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Abstract<br />

In response to known pharmacology, and an increasing weight of anecdotal evidence of<br />

efficacy, clinical trials have been performed to support the licensing of cannabis-based<br />

botanical medicines. The initial applications envisaged were the treatment of cancer<br />

pain, neuropathic pain and various symptoms associated with multiple sclerosis. With<br />

effective alternatives often unavailable, otherwise law-abiding UK patients have regularly<br />

turned to illicit cannabis for medical relief. The main active ingredients in this are the<br />

cannabinoids THC and CBD, but other pharmacologically active cannabinoids are also<br />

present. One study reported here quantifies these cannabinoids and assesses the likely<br />

implications for efficacy. Using light microscopy, studies are performed to expand current<br />

knowledge of the form and function of trichomes in Cannabis sativa L. Supporting<br />

chemical analyses ascertain what secondary metabolites are biosynthesised within<br />

these trichomes, and determines where and when this occurs. To comply with the<br />

demands of the pharmaceutical industry, and in marked contrast to illicit cannabis, a<br />

phytopharmaceutical feedstock must meet high expectations regarding the minimum<br />

and maximum content of a range of compounds. Specific studies are performed to<br />

ascertain how growing methods affect the secondary metabolite content. They also aim<br />

to find out how a tight specification can be met while satisfying commercial and<br />

environmental expectations. This involves studying plant development and secondary<br />

metabolite biosynthesis in both indoor and outdoor conditions. The first approved<br />

cannabis-based botanical medicine supported by this research is Sativex®. This<br />

became available in Canada in 2005 for the treatment of central neuropathic pain in<br />

multiple sclerosis and in 2007 for intractable cancer pain. The medicine is also available<br />

in the UK and many other countries on a ‘named patient basis’. This thesis has also<br />

supported the production of a range of other cannabinoids which are undergoing in-vitro<br />

and in-vivo testing. This could lead to the commercial production of an increasing range<br />

of phytopharmaceuticals.<br />

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