PsychopharmacologySep 15, 2026

How Psychedelic Therapy May Reset Memory Storage to Help Anxiety Disorders

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 16, 2026

Abstract

Psychedelics may influence anxiety-related brain mechanisms by altering the activity of the hippocampus and amygdala.

Anxiety-related contextual information from the hippocampus may bias the amygdala and salience network toward processing anxiety-related content.
Psychedelics could free cortical networks from these contextual constraints, potentially through 5-HT_2A receptor expression.
The inherent adaptability of the hippocampus, combined with psychedelic-induced changes, may facilitate a 'resetting' effect on anxiety processing.
Increased cortical plasticity following psychedelic use may help the hippocampus integrate new, less biased information into anxiety contexts.
Challenges remain in employing psychedelics for anxiety therapy, necessitating further research guided by cognitive neuroscience.

Simplified

Psychedelics (hallucinogenic 5-HT_2A agonists such as psilocybin) are being investigated for their potential to treat a range of conditions, including anxiety-related psychopathology. Despite promising results, the mechanisms by which psychedelic therapy may alleviate anxiety are not well understood. Here, we review neural and cognitive mechanisms underlying anxiety-related psychopathology and how psychedelics may impact these mechanisms. This review culminates in a tentative neurocognitive account of how psychedelics may promote long-term anxiolysis. We propose a model of anxiety related psychopathology wherein anxiety-related contextual information from the hippocampus may influence amygdala and salience network activity, biasing information processing toward anxiety-related content that thereby is encoded by the hippocampus and perpetuates this cycle. We posit that psychedelic may acutely free cortical networks from hippocampal-dependent contextual constraints in part through 5-HT_2A expression on excitatory and inhibitory neurons in the cortex and hippocampus, respectively, while the intrinsic plasticity of the hippocampus and/or psychedelic-mediated plasticity allows for a "resetting of the hippocampal buffer." Following acute effects, increased cortical plasticity may enable the hippocampus to adaptively integrate novel information into a contextual frame less biased or constrained by prior aversive conditioning, promoting an overall reduction in anxious thoughts and appraisals. We end by discussing potential challenges of psychedelic therapy for anxiety, and suggest directions for future research to determine the optimal treatment paths informed by cognitive neuroscience.

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How Psychedelic Therapy May Reset Memory Storage to Help Anxiety Disorders

Abstract

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