Mycology

By twisting the dials on key neurotransmitter systems in our brains, psychoactive compounds in a few kinds of mushrooms can provoke profound psychedelic experiences. The same compounds also show promise in treating illnesses such as therapy-resistant depression. But researchers don’t fully understand how they work in the brain—and why they evolved in the first place is a deeper mystery.

A new analysis, published on 21 September in Angewandte Chemie International Edition, adds to the confusion by confirming that two distinct genera of psychedelic mushrooms produce the same psychoactive compound, psilocybin, through entirely different chemical pathways. The research details a “completely novel path” to making psilocybin, says Jason Slot, a biochemist at Ohio State University who was not involved with the study. He adds that it could point toward “potentially very useful new enzyme tools for synthetic biology.” But it also underscores the puzzle of why two mushroom lineages would have independently arrived at making the same mind-bending molecule.

Mushrooms in the genus Psilocybe such as P. cubensis are the best-known source of psilocybin. But it’s also found in a few species from other genera, including a subset of fungi from the genus Inocybe commonly known as fiber cap mushrooms. When it binds to receptors for the neurotransmitter serotonin in the brain’s neurons, it triggers potent hallucinogenic experiences, which are central to some Indigenous rites and are cherished by modern recreational users.

Scientists don’t know exactly why psilocybin has this effect, but they have dissected the intricate chemical pathway by which Psilocybe mushrooms enzymatically make the compound. Scientists assumed fiber cap mushrooms made psilocybin with similar substrates and chemical reactions, but they hadn’t tested the idea. “We simply thought the order of biosynthetic events and the intermediates were the same,” says study co-author Dirk Hoffmeister, a biochemist at Friedrich Schiller University Jena. “Frankly, we weren’t really sure what to expect.”