Magic Mushrooms Without The Mind Trip? Scientists Are Getting Close To The Next Chapter In Psychedelic Medicine For Mental Health
Researchers in Italy are trying to fine-tune the way the compound psilocybin enters and behaves inside the brain.
Published : March 8, 2026 at 11:13 AM IST
Magic mushrooms have always had a slightly complicated reputation. On the one hand, they’ve been associated with people staring at trees and announcing that they finally “understand the universe”. On the other hand, scientists have been discovering that the same mushrooms might actually help treat some very serious mental health conditions.
The key ingredient in these mushrooms is psilocybin, a compound that turns into another chemical called psilocin once it enters the body. Psilocin interacts with serotonin receptors in the brain: the same system that influences mood, emotions, and a surprising number of things that determine whether you feel like getting out of bed in the morning. This is why researchers have been interested in psilocybin for years. Early studies suggest it could help with depression, anxiety, addiction, and even certain neurodegenerative diseases such as Alzheimer’s.
The only small complication is the hallucinations. While some people might be open to the idea of psychedelic therapy, many others are understandably hesitant about a treatment that could make the walls breathe. So scientists have begun asking: What if we could keep the therapeutic benefits of psilocybin without the psychedelic trip?
Makeover For Mushrooms
A group of researchers in Italy publishing their work in the Journal of Medicinal Chemistry decided to investigate exactly that. Led by scientists Sara De Martin, Andrea Mattarei and Paolo Manfredi, the team created five chemically modified versions of psilocin, the active compound responsible for psilocybin’s effects. The goal wasn’t to reinvent the mushroom entirely. Instead, they wanted to fine-tune the way the compound enters and behaves inside the brain. Their theory was that if the compound could be released more slowly and steadily, it might still activate the brain’s serotonin pathways (linked to mood improvement) without triggering the intense psychedelic experience.
As Mattarei explained: “Our findings are consistent with a growing scientific perspective suggesting that psychedelic effects and serotonergic activity may be dissociated. This opens the possibility of designing new therapeutics that retain beneficial biological activity while reducing hallucinogenic responses, potentially enabling safer and more practical treatment strategies.”
The researchers tested their five new compounds in a series of laboratory experiments designed to mimic what happens in the human body. Next came the animal studies. Researchers gave mice either pharmaceutical-grade psilocybin or the new compound 4e and monitored how the chemicals travelled through their bodies over 48 hours. Both substances crossed the blood-brain barrier, which is essential. But the behaviour inside the brain looked quite different. Psilocybin caused a higher and faster spike of psilocin, while compound 4e produced lower but more sustained levels.
The Results
Scientists often measure psychedelic activity in rodents using something called the “head twitch response.” It’s exactly what it sounds like: mice on psychedelics twitch their heads repeatedly. Mice that received the new compound showed significantly fewer head twitches than those given psilocybin.
If scientists can create compounds that activate the beneficial serotonin pathways without the hallucinations, it could make psychedelic-inspired therapies far more accessible and acceptable. Imagine antidepressant treatments derived from mushrooms, but without the part where the carpet spontaneously starts changing colours.
Source:
https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c01797
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