The Philadelphia observations in schizophrenics were corroborated by psychiatrists at the University of Sheffield in England, with similar conclusions.4 There have since even been reports of complete remission of the disease, such as the seventy-year-old schizophrenic woman described by Duke University doctors, suffering with delusions, hallucinations, and suicide attempts with sharp objects and cleaning solutions over a period of fifty-three years, who experienced complete relief from psychosis and suicidal desires within eight days of stopping wheat.5
While it seems unlikely that wheat exposure caused schizophrenia in the first place, the observations of Dr. Dohan and others suggest that wheat is associated with measurable worsening of symptoms. In the years since Dr. Dohan’s early observations, the explosion of more recent investigations suggests that consumption of gluten-containing foods is associated with increased intestinal permeability, or “leakiness,” along with alterations in the bowel microbiome that underlie the troublesome mind pathology of schizophrenia.6 Modern observations also corroborate Dohan’s observations with dramatic reversal of schizophrenic phenomena within days to weeks of gluten removal, even after years of unremitting symptoms.7 It has also become clear that celiac disease and schizophrenia are two different varieties of grain-induced disease and the psychotic behavior of schizophrenia can occur independently of celiac disease.8
Another condition in which wheat may exert effects on a vulnerable mind is autism. Autistic children suffer from impaired ability to interact socially and communicate. The condition has increased in frequency over the past forty years, from rare in the mid-twentieth century to 1 in 150 children in the twenty-first.9 Initial small samples have demonstrated improvement in autistic behaviors with gluten removal.10, 11 The most comprehensive clinical trials to date with formal measures of autistic behavior have demonstrated improvement with gluten elimination (sometimes combined with elimination of casein from dairy and a variety of different nutritional supplements).12, 13, 14
While it remains a topic of debate, a substantial proportion of children and adults with attention deficit/hyperactivity disorder (ADHD) may also respond to elimination of wheat. However, responses are often muddied due to sensitivities to other components of diet, such as sugars, artificial sweeteners, additives, and dairy.15
It is unlikely that wheat exposure was the initial cause of autism or ADHD but, as with schizophrenia, wheat appears to be associated with worsening of the symptoms characteristic of these conditions.
Though the laboratory rat treatment of the unsuspecting schizophrenic patients in the Philadelphia VA Hospital may send chills down our spines from the comfort of our fully informed and consenting twenty-first century, it is nevertheless a graphic illustration of wheat’s effect on mental function. But why in the world are schizophrenia, autism, and ADHD exacerbated by wheat? What is in this grain that worsens psychosis, prompts hearing voices and other abnormal behaviors?
Investigators at the National Institutes of Health (NIH) set out to find some answers.
EXORPHINS: THE WHEAT-MIND CONNECTION
Dr. Christine Zioudrou and her colleagues at the NIH subjected gluten, the main protein of wheat, to a simulated digestive process to mimic what happens after we eat bread or other wheat-containing products.16 Exposed to pepsin (a stomach enzyme) and hydrochloric acid (stomach acid), gluten is degraded to a mix of polypeptides. (Unlike the proteins in, say, eggs or pork chops that are broken down into single amino acids, the proteins of wheat are either indigestible or only digestible to polypeptides, small chains of amino acids, because humans lack the digestive enzymes to break down the components of seeds of grasses.) The dominant polypeptides were then isolated and administered to laboratory rats. These polypeptides were discovered to have the peculiar ability to penetrate the blood-brain barrier that separates the bloodstream from the brain. This barrier is there for a reason: The brain is highly sensitive to the wide variety of substances that gain entry to the blood, some of which can provoke undesirable effects should they cross into your amygdala, hippocampus, cerebral cortex, or other brain structure. Once having gained entry into the brain, wheat polypeptides bind to the brain’s morphine receptors, the very same receptors to which opiate drugs like fentanyl and oxycodone bind.
Zioudrou and her colleagues dubbed these polypeptides “exorphins,” short for exogenous morphine-like compounds, distinguishing them from endorphins, the endogenous (internally sourced) morphine-like compounds that occur, for instance, during a “runner’s high.” They named the dominant polypeptide that crossed the blood-brain barrier “gluteomorphin,” or morphine-like compound from gluten. The investigators speculated that exorphins might be the active factors derived from wheat that account for the deterioration of schizophrenic symptoms seen in the Philadelphia VA Hospital and elsewhere.
Even more telling, the NIH group found that the brain effects of gluten-derived polypeptides are blocked by administration of the opiate-blocking drug naloxone.
Let’s pretend you’re an inner-city heroin addict. You get knifed during a drug deal gone sour and get carted to the nearest trauma emergency room. Because you’re high on heroin, you kick and scream at the ER staff trying to help you. So these nice people strap you down and inject you with a drug called naloxone, and you are instantly not high. Through the magic of chemistry, naloxone immediately reverses the action of heroin or any other opiate drug such as morphine or oxycodone.
In lab animals, administration of naloxone blocks the binding of wheat exorphins to the morphine receptors of brain cells. Yes, opiate-blocking naloxone prevents the binding of wheat-derived exorphins to the brain. The very same drug that turns off the heroin in a drug-abusing addict to reverse life-threatening overdose also blocks the effects of wheat exorphins.
In a World Health Organization study of thirty-two schizophrenic people with active auditory hallucinations, naloxone was shown to reduce hallucinations.17 Unfortunately, the next logical step—administering naloxone to schizophrenics eating a “normal” wheat-containing diet compared to schizophrenics administered naloxone on a wheat-free diet—has not been studied. (Clinical studies that might lead to conclusions that don’t support drug use are often not performed. In this case, had naloxone shown benefit in wheat-consuming schizophrenics, the unavoidable conclusion would have been to eliminate wheat, not prescribe the drug.)
The schizophrenia experience shows us that wheat exorphins have the potential to exert distinct and peculiar effects on the brain. Those of us without schizophrenia don’t experience auditory hallucinations from exorphins resulting from a cinnamon raisin bagel, but these compounds are still there in the brain, no different from in a schizophrenic. It also highlights how wheat is truly unique among grains, since other grains such as millet and oats do not generate exorphins (because they lack the gliadin protein from gluten), nor do they cultivate obsessive behavior or opiate withdrawal in people with normal brains or people with abnormal brains.
So this is your brain on wheat: Digestion yields morphine-like compounds that bind to the brain’s opiate receptors. It induces a form of reward, a mild euphoria. When the effect is blocked or no exorphin-yielding foods are consumed, many people experience a distinctly unpleasant withdrawal.
What happens if normal (i.e., non-schizophrenic) humans are given opiate-blocking drugs? In a study conducted at the Psychiatric Institute of the University of South Carolina, wheat-consuming participants given naloxone consumed 33 percent fewer calories at lunch and 23 percent fewer calories at dinner (a total of approximately 400 calories less over the two meals) than participants given a placebo.18 At the University of Michigan, binge eaters were confined to a room filled with food for one hour. (There’s an idea for a new TV show: The Biggest Gainer.) Participants consumed 28 percent fewer wheat crackers, breadsticks, and pretzels with the administration