The Endogenous Cannabinoids and the Control of Drug Craving

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The Endogenous Cannabinoids and the Control of
Drug Craving

• Alexandros Makriyannis, Director

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D9-THC / D8-THC
(-)D9-tetrahydrocannabinol
(-)D8-tetrahydrocannabinol
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Medicinal Uses for Cannabinoids
Analgesic Anticonvulsive Sedative Antidepressive H
ypnotic Antiasthmatic
Immunomodulation Memory Enhancing Anesthetic Birth
Control Appetite Stimulation Antipyretic
Neuropathic Pain Antiemetic Antirheumatic Antimigr
aine Antineuralgic Reduction of Fatigue
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Two Cannabinoid Receptors CB1 CB2
Extracellular
179
e2
e3
174
e1
i1
i2
i3
CB2
472 amino acids
360 amino acids
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Endogenous Cannabinoid Receptor Ligands
Anandamide
2-Arachidonylglycerol
CB2
CB1
CB2
CB1
Ki (nM)
58 145
72
279
Palmitylethanolamide
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Cannabinoid Targets for Drug Discovery
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Nature Neuroscience, Vol. 2, 4, 304-5 (1999)
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Retrograde Signaling the Cannabinergic System
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Purification of FAAH

• MW 63 kDa
• pI 6.2

32.7
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AM404
AM403
Inhibition of 3Hanandamide accumulation by AM
404 and AM403
Science, Vol. 277, 1094-97 (1997)
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Pharmacological Tools
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Cannabinergic Ligands
D8-THC
AM356
Anandamides (AEAs)
Classical (CCs)
CP55,940
Non-Classical (NCCs)
AM630
AM 251
1,5-Biarylpyrazoles
Aminoalkylindoles(AAIs)
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