The first phase of the rats' LSD experience, Nichols found, was indeed mediated by the 5-HT2A receptor, the one responsible for the visuals. But the second phase of the rats' trip was a full-on dopamine response. The "coming down" phasewhere bad trips are more likely to formis where the dopamine D2 receptor kicks in, a receptor that's implicated, among other things, in schizophrenia. It seems that an LSD trip is a two-phase experiencea story that begins with serotonin and ends with dopamine.
Nichols hopes that this study and several others that his lab is on the brink of finishing will finally reveal answers to some of the basic questions about how LSD works, answers he's been chasing down for over half his lifetime.
photo: David Nichols
Albert Hofmann (left), discoverer of LSD, and Purdue's David Nichols at the 2004 ASC conference in Zurich