

placebo comparator: Brief Cognitive Behavioral Therapy + Placebo Titrated to Match Low-Dose Cannabidiol

Participants will receive a 5-week course of brief cognitive behavioral therapy (CBT) combined with a matched placebo oral solution. The placebo mimics the appearance, smell, and taste of EPIDIOLEX®. For blinding the low-dose cannabidiol arm, dosing is maintained at 5 milligram/kilogram/day (divided twice a day) throughout the treatment period. No titration is required.

Interventions

Low-Dose Cannabidiol

Oral cannabidiol solution (EPIDIOLEX®) administered as an adjunct to cognitive behavioral therapy. Low-dose participants receive 5 milligram/kilogram/day throughout. The intervention targets emotion regulation circuitry and symptom improvement.

Placebo Matched to Moderate-Dose Cannabidiol

The placebo mimics the appearance, smell, and taste of EPIDIOLEX®. For blinding the moderate-dose cannabidiol arm, dosing starts at 5 mg/kg/day and titrates to 10 milligram/kilogram/day (divided twice a day) after 6 days.

Moderate-Dose Cannabidiol

Oral cannabidiol solution (EPIDIOLEX®) administered as an adjunct to cognitive behavioral therapy. Moderate-dose participants receive 5 milligram/kilogram/day for 6 days, then titrate to 10 milligram/kilogram/day. The intervention targets emotion regulation circuitry and symptom improvement.

Placebo Matched to Low-Dose Cannabidiol

The placebo mimics the appearance, smell, and taste of EPIDIOLEX®. For blinding the low-dose cannabidiol arm, dosing is maintained at 5 milligram/kilogram/day (divided twice a day) throughout the treatment period. No titration is required.

Primary outcome measure

Change in dorsomedial prefrontal cortex activation when reappraising negative images [ Time Frame: Baseline to post-treatment (~Week 5) ]

Central Contacts and Locations

Central contacts

Hilary Marusak, PhD

(313) 577-1278 hmarusak@med.wayne.edu

Christine Rabinak, PhD, MBA

(313) 577-9875 rabinak@wayne.edu

Locations

Wayne State University School of Medicine, Tolan Park Medical Building

Recruiting

Detroit, Michigan, United States, 48201

Contacts

Hilary Marusak, PhD

(313) 577-1278 hmarusak@med.wayne.edu

Leslie Lundahl, PhD

(313) 993-1374 llundahl@med.wayne.edu

Principal Investigator:

Hilary Marusak, PhD

More Information

Sponsor

Wayne State University

Last update posted

Mar 9, 2026

Last verified

Mar, 2026

Keywords

Cannabidiol
EPIDIOLEX
Cognitive Behavioral Therapy
Generalized Anxiety Disorder
functional magnetic resonance imaging

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Wayne State University on 2026-03-09.