BEHAVIOURAL AND MOLECULAR EFFECTS OF CANNABIDIOLIC ACID IN MICE

Aims: Cannabidiolic acid (CBDA) is one of the most abundant phytocannabinoid acids in the Cannabis Sativa plant. It has been shown it is able to exert some therapeutic effects such as antiemetic, anti-inflammatory, anxiolytic or antidepressant, although some of them remain under debate. In the present study we aim to assess the potential effects of CBDA on different behaviours and on the modulation of neuroinflammatory markers in the prefrontal cortex (PFC). Main methods: the effects of acute and/or chronic CBDA (0.001-1 mg/kg i.p.) treatment were evaluated on cognitive, emotional, motivational and nociceptive behaviours in male CD1 mice. For this, Y-maze and elevated plus maze paradigms, spontaneous locomotor activity, social interaction, hot-plate, formalin and tail suspension tests were used. We also studied the effects of CBDA on the rewarding responses of cocaine in the conditioned place preference (CPP) paradigm. PFC was dissected after acute and chronic CBDA treatments to evaluate inflammatory markers. Key findings: acute CBDA treatment induced antinociceptive responses in the hot-plate test. A 10-day chronic CBDA treatment reduced despair-like behaviour in the tail suspension test. CBDA did not alter the remaining behavioural tests assayed, including cocaine-induced reward in the 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. Significance: these results show that CBDA has limited in vivo effects modulating mice behaviour, highlighting the current disagreement regarding its therapeutic potential.