Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention

Expert Opin Ther Targets. 2002 Apr;6(2):175-83. doi: 10.1517/14728222.6.2.175.


Autism is a lifelong condition usually described as affecting social, cognitive and imaginative abilities. For many years, parents and some professionals have observed that in concordance with the behavioural and psychological symptoms of the condition, there are a number of physiological and biochemical correlates which may also be of relevance to the syndrome. One area of interest that encompasses many of these observations is the opioid-excess theory of autism. The main premise of this theory is that autism is the result of a metabolic disorder. Peptides with opioid activity derived from dietary sources, in particular foods that contain gluten and casein, pass through an abnormally permeable intestinal membrane and enter the central nervous system (CNS) to exert an effect on neurotransmission, as well as producing other physiologically-based symptoms. Numerous parents and professionals worldwide have found that removal of these exogenously derived compounds through exclusion diets can produce some amelioration in autistic and related behaviours. There is a surprisingly long history of research accompanying these ideas. The aim of this paper is to review the accompanying evidence in support of this theory and present new directions of intervention as a result of it.

Publication types

  • Review

MeSH terms

  • Autistic Disorder / diet therapy
  • Autistic Disorder / etiology
  • Autistic Disorder / metabolism
  • Blood-Brain Barrier
  • Body Fluids / chemistry
  • Caseins / adverse effects
  • Child
  • Child Development Disorders, Pervasive / diet therapy
  • Child Development Disorders, Pervasive / epidemiology
  • Child Development Disorders, Pervasive / etiology*
  • Child Development Disorders, Pervasive / metabolism
  • Child, Preschool
  • Comorbidity
  • Epilepsy / epidemiology
  • Female
  • Food / adverse effects
  • Glutens / adverse effects
  • Humans
  • Infant, Newborn
  • Infections / complications
  • Intestinal Absorption
  • Male
  • Models, Biological
  • Neuropeptides / metabolism
  • Opioid Peptides / pharmacokinetics
  • Opioid Peptides / physiology*
  • Peptide Hydrolases / deficiency
  • Peptide Hydrolases / metabolism
  • Peptides / metabolism
  • Protein Processing, Post-Translational
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / physiology*
  • Secretin / therapeutic use
  • Sulfur / metabolism
  • United Kingdom / epidemiology


  • Caseins
  • Neuropeptides
  • Opioid Peptides
  • Peptides
  • Receptors, Opioid
  • Secretin
  • Sulfur
  • Glutens
  • Peptide Hydrolases