Psychedelics reopen the social reward learning critical period

Abstract

Abstract Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness 1,2 . These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies 3–9 . Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the ‘open state’ versus the ‘closed state’ provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening. Together these results have important implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

• State of the evidence: Psilocybin for addiction ↑Supports

  Psychedelics reopen the social reward learning critical period in mice, with a time course proportional to human subjective effects, mediated by oxytocin-dependent plasticity and extracellular matrix reorganization.

  Synthesized October 22, 2026

• State of the evidence: Addiction ↑Supports

  Psychedelic drugs reopen the social reward learning critical period in mice, with a time course proportional to human subjective effects, mediated by oxytocin-dependent plasticity and extracellular matrix reorganization.

  Synthesized October 25, 2026

Comparable studies

Other preclinical and animal studies on psilocybin for addiction, most cited first.