CANNABIS REVIEW Prepared by: Dr. Arno Hazekamp Department of Plant Metabolomics Leiden University Leiden, The Netherlands 2008-2009INDEX 1 Ll 12 13 14 21 22 221 2.22 23 24 241 24.2 243 244 245 246 247 248 Br 3.2 33 34 3S 4l 42 AN INTRODUCTION TO THE CANNABIS PLANT The Different Forms of Cannabis The Botany of Cannabis sativa A Short History of Cannabis Chemical Constituents of Cannabis CANNABINOIDS Cannabinoids Defined Biosynthesis of the Cannabinoids The acidic cannabinoids Occurence of short-chain cannabinoids and other homologues A Phytochemical Classification of Cannabinoids Chromatographic Analysis of Cannabinoids Decarboxylation Microscopy Color reactions Thin-layer chromatography Gas chromatography High-performance liquid chromatography Other techniques Spectroscopic and chromatographic data SITES AND MECHANISMS OF ACTION OF CANNABINOIDS The Cannabinoid Receptors: CBI and CB2 The Endocannabinoid System Pharmacokinetics of the Cannabinoids (ADME) Structure-Activity Relationships of Cannabinoids Administration Forms BIOLOGICAL EFFECTS OF THE CANNABINOIDS: Delta-9-Tetrahydrocannabinol (THC) Cannabidiol (CBD)43 Delta-8-Tetrahydrocannabinol (Delte-8-THC) 44 Cannabigerol (CBG) | 45 Cannabinol (CBN) | 46 Cannabichromene (CBC) 47 Tetrahydrocannabivarin (THCY) 48 The Acidic Cannabinoids 5. NON-CANNABINOID CONSTITUENTS OF CANNABIS. 51 Terpenoids 55.1 Biosynthesis and composition of Cannabis essential oils 5.12 Biological effects ofterpenoids 52 Flavonoids 5.2.1 Biosynthesis of flavonoids in cannabis 5.2.2 Biological effects of flavonoids | 523 ‘Therapeutic potential | 53 Hemp O11 53.1 Production methods 5.3.2 Composition of hemp oit 533 Therapeutic potential 5.34 Cannabinold contamination of hemp oil products 54 Other Components Found in Cannabis 5A Alkaloids and nitrogenous compounds | 542 Non-cannabinold phenols | 543 Stilbenoids 544 Lignanamides and phenolic amides 6. CANNABIS AS A MEDICINE 61 Therapeutic Potential of Cannabinoids 62 Current Status of Cannabinoid Medicines 63 Approaches for Further Development 63.1 Improving the biological availability of cannabinoids 632 Selective activation of cannabinoid receptors 63.3 Modulating the endocannabinoid system . 634 Interaction with other neurotransmitter pathways .