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The cannabinoid system and its role in nociception

The cannabinoid system and its role in nociception

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The cannabinoid system and its role in nociception

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  1. The cannabinoid system and its role in nociception Massimiliano Beltramo, PhD

  2. 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.

  3. SCHERING-PLOUGH RESEARCH INSTITUTE Department of Neurobiology 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

  4. United Nation World Drug Report 2008 World map of cannabis use (2006-2007)

  5. United Nation World Drug Report 2008 Annual prevalence of cannabinoid use

  6. (modified from Nutt et al Lancet 2007) Evaluation of drug harm potential

  7. 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 The use of cannabis in Western medicine(nineteenth century and early years twentieth century)

  8. 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

  9. (Herkenham et al 1990) Identification of cannabinoids’ binding site

  10. Autoradiographic study using [3H]CP55940 (Herkenham et al 1990) Localization of cannabinoids’ binding sites

  11. Discovery of the cannabinoid receptor 1(CB1) • Cloning by receptor homology with bovine Substance K

  12. In situ hybridization (Matsuda et al. 1990) Discovery of CB1

  13. Reduction of cAMP accumulation upon cannabinoid receptor stimulation (Matsuda et al. 1990) Discovery of CB1

  14. Immunolocalization of CB1 Hippocampus Basal ganglia (Tsou et al 1998) CB1 distribution

  15. Discovery of CB2 Homology cloning Polimerase chain reaction with degenerated primers

  16. Binding studies (Munro et al. 1993) Discovery of CB2