This paper aims to clarify the genetic mechanism that is responsible for the accumulation of cannabigerol (CBG) in certain phenotypes of Cannabis sativa L. CBG is the direct precursor of the cannabinoids CBD, THC and CBC. Plants strongly predominant in CBG have been found in different fibre hemp accessions. Inbred offspring derived from one such individual were crossed with true breeding THC predominant-and CBD predominant plants, respectively. The segregations in the cross progenies indicate that CBG accumulation is due to the homozygous presence of a minimally functional allele, tentatively called B 0 , at the single locus B that normally controls the conversion of CBG into THC (allele B T ) and/or CBD (allele B D ). The fact that CBG accumulating plants have so far been found in European fibre hemp populations that are generally composed of B D /B D plants, and the observation that the here investigated B 0 allele possesses a residual ability to convert small amounts of CBG into CBD, make it plausible that this B 0 is a mutation of normally functional B D . Therefore, B 0 is considered as a member of the B D allelic series encoding a CBD synthase isoform with greatly weakened substrate affinity and/or catalytic capacity.
A genetic factor that blocks the cannabinoid biosynthesis in Cannabis sativa has been investigated. Crosses between cannabinoid-free material and high content, pharmaceutical clones were performed. F 1 s were uniform and had cannabinoid contents much lower than the mean parental value. Inbred F 2 progenies segregated into discrete groups: a cannabinoid-free chemotype, a chemotype with relatively low cannabinoid content and one with relatively high content, in a monogenic 1:2:1 ratio. In our model the cannabinoid knockout factor is indicated as a recessive allele o, situated at locus O, which segregates independently from previously presented chemotype loci. The genotype o/o underlies the cannabinoid-free chemotype, O/o is expressed as an intermediate, low content chemotype, and O/O is the genotype of the high content chemotype. The data suggests that locus O governs a reaction in the pathway towards the phenolic cannabinoid precursors. The composition of terpenoids and various other compound classes of cannabinoid-free segregants remains unaffected. Backcrossing produced cannabinoid-free homologues of pharmaceutical production clones with potential applications in pharmacological research. A new variant of the previously presented allele 'B 0 ', that almost completely obstructs the conversion of CBG into CBD, was also selected from the source population of the cannabinoid knockout factor.
In 2005 and 2008, studies reported that cannabis in England had become dominated by the sinsemilla (unseeded female) form. The average potency (Δ -tetrahydrocannabinol [THC] content) of this material had doubled over the previous decade. Cannabis resin then circulating contained approximately equal ratios of THC and cannabidiol (CBD), whereas sinsemilla was almost devoid of CBD. Despite raised health concerns regarding sinsemilla use and the development of psychotic disorders, no update on street cannabis potency has been published since 2008. A total of 995 seized cannabis samples were acquired from the same 5 constabulary areas included in the 2005 study. The differing forms were segregated, and a representative 460 samples analyzed to assess their cannabinoid content using gas chromatography. The resultant median sinsemilla potency of 14.2% THC was similar to that observed in 2005 (13.9%). In each case, sinsemilla contained minimal CBD. Compared with 2005, resin had significantly higher mean THC (6.3%) and lower CBD (2.3%) contents (p < 0.0001). Although the average THC concentration in sinsemilla samples across the 5 constabularies has remained stable since 2005, the availability of this potent form of cannabis has further increased. Moreover, the now rarer resin samples show significantly decreased CBD contents and CBD:THC ratios, leaving the United Kingdom's cannabis street market populated by high-potency varieties of cannabis, which may have concerning implications for public health.
The mechanism that controls the proportion of cannabichromene (CBC), a potential pharmaceutical, in the cannabinoid fraction of Cannabis sativa L. is explored. As with tetrahydrocannabinol (THC) and cannabidiol (CBD), CBC is an enzymatic conversion product of the precursor cannabigerol (CBG). CBC is reported to dominate the cannabinoid fraction of juveniles and to decline with maturation. This ontogeny was conWrmed in inbred lines with diVerent mature chemotypes. A consistent CBC presence was found in early leaves from a diverse clone collection, suggesting that CBC synthase is encoded by a Wxed locus. Morphological variants possessing a 'prolonged juvenile chemotype' (PJC), a substantial proportion of CBC persisting up to maturity, are presented. PJC is associated with a reduced presence of Xoral bracts, bracteoles, and capitate-stalked trichomes. Genetic factors causing these features were independent of the allelic chemotype locus B that was previously postulated and regulates THC and CBD synthesis and CBG accumulation. In contrast to previously described Cannabis chemotypes, the cannabinoid composition of PJCs showed plasticity in that reduced light levels increased the CBC proportion. The ability of PJC plants to enable the production of pharmaceutical raw material with high CBC purity is demonstrated.
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