Association of Endothelial Dysfunction with Chronic Cannabis Smoking and THC-Edible Use:
The CANDIDE Study and What Led Up to It
April 23, 2026
At the April CMCR Investigators’ Meeting, Matthew Springer, Ph.D., Professor of Medicine in the Division of Cardiology at UC San Francisco, presented on the cardiovascular effects of inhaled and ingested cannabis products, culminating in findings from the CANDIDE (Cannabis: Does It Damage Endothelium) clinical study. Dr. Springer framed the presentation around a central question: whether the cardiovascular harms increasingly associated with cannabis in the epidemiological literature stem from the smoke, the THC, or both.
Using flow-mediated dilation (FMD) as a measure of vascular endothelial function in rats, Dr. Springer’s laboratory demonstrated that one minute of secondhand cannabis smoke impaired FMD to the same degree as tobacco smoke, and that THC was not required for the effect. Subsequent studies showed that cannabis leaf vaporizers, e-cigarettes, and heated tobacco products all impaired FMD similarly. Bilateral cervical vagotomy abolished the impairment across all product types, implicating an airway irritation reflex mediated by the vagus nerve rather than any specific chemical constituent. Inhibition of the RAGE (receptor for advanced glycation end products) pathway also prevented the effect. In chronic exposure experiments, rats exposed daily for eight weeks to any of these inhalational products exhibited reduced ejection fraction, decreased heart rate variability, increased arrhythmia susceptibility, and cardiac fibrosis. Daily exposure also resulted in approximately twice the myocardial tissue death following surgically induced infarction compared to air controls.
The CANDIDE study measured FMD in 55 carefully screened participants under age 50 without other cardiovascular disease, including chronic marijuana smokers, chronic THC edibles users (both at least three sessions per week), and non-users. Marijuana smokers showed roughly 50% lower FMD than non-users, consistent with decades of tobacco data. Unexpectedly, THC edibles users also showed significantly reduced FMD despite no smoke exposure. However, serum from marijuana smokers blunted endothelial nitric oxide production in vitro, while serum from THC edibles users did not, indicating that smoke and THC impair vascular function through distinct mechanisms. Dose-response relationships were observed in both groups.
Dr. Springer concluded by urging that smoking any combustible product should be avoided, while noting that the THC edibles finding complicates the public health message. He emphasized that future research and epidemiological studies should distinguish between cannabis smoking and oral THC consumption rather than grouping all forms under the imprecise label of “cannabis use.”
Matthew L. Springer, Ph.D.
Professor of Medicine, Division of Cardiology
UC San Francisco
Dr. Springer received his BA from UC Berkeley in 1985 and his PhD from Stanford University in 1992.
He did postdoctoral research at Stanford and continued his research there as a senior scientist until joining the UCS faculty in 2003, where he is currently one of the few non-clinicians on the faculty of the Division of Cardiology. The close juxtaposition of his basic research background with the clinical cardiologists has resulted in an active translational research program. His research interests include cell therapy and gene therapy approaches to studying cardiovascular disease, with the goals of exploring potential treatments for heart attacks and heart failure, and understanding how cardiovascular health is impacted by smoking/vaping of tobacco or cannabis products, or by secondhand exposure, in rodents and humans.