Prenatal THC Exposure Changed DNA Methylation in Macaque Placenta and Fetal Tissues at Genes Linked to Autism
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?Do the DNA methylation changes persist in offspring and translate to behavioral outcomes?
- ?Would different THC doses produce different methylation patterns?
Trust & Context
- Key Stat:
- 98% of THC-induced DNA methylation changes occurred in the placenta
- Evidence Grade:
- Controlled primate study with appropriate methodology, but small sample and DNA methylation changes do not guarantee functional outcomes.
- Study Age:
- Published in 2023.
- Original Title:
- Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes.
- Published In:
- Clinical epigenetics, 15(1), 104 (2023)
- Authors:
- Shorey-Kendrick, Lyndsey E(5), Roberts, Victoria H J(3), D'Mello, Rahul J(2), 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
- Database ID:
- RTHC-04935
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked 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 More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-04935APA
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
MLA
Shorey-Kendrick, Lyndsey E, et al. "Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes.." Clinical epigenetics, 2023. https://doi.org/10.1186/s13148-023-01519-4
RethinkTHC
RethinkTHC Research Database. "Prenatal delta-9-tetrahydrocannabinol exposure is associated..." RTHC-04935. Retrieved from https://rethinkthc.com/research/shorey-kendrick-2023-prenatal-delta9tetrahydrocannabinol-exposure-is
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.