Behavioural and molecular effects of cannabidiolic acid in mice

Abstract

Background: cannabidiolic acid (CBDA) is one of the most abundant phytocannabinoid acids in the Cannabis Sativa plant. It has been shown to exert some therapeutic effects such as antiemetic, anti-inflammatory, anxiolytic or antidepressant, although some of them with controversy. Hypothesis/Purpose: assess the potential effects of CBDA on different behaviours and on the modulation of neuroinflammatory markers in the prefrontal cortex (PFC). Study Design: the effects of CBDA were evaluated on cognitive, emotional, motivational and nociceptive behaviours in male CD1 mice. Methods: acute and/or chronic CBDA treatment (0.001-1 mg/kg i.p.) was evaluated in cognitive, emotional and nociceptive behavioural models, using the Y-maze, spontaneous locomotor activity, social interaction test, elevated plus maze, hot-plate test, formalin test and tail-suspension test in mice. We also assessed the effects of CBDA on the rewarding responses of cocaine in the conditioned place preference paradigm. PFC was dissected after acute and chronic CBDA treatments to evaluate inflammatory markers. Results: acute CBDA induced antinociceptive effects in the hot plate test. A 10-days chronic CBDA treatment also showed an effect on despair-like behaviour in the tail suspension test. CBDA did not show any other effect in the remaining behavioural tests assayed, including the cocaine-induced conditioned place preference (CPP). Regarding the biochemical analysis, chronic CBDA treatment diminished peroxisome proliferator-activated receptor gamma (PPAR-γ) and increased interleukin-6 (IL-6) protein levels in PFC. Conclusion: these results show that CBDA has “in vivo” limited effects modulating mice behaviour and highlight the lack of agreement regarding its therapeutic potential.