Psilocybin could be produced on an industrial scale for use in psychiatric medications!

in naturalmedicine •  5 months ago 

The future of psychiatric medicine is upon us. Soon we may see the use of psilocybin and other psychedelics instead of the numerous psychiatric drugs on the market. The original paper, In vivo production of psilocybin in E. coli was recently published in Metabolic Engineering , Volume 56, December 2019, Pages 111-119. Following are a pair of news articles that elaborate on the findings of the study.

'Trippy' E. coli Bacteria Engineered to Brew 'Magic Mushroom' Hallucinogen | Livescience.com


Scientists have transformed a common bacterial cell into a psychedelic "drug factory" capable of pumping out copious quantities of psilocybin, the chemical famously found in "magic mushrooms," according to a new study.

Psilocybin can be found in more than 100 'shroom species, most notably in one called Psilocybe cubensis, which has a domed cap and skinny stem. Although best known for inducing mind-bending hallucinations, psilocybin is currently being tested as a potential treatment for several psychiatric conditions, including addiction, major depressive disorder and post-traumatic stress disorder, according to ClinicalTrials.gov. If 'shroom-based drugs ever come to market, scientists will need a better method for harvesting psilocybin than farming tons of fungi, the authors said.

So, the researchers turned to bacteria, which can be engineered to churn out chemicals in high amounts. Some medications — including the hormone insulin — are already produced with the help of genetically engineered bacteria.

In the new study, the Miami University, researchers manipulated the metabolism of the bacteria Escherichia coli, so that its cells began producing psilocybin.Later, the research team scaled up production to brew the hallucinogen in huge batches, according to a statement from the university.

"We are taking the DNA from the mushroom that encodes its ability to make this product and putting it in E. coli," study co-author Andrew Jones, a professor of chemical and biological engineering, said in the statement. The team developed multiple strains of psychedelic E. coli and tested what environmental conditions — temperature, nutrients, culture medium — were required to consistently produce high concentrations of psilocybin with few unwanted side products. The team eventually selected the most efficient strain, dubbed pPsilo16, and cultivated it in a bioreactor for mass production, according to the study, published online Sept. 21 by the journal Metabolic Engineering.

"What's exciting is the speed at which we were able to achieve our high production," Jones said. Over the course of the 18-month-long study, the researchers were able to increase production by 500-fold.

According to the authors, their E. coli produced more psilocybin than any other organism retrofitted with "magic mushroom" DNA to date. The scientists assert that their results provide compelling evidence that psilocybin could be produced on an industrial scale for use in psychiatric medications.



Miami researchers discover process to sustainably produce psilocybin - a drug candidate that could help treat depression

Andrew Jones at Miami University and his team of students may have developed a research first.
Through metabolic engineering, they discovered a way to sustainably produce a promising drug candidate to help patients with treatment-resistant depression.
Their findings are published in the journal Metabolic Engineering titled, “In vivo production of psilocybin in E. coli.”

Psilocybin is now in clinical trials, and medical professionals see promising results for its use in treating addiction, depression and post-traumatic stress disorder in humans.

Jones, assistant professor in Miami’s department of chemical, paper, and biomedical engineering, believed he could come up with a process using genetically engineered bacteria to produce the drug candidate.

The chemical, psilocybin, is naturally found in a specific mushroom, Psilocybe cubensis. Jones said to mass produce psilocybin from its natural mushroom host, it would require extensive real estate and time. Currently, alternative synthetic chemical production methods are used but are very expensive. Jones, the principal investigator of this research, wanted a solution that maintains biological integrity and reduces production costs.
jones-andrew-o10418.jpg

Andrew Jones' idea sparked a research path where he guided students as they conducted experiments.
Finding an optimal organic host

Through metabolic engineering, which finds ways to increase a cell’s ability to produce a compound of interest, his team of students developed a series of experiments to identify optimal psilocybin production conditions. The recently published article describes their work to optimize the production of psilocybin in the Escherichia coli bacteria. The team is using a well-known E. coli strain that is engineered for safe lab production.

“We are taking the DNA from the mushroom that encodes its ability to make this product and putting it in E. coli,” he said. “It’s similar to the way you make beer, through a fermentation process. We are effectively taking the technology that allows for scale and speed of production and applying it to our psilocybin producing E. coli.”

Their end result is a significant step toward demonstrating the feasibility of producing this drug economically from a biological source.

“What’s exciting is the speed at which we were able to achieve our high production. Over the course of this study we improved production from only a few milligrams per liter to over a gram per liter, a near 500-fold increase,” Jones said.

He gives much credit and praise to his students who designed many of the experiments performed during the 18-month-long study.

“A big part of my job is training undergraduates to do this work. The basic idea was mine, but much of the experimental design fell on the students. Early on, I would help guide them in the experimental design process. Toward the end, they were becoming more independent. That’s the type of student we want as they near graduation,” Jones said.
Undergraduate students help mentor other students on the basics of working in a scientific laboratory.
Learning to run laboratory experiments

Lead author Alexandra (Lexie) Adams, a junior chemical engineering major, became a member of the research team her freshman year, just as the Jones Lab was getting started. Patient and meticulous, Jones worked with the admittedly nervous Adams on the basics of laboratory research. It paid off.

The initial work was done in the summer of 2018 as Adams and another undergraduate student co-author, Nicholas Kaplan, took part in Miami’s Undergraduate Summer Scholars Program. The program provides funding to students for undergraduate research.
Both students, working on separate studies, learned the ins and outs of research, gaining confidence and learning lessons as the summer progressed.
Kaplan, a junior chemical engineering major, studied the feasibility of cyanobacteria as another potential metabolic engineering host. His findings showed mixed results, and it was decided that the lab team would focus on Adams’ psilocybin in E. coli project.
Celebrating a research breakthrough

Adams remembers when they saw the breakthrough in their research. Their goal was to transfer the DNA from the mushroom and see activity in the E. coli host.

“Once we transferred the DNA, we saw [a tiny] peak emerge in our data. We knew we had done something huge,” she said.

Other members of the team included: graduate Zhangyue ‘Tom’ Wei (Miami ’19), graduate John ‘Jack’ Brinton (BS Miami ’17, MS Miami ’19), junior Chantal Monnier, senior Alexis Enacopol, and staff member Theresa Ramelot, instrumentation specialist.

Both Adams and Kaplan continue to work with Jones. The students are leading projects that build on the recent success of the psilocybin work. Each of them is starting to pass down what they have learned in the lab by mentoring new undergraduate students that join the Jones Lab.

“It’s important for [the new students] to understand the big picture so they see the reasons for the different steps of the experiments,” Kaplan said.

Jones is pursuing the next phase of this research by studying ways to make the E. coli bacteria a better host — the next step toward enabling sustainable production at levels required by the pharmaceutical industry.



The future is coming and it has a glimmer of hope for our health and well being. The "reintroduction" of psychedelics to our cultures, physical and mental states, and to our lives in general will go much farther towards helping and curing people than most if not all the designed drugs have.

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Psilocybin from E-coli? Impressive. Though I'm not sure what to think of the statement that growing it in mushroom form would require extensive real-estate and time. I mean, I used to grow it in jars on my shelf. I was a complete novice to it, following only instructional YouTube videos, with limited time and very little space. Within only a month I had more mushrooms that I could ever want to eat, so I was playing Santa Claus with it. Just imagine how much of it I could grow if I did it full-time, dedicating the entire studio apartment for it. Now applying the same thing to a warehouse... you could probably supply an entire city with psilocybin.

By the way, what I find super fascinating about psilocybin research is not only how it can be helped for mental disorders, but also such things as alcoholism (and other substance abuse / dependency), violence, lying, cheating, and other types of behavior deemed "antisocial". This also explains why it has been treated as a controlled substance by those who are not interested in people being socially responsible (such as the pharma industry, among others).

One problem with pharma research is they look at only one molecule, not a whole system. I guess because it is difficult to pinpoint mechanism when there is a soup of components. The big time saver is the fact that they get pure psilocybin without having to extract it from the fungus. Given that they just need a standard room for this method they could produce millions of doses without all the overhead of the fungus growing production site.

Looking at this from just the production side it looks incredible. Looking at it from the holistic side I find it slightly off putting. The mushroom experience is not just due to the psilocybin but from the various other alkaloids in the fungus. By stripping out just this alkaloid it will be interesting to see what happens clinically. The pharma side is looking for a patentable tech to make profits, not help people. If helping people were truly their motive than psychedelics would never have been deemed a controlled substance.

It is HIGH time that humanity relearns the astounding benefits of psychedelics for our mental and physical well being.

Fully agree on the holistic aspect!
As far as the pharma industry goes, one can argue whether it was developed with bad intentions to begin with, or whether it just grew into what it is by convenience and market forces. Fact is, it's not helping us. But I think the same thing could be said about any industry, anchored in our current system. So in the end they might not be so bad, if the concept of business ethics was more than just hipocrite lip service.

Business and Ethics are 2 things that diverged a long time ago, sadly. Our planet is a corporatocracy now thanks to that divergence and is completely controlled by the lack of ethics in general. Some companies attempt to be generally conscious but the "investors are always right" mentality needs to frickin stop.

Agree, though I don't see a chance of that happening as long as you can't get your hands on any money without immediately owing to someone...

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Haha Psilocybin is the best. I would like them to produce it on an industrial scale for my personal consumption lol.

"According to the authors, their E. coli produced more psilocybin than any other organism retrofitted with "magic mushroom" DNA to date."

Interesting, I kind of want to know what other organisms they have tried this with. I have always wondered if one could produce 'GMO designer drugs" (for lack of a better term) because I would super want some DMT producing weed.

I would super want some DMT producing weed.

HOLY SHIT ME TOO!!!!! That would be some serious shit though I bet super fun!

I would assume a bunch of various bacteria and other fungus have gotten the DNA. Be very interesting to see the full list.

Yeah the truth is never as fun as my fantasies, sadly. This is still interesting, though. I never expected to see this strong of a mainstream movement to study psychedelics but I am happy that is happening. Outlawing those substances (at least, the classic ones) is one of the worst mistakes our species has ever made, in my opinion.

It's sad. Humans have locked up, silenced, and killed all the shamans. Then with prohibition so strong and societies too complacent, we have the current state. At least the tide is starting to turn and the "medical" value is finally being researched.

Truth.

I do see the shift coming. The younger generation seems to have more of an interest in those drugs than my fellow "80's babies" did. I remember that scene being fairly small when I was a teenager and in my twenties. Now, I see the "kids" memeing about DMT and shit. Hopefully, they push us over the line and I can get some damn mushrooms at the store like a civilized human being. lol

I'd be down for this!!

Nice. Hawaian sounds interesting.

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Not specifically Psilocyben, but muscimol has made my life so much better! Some people believe it is a sanctioned being because the intelligence it possesses to target out individuals specific issues that need to be held. Bring back the shamans!!!like you say 😎