The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review

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The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review ( the-use-cannabinoids-animals-and-therapeutic-implications-ve )

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Review Article Veterinarni Medicina, 61, 2016 (3): 111–122 doi: 10.17221/8762-VETMED 4. Prospective veterinary use of cannabinoids 5. Conclusions 6. References Attention will then be turned to the therapeutic potential of cannabinoids with regard to veterinary medicine. 2. The endocannabinoid system and classification of cannabinoids The endocannabinoid system consists of sev- eral subtypes of cannabinoid receptors (the best characterised are subtypes CB1 and CB2), endo- cannabinoids (endogenous substances that bind to the receptors) and enzymes involved in endo- cannabinoid biosynthesis through phospholipases or degradation: post-synaptically by FAAH (fatty acid amide hydrolase) and pre-synaptically by MGL (monoacylglycerol lipase) (Pertwee 2005; Muccioli 2010; Battista et al. 2012). This system represents a ubiquitous lipid signalling system (that appeared early in evolution), which plays important regula- tory roles throughout the body in all vertebrates (De Fonseca et al. 2005). Below, we will focus on the cannabinoid receptors and their ligands (can- nabinoids) because of their principal therapeutic significance. Cannabinoids are chemical substances which act primarily on specific cannabinoid receptors and are basically divided into three groups; beside endoge- nous cannabinoids (endocannabinoids) also herbal cannabinoids (phytocannabinoids) and synthetic cannabinoids have been described (Fisar 2009). Endocannabinoids are endogenously formed from membrane phospholipids in response to in- creases in intracellular calcium; they are immedi- ately released and act as ligands of cannabinoid receptors (Miller and Devi 2011). The first endog- enous ligand, n-arachidonoylethanolamine, was identified in 1992 from porcine brain (Devane et al. 1992). It was named anandamide (AEA) based on the Sanskrit word ‘ananda’ which means ‘inter- nalbliss’.Otherendogenouscannabinoidsinclude 2-arachidonoylglycerol (2-AG), 2-arachidonyl glyceryl ether (2-AGE, noladin ether) (Hanus et al. Contents 1. Introduction 2. The endocannabinoid system and classifica- tion of cannabinoids 3. The use of cannabinoids in animals 1. Introduction Cannabinoids have been used in traditional medicine for thousands of years. There are re- ports going back to ancient China (Unschuld 1986; Zuardi 2006), medieval Persia (Gorji and Ghadiri 2002) or in Europe to the 19th century (following the Napoleonic invasion of Egypt) (Kalant 2001). It is important to emphasise that the use of can- nabinoids in ancient or medieval cultures was not only because of the psychoactive effects of these substances; treatment was largely aimed at vari- ous somatic disorders including headache, fever, bacterial infections, diarrhoea, rheumatic pain or malaria (Kalant et al. 2001; Gorji and Ghadiri 2002; Zuardi 2006). Despite this fact, the use of cannabinoids is still illegal in many countries due to their psychoactive effects and addictive potential. Attempts by pharmaceutical companies in the sixth decade of the twentieth century to produce can- nabinoids with pharmacological effects and with- out psychotropic activity were not successful (Fisar 2009; Pertwee 2009), although cannabinoids with very weak or no psychotropic activity are known (e.g. cannabidiol, cannabigerol, cannabichromene) (Izzo et al. 2009; Hayakawa et al. 2010). Although cannabinoids have been attracting at- tention for many years, the last four decades have brought completely new and scientifically well- founded insights into their therapeutic potential. Since 1975 more than 100 controlled clinical tri- als with cannabinoids (or whole-plant prepara- tions) for several indications have been carried out and the results of these studies have led to the approval of cannabis-based medicine in various countries (Grotenhermen and Muller-Vahl 2012). Consequently, there is increasing interest, particu- larly in companion animal owners, regarding the possible use of cannabinoids in veterinary medi- cine. In order to cover this broad theme in a concise manner the text will first be focused on the classifi- cation of cannabinoids and cannabinoid receptors. 112

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