Acute oral cannabidiolic acid methyl ester reduces depression-like behavior in two genetic animal models of depression

Background and purpose: Cannabidiolic acid methyl ester (HU-580) was recently shown to reduce stress-induced anxiety-like behavior in rats. The aim of this study was to examine the antidepressant effect of HU-580 in two different rat models of depression. Experimental approach: Using the forced swim test (FST), we evaluated the effect of HU-580 in 43 Wistar Kyoto (WRY) and 23 Flinders Sensitive Line (FSL) adult male rats. Key results: 1 mg/kg HU-580 reduced immobility and increased swimming in WKY rats, compared to vehicle treated controls (p < 0.05). This dose exerted similar effects in FSL rats (p < 0.05). Conclusion and implications: This is the first report of antidepressant efficacy of HU-580. These findings expand the very limited existent results, suggesting that HU-580 is a potent anxiolytic agent. Taken together with its chemical stability, HU-580 emerges as a candidate for a future antidepressant medication.