Cannabidiol-Assisted Learning for Managing Generalized Anxiety Disorder

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.

Timeline

Start

2025-11-03

Primary completion

2027-08-31

Completion

2027-08-31

Publications

• Background Zabik NL, Iadipaolo A, Peters CA, Baglot SL, Hill MN, Rabinak CA. Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study. Psychopharmacology (Berl). 2026 Feb;243(2):235-250. doi: 10.1007/s00213-024-06702-w. Epub 2024 Oct 16.
• Background Zabik NL, Rabinak CA, Peters CA, Iadipaolo A. Cannabinoid modulation of corticolimbic activation during extinction learning and fear renewal in adults with posttraumatic stress disorder. Neurobiol Learn Mem. 2023 May;201:107758. doi: 10.1016/j.nlm.2023.107758. Epub 2023 Apr 22.
• Background Pacitto R, Peters C, Iadipaolo A, Rabinak CA. Cannabinoid modulation of brain activation during volitional regulation of negative affect in trauma-exposed adults. Neuropharmacology. 2022 Nov 1;218:109222. doi: 10.1016/j.neuropharm.2022.109222. Epub 2022 Aug 15.
• Background Mayo LM, Rabinak CA, Hill MN, Heilig M. Targeting the Endocannabinoid System in the Treatment of Posttraumatic Stress Disorder: A Promising Case of Preclinical-Clinical Translation? Biol Psychiatry. 2022 Feb 1;91(3):262-272. doi: 10.1016/j.biopsych.2021.07.019. Epub 2021 Jul 24.
• Background Gorka SM, Phan KL, Lyons M, Mori S, Angstadt M, Rabinak CA. Cannabinoid Modulation of Frontolimbic Activation and Connectivity During Volitional Regulation of Negative Affect. Neuropsychopharmacology. 2016 Jun;41(7):1888-96. doi: 10.1038/npp.2015.359. Epub 2015 Dec 9.
• Background Gowatch LC, Evanski JM, Ely SL, Zundel CG, Bhogal A, Carpenter C, Shampine MM, O'Mara E, Mazurka R, Barcelona J, Mayo LM, Marusak HA. Endocannabinoids and Stress-Related Neurospsychiatric Disorders: A Systematic Review and Meta-Analysis of Basal Concentrations and Response to Acute Psychosocial Stress. Cannabis Cannabinoid Res. 2024 Oct;9(5):1217-1234. doi: 10.1089/can.2023.0246. Epub 2024 Apr 29.

Drugs

Indications