At the University of California, Davis, a research team led by Professor Mark Mascal of the Department of Chemistry has developed a new chemical method that uses light to transform amino acids into molecules that resemble psychedelics in both structure and receptor activity. The work, carried out in collaboration with the UC Davis Institute for Psychedelics and Neurotherapeutics, explores whether it is possible to engage key brain pathways associated with therapeutic benefits while avoiding hallucinogenic effects.
Beckett, J. O. S., Buzdygon, R., Nguyen, S., Clark, A. A., Schalk, S. S., Svanholm, L. E. H., Brasher, T. J., Bazin, M., Cuccurazzu, B., Halberstadt, A. L., McCorvy, J. D., & Mascal, M. (2025). Transforming Amino Acids into Serotonin 5-HT 2A Receptor Ligands Using Photochemistry. Journal of the American Chemical Society, 147(52), 48400–48415. https://doi.org/10.1021/jacs.5c19817
Interest in psychedelic science has expanded rapidly as studies continue to link serotonin signaling to neuroplasticity and mental health outcomes. However, many compounds that activate these pathways also cause perceptual disturbances, which complicate their clinical use. Rather than modifying known psychedelic drugs, the UC Davis researchers pursued a more fundamental approach based on molecular design.
University of California, Davis, a research team led by Professor Mark Mascal of the Department of Chemistry stated,
“The question that we were trying to answer was, ‘Is there a whole new class of drugs in this field that hasn’t been discovered? The answer in the end was yes.”
Their strategy begins with amino acids, the basic components used by living systems to build proteins. These amino acids were chemically coupled with tryptamine, a naturally occurring molecule related to several psychedelic substances. When exposed to ultraviolet light, the combined molecules underwent photochemical reactions that rearranged their structures, producing compounds not typically found in biological systems.
This light-driven approach differs from conventional synthetic chemistry by reducing the number of reaction steps and avoiding extensive use of reagents. From an engineering perspective, photochemistry offers a controlled way to generate chemical diversity while maintaining efficiency and scalability.
The newly formed molecules were evaluated for their interaction with the serotonin 5 HT2A receptor, a primary target involved in both psychedelic effects and neural growth. Activation of this receptor has been associated with changes in cortical plasticity and has drawn interest for potential treatment of depression, post traumatic stress disorder, and substance use disorders.
Using computational modeling, the researchers screened a library of approximately one hundred candidate molecules to estimate receptor binding strength and signaling potential. Five compounds were selected for laboratory testing based on these predictions. The compounds displayed a wide range of activity, from partial activation to full agonism of the receptor.
One compound, identified as D5, showed full agonist behavior in receptor assays. Based on existing knowledge, this level of activation would normally be expected to produce hallucinogenic-like responses. To test this, the compound was administered in mouse models commonly used to detect psychedelic activity.
Despite fully activating the serotonin receptor, D5 did not trigger the head twitch response typically associated with hallucinogenic compounds. This result suggests that receptor activation alone may not determine perceptual effects, and that downstream signaling pathways or interactions with other serotonin receptors may influence behavioral outcomes.
The findings point toward the existence of previously unexplored therapeutic scaffolds that separate beneficial serotonin signaling from hallucinogenic effects. For chemical and biomedical engineers, this highlights how small structural changes can lead to significant differences in biological response.
The research team plans to conduct follow up studies to better understand why certain compounds activate serotonin receptors without inducing hallucinations. Future work will examine how these molecules interact with additional receptors and intracellular signaling mechanisms in the brain.
By combining photochemistry with rational molecular design, the study demonstrates a pathway for developing new neurotherapeutic candidates that are distinct from traditional psychedelics. While clinical applications remain in early stages, the work establishes a foundation for engineering molecules that target mental health disorders with greater specificity and fewer side effects.
Adrian graduated with a Masters Degree (1st Class Honours) in Chemical Engineering from Chester University along with Harris. His master’s research aimed to develop a standardadised clean water oxygenation transfer procedure to test bubble diffusers that are currently used in the wastewater industry commercial market. He has also undergone placments in both US and China primarely focused within the R&D department and is an associate member of the Institute of Chemical Engineers (IChemE).
