Laboratory tests showed the serotonin 2A receptor has two “on” positions; drugs like LSD make the receptor go into one “on” position, whereas non-psychedelic drugs like lisuride activate serotonin 2A receptor in a different way.

In a related finding, the research team also unraveled another neurochemical mystery. Previously, scientists had suspected that hallucinogenic drugs acted on the serotonin 2A receptors by traveling to the cerebral cortex, a key structure in the brain associated with multiple complex brain functions, including memory, attention, language, and consciousness. Using genetically-altered mice developed by their collaborators at the Laboratory of Mouse Genetics and Behavior led by Jay A. Gingrich, MD, PhD, an assistant professor at Columbia University, the two groups found that the serotonin 2A receptor was acted on in the cerebral cortex, but not by cells traveling to the cerebral cortex. “This clarified the pathway so that we could really narrow down where this serotonin 2A receptor activity was taking place,” Dr. Sealfon says.

The next step is to investigate and understand the patterns of serotonin 2A receptor activation. “This could open many doors,” Dr. Sealfon says. “When developing drugs to treat drug abuse or neurodegenerative disorders or psychiatric illnesses, scientists can look beyond just the target or the receptor they want to activate, and start tinkering with how they want to activate the receptor, which would then create very specific responses and results. Instead of prescribing a treatment and hoping for the best, this approach could put scientists and physicians in the driver’s seat, and give them better control, which ultimately will lead to better patient outcomes.”