Chronic pain is experienced by 75-90% of those with advanced cancer (van den Beuken-van Everdingen, Pain, 2007; Teunissen, J Pain Symptom Manage, 2007). Opioids are the mainstay of therapy for most patients experiencing moderate to severe pain and can be quite effective if used properly (Wiffen, Chochrane Databse Syst Rev, 2017). However, up to one-third of cancer patients with chronic pain are undertreated, and even more so in minority populations (Greco, J Clin Oncol, 2014).
Uncontrolled pain not only substantially impacts patient quality of life, but may also lead to unnecessary hospital admissions and interrupted primary treatment (Gibson, Support Care Cancer, 2016). Therefore, patients with opioid-refractory pain often require the use of complementary analgesics.
There is a growing interest in cannabis and its derivatives, including THC and cannabidiol (CBD), in the management of cancer pain, likely due to the successes demonstrated in preclinical studies and early stage clinical trials. Cancer pain is multifactorial. Causes of cancer pain include, but are not limited to, direct erosion of painful structures, inflammation, and chemotherapy-induced neuropathy (Portenoy, Lancet, 2011).
In animal models, cannabinoids were shown to dampen pain pathways relevant to each of these mechanisms. For instance, cannabinoid activity through the receptor CB1 was found to suppress transmission of painful stimuli at the levels of the peripheral nervous system, spinal cord, and brain in multiple animal models and across pain paradigms (Walker, Life Sci, 1999; Baker, Lancet Neurol, 2003).
Additionally, cannabinoids are thought to control inflammatory pain via the actions of both CB1 and CB2 receptors on immune cells (Facci, PNAS, 1995; Richardson, Pain, 1998). It follows that synthetic agonists of CB1 and CB2 synergistically reduced pain signaling in a mouse model of tumor pain (Khassabova, Behav Pharmacol, 2011). Finally, in models of chemotherapy-induced peripheral neuropathy, treatment with various cannabinoids effectively prevented the development of painful neuropathy (Ward, Br J Pharmacol, 2014; Rahn, Br J Pharmacol, 2007; Khassabova, J Neurosci, 2012).
These findings have been recapitulated, at least preliminarily, in the clinical setting. Two studies demonstrated that THC, the main psychoactive component of cannabis, reduced pain significantly more than placebo and with a magnitude comparable to that of codeine (Noyes, J Clin Pharmacol, 1975; Noyes, Clin Pharmacol Ther, 1975). It should be noted that THC had a more pronounced sedative effect. Additionally, an oromucosal spray with a 1:1 combination of THC and CBD, nabiximols, significantly improved pain not adequately controlled with opiates (Johnson, J Pain Symptom Manage, 2010).
Taken together, the evidence suggests cannabinoid supplementation may be beneficial in the management of multiple types of cancer-related pain, especially in treatment-refractory cases.