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.

Cannabinoid Receptor Type 1 and Its Role as an Analgesic: An Opioid Alternative?

“…Central nervous system action of cannabinoids has been clearly demonstrated and is historically established. Cannabis has been used throughout history and across various cultures to treat numerous ailments, including pain states (Hudson & Puvanenthirarajah, 2018). CB1 receptors are ubiquitously expressed within the CNS, with the highest aggregates in higher order brain structures like the hippocampus and cerebral cortex, as well as in the periaqueductal gray (PAG) and rostral ventral medulla (RVM) of the brainstem (Seltzman et al, 2016).…”

“…Cannabis has been used medicinally for millennia to treat numerous illnesses, including pain conditions (Hudson & Puvanenthirarajah, 2018). Its analgesic effects have been demonstrated empirically in animal models and human subjects alike (Skaper & Di Marzo, 2012).…”

Medical cannabis for orthopaedic patients with chronic musculoskeletal pain: does evidence support its use?

“…CBD, the second most prevalent cannabinoid in most strains of cannabis (with typical concentrations of < 1%), has effects counter to those of THC, with less psychoactive potential and more calming and anti-inflammatory effects. 22 The interaction between THC and CBD is complex, and there may be benefits to using them in combination as CBD may temper the undesired psychotropic side-effects associated with THC. 22,23 Other cannabinoids are present in the plant with lesser amounts (0.5%) and pre-clinical research suggest that they may have their own independent effects.…”

“…22 The interaction between THC and CBD is complex, and there may be benefits to using them in combination as CBD may temper the undesired psychotropic side-effects associated with THC. 22,23 Other cannabinoids are present in the plant with lesser amounts (0.5%) and pre-clinical research suggest that they may have their own independent effects. In vitro and in vivo mouse studies have indicated that cannabinol (CBN) may been associated with prolonged sleep, 24 and that non-psychoactive cannabigerol (CBG) and tetrahydrocannabinolic acid (THCA) may protect against neurodegeneration.…”

Cannabinoid effects on responses to quantitative sensory testing among individuals with and without clinical pain: a systematic review

“…Despite its extensive history as a folk treatment for numerous health conditions [28], controlled clinical studies on the efficacy of cannabis have only recently begun to accumulate. The past half-century has witnessed several notable achievements in the science of cannabis, including the extraction and identification of delta-9-tetrahydrocannabinol (THC) as the primary psychoactive constituent of the cannabis plant [20] and the identification of an endocannabinoid system in the mammalian brain [26,51,71].…”