Despite legal restrictions that have limited research into the potential medical applications of cannabis across the world, the synthetic cannabinoid market is on the rise.
The majority of clinicians are in favor of using medical marijuana to treat certain disease states, according to a survey conducted by NEJM. In this same survey, 76 percent of participants world-wide voted in favor of using marijuana for medicinal purposes even though the use of marijuana is still illegal in most of these countries. In North America, specifically, 78 percent voted in favor of medical marijuana use.
GBI Research’s latest white paper reports that—despite legal restrictions that have limited research into the potential medical applications of cannabis across the world—the synthetic cannabinoid market is on the rise. Pharmaceutical companies are introducing products with the main active ingredient being one (or more) synthetic cannabinoids indicated to treat a variety of conditions, including “anorexia nervosa related to HIV/AIDS, multiple sclerosis spasticity, and nausea and vomiting associated with chemotherapy.”
“More recently, products have been approved that contain cannabinoids extracted directly from the plant, as opposed to synthetic recreations,” said Thomas Jarratt, Associate Analyst for GBI Research. “Indeed, there are 90 pipeline cannabinoid products, including two in Phase III development.”
Regardless of the recent wide-spread approval of the use of cannabis medicinally, the plant isn’t new to the market.
“Cannabinoid-based therapies have been around for thousands of years in our documented history of cannabis being used as a therapeutic element,” said Jeffrey Korentur, CEO, Teewinot Life Sciences—a biopharmaceutical company that uses synthetic biology and advanced formulation for the production and implementation of cannabinoid-based therapies. “Over the past several decades, mostly through the use of chemically-synthesized cannabinoids, have there been pharmaceutical applications.”
The most prominent among chemically-synthesized cannabinoids is the generic form called dronabinol, a chemically-synthesized THC. It is “formulated in a specific way so that it’s very difficult to reverse that THC out of the formulation and therefore reduces diversion of the compound,” Korentur explained.
In addition to the limitation placed on cannabinoid therapies due to the plant’s status as a Controlled Substance and Schedule I drug, the production (or manufacturing) of the cannabis plant for therapeutic applications has also provided the pharmaceutical industry with a unique challenge.
“From a production and manufacturing perspective, there are (up until now) only two ways to produce the active components of a cannabis plant called cannabinoids,” said Korentur.
Historically, the two ways to produce cannabinoids are:
- Organically, or botanically, by growing the plants and extracting the plant for their oils and then separating those oils into different compounds that are contained therein.
- Producing specific compounds chemically.
“One of the problems with the plants—in addition to having to filter and purify—is the genetic drift of plant material,” said Korentur, “which means that it’s very hard to standardize what’s going to come out of any particular crop.”
With a focus on the use of synthetic biology and advanced formulation for the production and implementation of cannabinoid-based therapies, Teewinot does not have a direct hand in chemical manufacturing; though they work with companies who do.
Manufacturing THC, for example, “is a long process. It takes about 10 weeks to accomplish. In order to produce a kilogram of THC, there’s about 10 kilograms of waste material that has to be disposed of. So, you get a relatively pure chemical, but there’s a lot of contaminants that have to be disposed [of] through the manufacturing process—as opposed to the botanically-derived compounds, which contain contaminants with the molecule itself,” said Korentur.
Furthermore, the cannabis plant expresses chemicals in different amounts. One particular strain might have more of one molecule over another. In addition, most of the cannabinoids in the plants are expressed in a very low amount.
What Teewinot Brings to the Table
Teewinot Life Sciences is the U.S. parent company of two subordinate, wholly-own subsidiaries—one of which is in Canada and the other in Ireland. The biopharmaceutical company offers a patented, commercially-viable method of producing cannabinoids using biological processes with the specificity of a chemical process.
The process that Teewinot utilizes is called biosynthesis.
“We’ve recreated the biological process that the plant uses, and we’ve taken it out of the plant and put it into a bioreactor,” said Korentur. “We create authentic molecules, in other words chemically-identical cannabinoids to those that are grown botanically. But we do it in a controlled, clean environment so that you don’t have the waste associated with chemical synthesis and you have the authentic molecule associated with organic, or botanical, growth—but you don’t have any of the remnants or contaminants around that molecule.
“We’ve been able to scale this process commercially. We’re the first in the commercial space to have these patents in the United States.”
Biosynthesis is not a synthetic cannabinoid. It’s a process that creates the desired cannabinoid enzymes.
“Another way to look at this is we take the genes from the cannabis plant and put them into microorganisms—so we’re producing the cannabinoid biosynthetic enzymes in a microorganism to produce cannabinoids,” Richard Peet, PhD, JD, Executive Vice President, Teewinot Life Sciences, explained. “We take the machinery of a cannabis plant, put them in a microorganism, and make cannabinoids that way.”
The company uses the cannabis’ plants enzymes to produce the same chemical structure that the phytocannabinoids produce in plants.
“We’re just doing it in a microorganism,” said Peet. “So, we’re using both synthetic biology—meaning engineering a microorganism— and we’re using another process called biocatalysis.”
Biocatalysis, a process that is used for the production of a lot of different chemicals in manufacturing, essentially takes the enzyme, puts it in a bioreactor, and introduces the natural substrate that occurs in cannabis.
“You’re using an enzyme to do the work for you. In this case, we’re using the plant enzyme. We can take the plant enzyme, put it in a microorganism… The machinery is taking a chemical, CBGA (the naturally-occurring compound in cannabis), and it converts that into THCA [or another desired cannabinoid],” Peet explained, as one example.
In addition to the process cutting back on waste, it also comes with a significant time saver.
“The chemical synthesis takes about 10 weeks, and the agricultural process of the plants can take up to 14-17 weeks. Our process takes about a week,” said Korentur.
Current Challenges for Cannabinoid-Based Therapies
“What we’ve focused on to date is not the development of specific therapies against target indications,” said Korentur. “Clearly, there are pharmaceutical companies out there taking the chemical structure and seeing how effective it is against a particular indication or disease, and they’re hoping to develop a therapy based on the results of those tests and trials. We do not do that in-house right now.
“We have been focused exclusively on the development of the biosynthetic engine that Richard described and the ability to produce what would be effectively APIs for the cannabinoid pharmaceutical industry. Right now, the vast majority of the industry uses chemical synthesis, and our process is designed to effectively replace or augment that method.”
According to Korentur, one of the primary challenges that the company faces is the newness of their technology.
“This is something that hasn’t been used for cannabinoid medicine,” Korentur explained. Biocatalysis and biosynthesis are currently used in the pharmaceutical space to manufacture different compounds, but not in cannabinoids.
In addition to introducing a brand new process into the cannabinoid space, the other key challenge Teewinot faces is that there are a limited number of developed medicines.
“There are a lot of companies around the world that are looking at applying cannabinoids to a variety of indications,” said Korentur, but very few cannabinoid-based therapies that are on the market.
Only time will tell whether legal restrictions will continue to limit research into the potential medical applications of cannabis across the world.
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Filed Under: Drug Discovery