Phytocannabinoids restore seizure-induced alterations in emotional behaviour in male rats

Epilepsy often presents with severe emotional comorbidities including anxiety and abnormal fear responses which impose a significant burden on, and reduce, quality of life in people living with the disease. Our lab has recently shown that kindled seizures lead to changes in emotional processing resulting from the downregulation of anandamide signalling within the amygdala. Phytocannabinoids derived from the Cannabis sativa plant have attracted a lot of interest as a new class of drugs with potential anticonvulsant effects. Among the wide number of compounds occurring in Cannabis sativa, Δ9- tetrahydrocannabinol (THC), the one responsible for its main psychoactive effects, and the nonpsychoactive cannabidiol (CBD) have been extensively examined under pre-clinical and clinical contexts to control seizures, however, neither have been assessed in the context of the management of emotional comorbidities associated with seizure activity. We used two behavioural procedures to assess anxiety- and fear-like responding in adult male Long-Evans rats: elevated plus maze and auditory fear conditioning. In agreement with previous reports, we found seizure-induced increases in anxiety- and fear-like responding. These effects were reversed by either CBD (vaporized) or THC (oral). We also found that antagonism of serotonin 1 A receptors prior to CBD exposure prevented its protective effects. Phytocannabinoids offer a novel and reliable opportunity to treat seizure induced comorbid emotional alterations.