THE MAGIC OF MUSHROOMS

Research from Denmark reveals new information about how psilocin and psilocybin work

BY WILL BRENDZA

When Gov. Jared Polis signed Colorado’s SB23290, the Natural Medicine Regulation and Legalization bill (Weed Between the Lines, “Laying down the law,” May 11, 2023), it decriminalized five natural psychedelic compounds: DMT, ibogaine, mescaline, psilocybin and psilocin.

This column has covered the former three — DMT (Weed Between the Lines, “Your brain on DMT,” March 23, 2023), ibogaine (Weed Between the Lines, “The addiction therapy drug,” April 6, 2023), and mescaline (Weed Between the Lines, “The psychedelic succulent,” April 27, 2023). While those are slightly more obscure psychedelic compounds, the other two, psilocybin and psilocin, are more widely used and known. These are the compounds that put the “magic” in magic mushrooms. But research from the University of Southern Denmark sheds new light on these well-known psychedelics. It appears that not only do these compounds bind with serotonin receptors in the brain, but they actually bind stronger than serotonin itself. The finding gives researchers hope for new developments in pharmaceutical drugs for patients who have found little relief with current medications.

Psilocybin has become a household name in the last decade. It’s been decriminalized in two states — Colorado and Oregon — an in 11 U.S. cities, including Washington, D.C. Psilocybin has been all over mainstream news for its applications as a therapeutic drug that can help treat addiction, depression, anxiety and PTSD.

Psilocin, ironically, is the lesser-known compound. While both psilocybin and psilocin are equally psychotropic, it’s psilocin that is largely responsible for the high most magic-mushroom users are familiar with.

Any orally ingested psilocybin is broken down in the gut by the enzyme alkaline phosphatase and turned into its bioactive form, psilocin.

If you eat psilocybin mushrooms, you’re tripping on psilocin.

Albert Hoffman was one of the first chemists to isolate psilocybin and psilocin in 1959. His pharmaceutical employer then marketed and sold pure psilocybin to doctors and therapists across the country who used the medi- cine to treat their patients. But as the war on drugs ramped up in the ’60s, and psychoactive substances were thrown wholesale under the banner of Schedule I prohibited substances, those treatments and medications were abandoned.

A research team from the University of Southern Denmark was interested in determining what happens when psilocybin enters the body, is converted into psilocin and then reaches the human brain.

“My interest was piqued when I heard a podcast about treating smoking addiction with psilocybin,” Himanshu Khandelia, one of the University’s researchers, said in a press release. “And since psilocybin mushrooms grow everywhere in Denmark — I picked some in Svanninge Bakker — it wasn’t difficult to start our research.”

Biophysica Acta, they use molecular dynamics simulations and free energy calculations to describe how psilocin bonds to serotonin receptors.

Serotonin is commonly referred to as one of the “happy molecules.” It carries messages between nerve cells in the brain and throughout the body and plays a key role in modulating your mood, cognition, reward, learning, memory and other neurological processes. Serotonin receptors are the “receivers” built specifically to accept those nervous system messages.

According to these findings from the University of Southern Denmark, psilocin not only penetrates the cell membrane and binds to these very specific receptors, it binds stronger than serotonin does.

The scientists point out that this research may come in handy if you want to design a chemical analog for psilocin that could be turned into a pharmaceutical drug. Which is exactly what they’re hoping comes from this research.

Without the legal and bureaucratic hoops that U.S. scientists have to jump through to conduct psychedelic research, the Danish researchers gathered materials and got to work. In their paper, published in Biochimica et

“I would be very happy if society can use our research,” Khandelia said. “Maybe someone will take this further and create a molecule that can be used in medical treatment for conditions like depression.”

Along with team member Ali Asghar Hakami Zanjani, Khandelia is continuing this line of research. They are now investigating the mechanism behind the mushroom high, exploring how psychoactive responses are triggered when compounds bind to serotonin receptors.