The process of fermentation has been around for centuries – most notably in the production of beer and bread. Most biology textbooks would describe this process as the anaerobic conversion of simple sugars into carbon dioxide and ethanol by yeast, but scientists have begun to untap a whole new potential for what fermentation can construct. Drugs.
With the advent of genetic modification, it has become possible to cut genes that code for a particular metabolic pathway from one organism and paste into another, such as yeast. When placed in the correct environment, the new, modified pathway will not synthesize ethanol, but rather, other extremely complex compounds that can be impossible to create by scratch in a lab.
In August of this year, scientists at Stanford announced they had successfully engineered yeast to produce the opioid painkiller, hydrocodone. Just one month later, The New York Times ran an article announcing yet another success. Researchers at several laboratories around the world have created strains of yeast that can synthesize the main, most notorious psychoactive compound in marijuana, THC. However, synthetic versions of THC have existed since the 1980s and can be found in HIV drugs such as Marinol and Cesamet. This then raises the question: why are we experimenting with fermentation?
First, if labs are able to streamline an industrial process to synthesize THC using yeast, the price can potentially decrease tremendously. THC supplements for patients could therefore become more economically viable, which is becoming increasingly important as medical marijuana licensing is rapidly expanding to include treatments for diseases such as Alzheimer’s, Multiple Sclerosis, and even PTSD. On the other hand, producing THC in mass quantities and analyzing how it is made can give invaluable insight into its medicinal properties, which are still ambiguous. However, yeast has one very large competitor: the plant itself. Cannabis is able to produce extremely large quantities of certain cannabinoids, the majority of which is THC. In fact, THC has been reported to compose up to 30 percent of the dry weight in the flowers, but it is difficult for laboratories and companies to obtain permission to grow the plant itself. Therefore, an interesting dilemma arises. According to Dr. Jonathan Page, founder of Anandia Laboratories that has created strains of yeast to synthesize THC, it is still unknown if yeast can ever surpass the plant’s production, making industrial-scale operation uncertain, but producing THC through yeast for research purposes might be easier than obtaining the permits to grow cannabis itself.
On another note, the success of THC production has opened up another door that potentially has another promising future. Even though THC is the first chemical that pops into everyone’s mind when marijuana is mentioned, there are many other compounds in cannabis that might have a greater medicinal value. These other compounds could have a more economically feasible future for synthetic production, especially if they are only found in trace amounts in the plant itself. One such compound is cannabidiol.
Cannabidiol, or CBD, has recently caught a lot of media attention, as many Americans, especially parents, have been lobbying for its inclusion in medical marijuana legislation. Even though there is no published scientific literature that proves the beneficial or derogatory effects of CBD, some informal studies have shown promising effects of reducing seizures in children with epilepsy. Moreover, unlike THC, CBD does not produce psychoactive effects such as euphoria or intoxication. In addition to seizure disorders, scientists have begun to explore the effects of CBD on people diagnosed with anxiety disorders, schizophrenia, cancer, and certain inflammatory diseases. Biochemists at the Technical University of Dortmund in Germany have unofficially stated that they have successfully created a yeast strain that can synthesize CBD, opening the door to further studies in this area.
So far, scientists have successfully produced only a couple of individual compounds found in cannabis, but there are over 80 active cannabinoid chemicals found in the plant in general. Each compound has its own medicinal value, some of which are more valuable than others. However, when analyzing this hodgepodge of chemicals, one major question pops up. Sure, we can attempt to isolate these chemicals to make certain drugs, but is there more value in utilizing the plant as a whole?
In the 1990s, scientists S. Ben-Shabat and Raphael Mechoulam published a study on cannabis proposing a phenomena known as the Entourage Effect. This effect basically states that the whole is greater than the sum of its parts, or the real benefit of cannabis comes from using the plant as a whole. In other words, isolating certain compounds to make drugs will not be as effective as using the plant.
However, Dr. Jonathan Page believes that there could be value in both isolating compounds and using the plant as a whole. In an email he writes, “The whole plant and extracts from the plant have efficacy, but we also know that pure, single cannabinoid drugs (e.g. the synthetic cannabinoid nabilone) are useful too.” Nabilone, which can be found in certain prescription drugs, is often given to cancer patients to prevent nausea. Page continues to write that he sees isolated drugs and the plant coexisting in the future.
Even though it is too soon to tell if cannabinoid production in yeast will create a huge industrial wave, the production of individual compounds holds the potential to answer many questions about the true medicinal effects of marijuana. There is still a lot of data that needs to be collected, but it will be exciting to see exactly what role these discoveries play in the future of cannabis science.