A new study finds that ketamine’s benefits may stem from neuroplasticity. (Image credit: AKIO75 via Shutterstock)

DENVER—A single dose of ketamine may subtly reshape how different regions of the brain communicate, a new study suggests.

The research, presented June 19 at the Psychedelic Science 2025 conference, is one of the first to investigate ketamine’s impact on neuroplasticity — the ability to adapt to experiences by forming new connections and pathways — in the brains of living people. The findings have not been peer-reviewed yet.

In recent years, clinical trials have demonstrated ketamine’s effectiveness in treating depression within a few hours of a single dose. Animal studies suggest that ketamine almost immediately spurs the growth of new dendritic spines

Neuroplasticity and psychedelics: A comprehensive examination of classic and non-classic compounds in pre and clinical models

tiny protrusions that form synapses, the connections between brain cells. But it’s been hard to pin down how ketamine works in living humans.

Highlights

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  Psychedelics produce rapid and sustained reductions in symptoms of mood disorders.
• •
  Mood disorders are characterized by impaired neuroplasticity in brain regions critical for emotion regulation.
• •
  Psychedelics enhance structural and functional neuroplasticity after a single or few administrations.
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  Psychedelic-induced neuroplasticity may underpin their therapeutic effects, but human translation remains challenging.

Abstract

Neuroplasticity, the ability of the nervous system to adapt throughout an organism’s lifespan, offers potential as both a biomarker and treatment target for neuropsychiatric conditions. Psychedelics, a burgeoning category of drugs, are increasingly prominent in psychiatric research, prompting inquiries into their mechanisms of action. Distinguishing themselves from traditional medications, psychedelics demonstrate rapid and enduring therapeutic effects after a single or few administrations, believed to stem from their neuroplasticity-enhancing properties. This review examines how classic psychedelics (e.g., LSD, psilocybin, N,N-DMT) and non-classic psychedelics (e.g., ketamine, MDMA) influence neuroplasticity. Drawing from preclinical and clinical studies, we explore the molecular, structural, and functional changes triggered by these agents. Animal studies suggest psychedelics induce heightened sensitivity of the nervous system to environmental stimuli (meta-plasticity), re-opening developmental windows for long-term structural changes (hyper-plasticity), with implications for mood and behavior. Translating these findings to humans faces challenges due to limitations in current imaging techniques. Nonetheless, promising new directions for human research are emerging, including the employment of novel positron-emission tomography (PET) radioligands, non-invasive brain stimulation methods, and multimodal approaches. By elucidating the interplay between psychedelics and neuroplasticity, this review informs the development of targeted interventions for neuropsychiatric disorders and advances understanding of psychedelics’ therapeutic potential.

Claudio Agnorelli^a b, Meg Spriggs^a, Kate Godfrey^a, Gabriela Sawicka^a, Bettina Bohl^c, Hannah Douglass^a, Andrea Fagiolini^b, Hashemi Parastoo^c, Robin Carhart-Harris^a d, David Nutt^a, David Erritzoe^a

Animal studies suggest that ketamine almost immediately spurs the growth of new dendritic spines  …….

Science Direct

Ketamine treatment for depression:

clinical trials have demonstrated ketamine’s effectiveness in treating depression

This manuscript reviews the clinical evidence regarding single-dose intravenous (IV) administration of the novel glutamatergic modulator racemic (R,S)-ketamine (hereafter referred to as ketamine) as well as its S-enantiomer, intranasal esketamine, for the treatment of major depressive disorder (MDD). Initial studies found that a single subanesthetic-dose IV ketamine infusion rapidly (within one day) improved depressive symptoms in individuals with MDD and bipolar depression, with antidepressant effects lasting three to seven days. In 2019, esketamine received FDA approval as an adjunctive treatment for treatment-resistant depression (TRD) in adults. Esketamine was approved under a risk evaluation and mitigation strategy (REMS) that requires administration under medical supervision. Both ketamine and esketamine are currently viable treatment options for TRD that offer the possibility of rapid symptom improvement. The manuscript also reviews ketamine’s use in other psychiatric diagnoses—including suicidality, obsessive–compulsive disorder, post-traumatic stress disorder, substance abuse, and social anxiety disorder—and its potential adverse effects. Despite limited data, side effects for antidepressant-dose ketamine—including dissociative symptoms, hypertension, and confusion/agitation—appear to be tolerable and limited to around the time of treatment. Relatively little is known about ketamine’s longer-term effects, including increased risks of abuse and/or dependence. Attempts to prolong ketamine’s effects with combined therapy or a repeat-dose strategy are also reviewed, as are current guidelines for its clinical use. In addition to presenting a novel and valuable treatment option, studying ketamine also has the potential to transform our understanding of the mechanisms underlying mood disorders and the development of novel therapeutics.

• Mani Yavi,
• Holim Lee,
• Ioline D. Henter,
• Lawrence T. Park
• Carlos A. Zarate Jr

Springer Nature