LSD Neuroscience David E. Nichols, PhD Abstract: This talk will provide a foundation for understanding the importance of 5-HT2A receptors in the brain, now widely believed to be the key brain target for psychedelics. The study of this G protein-coupled receptor (GPCR) has required research efforts across several disciplines. Although it was initially thought to couple only to Gq, leading to activation of phospholipase C, it is now known to couple to multiple intracellular signaling pathways. The unique psychopharmacological properties of psychedelics clearly demonstrate that this receptor has special importance as a critical component of sensory perception in humans, and by extension, may be a key player in mediating consciousness. This presentation will focus on current understanding of the structure-activity relationships of psychedelics at the 5-HT2A receptor from a molecular perspective that has included synthesis of libraries of compounds, in vitro effects on cloned wild-type and mutated receptors, in vivo studies in rats, and computational chemistry. Until his retirement in June 2012, David E. Nichols, PhD, was the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology, and a Distinguished Professor of Medicinal Chemistry and Molecular Pharmacology at Purdue University. He also was an Adjunct Professor of Pharmacology and Toxicology at the Indiana University School of Medicine. He currently is an Adjunct Professor of Medicinal Chemistry at the University of North Carolina, Chapel Hill. Nichols received his PhD from the University of Iowa in 1973, followed by a postdoctoral stint in Pharmacology. From his time as a graduate student, Nichols focused his research on the relationship between molecular structure and the action of substances that modify behavior. His research took him to Purdue University in 1974, where he remained until his retirement this year. His research was funded by government agencies for more than three decades. Internationally recognized for his research on centrally active drugs, he is one of the world's foremost authorities on psychedelic agents, and founded the nonprofit Heffter Research Institute in 1993. He also was a pioneer in the study of the medicinal chemistry of dopamine D1 receptor agonists, and in 1991 he and his colleagues first showed that dopamine D1 agonists had remarkable efficacy in a primate model of Parkinson's disease. He consults for the pharmaceutical industry and has served on numerous committees and government review groups. More videos available at http://psychedelicscience.org