Annual review of neuroscienceApr 16, 2026

How Psychedelics May Change Brain Flexibility and Support Systems During Key Learning Periods

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 17, 2026

Abstract

Psychedelics may induce metaplasticity and reorganize the extracellular matrix.

Psychedelics are associated with altered states of consciousness.
These compounds have shown promise for treating disorders like posttraumatic stress disorder, depression, and addiction.
Early studies primarily focused on biochemical targets, which do not fully explain the effects of psychedelics.
Neurobiological explanations suggest that psychedelics reopen critical periods in brain development.
The therapeutic effects of psychedelics support a learning model rather than the traditional biochemical imbalance model.

Simplified

Psychedelics are a broad category of compounds that induce altered states of consciousness. These drugs have shown remarkable promise for the treatment of debilitating disorders ranging from posttraumatic stress disorder to depression and addiction. Although early studies focused on linking binding targets of psychedelics to their therapeutic effects, these pharmacological and biochemical explanations fail to account for the diversity, durability, and context dependence of psychedelics' clinical and acute subjective effects. More recently, neurobiological explanations offer fresh insights and demonstrate that a unifying property of psychedelics is that these compounds reopen critical periods, induce metaplasticity, and reorganize the extracellular matrix. Here we review this evidence and argue that the neurobiological and therapeutic effects of psychedelics challenge the biochemical imbalance model that has dominated translational neuroscience since the 1950s and favor instead a learning model that better accounts for psychedelics' unique therapeutic profile.

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How Psychedelics May Change Brain Flexibility and Support Systems During Key Learning Periods

Abstract

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