Introduction to theEndocannabinoid System Dr Mark A. Ware MD MRCP MSc Alan Edwards Pain Management Unit McGill University Montreal, Quebec, Canada
Learning objectives• Review components and role of endocannabinoid system (ECS)• Summarize pharmacological strategies to harness ECS
Cannabinoids and Opioids: A Historical Perspective Cannabinoids 1988: CB1 receptor identified. 9-THC identified 1990: CB1 receptor cloned as main 1992: Anandamide discovered, CB2First Medicinal psychoactive receptor identifiedevidence of cannabis agent in 1993: CB2 receptor cloned W.B. O’Shaughnessey’smedicinal use declines Cannabis sativa 1998: Endogenous cannabinoid work popularizesuse in China cannabis use plant ligands shown to be analgesic 1900’s 1964 1988 19983000 BC 1800’s 500 BC 1522 1804 1817 1874 1900’s 1970 1975Earliest known Paracelsus 1804: Morphine Morphine analogs 1970s: Discovery of opioid receptors –reference for reference to extracted from opium synthesized: µ (mu), к (kappa), δ (delta)opium-based “laudanum”, poppy plant 1874: Diacetylmorphineelixir opium-based (heroin) 1975: Discovery of endogenous opioid elixir, as a potent 1817: Morphine first 1900s: codeine, peptides - endorphins painkiller marketed in Germany dihydromorphine, as analgesic oxycodone, pethidine, oxymorphone Opioids 1. Mack A & Joy J., 2001. 2. Notcutt W., 2004.
Source: Health Canada January 2013
Peripheral CB1 receptors
Mechanisms Of ActionOpioids Cannabinoids 1. Cappendijk S., 2010. 2. Hanks G et al., 2003. 3. Mackie K., 2006.
Metabolic pathways of endocannabinoids
Cannabinoids as immune modulators Nature Rev Drug Disc 2008;7:438-455