the cannabinoid system and its role in nociception
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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. - PowerPoint PPT PresentationTRANSCRIPT
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The cannabinoid system and its role in nociception
Massimiliano Beltramo, PhD
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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.
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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
Department of NeurobiologySCHERING-PLOUGHRESEARCH INSTITUTE
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World map of cannabis use (2006-2007)
United Nation World Drug Report 2008
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Annual prevalence of cannabinoid use
United Nation World Drug Report 2008
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Evaluation of drug harm potentialDrugs effects
4-MTA Alcohol
Heroin
CocaineBarbiturates
KetamineMethadone
Cannabis
Amphetamine
Ectasy
Benzodiazepine
LSD
Khat
Tobacco
0
0.5
1
1.5
2
2.5
3
0 0.5 1 1.5 2 2.5 3 3.5
Dependence
Phy
sica
l har
m
(modified from Nutt et al Lancet 2007)
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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
Department of NeurobiologySCHERING-PLOUGHRESEARCH INSTITUTE
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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
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Identification of cannabinoids’ binding site
(Herkenham et al 1990)
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Localization of cannabinoids’ binding sites
(Herkenham et al 1990)
Autoradiographic study using [3H]CP55940
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Discovery of the cannabinoid receptor 1(CB1)
• Cloning by receptor homology with bovine Substance K
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Discovery of CB1
(Matsuda et al. 1990)
In situ hybridization
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Discovery of CB1
Reduction of cAMP accumulation upon cannabinoid receptor stimulation
(Matsuda et al. 1990)
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CB1 distribution
(Tsou et al 1998)
Immunolocalization of CB1
Basal ganglia
Hippocampus
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Discovery of CB2Homology cloningPolimerase chain reaction with degenerated primers
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Discovery of CB2
(Munro et al. 1993)
Binding studies