Dave Nichols



President, Co-Founder, Director of Preclinical Research

Dr. Nichols originally conceived of a privately funded Institute as the most effective mechanism for bringing research on psychedelic agents into the modern era of neuroscience. This vision led to the founding of the Heffter Research Institute in 1993. Prior to his retirement in June 2012, he was the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at the Purdue University College of Pharmacy, and also was adjunct Professor of Pharmacology at the Indiana University School of Medicine. He is currently an Adjunct Professor at the University of North Carolina Chapel Hill, NC, where he continues his research. In 2004 he was named the Irwin H. Page Lecturer, and in 2006 was named the first Provost’s Outstanding Graduate Mentor at Purdue. The focus of his graduate training, beginning in 1969, and of much of his research subsequent to receiving his doctorate in 1973 has been the investigation of the relationship between molecular structure and the action of psychedelic agents and other substances that modify behavioral states. His research has been continuously funded by government agencies for more three decades. He consults for the pharmaceutical industry and has served on numerous committees and government research review groups. Widely published in the scientific literature and internationally recognized for his research on centrally active drugs, he has studied all of the major classes of psychedelic agents, including LSD and other lysergic acid derivatives, psilocybin and the tryptamines, and phenethylamines related to mescaline. Among scientists, he is recognized as one of the foremost experts on the medicinal chemistry of hallucinogens. His high standards and more than four decades of research experience set the tone to ensure that rigorous methods and quality science are pursued by the Institute.


N.V. Cozzi, S. Frescas, D. Marona-Lewicka, X. Huang and D.E. Nichols, “Indan analogs of fenfluramine and norfenfluramine have reduced neurotoxic potential,” Pharmacol. Biochem. Behav., 59, 709-715 (1998).

M Troconis, W. Ma, D.E. Nichols, and J.L. McLaughlin, “Molecular modeling study of tubulosine and other related ipecac alkaloids,” J. Comp. Assisted Drug Design, 12, 411-418 (1998).

J.B. Blair, D. Marona-Lewicka, A. Kanthasamy, V.L. Lucaites, D.L. Nelson, and D.E. Nichols, “Thieno[3,2-b]- and thieno[2,3-b]pyrrole bioisosteric analogues of the hallucinogen and serotonin agonist N,N-dimethyltryptamine,” J. Med. Chem., 42, 1106-1111, (1999).

C. Scorza, R. Silveira, D.E. Nichols, and M. Reyes-Parada, “Effects of 5-HT-releasing agents on extracellular hippocampal 5-HT of rats. Implications for the development of novel antidepressants with a short onset of action,” Neuropharmacology, 38, 1055-1061, (1999).

D.E. Nichols and S. Frescas, “Improvements to the synthesis of psilocybin and a facile method for preparing the O-acetyl prodrug of psilocin,” Synthesis, 935-938, (1999).

M. Gerasimov, D. Marona-Lewicka, D. Kurrasch-Orbaugh, A.M. Qandil, and D.E. Nichols, “Further studies on oxygenated tryptamines with LSD-like activity incorporating a chiral pyrrolidine moiety into the side chain.” J. Med. Chem., 42, 4257-4263 (1999).

J.B. Blair, D. Kurrasch-Orbaugh, D. Marona-Lewicka, M.G. Cumbay, V.J. Watts, E.L. Barker, and D.E. Nichols. “Effect of Ring Fluorination on the Pharmacology of Hallucinogenic Tryptamines.” J. Med. Chem., 43, 4701-4710 (2000).

.J. Chambers, D.M. Kurrasch-Orbaugh, M.A. Parker, and D.E. Nichols. “Enantioselective Synthesis and Pharmacological Evaluation of a Series of Super-Potent, Conformationally Restricted 5‑HT2A/2C Receptor Agonists.” J. Med. Chem., 44, 1003-1010 (2001).

U. Laban, D. Kurrasch-Orbaugh, D. Marona-Lewicka, and D.E. Nichols. “A novel fluorinated tryptamine with highly potent and selective serotonin 5-HT1A receptor agonist properties,” Bioorg. Med. Chem. Letters, 11, 793-795 (2001).

E.M. Falk, V. Cook, D.E. Nichols, and J.E. Sprague. “An antisense targeted at MAO-B attenuates rat striatal serotonergic neurotoxicity induced by MDMA,” Pharmacol. Biochem. Behav., 72, 617-622 (2002).

J.J. Chambers, D.M. Kurrasch-Orbaugh, and D.E. Nichols. “Translocation of the 5-Alkoxy Substituent of 2,5-Dialkoxyarylalkylamines to the 6-position: Effects on 5-HT2A/2C Receptor Affinity,” Bioorg. Med. Chem. Letters, 12, 1997-1999 (2002).

D.E. Nichols, S. Frescas, D. Marona-Lewicka, and D. Kurrasch-Orbaugh. “Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in N,N-Diethyl lysergamide (LSD),” J. Med. Chem., 45, 4344-4349, (2002).

M.S. Whiteside, D. Kurrasch-Orbaugh, D. Marona-Lewicka, D.E. Nichols, and A. Monte. “Substituted Hexahydrobenzodipyrans as conformationally restricted serotonin 5-HT2A/2C receptor probes,” Bioorg. & Med. Chem., 10, 3301-3306, (2002).

D. Marona-Lewicka, D.M. Kurrasch-Orbaugh, J.R. Selken, M.G. Cumbay, J.G. Lisnicchia and D.E. Nichols. “Reevaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties,” Psychopharmacology, 164, 93-107 (2002).

J. Chambers and D.E. Nichols, “A Homology-Based model of the human 5-HT2A receptor derived from an In Silico activated G-protein coupled receptor,” J. Computer-Aided Molecular Design, 16, 511-520, (2002).

A. Kanthasamy J.E. Sprague, J.R. Shotwell and D.E. Nichols, “Unilateral Infusion of a Dopamine Transporter Antisense into the Substantia Nigra Protects Against MDMA-Induced Serotonergic Deficits in the Ipsilateral Striatum,” Neurosci., 114, 917-924, (2002).

D.M. Kurrasch-Orbaugh, V.J. Watts, E.L. Barker, and D.E. Nichols. “Serotonin 5-HT2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves,” J. Pharmacol. Exp. Ther., 304, 229-237, (2003).

J.J. Chambers, J.C. Parrish, N.H. Jensen, D. Kurrasch-Orbaugh, D. Marona-Lewicka, and D.E. Nichols. “Synthesis and pharmacological characterization of a series of geometrically constrained 5-HT2A/2C receptor ligands,” J. Med. Chem., 46, 3526-3535 (2003).

D.M. Kurrasch-Orbaugh, J.C. Parrish, V.J. Watts, and D.E. Nichols. “A complex signaling cascade links the serotonin2A receptor to phospholipase A2 activation: the involvement of MAP kinases,” J. Neurochem., 86, 980-991 (2003).

D. E. Nichols. “Hallucinogens.” Invited review for Pharmacology & Therapeutics, 101, 131-181 (2004).

S.L. Hrometz, A.W. Brown, D.E. Nichols, and J.E. Sprague. “3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)-Mediated Production of Hydrogen Peroxide in an In Vitro Model: The Role of Dopamine, the Serotonin-Reuptake Transporter, and Monoamine Oxidase-B,” Neuroscience Letters, 367, 56-59 (2004).

A. Gallardo-Godoy, A. Fierro, T.H. McLean, M. Castillo, B.K. Cassels, M. Reyes-Prada, and D.E. Nichols. “Sulfur-substituted α-alkyl phenethylamines as selective and reversible MAO-A inhibitors: biological properties, CoMFA analysis, and active site modeling, J. Med. Chem., 48, 2407-2419 (2005).

D. Marona-Lewicka, R.A. Thisted, and D.E. Nichols. “Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 Receptor-mediated effects in the rat and implications for psychosis,” Psychopharmacology, 180, 427-435 (2005).

J.C. Parrish, M.R. Braden, E. Gundy, and D.E. Nichols. “Differential phospholipase C activation by phenylalkylamine serotonin 5-HT2A receptor agonists,” J. Neurochem., 95, 1575-1584, (2005).

M.M. Lewis, X. Huang, D.E. Nichols, and R.B. Mailman. “D1 and functionally selective dopamine agonists as neuroprotective agents in Parkinson’s disease.” Current Drug Targets: CNS and Neurological Disorders, 5, 345-353, (2006)

T. McLean, J.J. Chambers, J.C. Parrish, M.R. Braden, D. Marona-Lewicka, D.M. Kurrasch-Orbaugh, and D.E. Nichols. “C-(4,5,6-trimethoxyindan-1-yl)-methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor,” J. Med. Chem., 49, 4269-4274 (2006).

T.H. McLean, J.C. Parrish, M.R. Braden, D. Marona-Lewicka, A. Gallardo-Godoy, and D.E. Nichols. “1-Aminomethylbenzocycloalkanes: conformationally-restricted hallucinogenic phenethylamine analogues as functionally-selective 5‑HT2A receptor agonists,” J. Med. Chem., 49, 5794-5803 (2006).

J.C. Parrish and D.E. Nichols. “Serotonin 5-HT2A receptor activation induces 2-arachidonoylglycerol (2-AG) release through a Phospholipase C-dependent mechanism,” J. Neurochem., 99, 1164-1175 (2006).

M.R. Braden, J.C. Parrish, J.C. Naylor, and D.E. Nichols. “Molecular interaction of serotonin 5‑HT2A receptor residues Phe339(6.51) and Phe340(6.52) with super-potent N-benzyl phenethylamine agonists,” Mol. Pharmacol., 70, 1956-1964 (2006).

J.D. Urban, W.P. Clarke, M. von Zastrow, D.E. Nichols, B. Kobilka, H. Weinstein, J.A. Javitch, B.L. Roth, A. Christopoulos, P.M. Sexton, K.J. Miller, M. Spedding, and R.B. Mailman. “Functional selectivity and classical concepts of quantitative pharmacology,” J. Pharmacol. Exp. Ther., 320, 1-13 (2007). PM:16803859

J. Selken and D.E. Nichols. “Role of α1-adrenergic receptors in the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) to rats,” Pharmacol. Biochem. Behav., 86, 622-630 (2007). PM:17363047

D. Marona-Lewicka and D.E. Nichols. “Further evidence that the delayed temporal dopaminergic effects of LSD are mediated by a mechanism different than the first temporal phase of action,” Pharmacol. Biochem. Behav. 87, 453-461 (2007). PM:17618679

M.R. Braden and D.E. Nichols. “Assessment of the roles of Serines 5.43(239) and 5.46(242) for binding and potency of agonist ligands at the human serotonin 5‑HT2A receptor,” Mol. Pharmacol. 72, 1200-1209 (2007). PM:17715398

M.L. Banks, J.E. Sprague, D.F. Kisor, P.W. Czoty, D.E. Nichols, and M.A. Nader. M.A. Nader. “Effects of ambient temperature and thermoregulation on 3,4-methylenedioxymethamphetamine (MDMA) disposition in monkeys,” Drug Metabolism and Disposition, 35, 1840-1845 (2007). PM:17640955

Parker, M.A. Kurrasch, D.M. and Nichols, D.E. “The Role of Lipophilicity in Determining Binding Affinity and Functional Activity for 5‑HT2A Receptor Ligands,” Bioorganic and Medicinal Chemistry, 16, 4661-4669 (2007) doi:org/10.1016/j.bmc.2008.02.033

Nichols, D.E. and Nichols, C.D. “Serotonin Receptors.” Invited review. Chem. Reviews, 108, 1614-1641 (2008). DOI:10.1021/cr078224o

Schultz, D.M., Prescher, J.A., Kidd, S., Marona-Lewicka, D., Nichols, D.E. and Monte A. “Hybrid” Benzofuran–Benzopyran Congeners as Rigid Analogues of Hallucinogenic Phenethylamines,” Bioorg. Med. Chem. 16, 6242-6251 (2008). doi:10.1016/j.bmc.2008.04.030

Nichols, D.E., Frescas, S.P., Chemel, B.R., Lewin, A.H., and Zhong, D. “High Specific Activity Tritium-Labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): A High Affinity 5-HT2A Receptor-Selective Agonist Radioligand,” Bioorg. Med. Chem. 16, 6116-6123 (2008). doi:10.1016/j.bmc.2008.04.050

Marona-Lewicka, D., Chemel, B.R., and Nichols, D.E. “Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI,” Psychopharmacology, 203, 265-277 (2009).

Trachsel, D., Nichols, D.E., Kidd, S., Hadorn, M., and Baumberger F. “4-Aryl-substituted 2,5-dimethoxyphenethylamines: Synthesis and serotonin 5-HT2A receptor affinities,” Chemistry & Biodiversity, 6, 692-704 (2009) PMID: 19479848.

Book Chapters and Monographs

D.E. Nichols “Chapter 4. CNS Stimulants,” Burger’s Medicinal Chemistry and Drug Discovery, Sixth edition, John Wiley & Sons, Inc. New York, (2003).

D.E. Nichols and B.R. Chemel, “ HYPERLINK Chapter 2: The Neuropharmacology of Religious Experience: Hallucinogens and the Experience of the Divine.” Volume III: Psychology of Religious Experience, Editor, Patrick McNamara, Praeger Publishers, Greenwood Press, Boston, MA. 2007.

D.E. Nichols “Hallucinogens.” Encyclopedia of Psychopharmacology, Springer Publishing, Heidelberg, 2009.

A.L. Halberstat and D.E. Nichols “Serotonin and Serotonin Receptors in Hallucinogen Action.” The Behavioural Neurobiology of Serotonin, C.P. Muller and B. Jacobs, eds, Elsievier, New York, 2009.

D.E. Nichols “Hallucinogenic Drugs” Oxford Companion to Consciousness, Oxford University Press, Oxford, UK, 2009.

D.E. Nichols “Hallucinogens.” Encyclopedic Reference of Neuroscience, Springer Publishing, New York, 2009.

M.A. Geyer, D.E. Nichols, and F.X. Vollenweider “Serotonin-related psychedelic drugs.” In Encyclopedia of Neuroscience, Squire LR (editor), Volume I, pp 741-748. Oxford: Academic Press, UK 2009.

Writings for “Popular Culture”

D.E. Nichols, “The Chemistry of MDMA” in, Ecstasy: the complete guide, ed. J. Holland, Park Street Press, Rochester, VT, 2001.

D. Presti and D. Nichols, “Biochemistry and Neuropharmacology of psilocybin mushrooms”, in Teonanacatl Sacred Mushroom of Visions, ed. R. Metzner, Four Trees Press, El Verano, CA 95433, 2004.

D. Nichols, “LSD: cultural revolution and medical advances” in Chemistry World, the Royal Society of Chemistry publishing, Cambridge, UK, January 2006.

D.E. Nichols, “Psychedelics (Hallucinogens)” in Paradigm, Published by the Illinois Institute for Addiction Recovery at Proctor Hospital, Peoria, Ill, Summer 2009, pp 14-18.