In recent years, the potential of psychedelic drugs in treating mental health disorders like substance use disorder, PTSD, and depression has garnered increasing attention. Numerous studies have highlighted the therapeutic effects of psychedelic compounds such as psilocybin, DMT, and LSD, particularly their ability to promote the growth and strengthening of neurons in the prefrontal cortex. This area of the brain is critical for executive functions like reasoning and decision-making.
Researchers at UC Davis have now developed a groundbreaking tool designed to track the activation of biomolecules and neurons in the brain by psychedelic substances. This innovative, non-invasive tool, named Ca2+-activated Split-TurboID (CaST), has been tested in mouse models, providing a novel method to monitor the molecular signaling processes responsible for inducing neuroplastic changes.
The CaST tool represents a significant advancement in neurobiological research. Traditional cellular tagging methods often take several hours to deliver results. In contrast, CaST can achieve cellular tagging within a mere 10 to 30 minutes, offering a much more rapid assessment of neuronal activity. According to the researchers, this tool tracks changes in intracellular calcium concentrations to mark active neurons. High levels of calcium in neurons indicate heightened activity, which CaST detects and tags using biotin.
This pioneering study was conducted in collaboration with David Olson, an associate professor of chemistry, biochemistry, and molecular medicine at UC Davis. Olson, who also serves as the founding director of the university’s Institute for Psychedelics and Neurotherapeutics, played a key role in this research.
During the study, the research team administered psilocybin to mice and used the CaST tool in conjunction with biotin to identify neurons in the prefrontal cortex with elevated calcium levels. Christina Kim, an assistant professor of neurology at UC Davis’s Center for Neuroscience and School of Medicine, emphasized the effectiveness of using biotin as a tagging substrate. She noted that biotin’s presence or absence could be easily determined using simple imaging and staining techniques, thanks to the availability of various commercial tools.
Looking ahead, the researchers aim to refine the CaST tool further. They are working on expanding its capabilities to allow for brain-wide cellular labeling and are exploring methods to enhance the individual protein signatures of neurons affected by psychedelic substances.
The findings of this study were published in the journal Nature Methods, highlighting the collaboration among several researchers, including lead authors Maribel Anguiano and Run Zhang, along with Sruti S. Vadde, Joshua Chandra, Sophia Lin, and Isak K. Aarrestad. The study was generously supported by grants from organizations such as the Boone Family Foundation, NSF, NIH, the Arnold and Mabel Beckman Foundation, Kinship Foundation, and the Brain and Behavior Research Foundation.
The development of tools like CaST marks a significant step forward in understanding how psychedelics impact the brain at a cellular level. Such innovations may eventually contribute to the efforts of companies like Mind Medicine Inc. (NASDAQ: MNMD) (NEO: MMED) (DE: MMQ), which are focused on commercializing new psychedelic-based treatments.