Cannabis e glaucoma

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Cannabis e glaucoma
Usi innovativi di farmaci antichiL'attuale
rivalutazione medica della Cannabis e dei
cannabinoidi

• Dott.ssa Anna Porcella Istituto di Neurogenetica
  e NeurofarmacologiaConsiglio Nazionale delle
  Ricerche, Cagliari
• Roma 6 ottobre 2001UNIVERSITÀ "LA SAPIENZA"

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• Glaucoma
• A condition of the eye where the intraocular
  pressure is elevated beyond the limit that will
  permit normal function of the optic nerve. 
• Almost 100 million people affected
• world wide
• 7 million totally blind due to the
• progression of their glaucomas

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PRIMARY OPEN ANGLE GLAUCOMA (POAG)
Open anterior chamber
The obstruction of the trabecular meshwork
Schlemms canal system blocks the outflow of
aqueous humor
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OUTFLOW OF AQUEOUS HUMOR
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Marijuana smoking was first reported to reduce
intraocular pressure (IOP) in 1971 (Hepler and
Frank, 1971) Cloning of CB1 and CB2 receptors
and the discovery of Endocannabinoids has opened
the field for research into their physiological
roles
Distribution studies in both the brain and the
periphery have shown that in some tissues these
receptors are colocalized
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DIAGRAMMATIC CROSS SECTION OF THE ANTERIOR CHAMBER
CILIARY MUSCLE
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CB1 mRNA IN THE RAT EYE
Porcella et al. Mol. Br. Res, 1998
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CB1 mRNA IN THE HUMAN EYE
Porcella et al. Eur. J. Neurosci, 2000
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CB1 PROTEIN IN THE HUMAN EYE
Porcella et al. Eur. J. Neurosci, 2000
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ARMAMENTARIUM OF DRUGS IN USE TO TREAT GLAUCOMA
a2 Adrenoreceptor agonists b2 Adrenoreceptor
antagonists Prostaglandin Agonist Dopamninergic
agonist Cholinergic Agonist Carbonic Anhydrase
Inhibitors Guanylate Cyclase Activators Adenosine
agonist NMDA Antagonist
Cannabinoids ?
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Natural cannabinoids
?8-tetrahydrocannabinol
?9-THC
Cannabinol
Cannabidiol
Endogenous cannabinoids
Anandamide
2-AG
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Synthetic cannabinoids
Nabilone
WIN 55,212-2
CP 55,940
HU 210
LY320135
SR141716A
Palmitoyl-EA (CB2 only)
SR144528
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EFFECT OF TOPIC WIN55212-2 ON IOP OF
GLAUCOMATOUS PATIENTS
Porcella et al. Eur. J. Neurosci, 2001
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SUMMARY (1)
THE HIGH LEVEL OF CB1 mRNA AND PROTEIN IN THE
CILIARY BODY SUGGEST A LOCALIZED VASODILATION BY
CANNABINOIDS IN ADDITION INHIBITION OF
PRESYNAPTIC Ca CHANNELS BY CANNABINOIDS MAY
REDUCE NORADRENALINE RELEASE IN THE EYE AND THE
PRODUCTION OF AQUEOUS HUMOR SR141716A
ANTAGONIZES IOP LOWERING EFFECTS OF CANNABINOIDS
IN RABBITS SUGGESTING A DIRECT CB1 INVOLVEMENT IN
THIS MECHANISM HOWEVER THE MECHANISM BY WHICH
CANNABINOIDS ARE ABLE TO DECREASE IOP REMAINS TO
BE FURTHER ELUCIDATED
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SUMMARY (2) IOP LOWERING EFFECTS OF TOPIC
WIN55212-2 IN GLAUCOMATOUS PATIENTS ARE TIME AND
DOSE DEPENDENT SYNTHETIC CB1 AGONISTS SHOULD
DESERVE FURTHER RESEARCH AND CLINICAL DEVELOPMENT