New Article Shows Promise of a Psychedelic Without the Hallucinations

A new article highlights how an old psychedelic drug, Ariadne, may improve brain health without hallucinogenic effects.

January 24, 2023

A new article in the journal ACS Chemical Neuroscience examines the potential of Ariadne, a non-hallucinogenic psychedelic, in producing a wide array of benefits in neurological and psychiatric disorders.

The research comes amid a widespread rising interest in the use of psychedelics to treat depression and other mental disorders, and suggests possible benefits in neurodegenerative disorders including Parkinson’s.

Ariadne is a psychedelic drug that was studied by the pharmaceutical company Bristol-Myers, but research on the drug was abandoned in the 1970s. In early unpublished trials, the drug was reported to have had wide-ranging effects. These include remission of symptoms in people with schizophrenia and people with Parkinson’s disease and improved cognition in older subjects, the paper’s authors (who include Columbia Chemistry Professor Dalibor Sames) write.

An illustration created by article co-authors David Lankri and Dalibor Sames with the artist Ksania Mariash.

The new article, “Pharmacological Mechanism of the Non-hallucinogenic 5-HT2A Agonist Ariadne and Analogs,” uses data from past clinical trials and new pharmacological examinations of the drug, and outlines a hypothesis for how Ariadne and other chemically similar compounds manage to exert clinical effects without inducing hallucinations.

The article also reports on a test run conducted by the authors on a mouse that carried all of the major hallmarks of Parkinson’s disease that humans exhibit. The symptoms were rapidly corrected after treatment with Ariadne, but more research is needed to determine if the drug has potential to help people with the disease.

“This research shows the great promise that this compound and others like it can have. We hope that it drives the rapid development of market-ready forms of Ariadne,” said Sames, who, in addition to his role in Columbia’s chemistry department, is the co-founder of Gilgamesh Pharmaceuticals, a company that is developing therapeutic psychedelics to treat mental illness.

The image at right is an illustration made to accompany the article by co-authors David Lankri and Dalibor Sames with the artist Ksania Mariash. Ariadne was named by the late chemist Alexander Shulgin in homage to the Greek myth of Ariadne, who led Theseus out of a labyrinth and then was abandoned by him; she later married Dionysus, a god of festivity and fertility. The compound, the article’s authors write, was also leading pharmaceutical firms “out of innovation malaise,” before being abandoned. Only recently has it been rediscovered in the “current revolution of psychiatric drug discovery” which the authors hope “will guide us to many new medicines of this class.”

Read the full article here.