Cannabis for pain management: Pariah or panacea?

Abstract

Cannabis has been used in a medicinal context throughout recorded history and across diverse cultures to aid in the treatment of a wide array of ailments. Remarkably, clinical and preclinical investigations are only recently beginning to reveal the neurobiological mechanisms responsible for the clinically-relevant actions of cannabis that have been acknowledged by medical pharmacopeia for millennia. The therapeutic potential of cannabis-derived phytochemicals such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are currently being explored in several contexts. Experimental evidence suggests that modulation of signal transduction pathways underlying cellular excitability, as well as interactions with the endocannabinoid and serotonin systems, which modulate emotion and pain sensitivity under physiological conditions, are among the mechanisms responsible for its clinical efficacy. Interestingly, the diverse pharmacodynamic profile of CBD suggests a synergistic interaction with current first- and second-line medications used in the treatment of neuropathic pain to produce clinically meaningful therapeutic benefits. To advance understanding of the neurobiological mechanisms underlying therapeutic cannabis use in pain management and to integrate its use into modern clinical practices, it is important to understand medicinal cannabis use in historic and medical contexts. This review highlights the copious history of medical practices incorporating the use of cannabis, and discusses the potential pharmacological mechanisms responsible for its therapeutic efficacy in the management of neuropathic pain.