Short ReportsCannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in miceAssareh, Nedaa,,b,,c; Gururajan, Ananda,,b,,d; Zhou, Cillaa,,b,,e; Luo, Jia Lina,,b,,d; Kevin, Richard C.a,,b,,d; Arnold, Jonathon C.a,,b,,e Author Information aLambert Initiative for Cannabinoid Therapeutics bBrain and Mind Centre, The University of Sydney cDementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University dSchool of Psychology, Faculty of Science eDiscipline of Pharmacology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia Received 11 November 2019 Accepted as revised 28 March 2020 Correspondence to Jonathon C. Arnold, PhD, The University of Sydney, New South Wales, Australia, E-mail: [email protected] Behavioural Pharmacology: September 2020 - Volume 31 - Issue 6 - p 591-596 doi: 10.1097/FBP.0000000000000565 Buy Metrics Abstract The major phytocannabinoid cannabidiol (CBD) has anxiolytic properties and lacks tetrahydrocannabinol-like psychoactivity. Cannabidiolic acid (CBDA) is the acidic precursor to CBD, and this compound appears more potent than CBD in animal models of emesis, pain and epilepsy. In this short report, we aimed to examine whether CBDA is more potent than CBD in disrupting expression of conditioned fear and generalised anxiety-related behaviour induced by Pavlovian fear conditioning. Mice underwent fear conditioning and 24 h later were administered CBD and CBDA before testing for fear expression and generalized anxiety-like behaviour. We found that CBD and CBDA had dissociable effects; while CBD but not CBDA disrupted cued fear memory expression, CBDA but not CBD normalized trauma-induced generalized anxiety-related behaviour. Neither phytocannabinoid affected contextual fear expression. Our findings form the basis for future experiments examining whether phytocannabinoids, alone and in combination, are effective in these mouse models of fear and anxiety. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.