Usona Researchers Discover New Compounds With Psychedelic Properties

Chemists synthesize novel series derived from psilocybin mushroom tryptamine

Scientists at the Usona Institute say they have designed several new compounds with characteristics similar to those found in psychedelic mushrooms.

The study, published Jan. 8 in ACS Chemical Neuroscience, illustrates how targeted chemical alterations in a specific part of the norpsilocin molecule yield novel lead compounds, advancing the quest for psychedelics with enhanced therapeutic properties.

Norpsilocin is a tryptamine natural product found in psychedelic mushrooms.

By making structural modifications to norpsilocin, the researchers say they can produce new compounds that demonstrate features critical for high activity at the serotonin 2A (5-HT2A) receptor. Psychedelics are known to impact 5-HT2A receptor activity.

The researchers tested eight compounds, with five showing psychedelic-like effects. The results indicate the compounds could impact additional therapeutically relevant receptors across the brain.

“Through traditional medicinal chemistry techniques paired with contemporary pharmacology assays, this research builds upon a rich and unique history of psychedelic discovery efforts inspired by natural products,” says Alex Sherwood, lead author on the paper and Head of Medicinal Chemistry at Usona. “We are excited to reveal a new branch on the tree of psychoactive tryptamines.”

Usona’s medicinal chemistry lab designed and synthesized the compounds reported in the publication, and the pharmacological studies were carried out in collaboration with the Designer Drug Research Unit of the National Institute on Drug Abuse Intramural Research Program and the National Institute of Mental Health’s Psychoactive Drug Screening Program.