Thirty-nine patients undergoing total knee arthroplasty were randomized to receive either a CBD-dominant oral cannabis formulation (n≈20) or placebo (n≈19) alongside standard care, beginning 4 weeks preoperatively and continuing for up to 12 weeks postoperatively. The primary outcome was feasibility of trial conduct. Secondary exploratory outcomes included persistent post-surgical pain (PPSP), opioid use, pain interference, physical and emotional function, return to activity, sleep quality, and adverse events. Outcomes were assessed up to 6 months postoperatively. Overall, the results of the study revealed moderate feasibility, with successful enrollment and drug administration at two sites but notable issues with adherence and adverse events. About one-third of participants reported PPSP at 3 and 6 months. These findings suggest further trials are possible but must address regulatory, tolerability, and adherence barriers.