The opioid excess theory is a theory which postulates that autism is the result of a metabolic disorder in which opioid peptides produced through metabolism of gluten and casein pass through an abnormally permeable intestinal membrane and then proceed to exert an effect on neurotransmission through binding with opioid receptors. It is believed by advocates of this hypothesis that autistic children are unusually sensitive to gluten, which results in small bowel inflammation in these children, which in turn allows these opioid peptides to enter the brain.
This hypothesis was first proposed by Jaak Panksepp in a 1979 paper, in which he speculated that autism might be "an emotional disturbance arising from an upset in the opiate systems in the brain."Kalle Reichelt then emerged as one of the leading advocates of this theory, publishing papers alleging that "the patterns of peptides and associated proteins from urinary samples [from people with autism] differ considerably from each other and from normal controls." In addition, Reichelt's research has concluded that autistic individuals have increased levels of these peptides in their cerebrospinal fluid. Additionally, in a 1991 paper, Reichelt argued that gluten and casein may play a causative role in autism, as the incomplete digestion thereof may produce certain opioid peptides. Thus, those, such as , who advocate this theory also advocate the use of a gluten-free, casein-free diet as a treatment for autism.
In 1998, a fraudulent paper was published in The Lancet by Andrew Wakefield presenting apparent evidence of a link between the MMR vaccine, gastrointestinal disease and autism. In this paper, which has since been retracted, Wakefield et al. speculated that food-derived peptides "may exert central-opioid effects, directly or through the formation of ligands with peptidase enzymes required for breakdown of endogenous central-nervous-system opioids, leading to disruption of normal neuroregulation and brain development by endogenous encephalins and endorphins."