Abstract
INTRODUCTION: Chronic kidney disease (CKD) affects approximately 10% of the global population and is associated with a large symptom burden. Medicinal cannabis is advised against in patients with severe CKD. However, pharmacokinetic and pharmacodynamic knowledge regarding their use in patients with CKD is lacking. METHODS: We aimed to investigate the pharmacokinetics and side effects of a single dose of Sativex, corresponding to 5.4 mg Δ(9)-tetrahydrocannabinol (THC) and 5 mg cannabidiol (CBD), in patients with CKD stages 4 and 5 compared with healthy volunteers (controls). The study was a nonrandomized and unblinded clinical study. RESULTS: Twenty controls and 29 patients with CKD completed the study. The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77-3.48), 4.16 (3.35-5.28), and 4.31 (3.16-5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls. AUC for CBD and metabolites, and other pharmacokinetic parameters, such as maximum concentration (C (max)) and excretion of metabolites in urine were also significantly different between patients with CKD and controls. After 1.5 hours, numeric rating scale (NRS) scores for dizziness were significantly higher for each CKD group compared with controls (mean NRSscores: 0.7 and 1.5 vs. 0.1). CONCLUSION: Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared with controls, and side effects may be more pronounced; however, the intersubject variability was high. If cannabis products are administered to patients with severe CKD, caution is needed.