Psilocybin is undergoing rapid advancements in the medical and therapeutic sphere. The development of production methods for synthetic psychoactive compounds, at first glance, feels more like an explosion than a linear progression. There are many reasons for this. For the budding industry, it’s important to produce results that are cost-effective, efficient, and easily reproduced. On a different level, various new methods of psilocybin synthesis can be patented, while the naturally-occurring molecule cannot.
In our previous article on psilocybin economics, we mentioned that there is concern over the prohibitive cost of synthetic psilocybin, which can reach up to $7,000-$10,000 per gram compared to the much lower cost of the natural product. Synthetic psilocybin is a pure product compared to natural mushrooms, which only count psychoactive compounds at around 1% of their total mass. This alleviates the cost concern of synthetic psilocybin greatly since the average patient would need a considerably smaller amount to enjoy a therapeutic benefit.
So what does the landscape of synthetic psilocybin look like right now?
Chemically-Synthesized Psilocybin
This is the older method for producing synthetic medical psilocybin. In plain terms, chemical synthesis involves producing a naturally-occurring molecule by facilitating a series of chemical reactions between smaller compounds. All of these reactions can produce chemical byproducts that interfere with the desired result, making it more difficult to produce a pure final product. This can be costly due to the precision required, as well as the need to meet requirements for GMP (Good Manufacturing Practice) Certifications. The above-mentioned cost of synthetic psilocybin considers this method of production.
Currently, two organizations that employ chemical synthesis are Compass Pathways and the Usona Institute —each of which have their own proprietary methods of synthesis. Compass’ “COMP360” is already in phase IIb of clinical testing and Usona recently claimed to have made new strides in synthesizing larger amounts of high-quality products more efficiently.
Medical Psilocybin Biosynthesis
Another, newer, form of psilocybin synthesis involves genetically altering bacteria and yeast so that they can convert sugar into the desired molecular compound. Harnessing yeast fermentation this way has long been used for wine and beer production — but in 1987, Novo was able to produce insulin using the yeast strain S. cerevisiae. Today, nearly 20 percent of biopharmaceuticals are made with this strain. Years before, E. coli bacteria had been used to produce human growth hormone, as well as insulin. Biosynthesis has since been used in the production of vaccines, including hepatitis and HPV.
Today, medical psilocybin producers have started using both E. coli and S. cerevisiae to synthesize the molecule efficiently. Psybio Therapeutics uses E. coli bacteria to produce over 20 psychedelic compounds. They consider both speed of production and stability at room temperature to be advantages of E. coli over yeast.
Organizations such as Psygen, Octarine Bio, and CB Therapeutics are using yeast fermentation to produce their synthetics. In an interview with Psilocybin Alpha, Nick Milne, CSO of Octarine, claimed that a major advantage of biosynthesis over some forms of chemical synthesis is that the latter requires a greater use of non-renewable fuels to facilitate reactions. He also claims that yeast adapts to the genetic material of psilocybin mushrooms more readily than bacteria, since they are both types of fungus. CB also points to the lack of environmental impact, as well as the inexpensive feedstock (sugar), as advantages to their yeast-based method of production.
The efficiency and low cost of biosynthesis seem likely to improve the consumer costs for psilocybin production, although CaaMtech CEO Andrew Chadeayne still feels that chemical synthesis can produce psilocybin more efficiently.
The Entourage Effect
While all of the above methods consider the cost and benefit of medical psilocybin synthesis, natural mushroom production still has the advantage of variability in tryptamine compounds. Similar to cannabis, psilocybin mushrooms contain minor tryptamines that may work with psilocybin to enhance therapeutic benefits. In Jamaica, where psilocybin mushrooms are decriminalized, Field Trip Health is currently researching the potential benefits of these compounds.
Eventually, we may be able to get the best of both worlds. In his interview with Psilocybin Alpha, Milne also suggested that yeast’s ready-adaption to fungal psilocybin genetics could be used to produce these minor tryptamines —hopefully making the entourage effect more cost-effective and widely available in a medical setting.
