Abstract: During specific periods of brain development, the nervous system exhibits heightened sensitivity to ethologically relevant stimuli, as well as increased malleability for synaptic, circuit, and behavioral modifications. These mechanistically constrained windows of time are called ‘critical periods’ and neuroscientists have long sought methods to reopen them for therapeutic benefit. Meanwhile, although the medicinal properties of psychedelics have been recognized for millennia, delineating their subjective characteristics, chemical structures, principal binding targets, and downstream signaling pathways has failed to identify unifying mechanisms. Bridging this gap, here we demonstrate that the ability to reopen the social reward learning critical period is a shared property across psychedelics. Furthermore, the duration of the critical period open state induced by psychedelics parallels the durability of their therapeutic effects. Although neither serotonin 2A receptor activation nor β-arrestin 2 biased signaling are universally required for psychedelic mediated critical period reopening, using RNA sequencing, we have identified long-lasting changes in DNA transcription that correspond to the ability of psychedelics, but not non-psychedelics, to reinstate social reward learning in adulthood. These findings have significant implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.