Download 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)