Pediatric researchJul 7, 2026

Using both cannabinoids and nicotine during pregnancy may increase aging in developing human lungs

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 8, 2026

Abstract

Co-exposure to nicotine and cannabis is associated with altered cellular proliferation and differentiation in human fetal lung cultures.

Treatment with THC led to increased epithelial cysting in lung explants from 10-16 weeks of gestation.
Decreased cellular proliferation was observed with CBD and CBD combined with THC and nicotine.
Smooth muscle cell differentiation was reduced across all treatment conditions.
Combination treatments induced a senescence-like phenotype, indicated by elevated expression of CDKN1A and CDKN2A.
DNA damage response markers, including γH2A.X and 53BP1, were significantly increased with combined cannabinoid and nicotine exposure.
Senolytics Dasatinib and Quercetin reduced markers associated with senescence and reversed activation of the interferon pathway.

Simplified

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.

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Funding

Competing interests

Competing interests: The authors declare no competing interests. Institutional Review Board Statement: The tissue used is de-identified and does not meet the definition of Human Subjects, per the Lundquist Institute IRB determination (The Lundquist Institute 18CR-32223-01).

PubMed

Using both cannabinoids and nicotine during pregnancy may increase aging in developing human lungs

Abstract

Full Text

Funding

Competing interests

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