Bortoletto Riccardo, Piscitelli Fabiana, Candolo Anna, Bhattacharyya Sagnik, Balestrieri Matteo, Colizzi Marco
Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy.
Department of Chemical Sciences and Materials Technologies, Institute of Biomolecular Chemistry, National Research Council (CNR), Pozzuoli, Italy.
Front Psychiatry. 2023 Jul 18;14:1231710. doi: 10.3389/fpsyt.2023.1231710. eCollection 2023.
The endocannabinoid (eCB) system disruption has been suggested to underpin the development of psychosis, fueling the search for novel, better-tolerated antipsychotic agents that target the eCB system. Among these, palmitoylethanolamide (PEA), an N-acylethanolamine (AE) with neuroprotective, anti-inflammatory, and analgesic properties, has drawn attention for its antipsychotic potential.
This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review aimed at reappraising all clinical and preclinical studies investigating the biobehavioral role of PEA in psychosis.
Overall, 13 studies were eligible for data extraction (11 human, 2 animal). Observational studies investigating PEA tone in psychosis patients converged on the evidence for increased PEA plasma (6 human) and central nervous system (CNS; 1 human) levels, as a potential early compensatory response to illness and its severity, that seems to be lost in the longer-term (CNS; 1 human), opening to the possibility of exogenously supplementing it to sustain control of the disorder. Consistently, PEA oral supplementation reduced negative psychotic and manic symptoms among psychosis patients, with no serious adverse events (3 human). No PEA changes emerged in either preclinical psychosis model (2 animal) studied.
Evidence supports PEA signaling as a potential psychosis biomarker, also indicating a therapeutic role of its supplementation in the disorder.
内源性大麻素（eCB）系统功能紊乱被认为是精神病发生发展的基础，这促使人们寻找针对eCB系统的新型、耐受性更好的抗精神病药物。其中，棕榈酰乙醇胺（PEA）作为一种具有神经保护、抗炎和镇痛特性的N-酰基乙醇胺（AE），因其抗精神病潜力而受到关注。
本系统评价遵循《系统评价与Meta分析的首选报告项目》（PRISMA）2020标准，旨在重新评估所有研究PEA在精神病中生物行为作用的临床和临床前研究。
总体而言，有13项研究符合数据提取条件（11项人体研究，2项动物研究）。调查精神病患者体内PEA水平的观察性研究一致表明，血浆（6项人体研究）和中枢神经系统（CNS；1项人体研究）中PEA水平升高，这似乎是对疾病及其严重程度的一种潜在早期代偿反应，但在长期（CNS；1项人体研究）中这种反应似乎消失了，这为通过外源性补充PEA来维持对该疾病的控制提供了可能性。同样，口服补充PEA可减轻精神病患者的阴性精神病性症状和躁狂症状，且无严重不良事件（3项人体研究）。在所研究的两种临床前精神病模型（2项动物研究）中，PEA水平均未出现变化。
有证据支持PEA信号作为一种潜在的精神病生物标志物，也表明补充PEA在该疾病中具有治疗作用。
