Cannabinoid Synthesis

Cannabinoid Synthesis

The most valuable component of cannabis Sativa is its resin, which is usually produced on female hemp flowers. This compound constitutes two closely related molecules – cannabinoids and terpenes. Accumulating scientific evidence shows that some cannabinoids like CBD have medicinal properties while others like THC have psychoactive properties. The second component of cannabis resin is terpenes, which are responsible for different cannabis aromas.

Until recently, nearly all cannabinoid-based products relied on the extraction of CBD and HTC from the hemp plant. But this ‘grow-harvest-extract’ technique has some limitations. For instance, only CBD and HTC compounds are extracted in large quantities. Besides, growing hemp plants requires several months with heavy production costs. This is an inconvenience to most American hemp farmers and healthcare facilities that offer medicinal marijuana.

Many researchers believe that cannabinoid synthesis could address these challenges without compromising the end product’s quality and quantity – cannabinoids.

What is biosynthesis?

Biosynthesis is the formation of highly complex compounds from simple substances by living organisms. It is a multi-step, enzyme-catalyzed process that facilitates the modification of simple compounds into more complex compounds through various biosynthetic pathways found in a single cell or multiple cellular organelles.

To understand this concept, think of CBD and HTC. These compounds are found in the hemp plant. But hemp farmers and various research facilities can produce cannabinoids in other ways. Contrary to synthetic cannabinoid production, which creates molecules in the laboratory, the cannabinoid biosynthesis process facilitates the production of high-quality cannabinoids just like those found in hemp plants.

How does biosynthesis work?

Here is how biosynthesis works in four steps:

  1. Identify the genetic details (DNA) from the hemp plant for a particular cannabinoid.
  2. Based on the genetic information of a cannabinoid, add the good bacteria intended to build a ‘DNA vector.’
  3. Place the DNA vector into the bacteria, where it offers a full set of instructions to produce a specific cannabinoid.
  4. Provide the optimal fermentation condition for the bacteria to replicate itself and produce cannabinoids simultaneously.

The last step involves purifying the product while adhering to pharmaceutical controls to ensure that the end product is a large-scale and pharmaceutical-grade process for preparing different cannabinoids. Generally, biosynthesis is revolutionizing the way most cannabinoids are manufactured.

If the hemp industry was all about vaping or smoking flowers, producing cannabinoids from using alternative methods would not be an issue. However, the recent changes in marijuana regulations have fueled exponential growth in both the consumer and medical cannabis market. That means hemp farmers and medical marijuana healthcare facilities need to produce higher quantities of cannabinoids.

Cannabinoid synthesis presents a unique opportunity to generate a large number of cannabinoids to meet the increasing demand. To be clear, there is a chance the hemp industry will be overbuilt considerably if biosynthesis emerges as a scalable cannabinoid production technology.

Several studies have suggested that biosynthesis creates cannabinoids with a higher level of purity, which is a unique factor beyond production cost that could spur its implementation. Besides, this technology can potentially create cannabinoids that are not expressed considerably in the plant itself. Such rare cannabinoids may be particularly appealing to most pharmaceutical companies.

Cannabinoid Synthesis

Cannaboid Biosynthetic Pathway on Greenpoint Seeds website

Biotechnology-based production of THC, CBD, and other cannabinoids requires a reliable biological system that offers a cellular supply of the precursor isoprenoid units. Also, it requires well-coordinated expression of all genes encoding the enzymes that catalyze the biosynthesis pathway for the required cannabinoid and enzyme engineering to use specific starter molecules.

Some of the currently known plant resources from which researchers can obtain biosynthetic genes include Radula marginata, Rhododendron dauricum, and Cannabis sativa. A synthetic biology approach is likely to involve combinatorial use of biosynthetic genes that encode the enzymes with optimal catalytic qualities independently of the plant species. Besides, functional interaction to prevent autoxicity from the accumulation of intermediates is a critical selection parameter.

Acid Synthase

Cannabinoids are classified into cannabinoid acids, and neutral cannabinoids base on whether they have a carboxyl group. In fresh hemp plants, the concentration of neutral cannabinoids is significantly lower compared to acid cannabinoids. For this reason, CBD and THC have often derived artificially from their acid precursors Cannabidiolic acid (CBDA) and tetrahydrocannabinol acid (THCA) through non-enzymatic decarboxylation.

CBDA (Cannabidiolic-acid) synthase is an enzyme that catalyzes the oxidative cyclization of cannabigerolic acid into Cannabidiolic acid (CBDA). This is the dominant cannabinoid constituent of cannabis Sativa (the fiber-type). It’s important to emphasize that the functional and structural properties of CBDA synthase are similar to that of THCA synthase. The latter is the enzyme responsible for the entire biosynthesis of THCA, the primary cannabinoid in the cannabis Sativa (drug-type).

With respect to cannabinoid synthesis, many researchers have reported the importance of identification and purification of novel enzymes CBDA synthase and THCA synthase usually expressed in fiber-type CBDA-rich and drug-type (THCA-rich) chemical phenotypes of the hemp plant.

These enzymes are the precursors of most pharmacologically active cannabinoids. Besides, these enzymes catalyze a somewhat unique biosynthetic reaction – the oxidative cyclization of CBGA (cannabigerolic-acid), for which no similar reaction has been reported. From the diagram above, it’s clear that CBGA serves as a critical branching point for many cannabinoids such as CBD, THC, CBE (cannabielsoin), cannabicyclol, and more.

Decarboxylation

Decarboxylation is necessary for consumers to enjoy the psychoactive properties of cannabinoids. It is the process that activates the compounds like THC in cannabis Sativa. Note that all cannabinoids within the trichomes of raw hemp flowers have an additional carboxyl group or ring (COOH) linked to their chain. For instance, THCA (tetrahydrocannabinolic acid) is synthesized in prevalence in the trichome heads of cannabis Sativa flowers. In many regulated markets, marijuana distributed in dispensaries contains labels with the product’s cannabinoid contents. In many cases, THCA prevails as the most abundant cannabinoid present in products that haven’t been decarboxylated, like cannabis concentrates and flowers.

THCA has several benefits when consumed. For example, having neuroprotective and anti-inflammatory properties. However, this compound isn’t intoxicating and should be decarboxylated to form THC to have the ‘high’ effect.

What causes decarboxylation, and is it necessary?

There are two catalysts for decarboxylation – time and heat. Drying and curing hemp over time can lead to partial decarboxylation. This is the main reason some hemp flowers test for the presence of low levels of THC. Vaporizing and smoking will instantly decarboxylate cannabinoids because of the high temperatures involved, making them instantly available for absorption via inhalation.

From the illustration given above, it is evident that decarboxylation transforms THCA compound into THC compound. During cannabinoid synthesis, decarboxylation is necessary to eliminate the carboxyl group attached to the cannabinoid chain.

Oxidative

The last step of cannabinoid biosynthesis is oxidative aromatization. During this process, tetrahydrocannabinol is converted into CBN, which is in turn photochemically transformed into CBND. It’s important to emphasize that the specific cannabinoid biosynthesis pathway depends on the desired end product. For example, the biosynthesis pathway for CBD production is different from that of CBN.

The Delta-8-THC

In the past decade, researchers have introduced amazing cannabinoids like THCV, CBG, and CBD, which are much sought after for their medicinal or therapeutic properties. What most people don’t know is that there are different molecules of THC. Actually, there are 30 known different THC molecules, and Delta-8-THC is one of them.

Delta-8-Tetrahydrocannabinol is also known as Delta-8-THC and is a psychoactive cannabinoid found in the hemp plant. A regular THC bud or hemp flower contains less than one percent of Delta-8-THC.

Studies have shown that Delta-9-THC (the common THC compound) is the most abundant cannabinoid in weed, followed by the CBD compound. In a hemp plant, CBD is the most abundant compound. It’s also known that American hemp farmers and geneticists have been carrying out experiments with different hemp strains in which the two primary compounds (CBD and THC) tip the scales or come to a balance. These activities are medically motivated.

Further studies have proved that there are over 100 cannabinoids in the marijuana plant. Most of these compounds emerge out of some kind of chemical process that involves enzymatic synthesis. These processes begin with acids such as cannabigerolic acid (CBGA). Other compounds used in cannabinoid synthesis processes include CBDA, CBCA, and THCA or CBCVA, THCVA, CBDVA, and more.

Like cannabinol (CBN), Delta-8-THC isn’t produced like many cannabinoids. It is created through the degradation of Delta-9-THC compound through oxidation. The result is a different chemical structure that will cause an entirely unique experience with THC effects. Besides, the Delta-8-THC molecule is more stable than the Delta-9-THC molecule, which means it has a longer shelf life.

Studies have shown that Delta-8-THC naturally occurs in low quantities in marijuana and hemp plants. Therefore, cannabis farmers and extractors must find another way to manufacture large quantities of this stable molecule. This is done by deriving the compound from CBD or Delta-9-THC in the laboratory. There is a lot of debate about whether or not Delta-8-THC is illegal. So, consumers, farmers, and hospitals that offer medical marijuana should seek help from a legal expert.

D8 THC vs. Regular THC

Just like Delta-9-THC, D8 THC binds with the user’s CB1 receptors, which are majorly in the central nervous system. This compound is believed to have a higher affinity for CB2 receptors, but in-depth research is necessary to prove this theory.

What makes D8 THC different is its low psychotropic potency. Recent research and anecdotal evidence suggest that D8 THC is a somewhat tame version of the regular THC. For consumers who are not just in to get high, D8 THC can be beneficial for people in need of nausea relieving and appetite-stimulating properties of Delta-8-THC. It’s important to mention that D8 doesn’t cause mental stimulation such as paranoia, anxiety, racing heart, and other negative effects of D9 THC. This makes Delta-8-THC a more patient-friendly alternative to the regular THC (D9) for individuals undergoing cancer treatment.

How to use D8 THC

Some of the common ways to use D8 THC include dabbing, edibles, vaping, sublingual consumption, and mixing with flower. This THC molecule is extracted from flowers or trim and then made into concentrate. As mentioned earlier, cannabis Sativa contains low levels of D8 THC, manufacturers often extract and distill it into a thick translucent fluid that’s similar to CBD distillate.

This distillate is edible and can be consumed orally. However, further scientific studies and research are necessary to determine if it’s absolutely safe to consume D8 THC distillate orally. When ingested, this compound turns into delta-11 THC.

Summary

A recent analysis of the current and future market demand for cannabinoid products shows that consumers are focused on consistency, purity, and stability of product supply. For many reasons, many American cannabis farmers and medical marijuana facilities will find it challenging to meet the growing demand unless there is a more effective and still safe way to address the growing demand.

Inspired by these challenges, researchers have been exploring another option to supplement the traditional ‘grow-harvest-extract’ method of producing cannabinoids. Cannabinoid biosynthesis is a concept that could potentially help address the growing demand for cannabinoids and the manufacture of rare cannabinoids such as Delta-8-THC and other related compounds.