The cannabinoid system and its role in nociception Massimiliano Beltramo, PhD
Dec 30, 2015
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
Department of NeurobiologySCHERING-PLOUGHRESEARCH INSTITUTE
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 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)
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
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
(Herkenham et al 1990)
Autoradiographic study using [3H]CP55940
Discovery of the cannabinoid receptor 1(CB1)
• Cloning by receptor homology with bovine Substance K
Discovery of CB1
(Matsuda et al. 1990)
In situ hybridization
Discovery of CB1
Reduction of cAMP accumulation upon cannabinoid receptor stimulation
(Matsuda et al. 1990)
CB1 distribution
(Tsou et al 1998)
Immunolocalization of CB1
Basal ganglia
Hippocampus
Discovery of CB2Homology cloningPolimerase chain reaction with degenerated primers
Discovery of CB2
(Munro et al. 1993)
Binding studies