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NIMH study suggests therapeutic utility of LSD

Recent findings from an NIMH-funded study showed an interaction between LSD and a serotonin receptor in the human brain, suggesting therapeutic utility of LSD.

“This study sheds light on the mechanism of psychoactive drug action, including how certain drugs activate one signaling pathway inside cells while avoiding another,” Laurie Nadler, PhD, chief of NIMH’s Neuropharmacology Program, said in a press release. “Taken together with other recent studies of drug-receptor complexes, this work provides proof-of-concept for the design of drugs with desired signaling properties and fewer undesired side-effects.”

Daniel Wacker, a research associate in the department of pharmacology at the University of North Carolina at Chapel Hill, and colleagues used x-ray crystallography to explore the structure of LSD in complex with the serotonin receptor 5-HT_2B.

Analysis indicated that unique features of LSD, such as its long-lasting effects, rely on its strong tendency to act through two key pathways in the brain. LSD’s molecular structure interacted with its receptor through a beta-arrestin pathway, rather than a G-protein pathway.

Researchers linked significantly different properties of LSD chemical cousins with differences in their structural interaction with the receptor.

These findings build upon the researchers’ previous findings, which indicated the potential of a designer painkiller they created based on similar concepts of the molecular structure of an opioid receptor.

Wacker and colleagues are currently investigating molecular functions of the 5-HT_2A receptor.

Disclosure: Please see the study for a full list of relevant financial disclosures.