Cultivation

Breeding programme

GW's team includes experts in Cannabis breeding. In the genetic model used, the cannabinoid content of each chemical phenotype (chemotype) is controlled by four independent loci. By manipulating the genes at these four positions, our scientists can precisely control the cannabinoid composition of a plant. This is explained in the diagram below:

 

cannabinoid compounds

The gene at locus O allows the production of the initial phenolic precursors (resorcinolic acids). These combine with geranyl pyrophosphate to create the intermediate cannabinoids CBG and/or CBGV, the central precursors for the end-product cannabinoids THC(V), CBD(V) and CBC(V). The functional allele O is co-dominant; O/o hybrids have a low cannabinoid content and o/o plants are cannabinoid-free.

The ratio of propyl- and pentyl cannabinoid precursors is determined by a postulated locus A, which is still under investigation.

 

The CBG/CBGV intermediate is further processed by the alleles of locus B. BD and BT are co-dominant; the BD gene converts CBG(V) into CBD(V) and the BT gene converts CBG(V) into THC(V). In the BD/BT genotype, codominance allows the expression of a mixed CBD/THC chemotype. Also at this locus, non-functional alleles, designated B0 can exist; these are unable to convert the CBG(V) intermediate and leave the plant with a CBG(V) predominant chemotype.

 

Locus C is fixed so all plants have CBC synthase activity. CBC synthase competes for the same CBG(V) precursor as the synthases encoded by locus B (THC and/or CBD synthase). In 'normal' Cannabis plants, CBC synthase is only active in the juvenile state. However, our scientists have discovered genetic factors that induce morphological mutations that are associated with a 'prolonged juvenile chemotype'. Prototype CBC production plants carry these factors in combination with B0/B0 at locus B. In these plants CBC synthase has no competition from THC or CBD synthase.


References

Meijer EPM de, Bagatta M, Carboni A, Crucitti P, Cristiana Moliterni VM, Ranalli P, Mandolino G. 2003. The inheritance of chemical phenotype in Cannabis sativa L. Genetics 163: 335–346.


Meijer EPM de, Hammond KM. 2005. The inheritance of chemical phenotype in Cannabis sativa L. (II): cannabigerol predominant plants. Euphytica145: 189-198.


Meijer EPM de, Hammond KM, Micheler M. 2009. The inheritance of chemical phenotype in Cannabis sativa L. (III): variation in cannabichromene proportion. Euphytica 165:293-311.


Meijer EPM de, Hammond KM, Sutton A. 2009. The inheritance of chemical phenotype in Cannabis sativa L. (IV): cannabinoid-free plants. Euphytica 168: 95-112.


Licensed and controlled cultivation

GW is licensed by the UK Home Office. Cultivation of GW's first Cannabis plants began in August 1998. Selected seedlings are maintained as clones. Clones are genetically identical, thus ensuring that the ratio of plant constituents is fixed within narrow limits. Clonal propagation does not involve genetic modification.

 

GW's botanical research team continues to develop new chemotypes. These will produce the raw material bases for future pharmaceutical research.

 

GW's Cannabis plants are grown in highly secure computer-controlled glasshouses. All aspects of the growing climate, including temperature, air change and photoperiod, are computer-controlled and the plants are grown without the use of pesticides. Careful control of the growing environment ensures that GW’s plant material is grown to very strict pharmaceutical standards and that growth is phased to ensure continuity of supply.

 

Cultivation capability has been increased to cater both for commercial supply of our first product Sativex® and research quantities of novel chemotypes for the production of other medicines. Pharmaceutical production capacity has also been scaled up, both in-house and through external contractors, to supply tens of thousands of patients.

 

High levels of chemical consistency are important in applications made to medical regulatory authorities. Routine laboratory analysis demonstrates that GW’s botanical raw materials meet strict specifications of quality.

 

References

Potter D. 2004. “Growth and morphology of medical cannabis,” pp. 17-54 in Guy G, Robson R, Strong K, Whittle B, eds. The Medicinal Use of Cannabis. Royal Society of Pharmacists, London.


McPartland JM, Clarke RC, Watson DP. 2000. Hemp Diseases and Pests - Management and Biological Control. CABI Publishing, Oxford University Press, UK. 251 pp.