Cannabis and cigarettes together threaten fetal lung development

Co-exposure to cannabinoids and nicotine increases senescence in prenatal human lung development.

Pediatric research • • Moderately Relevant
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AI Summary

This groundbreaking study examines what happens to fetal lung development when a pregnant person is exposed to both cannabis and cigarettes—a concerning trend in areas where recreational marijuana is legal. Researchers used human fetal lung tissue from weeks 10-16 of pregnancy and exposed it to THC, CBD, and nicotine, either individually or in combination. The results were alarming: the combination of all three substances triggered a "senescence-like" state, meaning the cells began to age prematurely and malfunction. This included reduced cell proliferation, increased DNA damage markers, and elevated inflammatory signals that could compromise healthy lung development.

The study revealed multiple harmful effects from combined exposure. Cell proliferation decreased significantly with CBD and the three-substance combination, while smooth muscle cells failed to differentiate properly across all treatment conditions. Most concerning, the combination triggered cellular senescence (premature aging) along with DNA damage responses, indicated by upregulation of specific aging markers and damaged DNA indicators. The cells also released excessive inflammatory proteins like IL-6, IL-8, and TNF-α, which create a harmful inflammatory environment in developing lung tissue and could lead to long-term respiratory problems.

Importantly, the researchers discovered a potential intervention: senolytics (compounds including Dasatinib and Quercetin) partially reversed the damage by reducing senescence markers and inflammatory secretions. While this finding offers hope for potential therapeutic approaches, the primary takeaway is clear—concurrent use of cannabis and nicotine during pregnancy poses serious risks to fetal lung development that extend well beyond either substance alone. This research underscores the importance of pregnancy safety counseling as cannabis legalization expands.

📄 Original Abstract

Tandem use of cigarettes and cannabis is increasing, particularly where recreational marijuana is legalized, posing a serious risk to fetal development. This study investigates the impact of cannabinoids (THC and CBD) and nicotine on fetal lung development using human lung explants from 10-16 weeks of gestation. Our results show that THC promotes epithelial cysting RESULTS: Our data revealed decreased proliferation (Ki-67) following treatment with CBD and CBD + THC+nicotine, whereas smooth muscle cell differentiation decreased across all conditions. Furthermore, the combination treatments induced a senescence-like phenotype as demonstrated by increased CDKN1A and CDKN2A expression and a strong reduction in LAMIN B1 staining. Additionally, DNA damage response markers ɣH2A.X and 53BP1 were significantly upregulated in the combination treatments. This was accompanied by an activation of the interferon pathway with increased expression of the downstream targets MX1 and IFI2. The addition of senolytics, Dasatinib and Quercetin (D + Q), reduced the senescence-associated secretory phenotype (SASP), such as IL-6, IL-8, M-CSF, MCP-3, MIP-1β, TNFα, MIP-3β, and TSLP, the senescence gene expressions, and reversed interferon pathway activation CONCLUSION: Our results demonstrate that co-exposure to nicotine and cannabis alters cellular proliferation and differentiation, induces a senescence-like phenotype and DNA damage response in human fetal lung cultures, which may be partially rescued using senolytics. This study aims to assess the effect of cannabis and nicotine use during pregnancy on fetal human lung development. The combinatorial exposure to CBD, THC, and nicotine during pregnancy increases senescence-like phenotype, DNA damage response, and senescence-associated secretory phenotypes (SASP) secretion. The use of senolytics (D + Q) may prove to be a promising therapeutic option, alleviating several of the adverse effects induced by the different substances.

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