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 that 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 behavioural effects of CBDA as well as its modulation of neuroinflammatory markers in the prefrontal cortex (PFC).

Main methods: The effects of acute and repeated CBDA (0.001-1 mg/kg i.p.) treatments 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. Finally, PFC was dissected after acute and repeated CBDA treatments to evaluate inflammatory markers.

Key findings: Acute CBDA treatment induced antinociceptive responses in the hot-plate test. A 10-day CBDA treatment reduced despair-like behaviour in the tail suspension test. CBDA did not alter the results of the remaining behavioural tests assayed, including cocaine-induced reward in the CPP. Regarding the biochemical analysis, repeated CBDA treatment diminished the level of peroxisome proliferator-activated receptor gamma (PPAR-γ) and increased that of interleukin-6 (IL-6) protein in PFC.

Significance: These results show that CBDA has limited in vivo effects on the modulation of mice behaviour, supporting the current skepticism regarding its therapeutic potential.

Keywords: Cannabidiolic acid; Cocaine; Despair-like behaviour; Neuroinflammation; Nociception.