Cannabis use and non-cancer chronic pain – Authors' reply
Authors: Gabrielle Campbell, Wayne Hall, Louisa Degenhardt, Timothy Dobbins, Michael Farrell
Journal: The Lancet Public Health (2018)

In their letters, Iain McGregor and Alex Bekker state that previous systematic reviews have provided evidence of the effectiveness of cannabinoids for chronic non-cancer pain. However, three systematic reviews1Hauser W Petzke F Fitzcharles MA Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management—an overview of systematic reviews.Eur J Pain. 2018; 22: 455-470Crossref PubMed Scopus (92) Google Scholar, 2Mücke M Phillips T Radbruch L Petzke F Häuser W Cannabis-based medicines for chronic neuropathic pain in adults.Cochrane Database Syst Rev. 2018; 3 (CD012182.)PubMed Google Scholar, 3Stockings E Campbell G Hall WD et al.Cannabis and cannabinoids for the treatment of people with chronic non-cancer pain conditions: a systematic review and meta-analysis of controlled and observational studies.Pain. 2018; (published online May 25.)DOI:10.1097/j.pain.0000000000001293Crossref PubMed Scopus (215) Google Scholar published this year have suggested caution regarding use of cannabinoids, because of a paucity of high quality studies, and concluded that evidence for the effectiveness of cannabinoids in chronic non-cancer pain is limited by the very short duration of studies, small participant numbers, the exclusion of patients with complex comorbidities, and failure of studies to date to include common forms of chronic non-cancer pain (eg, back and neck pain, arthritis). Our observational study examined the relationship between cannabis and pain over 4 years in a large cohort of patients with pain, including those with multiple comorbidities and the most common pain conditions.4Campbell G Hall WD Peacock A et al.Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study.Lancet Public Health. 2018; 3: e341-e350Summary Full Text Full Text PDF PubMed Scopus (127) Google Scholar We also obtained participant-level data on the potential opioid-sparing effects of cannabis, rather than relying on ecological data. We presented comprehensive data by including not only pain intensity scores (often the only outcome measured in clinical trials), but also participants' reports of pain interference, perceptions of the effectiveness of cannabis, their reasons for using and stopping cannabis, and their opinions regarding the effect that cannabis had on their use of opioid medication. We clearly reported conflicting findings: cross-sectionally, pain levels and interference were higher among people who used cannabis than those who did not, and no association was found between cannabis use and pain and opioid dose prospectively, although participants perceived cannabis to be effective on their pain. We acknowledged the possibility that cannabis might affect other domains that could subsequently affect perceptions of the effect of cannabis on pain. Our study has clearly stimulated debate around these potential explanations, and we hope future work will explore these possibilities. The possibility of confounding was acknowledged, addressed, and reported in our paper. We adjusted for several confounders identified in our previous study,5Degenhardt L Lintzeris N Campbell G et al.Experience of adjunctive cannabis use for chronic non-cancer pain: findings from the Pain and Opioids IN Treatment (POINT) study.Drug Alcohol Depend. 2015; 147: 144-150Summary Full Text Full Text PDF PubMed Scopus (83) Google Scholar such as age, sex, pain duration, anxiety, history of substance use, pain severity, pain interference, oral morphine equivalent dose, and pain self-efficacy. We could not control the dose or type of cannabis that patients used, and did not obtain objective confirmation of their self-reported cannabis use. The same is true of surveys used to justify patients smoking cannabis for pain control. We discussed this in the limitations section of the paper. Finally, regarding potential competing interests, we have previously documented deaths from opioid overdose in Australia6Roxburgh A Dobbins T Degenhardt L Peacock A Opioid, amphetamine, and cocaine-induced deaths in Australia. National Drug and Alcohol Research Centre, UNSW Sydney, SydneyAugust 2018https://ndarc.med.unsw.edu.au/resource/opioid-amphetamine-and-cocaine-induced-deaths-australia-august-2018Date accessed: September 18, 2018Google Scholar and attributable to over-the-counter codeine,7Roxburgh A Hall WD Burns L et al.Trends and characteristics of accidental and intentional codeine overdose deaths in Australia.Med J Aust. 2015; 203: 299Crossref PubMed Scopus (62) Google Scholar which informed decisions to make codeine a prescription-only drug in Australia. We value our independence extremely highly and retain academic independence in all its forms. GC and LD report National Health and Medical Research Council fellowships (#1119992 and 1135991). The National Drug and Alcohol Research Centre at University of New South Wales, Australia, is supported by funding from the Australian Government, under the Substance Misuse Prevention and Service Improvements Grant Fund. Some of the authors report investigator-initiated untied educational grants from Reckitt Benckiser/Indivior for studies of buprenorphine-naloxone (LD and MF), buprenorphine depot (LD and MF), the development of an opioid-related behaviour scale (LD), and a study of opioid substitution therapy uptake among patients with chronic non-cancer pain (LD and GC). LD and MF also report an untied educational grant from Seqirus for studies of tapentadol. All are outside the submitted work. WH reports grants from Australian Therapeutic Goods Administration and personal fees as a Member of the Australian Advisory Council on Medical Uses of Cannabis, both outside the submitted work. TD declares no competing interests. Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort studyCannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain. Full-Text PDF Open AccessCannabis use and non-cancer chronic painI read with interest the Article by Gabrielle Campbell and colleagues.1 The authors should be commended on completion of this long prospective study exploring the effect of cannabis on pain outcome measures in patients who used prescribed opioids for the treatment of non-cancer pain. Although the study is thought-provoking, I have noticed a number of potential inconsistencies that require further explanation by the authors. Full-Text PDF Open AccessCannabis use and non-cancer chronic painThe Article by Gabrielle Campbell and colleagues in The Lancet Public Health (July 2018)1 has received worldwide publicity as a demonstration that cannabis is ineffective in treating non-cancer pain. With medicinal cannabis policy in rapid transition, and chronic pain a leading indication for cannabis use,2 high-quality studies are needed to better inform current debates. Unfortunately, this study1 is not one of them. 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