How did magic mushrooms evolve to contain psilocybin?

Psilocybin, the primary psychoactive component in “magic mushrooms” of the genus Psilocybe, has recently gained attention not only as a popular recreational drug but also in the realm of medicine for its potential therapeutic benefits. 

How is psilocybin produced by magic mushrooms?

Notably, the psilocybin found in magic mushrooms has shown promise in treating depression, addiction, and anxiety, reaching advanced stages of clinical trials as a potential pharmaceutical treatment. Now, a study led by the Medical University of Innsbruck has comprehensively examined how psilocybin is produced by magic mushrooms.

Produced by a complex biochemical process from the amino acid L-tryptophan, psilocybin’s synthesis involves critical enzymes, including PsiM, a methyltransferase. 

“There are many methyl transfer reactions in nature,” said co-author Dirk Hoffmeister, a professor of pharmaceutical microbiology at Friedrich Schiller University Jena and leader of a research group at the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI). “Here, we asked ourselves how exactly psilocybin production is accomplished.”

PsiM enzyme’s role in psilocybin production

In  a collaborative effort, experts from the Medical University of Innsbruck, led by crystallographer Bernhard Rupp, and Hoffmeister’s team at Jena delved into the PsiM enzyme’s role in psilocybin production using biochemical analysis and X-ray crystal structure analysis, which visualizes proteins at the atomic level. 

Their findings revealed that PsiM, crucial for the last two steps of psilocybin synthesis, bears significant structural similarities to enzymes typically involved in RNA modification. Despite some differences, these similarities suggest that PsiM evolved from an RNA methyltransferase, which originally could attach only one methyl group to its target.

The experts also found that a single amino acid change in PsiM enabled it to carry out two consecutive methylation reactions, crucial for converting the psilocybin precursor norbaeocystin into psilocybin. This precursor structurally mimics part of RNA but undergoes double methylation, a key step in psilocybin production.

Future biotechnological applications in creating psilocybin

Moreover, the researchers explored whether PsiM could add a third methyl group to convert psilocybin into aeruginascin, a naturally occurring psilocybin analog. The scientific community has long debated whether aeruginascin is a byproduct of psilocybin biosynthesis. 

“This is clearly not the case. PsiM is not able to convert psilocybin to aeruginascin,” Hoffmeister said. While definitively ruling out PsiM’s involvement in aeruginascin production, this finding highlights its potential for future biotechnological applications in creating psilocybin.

“Overall, our results can help to develop new variants of psilocybin with improved therapeutic properties and to produce them biotechnologically,” Hoffmeister concluded.

More about magic mushrooms

Magic mushrooms have been used for thousands of years in various cultural and religious rituals, primarily for their ability to induce profound changes in perception, mood, and thought. Upon ingestion, psilocybin is converted in the body to psilocin, which is responsible for the psychedelic effects.

Experience of magic mushrooms 

The experience of taking magic mushrooms can vary greatly depending on the dose, individual psychology, and environmental setting.

Common effects include visual and auditory hallucinations, an altered sense of time, euphoria, and a feeling of deep connection to others and the natural world. However, users can also experience negative effects such as anxiety, paranoia, and nausea.

Scientific interest 

Scientific interest in psilocybin has grown in recent years, especially for its potential therapeutic benefits. Research suggests that psilocybin may help treat depression, anxiety, PTSD, and addiction. 

These studies have shown that psilocybin can create lasting changes in personality and attitude towards life, often characterized by increased openness and a greater sense of peace.

Legal landscape 

Despite their potential benefits, magic mushrooms are classified as Schedule I substances in the United States and are illegal in many other countries. This classification is due to their high potential for abuse and lack of recognized medical value under current laws. 

However, the legal landscape is slowly changing as more research highlights the therapeutic potential of psilocybin, leading some regions to reconsider their stance on these substances.

The study is published in the journal Nature Communications.

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