The recent federal approval of hemp agriculture and its vast array of non-tetrahydrocannabinol cannabinoids has opened up new and exciting possibilities regarding clinical research using these cannabinoids across a variety of disorders. Most intriguing is the use of cannabidiol (CBD) as an anti-proliferative agent in canine cancer, considering limited study in human in-vitro systems suggests a mixed mechanism for dampening cancer cell proliferation at physiological and supra-physiological concentrations. We have recently examined the cytotoxic effects of CBD in canine cell culture showing strong anti-proliferative properties in the 1-3 μg/ml range and apoptosis within 8 hrs of treatment using modestly higher doses. This anti-proliferative effect translates into approximately 3-10 μM which is close to what can be achieved in the bloodstream based on a recent study examining CBD absorption in dogs. These rapid cytotoxic effects suggest alteration in cell signaling events and/or rapid mitochondrial permeability effects that should be explored due to the potential for CBD to alter AKT and MAP kinase signaling, which are current chemotherapeutic targets (rapamycin, c-kit inhibitors) and may possibly alter chemotherapeutic choices. More importantly, it is entirely possible that the anti-oxidant properties of CBD may hinder some chemotherapeutic effects which can be interrogated in cell culture systems prior to clinical use, in hopes of providing the necessary knowledge regarding appropriate doses, timing of administration and safe use of CBD pharmaceuticals or nutraceuticals in oncology patients.