David Nichols, Ph.D., and Franz Vollenweider, M.D., with Katrin Preller, Ph.D.
Thursday, April 20, 2017 • 9:00 AM - 6:00 PM • OCC 208
Continuing Education (7.5 CEU)
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The Basic Science of Psychedelics
The first part of the workshop will be given by Dr. David Nichols. He will make no assumptions about the level of knowledge of the participants and will start his discussions covering basic pharmacology principles, such as how drugs bind to receptors, and how to interpret dose-response curves. That will serve as a backdrop for discussions specific to understanding the preclinical actions of psychedelics, and the receptor basis for their actions in the brain. What happens after a psychedelic binds to the receptor? How is a cellular signal generated? A computer-based model of the target for psychedelics, the serotonin 5-HT2A receptor, as well as a recent x-ray crystallographic structure of the 5-HT2B receptor will be discussed. There will be a general discussion of how mutations in the 5-HT2A receptor were used to lead to understanding better how psychedelics bind to the receptor. Also, examples of an approach called “rigid analogue” design will be presented, and how certain rigid analogues of LSD and phenethylamine compounds led to hypotheses about the orientation of different psychedelics when they bind to the receptor.
Recent Advances in the Neurobiology of Psychedelics: From Theory to Practice
Classic serotonergic hallucinogens or psychedelics such as psilocybin or LSD produce an Altered States of Consciousness (ASC) that is characterized by profound alterations in sensory perception, mood, thought, the perception of reality, and the sense of self. Recent developments in neuroimaging and computational neuroscience have dramatically changed the empirical study and explanation of psychedelic-induced ASCs. These developments have led to new insights into the molecular, cellular, and system basis of different psychological features and dimensions of psychedelic states, including visual experiences and ego dissolution. Recent studies have also begun to identify the neuronal mechanism of how psychedelics facilitate emotion processing, social cognition, and memory recollection. This work has shifted our understanding of how psychedelic may improve affective disorders - away from a mere acute symptom reduction to a psychedelic-driven facilitation of neuronal plasticity and an enduring symptom improvement and behavioral change. This research has also led to the identification of promising candidate physiological markers and out-come measures which are important for the application of psychedelics in the treatment of affective disorders.
The workshop will review these advances and address important emerging areas. Emphasis will be led on cutting-edge methods and hypotheses for understanding psychedelic states. Franz X. Vollenweider will describe research strategies to identify molecular, cellular, and circuit-based correlates of psychedelic-induced psychological dimensions (e.g. altered time sense, hallucinations, and ego dissolution) with an emphasis on the assessment and cartography of the subjective experiences. Katrin Preller review new insight into the effect of psychedelics on emotion regulation and cognitive functions, and discuss how behavioral and neuroimaging approaches can shed light on the effect of psychedelics on emotion processing, empathy, and social interaction. The role of glutamate and synaptic plasticity in learning and memory, and it implication for affective disorders will also be discussed. The workshop will be an interactive, multidisciplinary forum.
David Nichols, Ph.D, was born on December 23, 1944 in Covington, Kentucky. He received a B.S. in Chemistry from the University of Cincinnati in 1969 and a Ph.D. in Medicinal Chemistry from the University of Iowa in 1973. His doctoral work at Iowa was supported by an NDEA-IV fellowship. He then accepted a postdoctoral appointment in the Department of Pharmacology at the University of Iowa College of Medicine, after which he began his career at Purdue. Nichols taught and researched at Purdue University from 1974 until his retirement in 2012. He received the Heine Best Teacher award from the School of Pharmacy in 1981, in 2004 was named the Irwin H. Page Lecturer by the International Society for Serotonin Research, and in 2006 he was named the first Provost’s Outstanding Graduate Mentor at Purdue. He held joint professorial appointments in the Departments of Medicinal Chemistry and Pharmacognosy, and of Pharmacology and Toxicology. From 1994 until 1996 he was the Interim Head of both Departments, and oversaw their merger into the current Department of Medicinal Chemistry and Molecular Pharmacology. He also held a joint appointment in the Indiana University School of Medicine, and taught in the medical curriculum at Purdue. In 2012 he was honored as an Outstanding Alumnus by the University of Iowa College of Pharmacy. Prior to his retirement, he was the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology and also a Distinguished Professor of Medicinal Chemistry and Molecular Pharmacology at the Purdue College of Pharmacy. He is currently an Adjunct Professor in the Eshelman School of Pharmacy at the University of North Carolina Chapel Hill, NC, where he continues research. During his years of research, Nichols appeared as an author of more than 300 scientific publications. Believing that psychedelic drugs could have positive therapeutic results, Nichols initiated the founding of the Heffter Research Institute in 1993 to support high-quality basic and clinical psychedelic research. Nichols also is known for coining the term ‘entactogen’ to differentiate the effects of MDMA and related chemicals from the phenethylamine hallucinogens. In addition to developing novel psychoactive substances in his lab at Purdue, the Nichols’ lab also synthesized high-purity MDMA, DMT, psilocybin, and other substances for research programs at other institutions. It became apparent to him that even if researchers could obtain the necessary approvals for their studies, there was no source for the pure drugs they required for human studies. Therefore, he made the DMT for Rick Strassman’s groundbreaking DMT study, published in 1994. The MDMA from his laboratory was used for most of the preclinical and all of the clinical studies employing MDMA from about 1986 until 2016, including Phase 2 clinical studies for the use of MDMA for treating post-traumatic stress disorder (PTSD.) Psilocybin made in his laboratory was used for Roland Griffith’s study of the effects of psilocybin in normal subjects, published in 2006, as well as for the Phase 2 clinical study of psilocybin-assisted treatment of distress in patients with a life-threatening diagnosis, published in 2016.
Nichols also had a parallel, but less well recognized, research track in discovering novel full efficacy agonists for the dopamine D1 receptor, and developed a number of such molecules, the first of which was named dihydrexidine. He was awarded eight patents in the field of dopamine D1 agonists. Studies published in 1986 reported that dihydrexidine was efficacious in reversing parkinsonian symptoms in a monkey model of Parkinson’s disease. This proof-of-principle study indicated that dopamine D1 agonists might be useful therapy in late stage Parkinson patients who had become resistant to the therapeutic effects of the gold standard treatment, levo-dopa. He was a cofounder in 2000 of a small biotech company in Chapel Hill, NC, known as DarPharma, Inc., which attempted to commercialize dopamine D1 agonists for use in Parkinson’s disease, as well as potential drugs to improve working memory in schizophrenia. The company was unable to commercialize his drugs and was bought in 2006.
Prof. Franz X. Vollenweider, M.D., F.M.H. Psych, is Director of the Centre for Psychiatric Research in the Department of Psychiatry, Psychotherapy, and Psychosomatics (DPPP), and Professor of Psychiatry in the School of Medicine, University of Zurich. His current research focuses on the foundations of the sense of self, emotion regulation, and social interaction, relevant for human well being and for the further understanding of mental disorders related to these domains. In 1999, he founded the Heffter Research Centre Zürich at the DPPP and recently the Swiss Neuromatrix Foundation to support multidisciplinary studies into the mind-brain interface of pharmacological (e.g. psychedelic) and non-pharmacological (e.g. meditation) induced altered mental states. He has published over 150 peer-reviewed papers and book chapters on the neurobiology of psychostimulants, psychedelics, and entactogens in humans. His research has been continuously supported by the Swiss National Science Foundation, the Swiss Federal Health Office, the Heffter Research Institute, USA, and by multiple AWARDS from NARSAD and the Fetzer Institute, USA. He has received the Achievement Award of the Swiss Society of Psychiatry, the Heffter Research Institute Award, the Götz Prize of the University of Zurich, the British Association of Psychopharmacology Prize, and multiple Awards from the European College of Neuropsychopharmacology, among others.
Katrin Preller, Ph.D., received her M.Sc. (Neuropsychology) from University of Konstanz, Germany, after completing an undergraduate research project at the Centre for Brain Research, University of Auckland, New Zealand. For her PhD she went to University of Zurich, Switzerland, where she run several studies investigating the neurobiological and social-cognitive long-term effects of cocaine, MDMA, and heroin use. Furthermore, she was involved in studies investigating acute effects of MDMA and GHB on social cognition. After completing her PhD, she joined Dr. Vollenweider’s Neuropsychopharmacology and Brain Imaging lab at the Psychiatric University Hospital Zurich and Heffter Research Center (HRC) Zürich, investigating the effects of psilocybin and LSD on self-perception, social cognition, and multimodal processing using different brain imaging techniques. She recently spent six months at Dr. Friston’s Imaging Neuroscience & Theoretical Neurobiology Group at the Wellcome Trust Centre for Neuroimaging, UCL, London, before moving on to Yale University, New Haven, CT, USA to work with Dr. Anticevic and Dr. Krystal since August 2016. Dr. Preller has received the Pfizer Prize 2015, the Young Scientist Award of the Swiss Society of Biological Psychiatry (2016), and multiple Travel and Poster Awards from the European College of Neuropsychopharmacology (ECNP). Katrin Preller is an affiliated member of the HRC Zürich.