Cannabidiol enhancement of exposure therapy in treatment refractory patients with social anxiety disorder and panic disorder with agoraphobia: A randomised controlled trial

Caroline M. B. Kwee*, Johanna M. P. Baas, Febe E. van der Flier, Lucianne Groenink, Puck Duits, Merijn Eikelenboom, Date C. van der Veen, Mirjam Moerbeek, Neeltje M. Batelaan, Anton J. L. M. van Balkom, Danielle C. Cath

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    Abstract

    Preclinical research suggests that enhancing CB1 receptor agonism may improve fear extinction. In order to translate this knowledge into a clinical application we examined whether cannabidiol (CBD), a hydrolysis inhibitor of the endogenous CB1 receptor agonist anandamide (AEA), would enhance the effects of exposure therapy in treatment refractory patients with anxiety disorders. Patients with panic disorder with agoraphobia or social anxiety disorder were recruited for a double-blind parallel randomised controlled trial at three mental health care centres in the Netherlands. Eight therapist-assisted exposure in vivo sessions (weekly, outpatient) were augmented with 300 mg oral CBD (n = 39) or placebo (n = 41). The Fear Questionnaire (FQ) was assessed at baseline, mid-and post-treatment, and at 3 and 6 months follow-up. Primary analyses were on an intent-to-treat basis. No differences were found in treatment outcome over time between CBD and placebo on FQ scores, neither across (beta = 0.32, 95% CI [-0.60; 1.25]) nor within diagnosis groups (beta = -0.11, 95% CI [-1.62; 1.40]). In contrast to our hypotheses, CBD augmentation did not enhance early treatment response, within-session fear extinction or extinction learning. Incidence of adverse effects was equal in the CBD (n = 4, 10.3%) and placebo condition (n = 6, 15.4%). In this first clinical trial examining CBD as an adjunctive therapy in anxiety disorders, CBD did not improve treatment outcome. Future clinical trials may investigate different dosage regimens. (c) 2022 Published by Elsevier B.V.

    Original languageEnglish
    Pages (from-to)58-67
    Number of pages10
    JournalEuropean Neuropsychopharmacology
    Volume59
    DOIs
    Publication statusPublished - Jun-2022

    Keywords

    • Cannabidiol
    • Cannabinoids
    • Anxiety disorders
    • Therapeutics
    • D-CYCLOSERINE ENHANCEMENT
    • ACID AMIDE HYDROLASE
    • FEAR EXTINCTION
    • RAT-BRAIN
    • DELTA-9-TETRAHYDROCANNABINOL
    • LOCALIZATION
    • RECEPTORS
    • SYSTEM

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