Cannabis By Any Other Name

The number of species that compose the genus Cannabis is often debated. Some experts’ claim that the genus is composed of three distinct species designated Cannabis sativa, Cannabis indica and Cannabis ruderalis (1, 2). Others contend that the genus is composed of a single species—C. sativa L—which exhibits high degrees of variations and heterogeneity within different subpopulations.

According to most current scientific conventions, the plant is usually classified as a single species C. sativa.  Historically, most of the groupings or subdivisions in the genus have been made on physical characteristics or uses of the plant. For example, hemp plants are described as tall and skinny do not produce cannabinoids or terpenes (3) are not psychoactive when consumed and are mainly used for the extraction of fiber and oil (4).  Indica plants are typically short with broad leafs and generally are associated with sedative effects after consumption. Sativa plants are tall and skinny with narrow leafs, produce high levels of cannabinoids and terpenes and mediate psychoactive effects after consumption. (4). In addition, a large number of so-called Cannabis hybrids (crosses between the three Cannabis types) also exist.

Recent genomic and molecular biological analyses are beginning to provide new insights into the actual classification of the Cannabis genus. At present, there are six whole-genomes assemblies (two each) of three different strains of C. sativa. (4) These include Purple Kush (5, 6); Chemdawg (4) and LA confidential (4). In addition, there are two sativa transcriptomes (whole genome RNA analyses) [5], four mitochondrial genome assemblies (three sativa and one hemp) [4, 5, 7, 8], 6 chloroplast genome assemblies (5, 7, 9) and over 393 additional genomic resources that are being used to learn more about Cannabis classification (4).

Result of studies using the above mentioned genetic tools suggest that hemp is a distinct group and that two marijuana-type groups may also exist (5, 10, 11). To interpret their results, researchers suggested a naming convention based on leaf phenotypes: narrow-leaf drug type (NLDT) aka sativa, broad-leaf drug type (BLDT) aka indica and hemp (11). While 86% of plants classified as hemp fell into the hemp category, only 19% of popular sativa cultivar/brands fell into the NLDT category (sativa) and 27% of indica strains clustered within the BLDT (indica) group. Interestingly, 36% of so-called hybrid strains fell into the BLDT (indica) group and 62% were placed in the NLDT (sativa) category (4). Further, cultivars/brands that are most popularly reported as 100% sativa can be more closely related to be 100% indica (4).

Thanks to these genomic analyses it appears that the colloquial classifications given to individual Cannabis plants are not accurate. That said, it is important to note that the current genomic classification scheme is based on a small sample size and may not represent the actual genetic variation that exists in the Cannabis genus. To confirm or refute this possibility, more genomic analyses of existing Cannabis cultivars/brands must be performed before the genus can be accurately classified.

While current genomic studies may appear to be a purely academic exercise to some, accurate classification of Cannabis plants will be vitally important as Cannabis growers attempt to validate the identity, quality and properties of the cultivars/brands that they sell for medical or recreational purposes.

References 

  1. Hillig, K. W., and Mahlberg, P. G. A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae) Am. J. 2004; Bot. 91:966–975
  2. Hillig, K. W. Genetic evidence for speciation in Cannabis (Cannabaceae). Genet. Resources Crop Evol 2005; 52: 161–180
  3. Small, E, and Cronquist, A. A practical and natural taxonomy for Cannabis. Taxon. 1976; 25:405–435
  4. Vergara D,  Baker, H, Clancy K,  Keepers KG, Mendieta JP, Pauli CS,  Tittes SB, White KH, Kane,NC  Genetic and Genomic Tools for Cannabis sativa, Critical Reviews in Plant Sciences, 2016; 35:5-6, 364-377, DOI:10.1080/07352689.2016.1267496
  5. van Bakel,H., Stout, J. M., Cote, A. G., Tallon, C. M., Sharpe, A. G., Hughes, T. R., and Page, J. E. The draft genome and transcriptome of Cannabis sativa. Genome Biol. 2011;   12:1241–1250
  6. Li, R., Zhu, H., Ruan, J., Qian, W., Fang, X., Shi, Z., Li, Y., Li, S., Shan, G., and Kristiansen, K. De novo assembly of human genomes with massively parallel short read sequencing. Genome Res. 2010; 20: 265–272
  7. Vergara, D.,White, K. H., Keepers, K. G., and Kane, N. C. The complete chloroplast genomes of Cannabis sativa and Humulus lupulus. Mitochondrial DNA Part A 2015; 27: 3793–3794
  8. White, K. H., Vergara, D., Keepers, K. G., and Kane, N. C. The complete mitochondrial genome for Cannabis sativa. Mitochondrial DNA Part B 2016; 1: 715–716
  9. Oh, H., Seo, B., Lee, S., Ahn, D.-H., Jo, E., Park, J.-K., and Min,G.-S. Two complete chloroplast genome sequences of Cannabis sativa varieties. Mitochondrial DNA Part A. 2015; 27:2835–2837
  10. Sawler, J., Stout, J. M., Gardner, K. M., Hudson, D., Vidmar, J., Butler, L., Page, J. E., and Myles, S. The genetic structure of marijuana and hemp. PloS One 2015; 10: e0133292
  11. Lynch, R. C., Vergara, D., Tittes, S., White, K., Schwartz, C. J., Gibbs, M. J., Ruthenburg, T. C., Land, D. P., and Kane, N.C. Genomic and Chemical Diversity in Cannabis. Crit. Rev. Plant Sci. 2016: 35: 349–363

Cannabis Genomics, Terpenes and the “Entourage Effect”

In addition to pharmacologically active cannabinoids, cannabis resins also contain a variety of terpenes (monoterpenes and sesquiterpenes) that are responsible for the scent of cannabis flowers and contribute to the unique, characteristic flavor qualities of cannabis-derived products. (1)  Over 200 terpenes have been reported in Cannabis sativa (2)

Differences in the medicinal properties of different cannabis strains have been attributed to interactions (or entourage effect) between cannabinoids and various terpenes (2, 3). For example, several cannabis terpenes (most notably, β-Caryophyllene (BCP) have been reported to interact with human cannabinoid receptors (4).  Put simply, terpenes plus cannabinoids—not cannabinoids alone—may be responsible for some of the medicinal benefits attributed to cannabis.  Consequently, it has been proposed that blends of cannabinoids and terpenes could be used in medicinal cannabis preparations to maximize therapeutic benefits via the so-called entourage effect (5). Finally, other research shows that terpenes may contribute to the anxiolytic, antibacterial, anti-inflammatory and sedative effects of Cannabis (2).

While much is known about the phytochemical composition of terpenes for forensic analysis and cannabis breeding, little is know about the molecular biology of terpene biosynthesis in cannabis.  In a recent paper, Booth et al (1) successfully identified nine terpene genes that appear to be involved in all stages of cannabis terpene biosynthesis. The authors suggested that knowledge of the genomics and gene functions of terpene biosynthesis may allow genetic manipulation of cannabis for desirable terpene profiles.  Further, genetic manipulation of terpene biosynthesis may help to scientifically unravel the so-called entourage effect and maximize the medicinal benefits of individual cannabinoids and cannabis-derived pharmaceuticals.

References

  1. Booth JK, Page JE, Bohlmann J. Terpene synthases from Cannabis sativa. PLoSOne 2017; 12:e0173911
  2. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. British Journal of Pharmacology. 2011; 163: 1344–64
  3. ElSohly MA, editor. Marijuana and the cannabinoids. Springer Science & Business Media; 2007. November 15.
  4. ElSohly MA, editor. Marijuana and the cannabinoids. Springer Science & Business Media; 2007. November 15.
  5. Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009; 16: 97–110

Science Job Opportunities Exist in the Cannabis Industry

According to a recent article, the 2013 to 2014 US market for legal Cannabis (medical and recreational) grew 74% from $1.3 billion to $2.7 billion. Industry analysts predict that the legal marijuana industry is (and will continue to be) the fastest-growing industry in the US over the next 5 years with annual revenues topping $11 billion by 2020.  And, as the industry grows so will employment opportunities.

At present, salaries associated with various job functions in the Cannabis industry range from $50,000 to $90,000. As many businesses that support the Cannabis industry continue to grow, the competition for qualified employed will intensify and salaries will concomitantly rise. Currently,, there aren’t enough trained job candidates to fill the many job openings at Cannabis companies. I am sure that many of you who hold graduate degrees in the life sciences are wondering why I am pitching jobs in the Cannabis industry.

First, traditional jobs for PhD-trained life scientist are getting scarcer and the election of Donald Trump suggests that this trend will not be reversed anytime soon.

Second, consider that growing and cultivating marijuana and extracting cannabinoids (the pharmaceutically active molecules in Cannabis buds) require a background in laboratory methods, chemistry, biology and in some cases plant science. For those of you who may not know, the medical Cannabis market is focusing almost exclusively on cannabis extracts and vaporization of these extracts (rather than smoking) is the preferred delivery methods. This suggests that those of you with backgrounds in biomedical engineering and medical devices  can leverage your expertise and skills to obtain jobs in the delivery side of the cannabis industry.  

Third, the expansive growth and sheer economic size of the Cannabis industry suggests that other jobs that require a life science background are likely to emerge. These include quality control/assurance jobs for strain identification, diagnostic jobs to determine THC levels/intoxication, molecular biology and bioinformatic jobs to continue to explore and unlike therapeutically relevant molecules from the Cannabis genome and synthetic biology jobs to increase cannabinoid yields and reduce production costs. Finally, there is currently a dearth of qualified job candidates with scientific backgrounds to fill entry level grow and extraction jobs in the Cannabis industry.

At present, the industry is mainly dominated by long time Cannabis growers, people who use marijuana on a regular basis and some moxy business people/investors who see an an enormous upside for the Cannabis industry.

Put simply, now is the time to get in on the ground floor of an industry that is exploding and will ultimately become a legal multibillion dollar a year industry. While I’m sure that neither you nor your parents/family envisioned a career in Cannabis, the jobs are there and ripe for the picking (pun intended).