Roth Labs

The Roth Lab is a part of the Department of Pharmacology at the University of North Carolina -Chapel Hill. Directed by molecular pharmacologist Dr. Bryan Roth, the Lab conducts research for the Psychoactive Drug Screening Program (PDSP)

The Psychoactive Drug Screening Program

A project of the National Institute of Mental Health (NIMH), the PDSP uses state-of-the-art assay technology to “screen novel psychoactive compounds for pharmacological and functional activity” as described on its website.  Eligible academic investigators and small businesses conducting mental health research may request free screenings from the PDSP. The resulting data regarding the drugs’ binding affinities (or Ki values) with various molecular targets, including ion channels, receptors, and transporters, are publicly searchable via the PDSP Ki database.

According to a post dated May 25, 2017 on NIMH’s website, the PDSP “conducts screening of more than 400 molecular targets..and is one of the largest collections of clone human and rodent molecular targets available.” PDSP receives more than 100 requests and “tests an average of 4,000 compounds in over 215,000 assays annually,” with growing demand each year.

The Roth Lab

The Roth Lab “studies the structure and function of G-protein coupled receptors (GCPRs),” particularly those in the serotonin and opioid receptor families. GCPRs are common proteins in the human genome that are frequently targeted by medication. Understanding the specific binding mechanisms between these brain cell receptors and psychedelic substances allows scientists to pinpoint how the therapeutic properties of such drugs work. 

In December 2016, after the publications of landmark psilocybin clinical trial studies by Griffiths et al.1 and Ross et al.,2 Dr. Roth and his colleagues at the Lab co-authored a commentary in the Journal of Psychopharmacology that called for further research into harnessing the therapeutic potential of psychedelic compounds without the hallucinatory effects.3 

The Lab was awarded $26.9 million from the United States Department of Defense’s Defense Advanced Research Projects Agency (DARPA) in June 2020. The award serves to advance the Roth Lab’s work in developing more precisely targeted psychiatric pharmaceuticals with fewer undesirable side effects. Psychedelic Science Review detailed the Lab’s revolutionary research facilitated by the DARPA funding

In September 2020, the Roth Lab announced its breakthrough construction of high-resolution models of a 5-HT2A human serotonin receptor binding to LSD and 25-CN-NBOH, a comparable hallucinogenic compound.4 The publication’s summary states,

These findings could accelerate the discovery of more selective drugs for the treatment of a variety of neuropsychiatric disorders.

The study, covered by Psychedelic Science Review in a two-part article, was preceded by the Lab’s January 2017 discovery of the crystal structure of LSD bound to the serotonin 5-HT2B receptor5 (also reported by Psychedelic Science Review).

For research updates, see the Roth Lab’s Publications webpage and the PDSP’s Publications webpage

  1. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of psychopharmacology (Oxford). 2016;30:1181-1197. doi:10.1177/0269881116675513
  2. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of psychopharmacology (Oxford). 2016;30:1165-1180. doi:10.1177/0269881116675512
  3. McCorvy JD, Olsen RH, Roth BL. Psilocybin for depression and anxiety associated with life-threatening illnesses. Journal of psychopharmacology (Oxford). 2016;30:1209-1210.
  4. Kim K, Che T, Panova O, et al. Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor. Cell (Cambridge). 2020;182:1574-1588.e19. doi:
  5. Wacker D, Wang S, McCorvy JD, et al. Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell (Cambridge). 2017;168:377-389.e12. doi:10.1016/j.cell.2016.12.033