University of North Carolina-Chapel Hill School of Medicine

The University of North Carolina – Chapel Hill School of Medicine was established in 1879, eighty-six years after UNC itself –the first state university in the U.S.– was founded. Renowned for its exceptional education, patient care, and research, UNC-CH School of Medicine is affiliated with several key contributors to psychedelic science. 

The University also houses the Roth Lab, led by molecular pharmacologist and Michael Hooker Distinguished Professor Dr. Bryan Roth. The Roth Lab hosts the Psychoactive Drug Screening Program, which screens novel psychoactive compounds for “pharmacological and functional activity” at no cost to qualified researchers. PDSP is run through a partnership with the National Institute of Mental Health (NIMH). The collaboration supports the UNC-CH School of Medicine’s rank as sixth among public university medical schools for research funding from the National Institutes of Health (NIH). 

The Roth Lab uses cutting-edge techniques such as x-ray crystallography to study the molecular structures of psychedelic compounds and how they bind to serotonin receptors. Roth Lab alumni include Dr. John McCorvy and Dr. Daniel Wacker, molecular pharmacologists whose research has been central to clarifying how psychedelics work in the brain. Dr. Wacker was the lead author on a paper that revealed the crystal structure of LSD bound to a human 5-HT2B receptor.1 Psychedelic Science Review published a two-part article (Part 1, Part 2) on the landmark discovery, which helped to illustrate why LSD trips last so long. In an interview with Gizmodo about the study, Dr. Roth explained, “Once LSD gets in the receptor, a lid comes over the LSD, so it’s basically trapped in the receptor and can’t get out. LSD takes a really long time to get on the receptor, and then once it gets on, it doesn’t get off.” 

The Lab’s current postdoctoral researcher Kuglae Kim was the first author on a 2020 follow-up study that determined the crystal structure of LSD bound to a similar receptor, 5-HT2A.2 The findings, covered by Psychedelic Science Review, support efforts to design more tailored neuropsychiatric drugs. 

The LSD for the structural studies was supplied by Heffter Research Institute founder Dr. David Nichols, who is a researcher and Adjunct Professor of medicinal chemistry at the university. 

As a chemist and pharmacologist, Dr. Nichols has spent decades studying the molecular structure of hallucinogenic substances and their interaction with brain receptors. 

The School of Medicine was granted $26.9 million by US DARPA to conduct research toward the development of improved psychiatric medicines, to be carried out by Roth Lab. The research is focused on stabilizing G-protein coupled receptors (GCPRs, where psychiatric medicines and psychedelic compounds typically bind). The groundbreaking work of UNC’s Roth Lab was featured in the season three finale of the VICE documentary series Hamilton’s Pharmacopoeia.

    References
  1. Wacker D, Wang S, McCorvy JD, et al. Crystal structure of an LSD-bound human serotonin receptor. Cell. 2017;168(3):377-389.e12. doi:10.1016/j.cell.2016.12.033
  2. Kim K, Che T, Panova O, et al. Structure of a aallucinogen-activated Gq-coupled 5-HT2A serotonin receptor. Cell. 2020;182(6):1574-1588.e19.