Because this is a study on older children, fewer of the children with autism use acetaminophen (Tylenol) as the first choice for fever reduction. Furthermore, acetaminophen is not effective at reducing fever for significantly more children with ASD (autism), and they change to the use of ibuprofen.
The authors believe this is due to endocannabinoid system dysfunction. (See Schultz, 2010)
QUOTE: “We have shown that the acetaminophen metabolites AM404 and p-aminophenol are toxic for mouse embryonic cortical neurons”
In their Conclusion section is a very good description, quoted here in full:
“Suppose a susceptible young boy has a fever due to a viral infection or after the MMR vaccination. His parents give him acetaminophen which increases endocannabinoid stimulation in his brain making him feel better and bringing down his fever. But the increased activation of the endocannabinoid system also decreases immune system function which prolongs the illness and leads to even more acetaminophen use. Eventually, the boy recovers but his endocannabinoid system has been dysregulated to a lower level to compensate for the prolonged over-activation. Now the neurons in his brain are not getting the proper guidance for their growth through CB1 receptors and further suffer from increased inflammation due to lack of CB2 regulation in immune system cells. The boy develops ASD. When the boy gets a fever, his parents again give him acetaminophen but it no longer works well since his endocannabinoid tone is at a low level, and his parents switch to ibuprofen. Also, when he gets a fever, the increased anandamide levels briefly increase endocannabinoid tone and improve his sociability. After the fever, the endocannabinoid tone again drops back to low levels and his sociability decreases again. His condition, however, may be reversible with new cannabinoid medications to increase endocannabinoid system activation and allow his brain to slowly recover. Research needs to be conducted to see if PEA, cannabidiol, or other cannabinoids will be effective treatments for ASD.” (stress added)
Related papers mentioned above:
- Schultz (2010): Can autism be triggered by acetaminophen activation of the endocannabinoid system?
- Schultz et al (2012): Effects of the analgesic acetaminophen (paracetamol) and its para-aminophenol metabolite on viability of mouse-cultured cortical neurons.