Psilocybin is known as the active compound in so-called “magic mushrooms”, but most of the psilocybin used in clinical trials today are synthesized in the lab without the use of biological materials.
As psychedelic-assisted therapy gains momentum, investors need to understand the difference between currently available ways to get psilocybin.
One method will likely dominate the industry for decades to come.
- How is psilocybin produced?
- Are natural sources better than synthetics?
- Which method is the most profitable?
Four methods will compete for the intended legal markets for psilocybin, each with their own set of advantages and disadvantages, ranging from durability and therapeutic potential to cost of production and scalability.
1: Chemically synthesized psilocybin
“There are several different ways to produce psilocybin. The one that has been most sought after in the legal and medical space is the total chemical synthesis of psilocybin, ”explains Marshall Tyler, research director at Field Trip Health (CSE: FTRP) (OTCQB: FTRPF).
Isolated psilocybin was labeled in the late 1950s by Sandoz under the name Indocybin and sold commercially for therapeutic clinical research, until it was listed in the United Nations Convention on Psychotropic Substances. from 1971. The first chemical synthesis of psilocybin is attributed to Albert Hoffman, the Swiss chemist known to have also discovered LSD.
Today, synthetic psilocybin is the most widely used form of psilocybin in clinical trials around the world.
“I think chemical synthesis is a very efficient way to make these molecules because they are structurally very simple molecules to make. They are not like cannabinoids or antibiotics which have a lot of complications in molecular structure. They’re pretty easy to synthesize, ”says Andrew Chadeayne, founder and CEO of CaaMTech, an early-stage psychedelic research company.
Additionally, being a crystalline compound, synthetic psilocybin can be purified into 100% pure individual molecules.
Today, more and more companies are entering the market as suppliers of research-grade psilocybin, in what continues to be a congested supply chain. As other methods become available, Field Trip’s Tyler believes chemically synthesized psilocybin will continue to dominate clinical trials and medical applications of the drug for the foreseeable future.
“It’s getting easier and easier to do the chemical reaction that produces psilocybin. There is continuous progress and it’s actually not that expensive, ”says Tyler, who has a master’s degree in chemical biology.
From a regulatory standpoint, chemically produced psilocybin also makes sense.
“As with any drug development, it’s unfortunately very, very difficult to get approval for a botanical drug. And so isolating this unique molecule makes it much easier for clinical trials and ultimately drug approval for depression and other related disorders, ”says Tyler.
COMP360, Compass Pathways’ proprietary formulation of psilocybin (NASDAQ: CMPS) is currently undergoing a Phase IIb clinical trial to assess its effectiveness in the treatment of treatment-resistant depression.
The company told Benzinga that, being a modified version of synthetic psilocybin, COMP360 can be registered as a new chemical entity and have market exclusivity for up to 8-11 years in the European Union, and 5 at age 7 and a half in the United States
The Usona Institute, a nonprofit organization for psilocybin research, is also conducting Phase II clinical trials on the effectiveness of psilocybin for major depressive disorder, involving seven US sites and 80 participants.
Today, both organizations are providing their versions of the synthesized psilocybin free of charge to accredited researchers, although there is an additional cost involved in transporting and distributing the listed substance.
2: Whole mushrooms or full spectrum psilocybin
For millennia, mushrooms have been the only available source of psilocybin for human consumption. Today, they remain the most popular way to take psilocybin in informal circles outside of clinical trials.
Critics of chemically isolated psilocybin claim that psilocybin-producing mushrooms contain a number of other compounds that may contribute to their overall therapeutic effect.
“The biggest advantage of natural magic mushrooms is that [they] make a sort of cocktail of active ingredients, as long as it’s not just psilocybin, ”says Chadeayne.
He went on to say that the overall experience of consuming Psilocybe mushroom comes from the interaction of psilocybin with other ingredients such as monoamine oxidase inhibitors and aeruginascin.
“These molecules could contribute to the overall psychedelic experience. So they could have a lot of value in themselves. And if you do chemical synthesis, you don’t get any of those molecules. So you lose that kind of chemical complexity that organisms are able to produce naturally, ”Tyler adds.
Psilocybin-producing mushrooms are believed to work similarly to cannabis flowers or whole plant extracts, where THC and CBD are believed to interact with cannabinoids and minor terpenes to produce a different effect than the compounds. isolated alone.
In its laboratory located at UMass Dartmouth, CaamTech strives to understand the role of minor compounds in natural psychedelics. The company’s own research shows how psilocin (the end product of psilocybin after being metabolized by the body) affects serotonin 2A receptors differently on its own than accompanied by other molecules found in mushrooms.
Clinical research comparing the effects of consuming Psilocybe mushrooms versus isolated psilocybin is still scarce, as performing human studies using mushrooms requires even more difficult regulatory hurdles than studying the effects of the mushroom. isolated compound.
Field Trip Health is pursuing this goal in Jamaica, where psilocybin is decriminalized. The company is studying the effects of whole fungi in partnership with the University of the West Indies, although human trials have not been announced.
3: Psilocybin isolated from natural source
Psilocybin produced by fungi can also be isolated, to give a product chemically identical to psilocybin synthesized in the laboratory, but derived from fungi instead of a chemical reaction.
“Mushrooms are not a very efficient biological plant,” explains Chadeayne of CaamTech, “since the active components of the mushrooms make up about 1% of the total mass of the dried mushroom. Compare that to cannabis where it’s like 30 %.
Tyler of Field Trip added that by synthesizing psilocybin from a chemical reaction, the process involves “much less to filter” than with organic synthesis. In the latter case, a number of biological by-products must be separated from the final product in order to isolate the resulting psilocybin.
However, some companies in the sector are betting on the eventual success of this method over chemical synthesis. This year, Mydecine (CSE: MYCO) (OTC: MYCOF), a Denver-based psychedelic research company with operations in Alberta, Canada, announced a Schedule 1 distributor license from Health Canada to legally supply drug. Psilocybin of natural origin for therapeutic research around the globe.
CEO Joshua Bartch told us that in his opinion, sourcing psilocybin from its native organic matter may actually be more cost effective than chemical synthesis.
“Even when you put costs aside, it’s still easier to get psilocybin naturally than to create it. The process of synthesizing any compound can be complicated, let alone a psychedelic, and a lot can go wrong. Conversely, the supply of psilocybin naturally is just a simple process of extraction, ”Bartch said.
Mydecine is currently studying the effects of other compounds naturally found in
Psilocybe mushrooms to develop products that can deliver the benefits of full spectrum psilocybin while producing consistent pharmacological results.
“We strongly believe that there are many valuable active compounds that can have positive or negative effects on the overall consumer experience, and it is our responsibility to understand and correct the unpredictable results of Mother Nature,” said Bartch.
4. Biosynthesized psilocybin
Between the methods of nature and artificial chemical reactions, a new method is gaining momentum: the production of psilocybin from yeast.
Earlier this year, a group of Danish scientists published an article describing the successful biosynthesis of psilocybin from a genetically modified version of yeast fungi.
This process, which is already being produced for cannabinoids, is poised to produce large amounts of psilocybin at lower prices than natural extraction or chemical synthesis.
A Danish company called Octarine Bio is the industry leader in this regard. The company recently managed to raise $ 1.8 million to continue its research. The investment was supported by Canopy Growth founder and former CEO Bruce Linton as well as the Danish State Growth Fund.
Chadeayne from CammTech thinks biosynthesized psilocybin may be an interesting hybrid.
While the field is still new, Chadeayne projects that yeast and modified bacteria can produce psilocybin more efficiently than magic mushrooms, but less efficiently than chemical synthesis.
From a regulatory point of view, this approach could bring promising results.
“Is this going to be seen as a natural product that follows a regulatory path or perhaps a direct path to the consumer?” Or is it going to be treated as a virtually synthetic molecule? “Asks Chadeayne.
While there does not appear to be a consensus within the industry as to the most cost effective and convenient method of producing psilocybin, it is likely that the market will pick its winners in the years to come. Unexpected sets of nuances could also cause multiple methods to coexist for different applications and submarkets.
Image created from images from Pixabay, Unsplash, and Wikimedia Commons.