Cannabidiol-Assisted Learning for Managing Generalized Anxiety Disorder

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified February 2026 by Wayne State University
Sponsor
Wayne State University
Information Provided by (Responsible Party)
Hilary Marusak
Clinicaltrials.gov Identifier
NCT07123467
Other Study ID Numbers:
IRB-24-11-7333
First Submitted
August 1, 2025
First Posted
August 13, 2025
Last Update Posted
March 8, 2026
Last Verified
February 2026

ClinicalTrials.gov processed this data on March 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

The study is a randomized, double-blind, placebo-controlled clinical trial evaluating cannabidiol (CBD) as an adjunct to cognitive behavioral therapy (CBT) for treating generalized anxiety disorder (GAD) in adults aged 18-45. Participants will be randomly assigned to one of four arms: (1) Brief CBT with moderate-dose EPIDIOLEX® (10 milligrams(mg)/kilograms(kg)/day), (2) Brief CBT with low-dose EPIDIOLEX® (5 mg/kg/day), (3) Brief CBT with matched placebo with dosing matched to the moderate-dose EPIDIOLEX®, or 4) Brief CBT with matched placebo with dosing matched to the low-dose EPIDIOLEX®. The trial uses a neurobiologically informed experimental medicine approach to evaluate target engagement in the dorsomedial prefrontal cortex (dmPFC) during an emotion regulation functional magnetic resonance imaging (fMRI) task before and after treatment. Primary outcomes include change in dmPFC activation, while secondary outcomes include anxiety symptom severity, treatment tolerability, and plasma concentrations of cannabidiol and related biomarkers.

Condition or DiseaseIntervention/Treatment
Generalized Anxiety Disorder (GAD)Anxiety Disorders
Drug: Moderate-Dose CannabidiolDrug: Low-Dose CannabidiolDrug: Placebo Matched to Moderate-Dose CannabidiolDrug: Placebo Matched to Low-Dose Cannabidiol

Study Design

Study TypeInterventional
Actual Enrollment90 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleCannabidiol-Enhanced Cognitive Behavioral Therapy for Generalized Anxiety Disorder
Study Start DateNovember 2, 2025
Actual Primary Completion Date1yr 4mos from now
Actual Study Completion Date1yr 4mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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.
Drug: 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.
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.
Drug: 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.
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.
Drug: 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.
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.
Drug: 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.

Outcome Measures

Primary Outcome Measures
  1. Change in dorsomedial prefrontal cortex activation when reappraising negative images
    Within-participant change in dorsomedial prefrontal cortex (dmPFC) activation will be calculated as post-treatment minus baseline values during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
Secondary Outcome Measures
  1. Post-treatment dorsomedial prefrontal cortex activation when reappraising negative images
    Post-treatment dorsomedial prefrontal cortex (dmPFC) activation during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  2. Post-treatment amygdala activation when reappraising negative images
    Post-treatment amygdala activation during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  3. Change in amygdala activation when reappraising negative images
    Within-participant change in amygdala activation will be calculated as post-treatment minus baseline values during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  4. Post-treatment hippocampal activation when reappraising negative images
    Post-treatment hippocampal activation during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  5. Change in hippocampal activation when reappraising negative images
    Within-participant change in hippocampal activation will be calculated as post-treatment minus baseline values during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  6. Post-treatment inferior frontal gyrus activation when reappraising negative stimuli
    Post-treatment inferior frontal gyrus activation during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  7. Change in inferior frontal gyrus activation when reappraising negative images
    Within-participant change in inferior frontal gyrus activation will be calculated as post-treatment minus baseline values during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  8. Post-treatment anterior insula activation when reappraising negatives images
    Post-treatment anterior insula activation during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  9. Change in anterior insula activation when reappraising negative images
    Within-participant change in anterior insula activation will be calculated as post-treatment minus baseline values during an explicit emotion regulation task (Reappraise \> Maintain contrast). Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  10. Change in plasma concentration of anandamide from baseline to post-treatment
    Plasma anandamide levels will be measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline and post-treatment. Change will be calculated as post-treatment minus baseline values (nanogram per milliliter).
  11. Change in plasma concentration of 2-arachidonoylglycerol (2-AG) from baseline to post-treatment
    Plasma 2-arachidonoylglycerol (2-AG) levels will be measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline and post-treatment. Change will be calculated as post-treatment minus baseline values (nanogram per milliliter).
  12. Change in plasma concentration of cannabidiol from baseline to post-treatment
    Plasma cannabidiol levels will be measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline and post-treatment. Change will be calculated as post-treatment minus baseline values (nanogram per milliliter).
  13. Change in plasma concentration of 7-hydroxy-cannabidiol (7-OH-CBD) from baseline to post-treatment
    7-hydroxy-cannabidiol (7-OH-CBD; active metabolite) levels will be measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline and post-treatment. Change will be calculated as post-treatment minus baseline values (nanogram per milliliter).
  14. Post-treatment dorsomedial prefrontal cortex activation during implicit emotion regulation
    Post-treatment dorsomedial prefrontal cortex (dmPFC) activation during an implicit emotion regulation task. Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  15. Change in dorsomedial prefrontal cortex activation during implicit emotion regulation
    Within-participant change in dorsomedial prefrontal cortex (dmPFC) activation will be calculated as post-treatment minus baseline values during an implicit emotion regulation task. Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  16. Post-treatment ventromedial prefrontal cortex activation during implicit emotion regulation
    Post-treatment ventromedial prefrontal cortex (vmPFC) activation during implicit emotion regulation. Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  17. Change in ventromedial prefrontal cortex activation during implicit emotion regulation
    Within-participant change in ventromedial prefrontal cortex (vmPFC) activation will be calculated as post-treatment minus baseline values during an implicit emotion regulation task. Measured using blood-oxygen-level-dependent (BOLD) signal from multi-echo functional magnetic resonance imaging (fMRI).
  18. Change in depressive symptom severity
    Change in depressive symptom severity will be assessed using the 9-item Patient Health Questionnaire (PHQ-9), a validated self-report instrument that measures symptoms of depression over the past two weeks. Each item is rated on a 0-3 scale, producing a total score ranging from 0 to 27, with higher scores indicating greater severity. Scores will be collected at baseline and post-treatment. Change will be calculated as post-treatment minus baseline score.

Eligibility Criteria

Ages Eligible for Study(Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsWayne State University
Locations
Wayne State University School of Medicine, Tolan Park Medical Building | Detroit Michigan, United States, 48201
Investigators
Principal Investigator: Hilary Marusak, PhD, Wayne State UniversityPrincipal Investigator: Christine Rabinak, PhD, MBA, Wayne State UniverstyPrincipal Investigator: Leslie Lundahl, PhD, Wayne State University