The function of the endocannabinoid system

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The plant Cannabis sativa has been widely used by humans over many centuries as a source of fiber, for medicinal purposes, for religious ceremonies and as a recreational drug. Currently almost 500 compounds have been identified in this plant (ElSohly and Slade, 2005). Among them are at least 70 phytocannabinoids, all of which are terpenophenolic compounds uniquely present in Cannabis sativa. Two phytocannabinoids that have attracted particular attention are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the structures and stereochemistry of which were elucidated in the 1960s (Mechoulam and Shvo, 1963; Mechoulam and Gaoni, 1965; Pertwee, 2008). Δ9-Tetrahydrocannabinol is considered to be the main psychotropic constituent of cannabis, whereas CBD lacks psychotropic activity but does possess anti-inflammatory and anti-psychotic properties (see Chapter 2). Originally, because of its hydrophobic nature, it was suggested that the effects of THC were due to a non-specific perturbation of cell membranes. Subsequently, however, after the synthesis of the first THC enantiomers (Mechoulam et al., 1980, 1988), it was observed that the pharmacological actions of THC were stereoselective, raising the possibility that it might be targeting a specific receptor. Eventually a “cannabinoid receptor” was indeed discovered, opening up a new “era” in the field of cannabinoid research (Pertwee, 2006a). Although many of the effects of THC are cannabinoid receptor-mediated, evidence has emerged that at least some naturally occurring and synthetic cannabinoids can also target other receptors (Pertwee, 2010). These include the transient receptor potential (TRP) cation channel, TRPV1 (Zygmunt et al., 1999), nuclear peroxisome-proliferator-activated receptors (PPARs) (O’Sullivan, 2007), certain transmitter-gated channels and ion channels (Oz, 2006) and also several G-protein-coupled receptors, for example the orphan receptor, GPR55 (Ross, 2009). Review articles that provide more detailed information and list additional references have been cited throughout this chapter. The reader is also referred to Chapters 1 and 2 of this book.

Original languageEnglish
Title of host publicationMarijuana and Madness
Subtitle of host publicationSecond Edition
PublisherCambridge University Press
Number of pages12
ISBN (Electronic)9780511706080
ISBN (Print)9781107000216
Publication statusPublished - 1 Jan 2011

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© Cambridge University Press 2012.


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