High doses of cannabinoids like THC produce anxiety, but the underlying brain mechanisms were unclear. This study in mice identifies a specific neural circuit—projections from the anterior cingulate cortex to the dorsomedial striatum—where cannabinoid signaling promotes anxiety and aversion. Activating this circuit reduces anxiety, whereas cannabinoids suppress its activity via CB1 receptors. Deleting CB1 receptors specifically in this circuit reduced both innate anxiety and conditioned place aversion to THC. These findings reveal a circuit-level mechanism for cannabinoid-induced anxiety.
Classical psychedelics are being studied as potential treatments for PTSD. Research in rodents shows these substances affect fear learning, recall, and extinction. The amygdala, a brain region central to fear processing, is key to these effects. Psychedelics interact with different cell types in the amygdala, and specific neural circuits may underlie their fear-suppressing effects. Because rodent and human amygdalas are functionally similar, findings from animal studies can guide clinical trials for psychedelic-assisted PTSD therapy. The authors emphasize that each psychedelic's unique pharmacology and duration of action are important factors for future research.