Medical cannabis for pain management in patients undergoing chronic hemodialysis: randomized, double-blind, cross-over, feasibility study

Background Chronic pain is prevalent but difficult to treat in patients undergoing hemodialysis (HD). Effective and safe analgesics are limited in this patient population. Our aim in this feasibility study was to evaluate the safety of sublingual oil based medical cannabis for pain management in patients undergoing HD. Methods In a prospective randomized, double-blind, cross-over design, patients undergoing HD with chronic pain were assigned to one of three arms: BOL-DP-o-04-WPE whole-plant extract (WPE), BOL-DP-o-04 cannabinoid extraction (API) or placebo. WPE and API contained trans-delta-9-200f;tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:6 ratio (1:6, THC:CBD). Patients were treated for 8 weeks, with subsequent 2-week wash out, followed by a cross-over to a different arm. The primary endpoint was safety. Results Eighteen patients were recruited and 15 were randomized. Three did not complete drug titration period due to adverse events (AEs) and one patient died during titration due to sepsis (WPE). Of those who completed at least one treatment period, seven patients were in the WPE arm, five in the API and nine receiving placebo. The most common AEs were sleepiness, which improved after dose reduction or patient adaptation. Most AEs were mild to moderate and resolved spontaneously. Serious AEs considered related to study drug included one episode of accidental overdose (WPE) leading to hallucinations. Liver enzymes were stable during cannabis treatment. Conclusions Short-term medical cannabis use in patients treated with HD was generally well tolerated. The safety data supports further studies to assess the overall risk-benefit of a treatment paradigm utilizing medical cannabis to control pain in this patient population. LAY SUMMARY Pain management in patients treated with dialysis is challenging, with an unmet need for safer analgesics. The endocannabinoid system is a pharmaceutical target for pain management that could potentially improve additional pain-related symptoms; however, its safety in patients treated with dialysis has not been proven. In the current feasibility study, we conducted a randomized, double-blind, cross-over study to assess the safety of sublingual oil-based cannabis preparation for medical use in hemodialysis patients. The study was comprised of three arms: whole-plant cannabis extract, cannabinoid extraction or placebo. Fifteen patients were randomized. Most adverse events were mild to moderate and resolved spontaneously. Serious adverse event considered related to study drug included one episode of accidental overdose that led to hallucinations. Overall, we demonstrated that a supervised, carefully titrated, short-term medical cannabis use was generally tolerated and was not associated with increased safety signals. [GRAPHICS] .