Psychedelics have been used in indigenous cultures for centuries, with empirical evidence of their mood and perception altering effects. Recently, there has been a renewal of interest in psychedelics given putative therapeutic effects in psychiatric disorders such as anxiety and depression. However, it has remained a mystery as to how psychedelics actually bring about changes in mood-related behavior.

A team of researchers led by Prof. Vidita Vaidya from TIFR Mumbai, in collaboration with research groups from Cornell, Columbia and Yale University mapped the precise part of the brain, and the specific class of neurons within this brain region, that drives the decrease in anxiety caused by acute treatment with the psychedelic DOI. The psychedelic DOI when administered to rats or mice systemically, decreases anxiety behavior on approach-avoidance behavioral tasks, such as the elevated plus maze and open field test.

To precisely pinpoint the part of the brain that responds to DOI and drives this decrease in anxiety behavior, local infusions of the drug into targeted brain regions uncovered a critical role of the ventral hippocampus in mediating this effect of the psychedelic DOI. Further, the study uncovered that the psychedelic DOI targets the serotonin 2A receptor in the ventral hippocampus to exert its effects on anxiety. At the same time, the team also ruled out contributions from other brain regions including the prefrontal cortex and amygdala.

What was striking is that the .