Psilocybin, the key ingredient in magic mushrooms, can be produced in a few different ways: it can be extracted from Psilocybe mushrooms, a process requiring a considerable amount of fungi, and it can be produced synthetically. Both are costly and require ample starting materials, and neither is particularly sustainable.
One European psychedelics company is on its way to testing out another, more unusual method of production, one that effectively turns sugar into psilocybin. Octarine Bio, a synthetic biology company based in Copenhagen, will soon bring its biosynthetic psilocybin into human clinical trials through a new partnership with Clerkenwell Health, a London-based contract research organization that specializes in psychedelic medicines.
Biosynthesis: A Greener Choice
Nick Milne, Octarine’s co-founder and chief science officer, says the company’s unique use of synthetic biology to create and manufacture drug candidates sets it apart from other players in the space focused on more traditional means of drug development.
“[These means] are limited in the complexity of the molecules they can produce, and importantly, they rely heavily on non-renewable and environmentally hazardous resources,” he says. “Synthetic methods to produce psilocybin, for example, use benzene as the bulk starting ingredient, and generates several times its own weight in hazardous waste.”
Clerkenwell co-founder and chief science officer Henry Fisher notes that extracting psilocybin directly from fungi also has its drawbacks, including scale: this kind of production requires a large amount of organic matter.
“Biosynthesis carves a niche between those, to where it’s very scalable like chemical synthesis, but also it’s very green,” says Fisher. “It’s very suited to some of the concerns that people have environmentally, but it also fits the business’s need.”
Using a CO2 negative sugar as the bulk starting ingredient makes for a more sustainable method of production, says Milne, while also allowing Octarine’s team to generate more complex methods: “Biological processes can carry out chemical reactions far more efficiently than synthetic chemists can, and can even create molecules off-limits to synthetic chemistry.”
Even after 100 years of drug development, he says, “nature is still a far better chemist than any human.” By utilizing these biological processes, Octarine can focus on producing molecules that synthetic chemists might struggle to produce.
How It Works
According to Milne, producing psilocybin from sugar isn’t as farfetched as it sounds, and essentially mimics the way psilocybin is produced within Psilocybe mushrooms. In nature, a series of enzymes from the mushroom convert sugar to more complex molecules, eventually producing psilocybin.
“The problem is the Psilocybe mushrooms don’t convert sugar to psilocybin at the scale and consistency needed for pharmaceutical use,” says Milne. “We take the same biosynthetic machinery… and introduce it to yeast, giving the microorganism the ability to produce psilocybin from sugar. With further tweaks to the yeast’s own machinery, we can coax it into producing psilocybin more efficiently.”
While chemical starting materials can be prohibitively expensive, the price of glucose is cheap, at roughly USD$0.50 per kilogram. Octarine’s method is IP protected, scalable, and, in addition to psilocybin, can enable the production of other tryptamine psychedelics.
Partnering For Research
Clerkenwell Health is a contract research organizations with a sole focus on psychedelics in medicine, and particularly their applications in a psychotherapy context. In partnering with Octarine, the CRO will support the drug developer in conducting clinical trials of biosynthetic psychedelic medicines, starting with psilocybin, and develop the clinical protocols for its indications.
Co-founder Fisher says the CRO was launched when his team recognized that while all companies have a need for data, not all have the research background necessary to start from scratch.
“We wanted to do something meaningful for the whole sector, and with obviously a lot of drug developers appearing, we realized that they were all going to need clinical trials, and that that data and the strength of that data would basically make or break these companies,” he says.
More traditional CROs, Fisher says, are not generally equipped to deal with the nuances of the psychotherapy aspect of clinical trials for psychedelics, and this can have a detrimental effect on patients participating in such trials. Clerkenwell, on the other hand, is “patient-centric, and more mindful of what’s actually important in psychedelic assisted therapy.”
The Growing European Psychedelics Market
The partnership is a recent one among a growing number of psychedelic-focused companies based in Europe. While investors might be hesitant, Clerkenwell CEO Tom McDonald says any caution they have should be comforted by the fact that most companies operating in the space have partnered with leading universities and healthcare trusts. Companies like Octarine, he says, have even received funding from the Danish state investment fund.
“There is a deep heritage of life science innovation in Europe and the majority of companies in the space are working with psychedelic compounds within clinical trial settings—which brings with it layers of compliance and ethical approvals,” he says. Another reason McDonald suggests investors ought not to pass over Europe is its population: with twice as many people as the United States and similar rates of mental health disorders, it offers a more sizable target population.
McDonald also suggests that the possibility of decriminalization in the U.K. is incredibly slim, and as such, “psychedelics will remain a purely pharmaceutical play for the foreseeable future here.”