A Low Dose of Electro-Psychedelic Treatment Increases Neuronal Dendritic Arborization and Filopodic Spine Density

Neuropsychiatric disorders remain a formidable challenge to the global healthcare system, necessitating innovative treatments to address their complex pathophysiology. Alternative therapeutic approaches, including electroconvulsive treatment (ECT) and psychedelics, have gained attention for their capacity to relieve a broad range of symptoms. ECT is a long-standing effective therapy for patients, especially treatment-resistant ones. Psychedelics, like psilocybin, can induce profound and sustained therapeutic effects. The limited understanding of their mechanisms of action, compounded by the negative stigma surrounding ECT and psilocybin, prevents them from being used as adjunct agents. ECT and psilocybin promote synaptic plasticity and modulate neural remodeling, yet their comparative impact on spine morphology remains largely unexplored. Interactions between microglia and neurons protect against excessive stimulation and promote therapeutic spine pruning, enhancing plasticity. Activation of microglia has been implicated in the symptomology and treatment of many neuropsychiatric disorders, providing a potential clue to understanding the synergistic mechanisms between ECT and psychedelics. The study investigates the differential impact of varying doses of ECT and psilocybin on spine morphology to address their therapeutic potential. Results 35mA of ECS causes an elongation of microglia branches with large end feet, and psilocybin causes an increase in total spine density, specifically filopodia. The co-treatment of ECS and psilocybin shows augmented filopodic spine density in neurons and an increase in endfeet volume. Our findings contribute to the growing body of literature on ECT and psilocybin as potential adjunctive therapies, paving the way for future clinical trials and personalized treatment strategies for individuals with treatment-resistant neuropsychiatric conditions.