Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism

CNS Neurosci Ther. 2017 Jan;23(1):87-98. doi: 10.1111/cns.12648. Epub 2016 Oct 4.


Aims: Autism spectrum disorder (ASD) is a condition defined by social communication deficits and repetitive restrictive behaviors. Association of the fatty acid amide palmitoylethanolamide (PEA) with the flavonoid luteolin displays neuroprotective and antiinflammatory actions in different models of central nervous system pathologies. We hypothesized that association of PEA with luteolin might have therapeutic utility in ASD, and we employed a well-recognized autism animal model, namely sodium valproate administration, to evaluate cognitive and motor deficits.

Methods: Two sets of experiments were conducted. In the first, we investigated the effect of association of ultramicronized PEA with luteolin, co-ultramicronized PEA-LUT® (co-ultraPEA-LUT®) in a murine model of autistic behaviors, while in the second, the effect of co-ultraPEA-LUT® in a patient affected by ASD was examined.

Results: Co-ultraPEA-LUT® treatment ameliorated social and nonsocial behaviors in valproic acid-induced autistic mice and improved clinical picture with reduction in stereotypes in a 10-year-old male child.

Conclusion: These data suggest that ASD symptomatology may be improved by agents documented to control activation of mast cells and microglia. Co-ultraPEA-LUT® might be a valid and safe therapy for the symptoms of ASD alone or in combination with other used drugs.

Keywords: Autism; Inflammation; Luteolin; Palmitoylethanolamide.

Publication types

  • Case Reports

MeSH terms

  • Amides
  • Animals
  • Animals, Newborn
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Autistic Disorder / chemically induced
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / pathology
  • Autistic Disorder / psychology
  • Brain / drug effects
  • Brain / metabolism
  • Child
  • Chymases / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Enzyme Inhibitors / toxicity
  • Ethanolamines / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Luteolin / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Neuropeptides / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Palmitic Acids / therapeutic use*
  • Tryptases / metabolism
  • Valproic Acid / toxicity


  • Amides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Doublecortin Domain Proteins
  • Enzyme Inhibitors
  • Ethanolamines
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Palmitic Acids
  • Valproic Acid
  • palmidrol
  • Nitric Oxide Synthase Type II
  • Chymases
  • Tryptases
  • Luteolin