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

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

[Epub ahead of print]

Hen-Shoval D¹, Amar S², Shbiro L³, Smoum R⁴, Haj CG⁴, Mechoulam R⁴, Zalsman G⁵, Weller A¹, Shoval G⁶.

Author information

Highlights

• CBDA methyl ester (HU-580) is known to be more stable than CBDA.
• Oral administration in different genetic depression models: male WKY and FSL rats.
• 1 mg/kg HU-580 reduced immobility and increased swimming in both strains.
• This is the first report of antidepressant efficacy of HU-580.
• Support provided for a novel treatment for depression and associated disorders.

Abstract

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)