Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence

Abstract

IntroductionThe 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.MethodsThis 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.ResultsOverall, 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.DiscussionEvidence supports PEA signaling as a potential psychosis biomarker, also indicating a therapeutic role of its supplementation in the disorder.Systematic review registrationhttps://doi.org/10.17605/OSF.IO/AFMTK.

The Supplementation Therapy in Autism and Response to Treatment (START) Study: An Open-Label Feasibility Trial of Ultramicronized Palmitoylethanolamide Potential to Alleviate Psychic Distress among Autistic Adults

“…To this extent, in 2017, PEA was classified by the European Commission as a dietary supplement, being safe and effective for inflammatory disorders, neuropathic pain, and epilepsy management [25,[31][32][33]. In particular, ultramicronized (um)-and micronized (m)-PEA forms are characterized by increased dissolution, absorption, and bioavailability and hence better penetration of the nervous system, exhibiting more marked neuroprotective effects [25] with possible therapeutic implications for neuropsychiatric conditions, including affective disorders [34,35], psychosis [36,37], and cognitive decline [38,39]. Findings regarding the biobehavioral role of PEA among autistic children and adolescents pointed to the potential of PEA supplementation as both monotherapy and an add-on to treatment as usual (TAU) in improving autism core symptoms and modulating the inflammatory response [40][41][42][43].…”