Where does the cannabis plant come from? How do its genetics work? While there are biology focused scientists that can better answer this question than the chemistry-focused team at Digamma (and we will tag them in the final post), we will share what we have learned in this subject.
What we see here is a cladogram, which is basically a chart showing evolutionary origins of life forms by showing how closely they are related to each other by showing the last common ancestor. The timeline flows left-to-right events further in the past being farther to the left. Labeled here are the divergence of rosids from asterids, about 100 million years ago, and the divergence of cannabis from hops, about 20 million years ago. Other examples such as lavender, sage, and rosemary are labeled as well.
In this post we look at the 3 major sub-species of cannabis plants, Cannabis indica, sativa, and ruderalis. Sativa is the latin feminine form of “Sativus” which means to sow or plant, indicating that the plant is cultivated by humans. These sub-species tends to be taller and less dense and is more adjusted to wet tropical climates. Indica is latin for simply “of Indian origin” possibly a reference to the Hindu-Kush mountainous region being the geographic origin of the Cannabis plant family. Indica tends to be shorter and more dense than sativa, and prefers higher altitude and drier climates similar to its mountain homeland. The last, ruderalis, is a more wild or feral type of cannabis than the other two, and is often used for cross-breeding to mix up genetics that can grow stagnant in the indica and sativa sub-species. Please note that none of these directly correlate with the definition of “hemp”, which is simply any cannabis species plant that has a low THC, more specifically d9-THC, or more generally intoxicating cannabinoid content.
Here we get into a deeper dive into genetics and the intersection between biology and chemistry where genetics is best illustrated: biochemistry. Each gene in given life form creates an enzyme which catalyzes a chemical reaction. This reaction is either anabolic (building bonds) or catabolic (breaking bonds). Through these two switches life forms can make the molecules they need. Illustrated here is how two cannabis genes help to convert geranyl PP to linalyl PP and then the fragrant terpene limonene. Through this process cannabis, and all lifeforms, make molecules. When a breeder is selectively breeding two plants together (P for parent), they are shuffling those genes between the two parent plants to make a series of offspring (F for filius meaning child in Latin). Lets apply this biochemical genetic framework more specifically to cannabinoids in the next post.
Here we have a nice illustration of the enzyme mediated process that makes THC and CBD from a common precursor. While CBG can be thought of as a precursor it is actually CBGA that the two enzymes use as a substrate (or starting material) for making THCA and CBDA, which then decarboxylate to the more familiar cannabinoids. The ring structures are colored to show the mono- bi- and tricyclic nature of these three major cannabinoids. Enzymes are shown in black letters and compounds in grey letters.
Although the scheme shown here is a bit simple, it helps to show the key elements such as molecular structure and enzyme activity. In the next post we will expand this scheme a bit to take a wider look at the THC-CBD cannabinoid scheme.
Here we see an expanded scheme from the previous image. This scheme still only shows the activity of two enzymes, namely THCA and CBDA synthase, but shows all of the non-enzyme reactions that surround this scheme. Decarboxylation is one of the chemical processes but tautomerization, a reversible and dynamic switching between isomers, is the other key process illustrated here. This shows us the link to more rarely known cannabinoids such as cannabinerol, d8-THC, and CBG. The traditional bounds of psychoactive and non-psychoactive target compounds are indicated in red and green respectively. Notice that d8-THC has been conspicuously left out of both categories, which was very prescient given that this was made in 2014 long before the 2018 Farm Bill caused d8-THC to become the center of massive controversy. Now that we have gotten a sense for the wider scheme, we can expand it to the modern applications of cannabinoids in science and law in the following post.
Now that we have familiarity with simpler cannabinoid biochemistry we can expand it to include semi-synthetic cannabinoids which are increasingly relevant in the scientific, legal, and business landscape of cannabis. The old route of CBGA → CBDA, THCA can still be seen on the left in the acids section, and the decarboxylation to corresponding free cannabinoid can be seen just to the right in the blue. Modified chain length cannabinoids, such as THCV, go through a separate route that is upstream of CBGA. The semi-synthetics in purple show d8-THC, HHC, and THC-O-Ac as examples of chemically modified cannabinoids. The right shows fully synthetic cannabinoids which have a different, sometimes radically, chemical structure than the other 3 categories based on the cannabis plant.
Here we have a “components of cannabis” grab bag with unlabeled molecules. Just for fun, lets see if you can guess which of these is NOT present here:
1. d9-THCA
2. beta-pinene
3. CBGA
4. humulene
5. ocimene
6. CBDA
7. linalool
And to conclude our series on plant genetics in cannabis, we are sharing our wider “psychoactive plants” phylogeny tree that shows common evolutionary descent of some well known mind altering plant (and one mushroom) species. The active ingredient / compound is indicated with a molecular diagram, though there are limitations to the FDA model of a single molecule “active ingredient” that should be noted. Note that psychoactive does not mean illegal: Besides cannabis which is still in process being legalized, we have kava, coffee, tobacco, and chocolate all of which are unscheduled and have generally very minimal regulation when compared to controlled substances.
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