CHAPTER The renaissance in psychedelic research: What do preclinical models have 2 to offer Kevin S. Murnane1 Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, Mercer University Health Sciences Center, Atlanta, GA, United States 1Corresponding author: Tel.: +1-678-547-6290; Fax: +1-678-547-6423, e-mail address:
[email protected] Abstract Human research with psychedelics is making groundbreaking discoveries. Psychedelics mod- ify enduring elements of personality and seemingly reduce anxiety, depression, and substance dependence in small but well-designed clinical studies. Psychedelics are advancing through pharmaceutical regulatory systems, and neuroimaging studies have related their extraordinary effects to select brain networks. This field is making significant basic science and translational discoveries, yet preclinical studies have lagged this renaissance in human psychedelic research. Preclinical studies have a lot to offer psychedelic research as they afford tight control of experimental parameters, subjects with documented drug histories, and the capacity to elucidate relevant signaling cascades as well as conduct invasive mechanistic studies of neurochemistry and neural circuits. Safety pharmacology, novel biomarkers, and pharmaco- kinetics can be assessed in disease state models to advance psychedelics toward clinical practice. This chapter documents the current status of psychedelic research, with the thematic argument that new preclinical studies would benefit this field. Keywords Psychedelic, Preclinical, Serotonin, Neuroimaging, Alcoholism, Anxiety, Depression, Substance dependence 1 INTRODUCTION The term psychedelic has come to be associated with a broad class of drugs with diverse chemical, pharmacological, and psychoactive effects. Alternative nomencla- tures have used hallucinogen, entheogen, psychotomimetic and other appellations to Progress in Brain Research, Volume 242, ISSN 0079-6123, https://doi.org/10.1016/bs.pbr.2018.08.003 25 © 2018 Elsevier B.V.