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Prenatal THC Exposure Changed DNA Methylation in Macaque Placenta and Fetal Tissues at Genes Linked to Autism

Animal StudyModerate evidence
The takeaway

Pregnant rhesus macaques given daily THC edibles showed 581 differentially methylated DNA sites, with 98% in placenta, and these sites were enriched for genes in the SFARI autism database across all five tissues tested.

Epigenetics researchers, autism researchers, developmental toxicologists, obstetricians.

98% of THC-induced DNA methylation changes occurred in the placenta

What the researchers found

Prenatal THC exposure was associated with differential methylation at 581 CpGs, with 573 (98%) in placenta. Differentially methylated loci were enriched for candidate autism spectrum disorder genes from the SFARI database in all 5 tissues (placenta, lung, cerebellum, prefrontal cortex, heart). Placenta showed greatest SFARI gene enrichment, including genes also differentially methylated in placentas from a prospective human ASD study.

Why it matters

This is the first primate study linking prenatal THC to epigenetic changes at autism-associated genes. The convergence between macaque THC-exposed placentas and human ASD placentas strengthens the biological plausibility of a cannabis-autism connection.

The numbers in context

581 differentially methylated CpGs. 573 (98%) in placenta. 5 tissues tested. SFARI autism gene enrichment in all tissues. Daily THC dose: 2.5 mg/7 kg.

How the study worked

Pregnant rhesus macaques consumed daily THC edible (2.5 mg/7 kg/day) or placebo. DNA methylation measured in 5 tissues at cesarean delivery using Illumina MethylationEPIC platform filtered for rhesus-validated probes.

What this study cannot tell us

Rhesus macaque model, not human. Small number of animals per group (not specified in abstract). Single THC dose. DNA methylation changes may not translate to gene expression or behavioral changes. Long-term offspring outcomes not assessed.

How to read the evidence

Controlled primate study with appropriate methodology, but small sample and DNA methylation changes do not guarantee functional outcomes.

When this study was published

Published in 2023.

The bigger picture

This primate study adds mechanistic evidence to the controversial epidemiological associations between prenatal cannabis exposure and autism. While correlation studies in humans face many confounders, this controlled animal experiment removes most of them.

Questions still open

  • Do the DNA methylation changes persist in offspring and translate to behavioral outcomes?
  • Would different THC doses produce different methylation patterns?

Common questions

Does prenatal THC affect genes linked to autism?
In this macaque study, prenatal THC edible exposure changed DNA methylation at 581 sites, and these sites were enriched for genes in the autism database, particularly in the placenta.
Does this prove cannabis causes autism?
No. This shows a biological mechanism by which THC could influence autism-related genes, but DNA methylation changes do not necessarily lead to autism. The finding strengthens biological plausibility but is not proof of causation.

Read the original research

Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes.

Clinical epigenetics, 15(1), 104

Citation

Shorey-Kendrick, Lyndsey E; Roberts, Victoria H J; D'Mello, Rahul J; Sullivan, Elinor L; Murphy, Susan K; Mccarty, Owen J T; Schust, Danny J; Hedges, Jason C; Mitchell, A J; Terrobias, Jose Juanito D; Easley, Charles A; Spindel, Eliot R; Lo, Jamie O. (2023). Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes.. Clinical epigenetics, 15(1), 104. https://doi.org/10.1186/s13148-023-01519-4

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