In the second of a series of five articles, Oxford Cannabinoid Technologies will discuss their expertise on the use of cannabinoids in medicine
Following the first article that discussed the treatment of cancer, this second piece will focus on the use of cannabinoids to treat pain. Cannabinoids are active molecules found within the cannabis plant and include CBD and THC, two of the most notable cannabinoids currently being studied.
In the U.S. alone, the number of individuals suffering from chronic pain is close to 100m,1 with two-thirds of patients feeling that current medication does not meet their needs.2 More people suffer from chronic pain than cancer, heart disease and diabetes combined.3 Patients use cannabis to treat multiple forms of pain, with cannabis shown to address neuropathic (burning or lancinating), mechanical (dullness or aching) and inflammatory (acute or sharp) pain components or sensations.
Cannabinoid receptors are expressed in the peripheral and central nervous systems, as well as on immune cells. Pre-clinical data, in vivo animal model studies and a small number of clinical trials in acute, neuropathic, chronic and cancer pain models suggest that CB1 and CB2 receptors play an important role in pain processing and that modulation of the endocannabinoid system can alleviate pain.(4)
However, clinical trials have also shown that a thorough understanding of the interplay of various cannabinoids (e.g. THC vs. CBD)(5) and their specificity for different pain conditions, is essential to develop targeted pain medications that can help sufferers.
A growing body of research suggests that cannabis’ psychoactive ingredients may enhance the pain-killing effects of opiate drugs, allowing patients using cannabis to take lower doses of opiate medications. Research in JAMA Internal Medicine found that deaths associated with the use of opiate drugs fell in 13 states after medical cannabis laws were introduced.(6) Those states that permitted patients to consume medical cannabis saw a 24.8% drop in opiate-related overdoses over six years.
However, these findings have since been thrown into doubt following the publication of a recent paper which suggests that claims that the enactment of medical cannabis laws reduces opioid-related deaths should be met with cynicism.(7) The paper goes on to state that the association between these two factors does not hold when a more extensive data set from 2017 is analysed.
As cannabis continues to develop a foothold in the pain management market, product improvement cycles are likely to accelerate when research into individual cannabinoids becomes sufficiently advanced to allow the development of more personalised medicine. Current therapeutic options for patients living with pain are limited and consist predominantly of opioids and anti-inflammatory drugs. Over the years, it has become clear that the continued use of opioids has reached a crisis point in western economies, with many patients now dependent on these drugs. This fact, together with the large number of patients who do not react to the pain medication currently available on the market, highlights the need to develop additional methods of safer pain medication.
In drafted guidelines surrounding cannabis-based medicinal products published by NICE, the importance of collecting robust evidence regarding the long-term safety and effectiveness of medical cannabis was highlighted in order to remove barriers surrounding its prescription.(18) Rigorous, high-quality investigations into the use of cannabinoids in the treatment of pain are urgently required, as advised by The British Pain Society(19), in order for government policies surrounding the use of medical cannabis in pain treatment to be reformed and this, therefore, remains as one of Oxford Cannabinoid Technologies’ main areas of focus.
References
1 (2011) Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press. http://books.nap.edu/openbook.php?record_id=13172&page=1
2 A, Romero-Sandavol., et al. (2015) Peripherally restricted cannabinoids for the treatment of pain. Pharmacotherapy 35:917-925.
3 2017) American Academy of Pain Medicine AAPM Facts and Figures on Pain. Available from: http://www.painmed.org/patientcenter/facts_on_pain.aspx
4 Burston, JJ., et al. (2014) Endocannabinoid system and pain: an introduction. Proceedings of the Nutrition Society; Woodhams, SG., et al. (2015) The role of the endocannabinoid system in pain. Handbook of Experimental Pharmacology.
5 Alvarado-Vázquez, PA., et al. (2017) Cannabis and Cannabinoids for Chronic Pain. 5;19(11):67.
6 Bachhuber, MA., et al. (2014) Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med 174(10):1668-73.
7 Shover, C., et al. (2019). Association between medical cannabis laws and opioid overdose mortality has reversed over time. Proceedings of the National Academy of Sciences, 12624-12626.
8 Pinsger, M., et al. (2006) Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain—a randomized controlled trial. Wien Klin Wochenschr (11-12):327-35.
9 Blake, DR., et al. (2006) Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford) 1:50-2.
10 Abrams, DI., et al. (2007) Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology (7):515-21.
11 Pini, LA., et al. (2012) Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial. J Headache Pain 8:677-84.
12 Naftali, T., et al. (2013) Cannabis induces a clinical response in patients with Crohn’s disease: A prospective placebo-controlled study. Clinical Gastroenterology and Hepatology 10:1276–1280.
13 Serpell M., et al. (2014). A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. European Journal of Pain, 999-1012.
14 Yassin, M. (2018) Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study. Clin Exp Rheumatol. Jan-Feb;37 Suppl 116(1):13-20.
15 Wu, J. (2018) Cannabinoid Type 2 Receptor System Modulates Paclitaxel-Induced Microglial Dysregulation and Central Sensitization in Rats. Pain pii: S1526-5900(18)30791-0.
16 Riva, N., et al. (2018) Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 18(2):155-164.
17 De Gregorio, D., et al. (2019) Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behaviour in a model of neuropathic pain. Pain 1:136-150.
18 https://www.nice.org.uk/news/article/nice-draft-guidance-and-nhs-england-review-highlight-need-for-more-research-on-cannabis-based-medicinal-products
19 https://www.britishpainsociety.org/static/uploads/resources/files/BPS_Position_Statement_on_the_medicinal_use_of_cannabinoids_in_pain_management.pdf
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