At present, more than 70 cannabinoids have been isolated from cannabis plants, among which CBD (cannabis diphenol) and THC (tetrahydrocannabinol) have the highest CBD content and are isomers. The significant difference between CBD and THC is that THC is hallucinogenic addiction, while CBD is not hallucinogenic addiction, and it also inhibits the toxicity. It has prominent effects in analgesia, sleeping, anti-inflammatory, anti-oxidation, neuroprotection, anti-anxiety, anti-cancer, liver protection and anti-diabetes.
With the extensive research on the efficacy of CBD, its downstream applications are becoming more and more abundant. CBD can be used as skin care products, anti-oxidant, anti-inflammatory, acne and acne removal; CBD can be used as a medical treatment, and has mature products in the treatment of seizure and multiple sclerosis (MS) – English company GW has developed the Stativex and Epidiolex drugs with CBD as the main component; CBD can be used in food, with calming and sleep quality improving functions.
CBD is useful obviously so how to gain CBD from cannabis plants? Is there any other way to get CBD besides directly from plants?
1. CBD Extraction
Generally speaking, you can get CBD from the following cannabis plants:
Hemp, also known as cannabis, it contains less than 0.3% THC and does not show mental activity.
Marijuana, the drug cannabis, contains more than 0.5% THC, which can produce strong psychoactive and addictive characteristics.
Medical hemp, its content of THC ranges from 0.3% to 0.5%, which shows a tendency of medicinal use.
One of the preconditions for extracting CBD from cannabis plants is to reduce THC content as much as possible. Therefore, the THC content must be controlled from the source. That is, cannabis plants should be with as little THC content as possible and as much CBD content as possible, like hemp. So, how to extract CBD from industrial hemp? At present, the common methods are solvent extraction, supercritical CO2 extraction, olive oil extraction and so on.
2. CBD Chemical Synthesis
1. Traditional synthesis methods of CBD
- Catalyst: boron trifluoride
- Yield: 41%
- Disadvantages: low yield, high impurities; complex, high cost
2. Optimal synthesis of CBD
- Catalyst: Palladium
- Yield: 74%
- Highlights: The catalyst is replaced by palladium to reduce by-products, with high purity and high yield.
Because of the complex molecular space configuration of CBD, the yield of traditional synthesis methods is low (only about 40%) and a large number of by-products will be produced, which has great limitations in extraction. Although pure CBD can be obtained by optimizing the synthesis method, the yield has also been improved (74%), but the new method is still in the laboratory stage, and the synthetic conditions need to be improved. High industrialization costs are too high to meet the market requirements.
3. CBD Biosynthesis
On February 28, 2019, a paper entitled Complete biosynthesis of cannabinoids and their unnatural analogues in yeast, published by Dr. Luo Xiaozhou, a research group of Jay Keasling at the University of California, Berkeley, elaborated on the study of CBD biosynthesis by pouring CBD-related gene fragments from plants into yeast. The yeast was modified and amplified to realize the total biosynthesis of cannabinoid and its non-natural derivatives.
The mevalonate pathway of Saccharomyces cerevisiae was modified with galactose as raw material. A metabolic pathway for hexanoyl-CoA synthesis was introduced. Cannabinoid biosynthesis was completed in Saccharomyces cerevisiae by using exogenous genes and key catalytic enzymes from different species. The heterologous reconstitution of the synthetic pathway has led to the total biosynthesis of several major cannabinoids and their derivatives, including cannabinoid phenolic acid (CBGA), tetrahydrocannabinol (THCA) and cannabinol (CBDA). The metabolic pathway is as follows:
Several companies seize the market and are optimistic about the prospect of commercialization
As early as 2017, when Jay Keasling applied for a patent for this method, he collaborated with Demetrix, a biotechnology startup, to introduce the process from laboratory to commercial production, using technology to produce the rarest cannabinoid at a reasonable price, and to reduce production costs to less than $1,000 per kilogram. Hyasynth, headquartered in Montreal, also wants a slice of the pie after accepting a million-dollar investment from Canadian cannabis dealer OrganiGram to speed up its own biosynthetic cannabis promotion.
Difficulties in Commercialization of CBD Biosynthesis
Biosynthesis is the result of the human genome project that began in the 1990s, creating a variety of things, including biofuels, medicines and even clothing fibers, by altering the genes of simple microorganisms such as yeast, bacteria, molds, lichens and fungi. Biosynthesis is considered to be a cheaper way to obtain cannabinoid concentrates, but there are still difficulties:
- Yield problem: At present, the production of biosynthetic CBD is only 10 mg/L. To realize industrialization, it may need to expand 1000 times. (At present, the biosynthesis yield of artemisinin with industrial conditions reaches 25 g/L.
- Technical issues: Biosynthetic engineering bacteria require dozens of gene loci modification, which is difficult to control, and maintaining the stability of the bacteria is also a problem.
CBD extraction technology aims at improving the extraction rate and purity of CBD, removing THC residues as far as possible, avoiding the use of toxic organic solvents, ensuring the safety and environmental protection of products, and reducing costs as much as possible. Current CBD acquisition methods are still dominated by highly mature extraction methods, while chemical synthesis faces many challenges such as high cost and complex process. Biosynthesis may be worth further exploring.