Rat study finds salivary gland injury after cannabis nanoemulsions

Subchronic Exposure to Cannabis-Based Nanoemulsions Induces Histopathological and Molecular Alterations in the Rat Submandibular Gland.

Journal of applied toxicology : JAT • • Highly Relevant
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AI Summary

This study asked whether cannabis-based lipid nanoemulsions affect salivary gland tissue. Researchers gave 40 male rats daily oral treatments for 21 days, comparing a vehicle control with two doses of CBD alone and two doses of CBD combined with THC. The primary finding was that all treated groups had significant histopathological changes in the submandibular gland compared with controls. The most pronounced tissue injury occurred in the CBD-only groups; the abstract reports no human participants or outcomes.

Other findings included reduced PAS reactivity in the CBD and THC combination groups, increased oxidative DNA damage in the lower-dose CBD-only group, and increased collagen around ducts across treated groups, with different collagen patterns by treatment. The authors suggest THC may have moderated CBD-associated injury, but this rat study cannot establish that interaction in people or show whether the tissue changes cause dry mouth. This is an abstract-based summary; the abstract does not establish the long-term effects or clinical significance of these findings.

💡 Key Findings

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All tested cannabis-based nanoemulsion treatment groups showed significant histopathological changes in rat submandibular glands versus vehicle control.
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CBD alone produced the most pronounced tissue injury, including cytoplasmic vacuolization, hemorrhage, and severe acinar disorganization.
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The abstract reports increased oxidative DNA damage in the lower-dose CBD-only group and increased periductal collagen deposition across all treated groups, with collagen patterns differing by treatment.
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The authors propose that THC may moderate CBD-associated toxicity in rat salivary tissue; the animal findings do not establish this effect in humans.
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📄 Original Abstract

The increasing therapeutic incorporation of cannabis has expanded phytocannabinoid application, yet peripheral adverse effects like xerostomia raise concerns regarding emerging biotechnological formulations. This study evaluated the effects of cannabis-based lipid nanoemulsions on the rat submandibular gland parenchyma. Forty male Wistar rats were distributed into five daily oral treatment groups for 21&#x2009;days: vehicle control, CBD and THC (2.5 and 5&#x2009;mg/kg), and isolated CBD (2.5 and 5&#x2009;mg/kg). Submandibular glands were assessed via histopathology (H&E), acinar histomorphometry, periodic acid-Schiff (PAS) histochemistry, immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG), cleaved caspase-3, and cyclooxygenase-2 (COX-2) and collagen birefringence under polarized light. All treated groups exhibited significant histopathological alterations versus control (p&#x2009;<&#x2009;0.05). Isolated CBD groups displayed the most pronounced tissue injury, with extensive cytoplasmic vacuolization, hemorrhage, and severe acinar disorganization, although acinar density remained comparable among groups. PAS reactivity was significantly reduced only in CBD and THC groups, whereas oxidative DNA damage (8-OHdG) was significantly increased in the CBD 2.5-mg/kg group. All treated groups demonstrated enhanced periductal collagen deposition: isolated CBD groups showed a predominance of mature type I collagen fibers, whereas CBD and THC 5&#x2009;mg/kg exhibited a higher proportion of immature type III fibers, indicating distinct extracellular matrix remodeling patterns. In conclusion, cannabis-based lipid nanoemulsions induced histopathological injury, oxidative stress, and extracellular matrix remodeling in rat submandibular glands. Notably, isolated CBD produced more severe glandular damage than the CBD and THC combination, suggesting a protective modulatory effect of THC against CBD-induced toxicity in salivary tissue, consistent with a pharmacodynamic interaction between these phytocannabinoids.

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