Dr. Nichols’ research was recently featured in the cover article of the latest edition of the monthly magazine “The Scientist”. Click here to read the story.
Understanding the Brain on LSD
Charles Nichols, Ph.D.
Professor, Department of Pharmacology and Experimental Therapeutics
My father was a professor of pharmacology and my mother has a PhD in pharmacology. I wanted to be a rock star when I grew up, but if that didn’t work out becoming a scientist was my fallback plan. For my undergraduate degree, I went to Purdue and did undergraduate research studying bacterial metabolism. I went to graduate school to continue on my fallback path of becoming a scientist at Carnegie Mellon University. I was really impressed by a young investigator at CMU, Dr. John Pollock, who was combining sophisticated imaging methodologies with genetics to study Drosophila eye development. He had joined the department after a postdoc with Dr. Seymour Benzer only a year before I joined his lab.
After a few years when experiments were not working and I feared that I was wasting my life in grad school, I began pursuing Plan A of becoming a rock star… I joined with a few other people who played together once or twice a week. To make a long story short, we ended up being a formidable presence on the local Pittsburgh music scene and routinely headlined at the top local clubs. After a few years, much to my surprise, my science in the lab actually started working! I defended my dissertation on the genetics of the lozenge gene locus, and because I never wanted to see another fly again in my life, took a postdoctoral position at Vanderbilt University in mammalian systems studying the effects of LSD in rat brain as a model of schizophrenia with Dr. Elaine Sanders-Bush. Just in case the science faltered and I needed another career option I joined a polka band playing clarinet. For the next several years I enjoyed all the free beer and bratwurst I could want from the restaurants and events we played at. Fortunately, the science began working again, and I had a new found love for Drosophila after I started giving psychedelics to flies and realized that they could be used in behavioral pharmacology studies.
Armed with a research program studying serotonin neuropharmacology in both rats and flies, I went on the job market. I had always loved traveling to New Orleans for meetings, and when I saw an advertisement I sent in my application. I was very impressed by the department and the university and started in the fall of 2004. Almost a year later we were hit by hurricane Katrina, and I was away for 7 months. That fall, Dr. Bangning Yu joined my lab as a postdoc and brought his expertise with models of inflammation. It was around this time that we were attempting to identify cell-based models we could use to study psychedelic-mediated gene expression and discovered that they are potent anti-inflammatory agents. We characterized the effects to block TNF-alpha in vitro, then validated this in live mice. These effects were completely unexpected, and opened up a new area of my research program. In collaboration with Dr. Stephania Cormier we found that psychedelics could potently prevent the development of asthma in a mouse model. We now know that psychedelics can not only suppress TNF-alpha mediated inflammation, but can also suppress recruitment of innate and Th2 immune cells. Further, psychadelics suppress expression of subsets of proinflammatory cytokines at levels 50-100 times less than what would be necessary to produce any behavioral effects. We also have preliminary data from several other models of human diseases including atherosclerosis and metabolic disease. Recently, a small company has licensed this technology, which we have patented, and is developing our lead compound for human clinical trials for asthma and other indications. I am very optimistic for the future of the study of 5-HT2A receptor therapeutics for the treatment of inflammatory diseases!