Usona Institute Research Unveils New Compounds with Observed Psychedelic-like Activity

Medicinal chemists at Usona Institute have designed a series of new compounds inspired by norpsilocin, a tryptamine natural product found in psychedelic mushrooms. The research, published this week in ACS Chemical Neuroscience, sheds light on the impact of strategic chemical modifications at a specific region of the norpsilocin molecule, providing new lead compounds in pursuit of psychedelics with optimized therapeutic properties.

Key findings reported in the publication include:

• Structural modifications to norpsilocin result in new compounds with improved ability to enter the brain.
• Brain activity and potency measurements in animal behavioral models indicate five out of the eight tested compounds can produce psychedelic-like effects.
• Testing with cell-based models elucidated chemical features important for high activity at the serotonin 2A (5-HT_2A) receptor, a common characteristic of all known psychedelics.
• High-throughput screening experiments demonstrate that compounds in the series activate additional therapeutically relevant receptors across the brain, warranting further research.

"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 (NIDA IRP) and the National Institute of Mental Health's Psychoactive Drug Screening Program (NIMH-PDSP).

Usona Institute is a non-profit medical research organization that takes an open science approach to established findings, therefore making public the scientific discoveries and processes that arise from its research. The study published January 8, 2024, in ACS Chemical Neuroscience is an open access paper.

To learn more about Usona, visit www.usonainstitute.org

About Usona Institute

Usona Institute is a 501(c)(3) nonprofit medical research organization (MRO) that conducts and supports pre-clinical and clinical research to further the understanding of the therapeutic effects of psilocybin and other consciousness-expanding medicines. Its focus is on alleviating depression and anxiety in people for whom current medical treatments fall short in offering relief and a better quality of life.

Research reported in this press release was supported by the National Institute on Drug Abuse (NIDA) and National Institute of Mental Health (NIMH) of the National Institutes of Health under award number ZIADA000522 and through a Cooperative Research and Development Agreement with NIDA, and under Contract No. HHSN-271-2018-00023-C with NIMH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.