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Cannabinoid synthesis has caused a heated debate among researchers. So, what’s cannabinoid biosynthesis? Could it be the key to unlock the mass production of cannabinoids?
The most valuable component of cannabis Sativa is its resin, which primarily develops in the crystal-like trichomes that coat 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 hemp plants from which to extract CBD and THC. But this ‘grow-harvest-extract’ technique has some limitations. For instance, processors can only extract CBD and THC in large enough quantities to sell. Moreover, growing hemp requires several months of work, heavy production costs, and extensive regulatory provisions. The inconvenience is enough to deter many American farmers and healthcare facilities from joining in the green rush, to begin with.
Many researchers believe that cannabinoid synthesis could address these challenges without compromising the end product’s quality and quantity – cannabinoids.
What is Cannabinoid Synthesis?
Biosynthesis is the formation of highly complex compounds from simple substances by living organisms. It is a multi-step, enzyme-catalyzed process that helps modify simple compounds into more complex compounds. The process involves various biosynthetic pathways found in a single cell or multiple cellular organelles.
To understand this concept, think of CBD and THC, both of which are highly valuable compounds that develop in the hemp plant. But hemp farmers and various research facilities can produce cannabinoids in other ways, too. 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.
Though it may sound complicated, cannabinoid biosynthesis is actually quite simple. Here is how biosynthesis works.
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 many manufacturers develop cannabinoids.
If the hemp industry was all about vaping or smoking flower, producing cannabinoids 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.
Biosynthesis presents a unique opportunity to generate a large amount of cannabinoids to meet the increasing demand. To be clear, the hemp industry may take on a whole new identity 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 many patients and pharmaceutical companies.
Medical researchers were borrowing decades of knowledge of insulin production and modified this process to make cannabinoids. To understand the cannabinoid biosynthesis process, check this illustration.
Biotechnology-based production of THC, CBD, and other cannabinoids require 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 will likely involve combinatorial use of biosynthetic genes that encode the enzymes with optimal catalytic qualities that are independent of the plant species. Besides, functional interaction to prevent autotoxicity from the accumulation of intermediates is a critical selection parameter.
Scientists classify cannabinoids as either cannabinoid acids or 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 often develop artificially from their acid precursors Cannabidiolic acid (CBDa) and tetrahydrocannabinol acid (THCa) through non-enzymatic decarboxylation. Hemp decarboxylation improves bioavailability, and the efficiency through it absorbs.
CBDa (Cannabidiolic-acid) synthase is an enzyme that catalyzes the oxidative cyclization of Cannabigerolic acid (CBGa) 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 both CBDa-rich hemp THCa-rich marijuana.
These enzymes are the precursors of most pharmacologically active cannabinoids. Interestingly, these enzymes catalyze a somewhat unique biosynthetic reaction – the oxidative cyclization of CBGa (Cannabigerolic-acid). What’s especially exciting is that no researchers have reported a similar reaction elsewhere. 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.
Here is a common scenario in films: a person consumes a huge chunk of raw weed to avoid getting caught by the police. Eyes pop open, and gasps ensue. But the aftermath of such a scene involves a different representation of what happens whenever a person consumes raw weed. The impact will be lackluster at best! Why?
The answer lies in a process commonly known as decarboxylation, which 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, the trichome heads of cannabis Sativa flowers primarily develop THCa (tetrahydrocannabinolic acid) from CBGa (Cannabigerolic-acid). 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.
Notably, THCa has several benefits when consumed, like having neuroprotective and anti-inflammatory properties. However, this compound isn’t intoxicating; consumers must decarboxylate it to produce the ‘high’ effect.
So, 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 immediately available for absorption via inhalation.
From the illustration given above, it is evident that decarboxylation transforms THCa compound to THC compound. During cannabinoid synthesis, decarboxylation is necessary to eliminate the carboxyl group attached to the cannabinoid chain.
The last step of cannabinoid biosynthesis is oxidative aromatization. During this process, tetrahydrocannabinol converts into CBN, which then photochemically transformes 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.
Researchers have introduced amazing cannabinoids like THCV, CBG, and CBD, which are much sought after for their medicinal or therapeutic properties in the past decade. What most people don’t know is that there are different molecules of THC. Actually, there are 30 known other THC molecules, and Delta-8-THC is one of them.
Delta-8-Tetrahydrocannabinol is also called 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. So, why does it occur in low quantities?
Studies have shown that Delta-9-THC (the common THC compound) is the most abundant cannabinoid in weed, followed by the CBD compound. Conversely, in a hemp plant, CBD is the most abundant compound. 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.
Developing Cannabinoids Beyond the Plant
Further studies have proved that there are over 100 cannabinoids in the marijuana plant. Most of these compounds develop through chemical processes that involve 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 develops uniquely compared to most other cannabinoids. Specifically, it develops through the degradation of Delta-9-THC compound via oxidation. The result is a different chemical structure that produces a unique experience that is comparable to THC. Interestingly, the Delta-8-THC molecule is more stable than the Delta-9-THC molecule, which means it has a longer shelf life, too.
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. They do this 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. As such, consumers, farmers, and hospitals considering D8 as an alternative to D9 THC should seek help from a legal expert.
D8 THC vs. regular THC
Like Delta-9-THC, D8 THC binds with the user’s CB1 receptors, which primarily occur in the central nervous system. This compound may 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. So, what are the benefits of this compound? Well, 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 adverse effects of D9 THC.
This makes Delta-8-THC a more patient-friendly alternative to the regular THC (D9) for individuals enduring cancer treatment. It has even been used successfully in a study involving children undergoing cancer treatment. The point is; Delta-8-THC has many THC-related effects but lacks the souped-up mental impact.
How to Use D8 THC
Some of the common ways to use D8 THC include dabbing, edibles, vaping, sublingual consumption, and mixing with hemp 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.
Many consumers prefer to ingest this distillate orally, making it a prime choice for DIY edibles. 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.
Summarizing Cannabinoid Synthesis
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 synthesis 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.
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