Repeated whole-body inhalation of cannabidiol vapor induces progressive pulmonary inflammatory and vascular remodeling without systemic toxicity in Sprague-Dawley rats.

Piewbang C.; Bunman S.; Kasantikul T.; Muengtaweepongsa S.; Wannapaschaiyong P.; Techangamsuwan S. · Veterinary world · 2026

**Background & Methods** This experimental study exposed 30 male Sprague-Dawley rats to purified cannabidiol (CBD) vapor via whole-body inhalation chamber for 5 minutes daily over 15, 30, 60, or 90 consecutive days (n=6 per group), with saline-exposed controls. Comprehensive monitoring included clinical assessment, hematology, biochemistry, electrolytes, and histopathological examination of pulmonary and extrapulmonary tissues, with blinded pathologist evaluation using semi-quantitative grading scales. **Key Findings** • **Progressive pulmonary pathology without systemic effects**: Repeated CBD vapor inhalation induced dose-dependent pulmonary inflammatory and vascular changes including interstitial pneumonia (evident by day 15), bronchus-associated lymphoid tissue hyperplasia, perivascular eosinophilic infiltration, and pulmonary arterial smooth muscle hypertrophy that intensified through day 90. Most severe lesions at 60-90 days included marked interstitial inflammation, dense eosinophilic infiltrates, hemorrhagic foci, and advanced arterial remodeling. • **No clinically apparent systemic toxicity**: No mortality, clinical morbidity, abnormal respiratory signs, or significant body weight changes occurred. Hematological and biochemical variables showed some statistical differences among groups but remained within physiological reference intervals with predominantly nonsignificant post hoc comparisons. • **Preserved organ function**: Histopathological examination revealed no abnormalities in liver, gastrointestinal tract, kidneys, or brain, indicating selective pulmonary targeting without evidence of systemic organ involvement. **Dosage & Administration** Approximately 100 mg purified CBD isolate per exposure session delivered via electronic vaporization device; 5-minute whole-body chamber inhalation daily for up to 90 consecutive days. **Safety & Adverse Effects** No mortality or clinically apparent adverse effects. Progressive pulmonary inflammation and vascular remodeling represent the primary pathological findings without systemic toxicity. No hepatotoxicity, gastrointestinal, renal, or neurotoxic effects observed. **Evidence Quality** This is a controlled animal experimental study providing mechanistic insights into CBD vapor inhalation toxicity. Limitations include: animal model (rats) with uncertain human translatability; use of pure CBD isolate rather than clinically relevant vaping formulations; absence of pulmonary function testing, aerosol characterization, inhaled dosimetry data, and mechanistic biomarkers; no recovery assessment following exposure cessation; and limited generalizability to human vaping patterns. The authors acknowledge these gaps and recommend future studies incorporating these methodologies. Evidence quality is moderate for animal toxicity characterization but insufficient for direct clinical application.

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