Psychedelics reopen the social reward learning critical period
Romain Nardou, Young Jun Song, Noelle Wright, Carine Lama, Sehr Faltin, Gül Dölen, Edward J. Sawyer, M. F. Wilkinson, Yasmin Padovan‐hernandez, Júnia L. de Deus, Loyal A. Goff, Genevieve Stein-O’Brien
Nature June 14, 2023 DOI: 10.1038/s41586-023-06204-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study in mice Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Psychedelic drugs |
| Topics | Addiction Psilocybin |
| Keywords | Mechanism biology Period music Nucleus accumbens Disease Consciousness Hallucinogen |
| Citations | 335 |
| Post-publication review | 3 comments on PubPeer (opens in new tab) · last active June 2023 |
| Key findings | 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. |
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.
-
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
-
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
Comparable studies
Other preclinical and animal studies on psilocybin for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism | 2021 | Preclinical study | |
| Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse Male and female rats | 2020 | Preclinical animal study | |
| Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Healthy rats and a rat model of alcohol relapse | 2023 | Randomized, placebo-controlled crossover pharmaco-fMRI study | |
| Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories. Male and female Marchigian Sardinian alcohol-preferring (msP) rats | 2023 | Preclinical experimental study | |
| Sex-specific role of the 5-HT2A receptor in psilocybin-induced extinction of opioid reward. Male and female mice | 2025 | Experimental study |