What Tylenol might really tell us about autism?

Veterans who suffered a traumatic brain injury are considerably more likely to consume cannabis than vets without a TBI. But, that doesn’t mean that cannabis increases head injuries by 50% in combat personnel. Rather, correlations can falsely appear to be causative. And if you don’t think this particular example extends to the active ingredient in Tylenol. You might be surprised to learn about an association between those cannabis smoking veterans and a mother’s response to the analgesic. The Trump Administration tried claiming that the active ingredient in the non-opioid painkiller is linked to autism when taken during pregnancy. The claim was backed by a meta-analysis that showed a correlation, but what it told us about autism likely has little to do with Tylenol or acetaminophen. (1,2)

Author reputation

Dr. Andrea Baccarelli is a clinical endocrinologist who coauthored the study cited by the Trump administration. He currently serves as the Dean of Harvard University’s public health school. Baccarelli has contributed to the field of epigenetics and once received a $150,000 payment for his expert testimony. The study sounds reputable if we stop here. But, testimony provided by Baccarelli attempted to prove harms caused by acetaminophen, which was ultimately thrown out by the judge for “cherry-picking” and misrepresenting studies.

Enviromental Health published the analysis, which consisted of four studies selected from a public database of scientific studies and medical papers. Noteworthy results from within the collage of cited research included findings that countered the author’s conclusion. In a scenario where we choose to accept the existence of an association, correlation still does not equal causation. Expectant mothers who experience more complications, such as fever and headaches, will likely want to use more acetaminophen. But, is there a more direct link between autism and ‘Tylenol-Seeking’?

Causation or physiology?

In the realm of cannabinoidology, we have the mystery of cannabis-induced illnesses conflicted by a physiological attraction to the compounds in cannabis due to the illness. (3) Cannabis use is more acute in persons with early-stage psychosis compared to a control group, as one example. Studies suggest that cannabis is the cause, but this neglects our complex biology. (4) Cannabis seeking can be a symptom of a deficient endocannabinoid system, and psychosis is only one condition that features an off-balanced ECS. (5)

Neurological conditions, including migraine, (6,7) are also associated with cannabinoid and lipid deficiencies. Schizophrenia and autism, in particular, have known genetic crossovers with cannabis use. One gene known to be involved in autism is also associated with cannabis use. (8,9) Mothers of neurodivergent children might have had a high prevalence of acetemetophin use during pregnancy for a similar reason.

Tylenol facilitates a unique effect on the endocannabinoid system. (10) So, a specific endocannabinoid deficiency might cause ‘Tylenol-seeking’, per se. That is to say, a person will find relief from the drug more prominently due to a specific underlying condition that can offset their internal fatty acid system. Endocannabinoids are a specific type of fatty acid that the body synthesizes on demand, which is largely controlled by genetics, environment, and your own transient biology. (11) So, even if Tylenol is more prevalent in mothers of autistic children, the actual underlying cause is likely multifaceted and will vary per individual.

One gene associated with cannabis use disorder is also associated with autism. Can this gene also drive 'Tylenol-seeking' behavior?

Acetaminophen Madness

The question, “What caused a ‘Tylenol-seeking’ physiology in that individual?” can be answered by finding the cause of the ECS deficiency. But there can be many answers for just one person. (7) And we do not know the exact cause(s) of autism, although they likely overlap with atypical cannabinoid synthesis or transport. (9) But, that hypothesis only stands if we continue to believe the meta-analysis. (2) Did the authors simply misconstrue the results as a warning rather than a signal to explore?

We did find associations between parents’ gut microbiota and autism spectrum disorder in their offspring. And acetaminophen has been reported to cause dysbiosis, (12,13) although a conclusion would require actual research given the complexity of the microbiome. Experts outside of the White House and Baccerelli’s circle, however, affirm that no known causative link exists between Tylenol and autism. In its current capacity, the FDA followed a correlation through to a letter advising pregnant women to take the lowest possible dose of acetaminophen and limit the duration. But this is not a new policy decision. The drug can treat fevers, which carry a high risk for pregnant mothers and their children. So, the risk factor does not outweigh the reward in this case. The American College of Obstetricians and Gynecologists asserts that its guidance remains unchanged. It concludes that,

Acetaminophen remains the safest first-line analgesic and antipyretic in pregnancy. Clinicians should continue to recommend its judicious use, provide evidence-based counseling, and reassure patients that current data do not support a causal link to neurodevelopmental disorders.

Sources

1. Utter B, Anderson CA, Filley CM, Kelly JP, Johnston-Brooks C, Arciniegas DB. Cannabis Use in a Cohort of Healthcare-Seeking United States Military Veterans With Persisting Symptoms After Mild Traumatic Brain Injury: Preliminary Observations. Mil Med. 2023;188(7-8):usac011. doi:10.1093/milmed/usac011

2. Prada D, Ritz B, Bauer AZ, Baccarelli AA. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. 2025;24(1):56. Published 2025 Aug 14. doi:10.1186/s12940-025-01208-0

3. Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016;1(1):154-165. Published 2016 Jul 1. doi:10.1089/can.2016.0009

4. Schoeler, T., Baldwin, J.R., Martin, E. et al. Assessing rates and predictors of cannabis-associated psychotic symptoms across observational, experimental and medical research. Nat. Mental Health 2, 865–876 (2024). https://doi.org/10.1038/s44220-024-00261-x

5. Leweke FM, Giuffrida A, Koethe D, et al. Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use. Schizophr Res. 2007;94(1-3):29-36. doi:10.1016/j.schres.2007.04.025

6. Sarchielli P, Pini LA, Coppola F, et al. Endocannabinoids in chronic migraine: CSF findings suggest a system failure. Neuropsychopharmacology. 2007;32(6):1384-1390. doi:10.1038/sj.npp.1301246

7. Bottiroli S, Greco R, Franco V, et al. Peripheral Endocannabinoid Components and Lipid Plasma Levels in Patients with Resistant Migraine and Co-Morbid Personality and Psychological Disorders: A Cross-Sectional Study. Int J Mol Sci. 2024;25(3):1893. Published 2024 Feb 4. doi:10.3390/ijms25031893

8. Bortoletto R, Colizzi M. Cannabis Use in Autism: Reasons for Concern about Risk for Psychosis. Healthcare (Basel). 2022;10(8):1553. Published 2022 Aug 16. doi:10.3390/healthcare10081553

9. Stringer S, Minică CC, Verweij KJ, et al. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. Transl Psychiatry. 2016;6(3):e769. Published 2016 Mar 29. doi:10.1038/tp.2016.36

10. Klinger-Gratz PP, Ralvenius WT, Neumann E, et al. Acetaminophen Relieves Inflammatory Pain through CB1 Cannabinoid Receptors in the Rostral Ventromedial Medulla. J Neurosci. 2018;38(2):322-334. doi:10.1523/JNEUROSCI.1945-17.2017

11. Iannotti FA, Di Marzo V. The endocannabinoidomes: Pharmacological redundancy and promiscuity, and multi-kingdom variety of sources and molecular targets. Pharmacol Rev. 2025;77(4):100070. doi:10.1016/j.pharmr.2025.100070

12. Zádori ZS, Király K, Al-Khrasani M, Gyires K. Interactions between NSAIDs, opioids and the gut microbiota – Future perspectives in the management of inflammation and pain. Pharmacol Ther. 2023;241:108327. doi:10.1016/j.pharmthera.2022.108327

13. Maseda D, Ricciotti E. NSAID-Gut Microbiota Interactions. Front Pharmacol. 2020;11:1153. Published 2020 Aug 7. doi:10.3389/fphar.2020.01153