Progress in neuro-psychopharmacology & biological psychiatryAug 20, 2026

Changes in memory system activity and adjustment during psychedelic therapy

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 21, 2026

Abstract

Psychedelics may induce a transient destabilisation of excitation/inhibition dynamics in the brain, increasing neural flexibility.

In Phase I, psychedelics alter network organisation and loosen maladaptive activity patterns associated with acute experiences.
Phase II involves plasticity processes that support adaptive reorganisation and re-stabilisation of neural circuits.
The anterior-posterior hippocampal axis is proposed as a framework for understanding regionally differentiated effects of psychedelics.
Differential symptom responses across patients may be linked to these regionally differentiated dynamics.
The model connects acute network changes to long-term therapeutic effects, suggesting potential biomarkers for treatment response.

Simplified

Psychedelic-assisted therapy has emerged as a promising therapeutic approach across several psychiatric disorders, yet the mechanisms linking acute brain-state changes and subjective experience to sustained clinical improvement remain incompletely understood. Here, we extend a previously proposed excitation/inhibition (E/I)-centred dual-phase model of psychedelic action to the therapeutic context and develop the hippocampal longitudinal axis as a circuit-level framework for its spatially differentiated effects. In Phase I, psychedelics induce a transient destabilisation of E/I dynamics, increasing neural flexibility and altering network organisation while loosening maladaptive activity patterns that may contribute to the acute psychedelic experience. In Phase II, activity- and experience-dependent plasticity processes promote adaptive reorganisation and re-stabilisation of neural circuits. We further hypothesise that the anterior-posterior hippocampal axis provides a spatially organised substrate through which regionally differentiated E/I dynamics may contribute to transdiagnostic therapeutic effects across affective, cognitive, and behavioural symptom domains, and help explain differential symptom responses across patients. This framework links acute network destabilisation to sustained circuit reconfiguration, providing a spatially resolved account of psychedelic-assisted therapeutic change and generating experimentally testable predictions regarding candidate biomarkers (e.g., E/I-related neuroimaging measures and hippocampal connectivity profiles), treatment response, and risk.

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Changes in memory system activity and adjustment during psychedelic therapy

Abstract

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