Animal research shows prenatal THC and nicotine each disrupt fetal development through epigenetic changes, with sex-specific effects that persist into adulthood — and co-use may compound the risks.
Prenatal exposure researchers, epigenetics scientists, anyone interested in how cannabis and tobacco affect fetal development at the molecular level.
What the researchers found
This comprehensive review synthesized animal model research on prenatal exposure to both cannabis (primarily THC) and tobacco (primarily nicotine). The evidence showed that each substance independently disrupts critical developmental processes, but through overlapping mechanisms that raise concerns about combined exposure.
Prenatal THC exposure in animal models impaired offspring neurodevelopment, altered metabolic and cardiovascular function, and disrupted reproductive health. These effects were sex-specific — affecting males and females differently — and persisted into adulthood.
Prenatal nicotine exposure was associated with structural and functional deficits in pulmonary, neurological, behavioral, cardiac, and renal systems in offspring.
A key mechanistic finding was that both THC and nicotine exert their developmental effects partly through epigenetic modifications — changes to DNA methylation patterns that alter gene expression without changing the DNA sequence itself. These epigenetic changes may be how short-term prenatal exposure translates into long-term health consequences.
Why it matters
Cannabis and tobacco co-use during pregnancy is increasing. Animal models allow researchers to isolate the effects of each substance and examine mechanisms at the molecular level — something that's impossible in human studies with their many confounders. This review highlights that the epigenetic mechanism is shared between THC and nicotine, raising the possibility that co-exposure could have compounding effects on the developing fetus.
The numbers in context
Review covered THC effects on neurodevelopment, metabolic function, cardiovascular function, and reproductive health. Nicotine effects documented across pulmonary, neurological, behavioral, cardiac, and renal systems. Both substances produced widespread DNA methylation changes affecting gene expression in offspring.
How the study worked
Narrative review of animal model studies examining prenatal exposure to cannabis/THC and tobacco/nicotine. Synthesized findings on offspring outcomes across organ systems (brain, lungs, heart, kidneys, reproductive system) and mechanistic pathways (epigenetic modifications, DNA methylation, gene expression changes).
Who was studied
Not specified, but focuses on animal models related to prenatal exposure.
What this study cannot tell us
Animal models cannot perfectly replicate human pregnancy physiology, metabolism, or exposure patterns. THC and nicotine doses in animal studies may not match typical human use. Most studies examine single-substance exposure, with limited data on co-exposure effects. Epigenetic findings in animals may not directly translate to human epigenetic responses.
How to read the evidence
Narrative review of animal studies — provides mechanistic insights impossible to obtain from human research, but translation to human outcomes requires caution.
When this study was published
Published in 2026, capturing the current state of animal model research on prenatal substance exposure including recent epigenetic findings.
The bigger picture
This review brings together two bodies of research that are usually studied separately. The finding that THC and nicotine share epigenetic mechanisms of developmental disruption is important because co-use is common — many cannabis users also smoke tobacco, and dual-use products are proliferating. This connects to the prenatal THC imaging work (RTHC-00236) and the molecular brain fingerprint study (RTHC-00226) by providing the mechanistic bridge: epigenetic changes may be how prenatal exposure leads to the structural brain changes those studies documented.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Do the epigenetic changes from prenatal THC and nicotine exposure interact synergistically or additively when both substances are present? Are there critical windows during pregnancy when exposure is most damaging? Can epigenetic changes from prenatal exposure be transmitted to subsequent generations?
Read the original research
Prenatal Cannabis and Tobacco: Studies in Animal Models.
Advances in experimental medicine and biology, 1500, 253-302
Advances in Experimental Medicine and Biology is a reputable journal focusing on biomedical research.
Citation
Edenfield, R Clayton; D'Mello, Rahul; Shorey-Kendrick, Lyndsey E; Crosland, B Adam; Hagen, Olivia L; McEvoy, Cindy T; Spindel, Eliot R; Murphy, Susan K; Lo, Jamie O; Marbrey, Margeaux W. (2026). Prenatal Cannabis and Tobacco: Studies in Animal Models.. Advances in experimental medicine and biology, 1500, 253-302. https://doi.org/10.1007/978-3-032-12741-9_9
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