Transcript Cannabis
The cannabinoid system and its role in nociception Massimiliano Beltramo, PhD The plant: Cannabis • Cannabis is a genus of flowering plants that includes three putative species: – Cannabis sativa L. – Cannabis indica Lam., – Cannabis ruderalis Janisch. • These three taxa are indigenous to Central Asia, and South Asia. • Importance of the classification from a legal point of view, only Cannabis sativa products were considered illegals. Cannabis and Marijuana: Some historical information • First used for cord and cloths (around 10.000 B.C.). • Indian text Athera Veda (2000-1400 B.C.) refer to marijuana (bhang) for medical use. • Chinese herbal, Pen-ts’ao (1-2 Century A.D.) first indication of its use mixed with wine for its pain relieving properties. • O’Shaugnessey (1842) relieve of pain, anticonvulsant and muscle relaxant SCHERING-PLOUGH RESEARCH INSTITUTE Department of Neurobiology World map of cannabis use (2006-2007) United Nation World Drug Report 2008 Annual prevalence of cannabinoid use United Nation World Drug Report 2008 Evaluation of drug harm potential Drugs effects 3 Heroin 2.5 Physical harm Cocaine Barbiturates 2 Ketamine Methadone Amphetamine Benzodiazepine 4-MTA Alcohol 1.5 Tobacco LSD Ectasy Cannabis 1 0.5 Khat 0 0 0.5 1 1.5 2 2.5 Dependence (modified from Nutt et al Lancet 2007) 3 3.5 The use of cannabis in Western medicine (nineteenth century and early years twentieth century) • Chlorodyne (Squibb Co) • Corn collodium (Squibb Co) • Dr. Brown’s sedative tablets (Eli Lilly) • One Day Cough Cure (Eli Lilly) • Etc, etc, etc. • 28 different medicines contained cannabis as ingredient SCHERING-PLOUGH RESEARCH INSTITUTE Department of Neurobiology Cannabis active principles • Cannabis sativa produces about 70 compounds which are chemically related to Δ9-THC • These compounds are called cannabinoids • The psychotropic effects of cannabis product marijuana and hashish are mostly attributed to Δ9-THC Identification of cannabinoids’ binding site (Herkenham et al 1990) Localization of cannabinoids’ binding sites Autoradiographic study using [3H]CP55940 (Herkenham et al 1990) Discovery of the cannabinoid receptor 1 (CB1) • Cloning by receptor homology with bovine Substance K Discovery of CB1 In situ hybridization (Matsuda et al. 1990) Discovery of CB1 Reduction of cAMP accumulation upon cannabinoid receptor stimulation (Matsuda et al. 1990) CB1 distribution Immunolocalization of CB1 Hippocampus Basal ganglia (Tsou et al 1998) Discovery of CB2 Homology cloning Polimerase chain reaction with degenerated primers Discovery of CB2 Binding studies (Munro et al. 1993)