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Is Tylenol Messing With The Endocannabinoid System?

Dragana Komnenov PhD

Recent research connects acetaminophen and autism through the action of this drug on anandamide (endocannabinoid) in the brain.

Autism or autism spectrum disorder (ASD) is described as a deficit in social communication and interactions, along with repetitive patterns of behavior, interests and/or activities. Children diagnosed with ASD typically experience developmental delays.  Although some association between ASD and other genetic or chromosomal abnormalities exists, these are estimated to be less than 10 % of patients.

According to more recent estimates, more than half of the ASD cases can be attributed to environmental factors. This becomes obvious when a subset of children with ASD start developing normally, but then regress later in childhood.  Acetaminophen has been implicated as one probable trigger for this regression as it disrupts the endocannabinoid system.

acetaminophen and autism

Acetaminphen and Autism: Disrupting the Endocannabinoid System

One group of researchers blames acetaminophen, given to children for fever, for autism rates. They found that in those children who regressed in development, acetaminophen use increased the likelihood of developing ASD. Another study demonstrated that both prenatal and perinatal use of acetaminophen was associated with ASD. Some researchers argue that acetaminophen disrupts the endocannabinoid system thus predisposing children to ASD.

The use of acetaminophen as a painkiller started over 100 years ago, when its mechanism of action was not actually known. Now we know that the analgesic effect comes from its indirect action on cannabinoid receptors. This action prevents anandamide from leaving the cell and this anandamide levels go up.

In a case controlled study involving children 12-18 months of age, acetaminophen use increased the likelihood of ASD 8 times. In another study, older children (11 years old) with ASD were found to have used acetaminophen as the first choice of analgesic in their earlier years. Additionally, children with ASD were shown to be more sociable when they have a fever and are treated with acetaminophen, and it was hypothesized that this is due to the activation of anandamide since they normally have a low endocannabinoid tone.

chemical structure of anandamide

Animal Studies Find the Same Connection Between Acetaminophen and Autism

In fact, the same results were shown in animal studies. Metabolites of acetaminophen were found to be toxic to the mouse embryonic neurons that reside in the cortex of the brain. The drug also increased brain endocannabinoid levels by acting on cannabinoid receptors, thus preventing reuptake of anandamide.

It was also shown in a mouse model for autism that acetaminophen affects social aspects of the behavior differently than for neuro-typical mice. Additionally, neonatal exposure to acetaminophen induced changes in the immune system function that were long-lasting.

Patent for ASD Diagnostic Test Based on Endocannabinoid Levels

Whether the levels of circulating endocannabinoids can predict or diagnose ASD still remains to be determined, but there is already a patent pending on these methods. The working hypothesis for such diagnostic method is: acetaminophen activates the endocannabinoid system and this interferes with normal development. The response of the body is to down-regulate the endocannbinoid system to balance.

If these cycles of activation and down-regulation repeat multiple times, evidence from mouse studies suggests that neuronal development may be impaired. The specific impairment is regression that manifests as ASD.

It is certainly very exciting to think that a check on circulating anandamide levels and subsequent adjustment by supplementation with CB1 and CB2 agonists could be the therapy for such debilitating developmental disorder such as ASD.


Dragana Komnenov
  • Avatar
    Debra Rabedeau

    I’m curious where the information comes from. The article refers to studies and researchers but sites nothing and no one specific. This is quite a claim, and certainly an interesting one. Please provide sources.

    March 14, 2019 at 3:40 pm Reply
    • Jennifer Grant

      The author has linked the studies within the article. Look for text of a different color, hover over that and a link will appear. Alternatively, you can directly click and it will take you there.

      March 15, 2019 at 9:10 pm Reply
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    Candy Mercer

    yeah, so much blah, blah, this is dangerous territory, please do not give false hope, or false blame. People believe words, and this is so many words, with so little evidence.

    March 15, 2019 at 5:20 pm Reply
    • Jennifer Grant

      I think it’s important to discuss all information that comes out, all valid studies that are trying to find solutions. My child, for example, has PANDAS. I read every single thing I can get my hands on regarding autoimmune encephalitis. Originally thought to be autism…which is another potential avenue for some parents to research. Regressed development is gone with proper treatment. So, bottom line, there is no such thing as dangerous territory when research is valid and peer-reviewed. And there is no conversation more important than how to help our kids.

      March 15, 2019 at 9:09 pm Reply

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