Scientists Develop "Magic Mushroom" Compound Without Hallucinogenic Effects
Scientists are exploring new ways to harness the medical potential of psychedelic compounds without the accompanying intoxicating side effects. Researchers have successfully created a modified version of psilocin, the active form of psilocybin found in magic mushrooms, which continues to target the serotonin pathway associated with depression but with significantly reduced hallucinogenic effects.
Psilocybin has long attracted researcher interest for treating conditions such as depression, anxiety, substance use disorders, and neurodegenerative diseases. However, the intense hallucinogenic effects have often hindered widespread medical application.
In research published in ACS’ Journal of Medicinal Chemistry, scientists created a chemical variant of psilocin. Through preliminary studies in mice, this new molecule demonstrated stable biological activity but triggered fewer effects similar to hallucinations compared to pharmaceutical-grade psilocybin.
Many mood disorders and neurological conditions, including Alzheimer’s disease, are associated with serotonin dysfunction, a neurotransmitter that regulates mood. Researchers have spent decades exploring psychedelics due to their influence on serotonin signalling in the brain.
Andrea Mattarei, one of the corresponding authors of the study, stated that the findings open a new chapter in safer treatment strategies.
“Our findings are consistent with the emerging scientific perspective, which shows that psychedelic effects and serotonergic activity can be separated,” said Mattarei. “This opens the possibility of designing new therapies that maintain beneficial biological activity whilst reducing the hallucinogenic response, potentially enabling safer and more practical treatment strategies.”
The research team, led by Sara De Martin, Mattarei, and Paolo Manfredi, designed five chemical variants of psilocin. These compounds were engineered to release the active molecule into the brain more slowly and stably, aiming to reduce hallucinogenic effects without eliminating their therapeutic benefits.
Of the five variants, the candidate known as 4e showed the most promising results. In laboratory tests, 4e proved stable during absorption and released psilocin gradually, whilst remaining capable of activating major serotonin receptors at levels similar to the original psilocin.
When tested in mice, subjects receiving 4e exhibited “head twitches,” an indicator of hallucinogenic activity in animals, far less frequently than mice given conventional psilocybin. Researchers believe this difference is closely related to how much and how quickly psilocin is released within the brain.
These findings demonstrate that it is possible to design psilocin-based compounds capable of reaching the brain and activating serotonin receptors without triggering intense changes in consciousness.
Nevertheless, researchers emphasise that further research is still necessary to fully understand how these molecules work. Evaluation of safety and therapeutic potential in humans will be a crucial step before this drug can be widely used in medical practice.