Miami University may have found the solution to psilocybin’s scalability issue.
Jones, an assistant-professor at Miami University, recently published a paper detailing how psilocybin, the compound undergoing clinical trials for depression treatment, can be produced cheaply within E. coli bacteria.
“E. coli is referred to as the ‘workhorse’ bacteria. It’s an easy host to work with, but it’s still tricky to take DNA from a mushroom and make it functional in a bacteria so that’s the jump we made,” Jones said.
It’s akin to a ‘fermentation’ process, according to Jones, and its one that is proven within the pharmaceutical industry. The only difference is that this time the compound was psilocybin.
Given that 300 million people worldwide suffer from depression, and considering up to “40% of depressed patients fail to show a response to first-line antidepressant drug treatment,” the calls for alternative treatments are growing. But synthetic psilocybin has proven difficult to product at scale.
“Up to 50% of the cost of the production of medical and edible mushrooms can be labour,” and “The production of mushrooms has some of the highest start-up costs in agriculture,” according to ThinkMyco, a start-up in the psilocybin space.
“Despite significant improvements over early synthetic routes, current methods remain tedious and costly, involving numerous intermediate separation and purification steps,” according to the paper which says developing a milligram of pharma-grade psilocybin is between $2,000 and $5,000 per gram.
Mushrooms, the traditional source of psilocybin, are also difficult to harvest at scale, according to Jones.
“Alternatives to this process is growing fields of mushrooms which takes up a lot of space. It isn’t really scalable for worldwide production, and that’s kind of the dream right?” he said.
Jones’ research shows that psilocybin could be produced in large quantities from a bacterial culture in a similar way to how beer is made.
His team was able to produce the compound in grams per litre, a rate which is not yet industrially viable, but still “10 times” closer than anyone else, he says.
“If we can get somewhere in the 10g/L range, that could be a point where there would be some industrial partners that would be very interested in the technology,” Jones said.
Jones said he couldn’t put a dollar figure on his process in comparison to chemical synthesis, but he said his aim going forward is improving concentration, improving the rate of production and reducing the amount of materials used in the process.
Because psilocybin is a schedule I drug, the university wasn’t able to purify and concentrate the compound, according to Jones. Since purification is where most of the costs lie, estimating the cost of his process versus chemical synthesis was difficult.
“What I can say is that my fermentation process, to actually produce it on the front end, is a small fraction of that number,” Jones said.
Researchers at Johns Hopkins have made the argument psilocybin should be rescheduled from a schedule I drug to schedule IV, the same classification as sleep aids. Other schedule I drugs include Bath Salts, Heroin and Mescaline.
“We want to initiate the conversation now as to how to classify psilocybin to facilitate its path to the clinic and minimize logistical hurdles in the future,” says Matthew W. Johnson, associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “We expect these final clearance trials to take place in the next five years or so.”
Studies in both animals and humans show psilocybin has a low potential for abuse. According to Johns Hopkins, “When rats push a lever to receive psilocybin, they don’t keep pushing the lever like they do for drugs such as cocaine, alcohol, or heroin.”
Psilocybin was given its schedule I status due to “the rising tide of sensational media accounts of adverse consequences of classic psychedelic use” which “fueled the perception by many public and political leaders that psilocybin posed serious risks to patients and the public that did not outweigh its benefits,” according to researchers with the university.
Jones said he doesn’t believe a rollback in drug scheduling is a barrier to psychedelic research, clearance can be granted to researchers wishing to work with these compounds and once the FDA approves psilocybin for treatment, the compound will be rescheduled.
Scheduling isn’t as much an issue as is the inherent challenges of documenting the efficacy of psychedelics, according to Jones.
“It’s hard to have the standard double blind, placebo controlled trials. If you get the sugar pill instead of the hallucinogen, it’s painfully obvious so it’s hard to have a truly controlled trial.”
Set and setting are also crucial, Jones said. Since these drugs aren’t meant to be taken once before bed, rather once every few months under supervision, it is difficult to replicate these settings in a trial.
“Hopefully, as those problems start to get solved, others like me and others working in this field will be able to address the production side and we can converge on a drug that’s beneficial to a lot of other people and produce it in a way that’s cost effective.”