Background: Psilocybin has shown promise in neuropsychiatric disorders but presents a paradoxical relationship with seizures and epilepsy. Methods: A narrative review was conducted up to November 23, 2025. We conducted structured literature searches across PubMed/MEDLINE, Scopus, Web of Science. and Google Scholar using MeSH terms and keywords to identify studies on psilocybin, magic mushrooms, or psilocin related to seizures or epilepsy. We also covered our research on serotonergic modulation and epilepsy. We selected a set of core studies directly addressing the research question and additional publications providing mechanistic and contextual evidence for the narrative synthesis. The Risk of Bias of the studies was assessed according to their type. Results: Experimental models demonstrate that psilocybin’s action on 5-HT2A receptors may confer anticonvulsant effects, reducing seizure severity in certain contexts. Preclinical findings support serotonergic modulation as a therapeutic strategy, notably in Dravet syndrome models. However, observational studies report seizures associated with recreational psilocybin use, raising concerns about its pro-convulsant potential, particularly outside controlled environments. Our risk of bias assessment of this evidence revealed significant methodological limitations, urging a cautious interpretation. Nevertheless, clinical trials in neuropsychiatric populations have not shown increased seizure risks under medical supervision. Conclusions: Psilocybin holds potential as a novel adjunctive therapy for epilepsy through selective serotonergic modulation, although conflicting data emphasize the caution with which psilocybin should be implemented clinically, especially in high doses. Animal studies and clinical trials in the future should verify the efficacy and safety of psilocybin in the treatment of epilepsy.

Purpose: Antiseizure medications (ASMs) remain the cornerstone of epilepsy treatment, aiming to prevent seizures while minimizing adverse effects. Although new ASMs are continuously introduced worldwide, prescription trends are primarily documented in high-income countries (HICs), with limited evidence on evolving patterns in developing nations. This study evaluates changes in ASM utilization, efficacy, and safety across two distinct periods at a tertiary care center in Mexico. Methods: A retrospective cohort study was conducted, divided into two phases: Phase 1 (January 2011– December 2013, n=100) and Phase 2 (January 2021– December 2023, n=128). Data on seizure freedom rates, adverse effects, and ASM prescription patterns were analyzed using descriptive statistics, chi-squared tests, and t-tests. Additionally, a mathematical network analysis in MATLAB assessed the influence of individual ASMs through centrality and modularity measures, identifying key drug combinations and their therapeutic impact. Results: A total of 228 epilepsy patients were included. Seizure freedom rates significantly improved from 9% in Phase 1 to 25.8% in Phase 2 (p=0.001). Valproic acid remained a cornerstone ASM (44% in Phase 1 vs. 64% in Phase 2), while levetiracetam gained prominence (49% in Phase 2), as reflected in PageRank values. Adverse effects increased from 10% to 17%, despite a slight reduction in polytherapy (93% to 87.5%). Modularity analysis identified clusters of ASMs linked to seizure freedom, such as valproic acid, lamotrigine, and topiramate, whereas adverse effects were associated with phenobarbital and lamotrigine combinations. Conclusions: This study highlights the enduring role of valproic acid and the rising influence of newer ASMs in Mexico. The observed improvements in seizure freedom underscore advancements in personalized therapeutic strategies, while the persistence of adverse effects emphasizes the need for continuous evaluation of ASM combinations to optimize treatment outcomes.