Cannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in mice

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.

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

“…In the fear-conditioning model, a type of associative learning task, acute administration of CBD reduced contextual fear- and anxiety-related behaviors [ 127 , 140 ], whereas chronic administration induced just the opposite [ 123 ]. Similarly, microinjections/infusions on specific brain regions, such as intracerebroventricular [ 117 ] and prelimbic medial prefrontal cortex, reduced freezing and anxiety [ 118 ].…”

Current and novel pharmacological therapeutic approaches in Post-Traumatic Stress Disorder. A brief review

“…As such, cannabidiol has been researched for its potential in several psychiatric disorders, with focus on depression and PTSD; while studies on animals subjected to stress models assessed the anxiety like-behavior and its involvement in fear-memory with positive outcomes [42,43], human studies suggest reduction of PTSD severity [44,45] and positive results in both fear extinction and memory encoding processes [45,46], (for a review see Bitencourt et al, [47]). According to the World Health's Organization's review report on CBD, it has a good safety profile with limited side effects [48,49].…”

A primer on medicinal cannabis safety and potential adverse effects

“…Other products contain CBD and/or THC with a 'full-spectrum' of cannabis plant constituents including other phytocannabinoids (eg cannabichromene, cannabigerol, ∆ 9 -tetrahydrocannabinolic acid or cannabidiolic acid) as well as terpenes and flavonoids, all of which may have therapeutic effects. [7][8][9][10] To ascertain exactly what is contained in a given medicinal cannabis product, a request can be made to the manufacturer for a certificate of analysis. Therapeutic daily doses of CBD are typically between 50 mg and 1500 mg, which are greater than those for THC, which are between 5 mg and 20 mg. 1 When evaluating the safety profile of medicinal cannabis products, it is important to consider the relative THC and CBD content, as CBD generally has fewer safety concerns than THC.…”