Antidepressant and anxiolytic effects of activating 5HT2A receptors in the anterior cingulate cortex and the theoretical mechanisms underlying them - A scoping review of available literature.
Brain research January 1, 2025 Leonor Miranda 59 citations
Activating 5HT2A receptors in the anterior cingulate cortex (ACC) with psychedelic drugs reduces anxious preoccupation, obsessional thoughts, and anhedonia while promoting cognitive flexibility and long-lasting mood improvements. This occurs through enhanced AMPA receptor signaling that alters the AMPA-to-NMDA activity ratio, dismantling established neuronal connections and aiding new ones, which benefits fear extinction and reversal learning. Psychedelics also strengthen connectivity from the dorsal ACC and Salience Network to the Default Mode Network and Central Executive Network, improving attentional shifting and anti-anhedonic effects, while reducing the Default Mode Network's inhibitory influence over the Central Executive Network to decrease overevaluation of internal states. Downstream effects include reduced amygdala reactivity to threats and enhanced mesolimbic dopamine, improving anxiety and natural reward experience.