David E. Nichols, PhD is currently an Adjunct Professor at the University of North Carolina, Chapel Hill, NC, is a Distinguished Professor Emeritus at the Purdue University College of Pharmacy and was the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology, where he taught and did research for 38 years. He is also Director of Molecular Pharmacology at Eleusis Therapeutics.
In 2004 he was named the Irvine H. Page Lecturer by the International Society for Serotonin Research, received the first Purdue Provost’s Outstanding Graduate Mentor award in 2006 and was named a Distinguished Alumnus by the University of Iowa College of Pharmacy in 2012. He began studying psychedelics as a graduate student in 1969.
His lab synthesised DMT for Dr. Rick Strassman, the MDMA for MAPS Phase I and II clinical trials, and the psilocybin used for human clinical studies conducted at Johns Hopkins University. In 1993 he founded the Heffter Research Institute (HRI), which funded the first groundbreaking Phase I and II studies of psilocybin for the treatment of depression, and pilot studies for treating alcohol use disorder, and tobacco addiction.
Overview of Psychedelics, from Prehistory to the Present
Some of the groundbreaking projects supported by the Heffter Research Institute, founded by David Nichols in 1993, will be highlighted.
This talk will begin with a brief review of the natural sources of psychedelics that have been used for millennia. That will be followed by a discussion of the 5-HT2A receptors that are the targets for the classic psychedelics; where they are located, and brief comments on the nature and function of G-protein-coupled receptors (GPCRs). There will be brief discussion of how psychedelics are tested in animals and then description of some preclinical studies from the Nichols lab, including work to elucidate the conformation of the diethylamide function of LSD.
In particular, Leucine 229, in extracellular loop 2 of the receptor, was shown to be a critical residue in the receptor kinetics of LSD binding to the receptor. Brief comments will be made on the crystal structure of LSD bound in the 5-HT2B receptor, published in 2017, and of LSD and 25CN-NBOH structures published in 2020. A brief conclusion will note the effect of psychedelics on brain dynamics as a possible mechanism for their therapeutic potential.