Novel cannabis delivery mechanisms may provide improved efficacy for the standard routes of administration (e.g., oral / gastrointestinal, inhaled, sublingual, oral mucosa). Relief from chronic pain has been a common condition cited by patients for the medical use of cannabis. As such the use of the cannab is plant for ameliorating symptoms such as pain as a historical use over thousands of years across multiple geographical areas. Recently, clinical studies have shown moderate evidence of a therapeutic benefit for pain, although preclinical studies have suggested a narrow therapeutic window for cannabinoids. With an increasing number of patients turning to formulations with cannabinoids to manage symptoms of pain, further research is needed to better understand and improve the delivery of medicinal cannabis. A critical aspect to the therapeutic use of cannabinoids is developing a mode of delivery that provides pharmacokinetics that bestow safe and effective concentrations in humans. Especially, the development of a novel delivery systems to improve the rate of absorption from oral / gastrointestinal administration to enhance the therapeutic potential of a pharmaceutical grade cannabis pain medicine. A water soluble oro-buccal spray formulated as a racemic 1:1 mixture of a delta–9–tetrahydrocannabinol (D–9–THC) and cannabidiol (CBD) from whole plant extracts (i.e., from Cannabis sativa L. and Cannabis indica L.) would be presented, within an overall narrative review of the clinical literature. [1-3]