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Could psychedelics become a new generation of treatments for depression and other psychiatric disorders? This question is no longer confined to basic research. Several therapies based on classical psychedelics have advanced into late-stage clinical development and have reported encouraging results. DT120, an LSD-based candidate, and COMP360, a synthetic psilocybin formulation, have both received breakthrough therapy designation from the U.S. Food and Drug Administration.

Despite this progress, a key challenge remains: how can the rapid and long-lasting therapeutic effects of psychedelics be preserved while minimizing acute hallucinogenic experiences and the practical demands of supervised dosing? Addressing this question will be crucial not only for the further development and regulation of these therapies but also for making them safer and more accessible.

In a study published in Nature Neuroscience, a research team led by professor Wang Sheng from the Center for Excellence in Molecular Cell Science (Shanghai Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences, in collaboration with professor Cheng Jianjun at the iHuman Institute, ShanghaiTech University, integrates receptor signaling and ligand-binding kinetics to define the temporal features of downstream 5-HT₂AR pathways.

The study links the instantaneous peak of Gαq/Ca²⁺ signaling to hallucinogenic-like responses, while cumulative β-arrestin signaling over time supports sustained antidepressant-like effects, establishing a pharmacological strategy for separating the two.

A growing body of evidence suggests that classical psychedelics such as LSD and psilocybin can produce rapid and sustained antidepressant effects.

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