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

Behav Brain Res. 2018 Oct 1;351:1-3. doi: 10.1016/j.bbr.2018.05.027. Epub 2018 May 31.


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 (WKY) 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.

Keywords: Cannabidiolic acid methyl ester; Flinders Sensitive Line (FSL); Forced swim test (FST); Genetic animal models of depression; Major depression disorder (MDD); Wistar–Kyoto (WKY).

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Cannabinoids / pharmacology*
  • Depressive Disorder / drug therapy*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Motor Activity / drug effects
  • Rats, Inbred WKY
  • Species Specificity


  • Antidepressive Agents
  • Cannabinoids
  • HU-580