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The Endogenous Cannabinoids and the Control of Drug Craving Alexandros Makriyannis, Director.

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Presentation on theme: "The Endogenous Cannabinoids and the Control of Drug Craving Alexandros Makriyannis, Director."— Presentation transcript:

1 The Endogenous Cannabinoids and the Control of Drug Craving Alexandros Makriyannis, Director

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3  9 /  8 -THC  9 -THC /  8 -THC  9 -tetrahydrocannabinol  8 -tetrahydrocannabinol

4 Medicinal Uses for Cannabinoids AnalgesicAnticonvulsiveSedativeAntidepressiveHypnoticAntiasthmaticImmunomodulation Memory Enhancing Anesthetic Birth Control Appetite Stimulation Antipyretic Neuropathic Pain AntiemeticAntirheumaticAntimigraineAntineuralgic Reduction of Fatigue

5 Two Cannabinoid Receptors: CB1 & CB CB2 e1 e2 e3 i1 i2 i3 Extracellular 472 amino acids 360 amino acids

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7 Endogenous Cannabinoid Receptor Ligands Anandamide2-Arachidonylglycerol Palmitylethanolamide CB CB1CB2CB1 K i (nM)

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9 Cannabinoid Targets for Drug Discovery

10 Nature Neuroscience, Vol. 2, 4, (1999)

11 Retrograde Signaling & the Cannabinergic System

12 Purification of FAAH MW: 63 kDaMW: 63 kDa pI: 6.2pI:

13 Inhibition of [ 3 H]anandamide accumulation by AM 404 and AM403 Science, Vol. 277, (1997) AM404 AM403

14 Pharmacological Tools

15 Cannabinergic Ligands O N H OH AM 251 Anandamides (AEA’s) AM356 1,5-Biarylpyrazoles  8 -THC Aminoalkylindoles(AAI’s) Non-Classical (NCC’s) AM630 OH OH O H Classical (CC’s) CP55,940

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