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Low-dose combination of ultramicronized palmitoylethanolamide and docosahexaenoic acid on neurosteroid and neuroinflammatory dysregulation in autism spectrum disorders

Fabiana Filogamo, Fabrizio Maria Liguori, Giovanna La Rana, Roberto Russo, Claudia Cristiano. Neurotherapeutics. 2026 Jan;23(1):e00816.

Laboratory studyOther animalsWith docosahexaenoic acid (DHA)

This study tested palmitoylethanolamide together with docosahexaenoic acid (DHA). Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Laboratory study
Subjects
BTBR T+ tf/J mice (autism spectrum disorder model)
Dose used in the study
Low-dose combination of ultramicronised PEA and DHA; exact doses not stated in the abstract
Duration
Not stated in the abstract
What was measured
Hippocampal pregnenolone and allopregnanolone levels; repetitive and social behaviours; proinflammatory cytokines and BDNF; PPAR-alpha expression, including with a PPAR-alpha antagonist.

What the authors reported

This laboratory study found:

  • BTBR mice showed raised hippocampal pregnenolone and reduced allopregnanolone, alongside inflammation and repetitive, asocial behaviour.
  • Low-dose PEA-um plus DHA restored allopregnanolone production, reduced repetitive behaviours, improved social interaction, and lowered proinflammatory cytokines and BDNF in the hippocampus.
  • A PPAR-alpha antagonist blocked these effects.

Limits of this study

A mouse model study; it cannot show effect in people with autism spectrum disorder. One author (CC) is a co-inventor on a patent for a therapeutic use of PEA; other conflicts are not stated in the truncated declaration.

Source

PubMed 41390289 · doi:10.1016/j.neurot.2025.e00816

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.