Prolonged Cannabidiol Treatment Lacks on Detrimental Effects on Memory, Motor Performance and Anxiety in C57BL/6J Mice.

Eva M Schleicher,Frederik W Ott,Barbara Silcher,Jannek M Wagner,Yvonne Bouter,Maximilian J Löw,Melanie Müller,Marius E Sichler

doi:10.3389/fnbeh.2019.00094

Eva M Schleicher, Frederik W Ott + Show 6 more

Open Access

https://doi.org/10.3389/fnbeh.2019.00094

Copy DOI

Abstract

The Cannabis plant contains more than 100 currently known phytocannabinoids. Regarding the rising consumption of the non-psychotropic phytocannabinoid cannabidiol (CBD) in people’s everyday life (e.g., beauty products, food and beverages), the importance of studies on the influence of CBD on healthy humans and rodents is evident. Therefore, the behavioral profile of CBD was investigated with a battery of behavioral tests, including motor, anxiety, and memory tests after prolonged CBD treatment. Adult C57Bl/6J wildtype (WT) mice were daily intraperitoneally injected with 20 mg/kg CBD for 6 weeks starting at two different points of ages (3 months and 5 months) to compare the influence of prolonged CBD treatment with a washout period (former group) to the effects of long term CBD treatment (current group). Our results show that CBD treatment does not influence motor performance on an accelerating Rotarod test, while it also results in a lower locomotor activity in the open field (OF). No influence of CBD on spatial learning and long term memory in the Morris Water Maze (MWM) was observed. Memory in the Novel Object Recognition test (NORT) was unaffected by CBD treatment. Two different anxiety tests revealed that CBD does not affect anxiety behavior in the Dark-Light Box (DLB) and OF test. Although, anxiety is altered by current CBD treatment in the Elevated Plus Maze (EPM). Moreover, CBD-treated C57Bl/6J mice showed an unaltered acoustic startle response (ASR) compared to vehicle-treated mice. However, current CBD treatment impairs prepulse inhibition (PPI), a test to analyze sensorimotor gating. Furthermore, prolonged CBD treatment did not affect the hippocampal neuron number. Our results demonstrate that prolonged CBD treatment has no negative effect on the behavior of adult C57Bl/6J mice.

Highlights

Over the last years, there has been growing interest in the therapeutic potential of the phytocannabinoid cannabidiol (CBD) occurring naturally in the plant Cannabis sativa/indica, commonly known as marijuana
Mice of the current CBD treatment group showed a significant preference for the target quadrant (Figure 3G; one-way repeated measures analysis of variance (ANOVA) followed by Bonferroni multiple comparisons current vehicle: F(3,72) = 25.73, p < 0.0001, Bonferroni for target quadrant vs. left, vs. right and vs. opposite quadrant: p < 0.0001; current CBD: F(3,72) = 20.88, p < 0.0001, Bonferroni target quadrant vs. left, vs. right and vs. opposite quadrant: p < 0.0001;)
CBD has been discussed as a therapy for neurodegenerative diseases including multiple sclerosis as well as diseases known for involving activation of the immune system and associated with oxidative stress (Iuvone et al, 2009; Krishnan et al, 2009; Scuderi et al, 2009; Booz, 2011)

Summary

Introduction

There has been growing interest in the therapeutic potential of the phytocannabinoid cannabidiol (CBD) occurring naturally in the plant Cannabis sativa/indica, commonly known as marijuana. Several studies showed that CBD is involved, among others, in immunomodulatory, anti-inflammatory, antiemetic, anticonvulsant, anxiolytic, antipsychotic, Cannabidiol Treatment in C57Bl/6J Mice muscle relaxant and neuroprotective processes (Atakan, 2012; Burstein, 2015; Watt and Karl, 2017). The interest in studying CBD initially came through its interaction with the probably most commonly recognized constituent of the cannabis plant, 9-Tetrahydrocannabinol (THC). The pharmacological mechanisms of THC are the most well understood among the more than 100 other currently known phytocannabinoids (Mechoulam et al, 2014). Whereas THC is dependent from CB1-, and CB2-receptor binding, the mechanism of action for CBD is still not fully understood (De Petrocellis and Di Marzo, 2010). There are several other receptors that appear to be involved in the therapeutic effect of CBD, such as TRPV1-, PPARγ-, 5-HT1A-, and GPR55-Receptors (Zygmunt et al, 1999; Bouaboula et al, 2005; Russo et al, 2005; O’Sullivan, 2007; Ryberg et al, 2007)

Objectives

Methods

Results

Conclusion