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Anxiolytic Effects of Cannabinoid Receptor Agonists in the Zebrafish Species, Danio rerio
Author(s) -
Prasad Aleya,
Crowe Macey,
Burton Grace,
McGrew Lori
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02165
Subject(s) - anxiolytic , zebrafish , endocannabinoid system , cannabinoid receptor , cannabinoid , anxiogenic , pharmacology , anandamide , cannabidiol , cannabinoid receptor agonists , cannabinoid receptor type 2 , agonist , biology , cannabis , medicine , receptor , psychiatry , biochemistry , gene
As of July 2019, 34 states in the U.S. have legalized medical marijuana and an additional 12 have legalized “low THC, high cannabidiol (CBD)” substances (Hanson & Garcia, 2019). While acute cannabis use has been associated with decreased anxiety levels, users have also experienced adverse side effects including increased anxiety, panic reactions, and psychotic symptoms (Hall & Degenhardt, 2009). Plant‐derived pharmacological agents, like cannabis, can vary in quality and composition (and thus efficacy) due to a variety of environmental factors (Atanasov et. al. 2015). In order to use cannabinoids to treat anxiety safely, a synthetic cannabinoid that can produce consistent therapeutic (anxiolytic) effects without producing psychoactive effects is necessary. Zebrafish are an increasingly popular model organism used due to their high sensitivity to chemicals as absorbed through their gills and quantifiable behavioral phenotypes (Stewart 2014). Humans and zebrafish have comparable endocannabinoid pathways that each contain CB1 and CB2 receptors (Krug and Clark 2015). When observed in a Novel Dive Tank, anxiety levels in zebrafish can be quantified. Like humans, male and female zebrafish differ in hormonal composition and therefore respond to treatments differently. In this study, male and female zebrafish were treated with CB receptor agonists anandamide and WIN 55,212‐2 and CB2 inverse agonist JTE‐907 in order to model the how the endocannabinoid system influences anxiety. The reduced amount of time spent in the upper zone by the JTE + Anandamide treated fish, combined with the increased time classified as highly mobile, suggests that JTE‐907 had an anxiogenic effect. Significant anxiolytic effects were observed the WIN treatment group, particularly in male treated fish. These results suggest that male treated fish are more receptive to the anxiolytic effects of a non‐selective CB agonist such as WIN 55, 212. Future research with a water‐soluble CB1 inverse agonist could provide insight into the differing roles of CB1 and CB2 receptors in cannabis‐based treatments.