Patterns of Inheritance in the Biosynthesis of Cannabidiol (CBD)

Cannabidiol (CBD)

Cannabidiol (CBD) is one of the naturally occurring cannabinoids found in cannabis plant. CBD is 21-carbon terpenophenolic compound. It is formed naturally (biosynthetically) as a result of the decarboxylation of a cannabidiolic acid (CBDA) precursor which is derived from cannabigerolic acid (CBGA). However, the compound can also be produced synthetically. The study of the biosynthetic pathway of cannabidiol is important to scientific researchers and medical practitioners in helping them understand the process involved in the production of pure CBD which has been applied for medical purposes such as treatment of epilepsy (e.g. Epidiolex), psychosis, and other clinical conditions. The paper is about the description of the steps involved in the biosynthetic pathway of cannabidiol to understand the inheritance of the chemical phenotype the plant, Cannabis sativa L.

The Chemotypical Diversity in Cannabis

In the study, four crosses were made between inbred Cannabis sativa plants and pure cannabidiol (CBD) and tetrahydrocannabinol (THC) chemotypes and the F1phenotype plants were analyzed to determine the cannabinoid composition through gas chromatography(Meijer et al., 2018). The F1's were found to have a mixed CBD and THC chemotypes, however CBD if found in high concentration. The terpenophenolic substances, cannabinoids are found accumulated in glandular trichomes of Cannabis sativa plant. In an experiment to determine the chemotypical diversity in Cannabis, (Small and Beckstead, 1973), found out that in the population composition, there are three chemotypes, i.e. chemotype 1 (THC content greater than 0.3%; CBD content greater than 0.5%), intermediate chemotype 2 (CBD content is constant while the THC content varies in concentrations), and chemotype 3 (low THC content). It was observed also observed that plants which belonged to the same species showed distinct THC/CBD ratios of content composition.

The Biosynthesis of Cannabinoids

Cannabinoids are synthesized and accumulated in cannabis plants as cannabinoid acids (cannabidiolic acid, CBDA). When the herbal product is dried, stored, and heated, the acids present decarboxylize or neutralize into neutral forms (CBDA to CBA). In cannabinoid synthesis, the first step is a condensation reaction involving geranylpyrophosphate (GPP) and olivetolic acid (OA), a polyketide (2018). The reaction is catalyzed by an enzyme geranylpyrophosphate: oliveolate geranyltransferase (GOT). The CBG that is produced is later used to produce CBD and CBC. The THC was earlier considered to result from the cyclization of CBD and the pathway is: CBG to CBD to THC. Currently, THC is believed to be a derivative of CBG in all Cannabis strains. The final step, i.e. in vivo conversions of CBG into THC, CBD, and CBC end products are catalyzed by the enzyme, THC synthase, CBD synthase, and CBC synthase.

Chemotype Inheritance

The content of cannabinoids in different parts of the cannabis plant at different stages of growth is influenced by environmental factors. However, the distribution of CBD/THC ratios in many populations underlie a discrete pattern of inheritance of the chemotype trait (Meijer et al., 2018). The cannabinoid content of every plant is determined by the genetic background and chemical group of the plant in all its life cycle. (Fournier and Paris, 1979, 80): in French fiber cultivars, there is a segregation of CBD/THC ratios, i.e. 1:4. 1(plants with mixed CBD-THC profiles) and 4(plant with almost pure CBD profiles). An observation made after an analysis of the F2 from F1 hybrids with similar amounts of CBD and THC is that the segregation of chemotypes of pure CBD, mixed CBD-THC, and pure THC profiles is in ratio, 1:2:1. An investigation of pure CBD plants’ generations expressed a fixed CBD chemotype. A monogenic inheritance of THC and CBD ratios was observed after segregating the F2 plants. Other observations made by other researchers is that plants with one of the cannabinoids being dominant (CBD or THC), are usually present as 95-98%. These plants are referred to as pure chemotypes which can be found occurring naturally or can be produced by self-fertilization of plants of mixed chemotypes. A mutual cross of S2 parents produced plants with THC and CBD content in considerable amounts. Pure chemotypes were absent in the results. These are the characteristics of parental inbred strains.

Conclusion

In the above description, the knowledge of the patterns of inheritance in the biosynthesis of cannabidiol (CBD) led to the application of sex reversion or self -fertilization of female cannabis plants to obtain S2, F1, and F2 plants so as to determine the inheritance patterns of the chemical phenotypes (chemotypes) of the dioecious plants and if the CBD:THC ratio varies. This description data is therefore important in prediction of future genetic loci and cannabinoid composition of the cannabis plants which can be important in scientific and therapeutic research (especially CBD which is used as an herbal product).

References

 (2018). Retrieved from http://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf

Meijer, E., Bagatta, M., Carboni, A., Crucitti, P., Moliterni, V., Ranalli, P., & Mandolino, G. (2018). The Inheritance of Chemical Phenotype in Cannabis sativa L. Retrieved from http://www.genetics.org/content/163/1/335