NCT07123467 · Wayne State University
Cannabidiol-Assisted Learning for Managing Generalized Anxiety Disorder
(CALM)
What this study is about
This randomly assigned, where neither patients nor doctors know which treatment is given, compared against an inactive treatment 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).
View original scientific description
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.
Interventions
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.
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.
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.
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.
Primary outcome measures
Change in dorsomedial prefrontal cortex activation when reappraising negative images
Time frame: Baseline to post-treatment (~Week 5)
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).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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.
Where
- Detroit, Michigan
Collaborators
National Institute of Mental Health (NIMH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 9, 2026 · Source of record for eligibility and locations