Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious?

Molecules. 2021 Mar 25;26(7):1845. doi: 10.3390/molecules26071845.


Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.This mini-review article summarizes the current knowledge on this topic.

Keywords: acetaminophen; autism; endocannabinoid system; endocannabinoids.

Publication types

  • Review

MeSH terms

  • Acetaminophen / adverse effects*
  • Acetaminophen / therapeutic use
  • Autism Spectrum Disorder* / chemically induced
  • Autism Spectrum Disorder* / drug therapy
  • Autism Spectrum Disorder* / metabolism
  • Autism Spectrum Disorder* / pathology
  • Cannabinoids / therapeutic use*
  • Endocannabinoids / metabolism*
  • Humans
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / metabolism
  • Signal Transduction / drug effects


  • CNR1 protein, human
  • CNR2 protein, human
  • Cannabinoids
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Acetaminophen