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Chapter 1 Introduction A vast number of plant secondary metabolites form the active ingredients of modern drugs. By definition, these are organic compounds which are not directly involved in the normal growth, development or reproduction of organisms. However they add to the plant’s survival chances by improving its resistance to predators, parasites and a range of environmental stresses. Some secondary metabolites are highly purified before being formulated as medicines. Others provide a starter material from which semisynthetic drugs are produced. Examples of both types are shown in Table 1.1. Plant-derived ingredient/ precursor Codeine, Morphine Semi-synthetic drug Product Chemical Type Medical Use Plant Source _ Opiate alkaloid Analgesic Papaver somniferum Taxol _ Diterpene ester Antineoplastic Taxus Brevifolia Vinblastine, Vincristine _ Bis-indole alkaloid Antineoplastic Catharanthus roseus Podophyllotoxin Etoposide Lignan Antineoplastic Podophyllum peltatum Diosgenin Progesterone Aglycone Steroid Birth control Dioscoria sylvatica Camptothecin Topotecan Indole alkaloid Antineoplastic Camptotheca acuminata Physostigmine Neostigmine Alkaloid Cholinergic Physostigma venenosum Table 1.1 Examples of plant derived drugs and modern semi-synthetic drugs made from the secondary metabolites of outdoor grown plants. The plant kingdom has also enabled the production of so called phytopharmaceutical or ‘botanical drugs’. These are defined as well characterised, multi-component standardised drugs extracted from plant sources. The medicine Veregen TM , derived from green tea Camellia sinensis, and approved for the topical treatment of warts (Medigene Inc.) is such an example. In 2004 the United States Food and Drug Administration issued the Botanical Drug Guidance which made it possible to bring to market a complex mixture for which evidence of adequate safety and efficacy had been established (FDA, 2004). This could result in the successful company being awarded a period of exclusivity. By 2006 Veregen TM was the only medicine to have been successful (NDA 21-902). Other botanical medicines are prescribed in some European countries but as of 2008 none were dispensed in the UK. GW Pharmaceuticals 3
Chapter 1 Introduction commenced clinical trials in the US in 2008, to evaluate the efficacy of the cannabisbased botanical medicine Sativex ® for the control of pain in terminal cancer patients. If trials were successful, a New Drug Application (NDA) would be sought. 1.2 Cannabis Botany Cannabis is a tall upright annual herb. It is generally dioecious i.e. producing separate male and female plants (Figure 1.2a), but fibre hemp varieties have been specifically bred to be monoecious (hermaphrodite) (Small and Cronquist, 1976). The leaves are palmate, and in the iconic image of a cannabis leaf there are seven lobes, the lowest pair showing as backwards-facing spurs. However this number and shape is not fixed. On seedlings the first pair of leaves is typically monophylous (single lobed), the second pair having three lobes and the next pair five. In many plants, especially of central Asian origin, the number does not extend beyond five while in others the number can extend to around thirteen. Leaf size and shape differs markedly according to genetic origin, three contrasting examples being illustrated in Figures 1.1a – c. Figure 1.1. Contrasting leaf morphology in three clones of Cannabis sativa L., (a) CBD chemotype G5 M16 cv Gill, (b) THC chemotype G1 M3 cv Guinevere (c) Afghan landrace clone M146 (Illustrations by Valerie Bolas, commissioned by GW Pharmaceuticals). Cannabis is a wind pollinated species. The males, which are generally taller than the females (Figure 1.2a), commence flowering first. The specimen in Figure 1.2a was grown in still conditions and leaves appear yellow under the deep covering of pollen. When mature, the sepals on the male flowers open to expose the anthers, which hang freely on fine filaments (Figure 1.2c). The exposed anthers soon dehisce to shed pollen onto any passing air current. Shortly after the cessation of pollen production the male dies, but females from the same population will continue to mature for up to several weeks. Females produce inflorescences containing vast numbers of florets over a 4
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References Baker, R., 2002. Commerc
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References Cerniak, L., 1985. The G
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References Dayanandan, P. & Kaufman
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References Fairbairn, J.W., 1972. T
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References Ghosal, S., Singh, S., B
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References Henderson, S.M., 1973. E
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References Johnson, J.R. and Potts,
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References Mahlberg, P.G., Hammond,
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References de Meijer, E.D.M., 1994.
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References Page, C.P., Hoffman, B.,
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References Raman, A.R., 1998. The C
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References Russo, E. B., Jiang, H.
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References Struik, P.C., Amaducci,
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References UNODC. United Nations Of
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References Wilkinson, T. J., 2006.
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Appendix 8.1 Analysis of cannabinoi
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Appendix 8.1 Analysis of cannabinoi
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Appendix 8.2 Analysis of terpene co
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Appendix 8.3 A Comparison of the St
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Appendix 8.5 Definitions of Social
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