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Incredible Mushrooms from Yeast

Timothy Boyer Ph.D.'s picture
Incredible mushroom research

The latest news and a little history on one of botany’s most infamous fungi.

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Researchers announce the publication of a new study published in the journal Metabolic Engineering, that demonstrates success toward manufacturing the active component of commonly-called “Magic Mushrooms” in yeast. The active component— psilocybin—is credited with giving magic mushrooms their particular hallucinogenic properties that some medical scientists today believe may offer a groundbreaking alternative to several under-treated psychological conditions.

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Therapeutic Benefits of Psilocybin

In fact, according to a news report from scientists at the Technical University of Denmark (DTU Biosustain), treatment with psilocybin is associated with the following therapeutic effects:

1) When administered under psychologically supportive, double-blind conditions, a single dose of psilocybin resulted in lower depressed mood and anxiety along with better quality of life in patients with a life-threatening cancer diagnosis.
—Journal of Pharmapsychology (2016) R. Griffiths et al, Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.

2) Psilocybin treatment of alcoholism has shown promising potential in decreasing abstinence and craving after several weeks of treatment.
—Journal of Pharmapsychology (2015) MP. Bogenschutz et al, Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

3) Findings imply that psilocybin might manage treatment-resistant depression. Single oral administrations of 10 mg (safety dose) and 25 mg (treatment dose) psilocybin were well tolerated by patients and led to reductions in symptoms already after two sessions.
—The Lancet (2016) R. Harris et al, Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

A Note of Warning on Magic Mushrooms

Legally—it should be noted that possession and use of psilocybin mushrooms is illegal throughout most of the U.S. (with some exceptions in a few cities) and carries heavy penalties, Most U.S. state courts consider the mushroom a 'container' of the illicit drugs, and therefore illegal. However, possessing the spores of psilocybin mushrooms is legally ambiguous since the spores do not contain psilocybin. Magic mushrooms, however, are expected to follow the same or similar eventual legalization over time as observed with cannabis.

From a Safety Standpoint—the use of any plant with hallucinogenic properties carries both temporary and permanent risks, and as such should be avoided with the exception under the care and guidance of a medical professional. Recreational use is not to be considered condoned by this article or its publisher. Understanding the scientific and historical aspects of magic mushrooms is mind-expanding on its own and should be limited to this degree of inquiry and investigation.

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The Need for Non-Mushroom Derived Psilocybin

One of the problems with developing medications containing psilocybin is that it takes a lot of mushrooms to extract the active component as well as require expensive and laborious chemical processing.

“It’s infeasible and way too expensive to extract psilocybin from magic mushrooms and the best chemical synthesis methods require expensive and difficult to source starting substrates. Thus, there is a need to bring down the cost of production and to provide a more consistent supply chain,” says Nick Milne, former Postdoc at DTU Biosustain.

While earlier research efforts have focused on using E. coli bacteria as cellular factories to produce psilocybin, it was found to be inefficient due to that bacteria lack a critical enzyme needed in the cellular manufacturing process. It turned out that turning to yeast, which like fungi is a eukaryotic organism (whereas bacteria are prokaryotic) was a better approach to the psilocybin problem.

“Since yeast and Psilocybe mushrooms are quite closely related species, this enzyme works very well in yeast, providing a much more cost-efficient alternative,” says Group Leader at DTU Biosustain Irina Borodina.

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The news report also notes that “…yeast also performs better in large-scale fermentation due to its long history in the beer brewing process, and also in the purification process since E. coli produces additional potentially harmful compounds that you would not like to have in your final product.”

While the published study is a credited success, more work remains to be done. It turns out that there remains some chemical tweaking needed to optimize production of the active component.

“What we find in the study is that we get a lot of this non-phosphorylated compound psilocin. Essentially, we are losing half of our product because the phosphate group falls off. Dealing with this high amount of psilocin is something that absolutely needs to be solved before realistically moving to a production process,” explains Nick Milne.

The Value of the Research

There’s much more to the research than the lowering the cost and optimizing the manufacture of psilocybin. As it turns out, Psilocybe mushrooms also contain a range of molecules similar to psilocybin that have potential as future therapeutics. Working out how to produce affordable and easily available psilocybin cold lead to similar methodologies for synthesizing new medications.

“Our interest is not only to make kilogram scale production of psilocybin but to use the biological machinery to make new derivatives that aren’t available today. Thus, it is very useful that we could not only demonstrate the production of psilocybin but also find many derivatives that could turn out to have important therapeutic relevance,” says Nick Milne.

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A Little Lite-History Reading About Magic Mushrooms

For an interesting historical exploration of magic mushrooms, here is an online copy of the 1957 Life magazine article that started America’s fascination with it and its hallucinogenic properties.

If you have any thoughts about the value of magic mushrooms as an herbal medication, please enter your response in the comments section below.

Timothy Boyer has a Ph.D. in Molecular and Cellular Biology from the University of Arizona. For 20+ years he has been employed as a freelance health and science writer. Today, with a background in farming and an avid home gardener, Timothy continues writing about science with a focus on the connection between plant biology and gardening for healthy living. For continual updates about plants and health, you can also follow Timothy on Twitter at TimBoyerWrites

Image courtesy of Creative Commons attributed to By Arp: This image is Image Number 6514 at Mushroom Observer, a source for mycological images., CC BY-SA 3.0,

References:

1. “Psychedelic compound from magic mushrooms produced in yeast” News from Technical University of Denmark (DTU Biosustain).

2. “Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives” N. Milne, P. Thomsen, N. Molgaard Knudson, P. Rubaszka, M. Kistensen, I. Borodina ; Metabolic Engineering, Volume 60, July 2020, Pages 25-36, DOI: 10.1016/j.ymben.2019.12.007

3. “Seeking the Magic Mushroom” by R. Gordon Wasson; LIFE Magazine (June 10, 1957).

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