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

BACKGROUND AND AIM: Cannabidiol (CBD) is increasingly administered via electronic vaporizers because inhalation enables rapid pulmonary absorption and bypasses first-pass hepatic metabolism. However, the respiratory consequences of repeated exposure to purified CBD vapor remain insufficiently characterized. This study investigated the systemic and pulmonary effects of repeated whole-body inhalation of purified CBD vapor in Sprague-Dawley rats, with emphasis on the temporal progression of pulmonary histopathological changes. MATERIALS AND METHODS: Thirty 9-week-old male Sprague-Dawley rats were randomly allocated to five groups (n = 6/group): saline-exposed control and CBD vapor exposure for 15, 30, 60, or 90 consecutive days. Approximately 100 mg of purified CBD isolate was loaded into an electronic vaporization device for each exposure session, and individual rats underwent whole-body exposure for 5 min/day under standardized chamber conditions. Clinical status, body weight, and rectal temperature were monitored. Hematological, biochemical, and electrolyte parameters were measured at the end of each exposure period. Lung and extrapulmonary tissues were examined histopathologically. Pulmonary lesions were independently evaluated by two blinded veterinary pathologists using a semi-quantitative grading scale. RESULTS: No mortality, clinically apparent morbidity, abnormal respiratory signs, or significant differences in body weight were observed. Several hematological and biochemical variables differed significantly among groups; however, most post hoc comparisons were nonsignificant, and all values remained within physiological reference intervals. No histopathological abnormalities were detected in the liver, gastrointestinal tract, kidneys, or brain. In contrast, repeated CBD vapor exposure produced progressive pulmonary inflammatory and vascular alterations. Interstitial pneumonia and bronchus-associated lymphoid tissue hyperplasia were evident from 15 days, whereas perivascular eosinophilic cuffing and pulmonary arterial smooth muscle hypertrophy increased with exposure duration. The most severe lesions occurred after 60 and 90 days and included marked interstitial inflammation, dense eosinophilic perivascular infiltrates, hemorrhagic foci, and advanced arterial remodeling. CONCLUSION: Repeated whole-body inhalation of purified CBD vapor was associated with progressive, localized pulmonary inflammatory and vascular changes despite the absence of clinically meaningful systemic toxicity. These findings support further studies incorporating aerosol characterization, inhaled dosimetry, pulmonary function testing, mechanistic biomarkers, recovery assessment, and clinically relevant vaping formulations.