Intra-Articular Autologous Conditioned Serum Alone or Combined with Oral Cannabidiol in Dogs Undergoing Tibial Plateau Leveling Osteotomy: An Exploratory Randomized Controlled Trial

Autologous conditioned serum (ACS) contains anti-inflammatory mediators, whereas cannabidiol (CBD) may have analgesic and immunomodulatory effects. This exploratory randomized trial evaluated intra-articular ACS, alone or combined with oral CBD, after tibial plateau leveling osteotomy in dogs. Twenty-seven dogs were randomized to placebo, ACS, or ACS + CBD (n = 9/group). Outcomes included C-reactive protein (CRP), peak vertical force, orthopedic assessment scores (lameness, joint mobility, pain on palpation, weight-bearing, and overall clinical condition), Canine Brief Pain Inventory, radiographic outcomes, and safety. CRP peaked on Day 1. In the linear mixed model using a heterogeneous first-order autoregressive covariance structure, treatment-group (p = 0.001) and visit (p < 0.001) effects were significant, whereas the treatment-group × visit interaction did not reach significance (p = 0.053). Exploratory comparisons showed lower CRP in ACS + CBD than placebo on Days 3 (adjusted p = 0.007) and 5 (adjusted p = 0.001), with model-dependent sensitivity findings. No consistent treatment-group differences were identified in clinical or structural outcomes. One ACS-treated dog developed a surgical site infection, and alkaline phosphatase activity was higher in ACS + CBD on Day 28. The CRP findings remain hypothesis-generating, with uncertain clinical relevance.