Cannabis hyperalgesia

This Invited Commentary accompanies the following original article: Jamal N, Korman J, Musing M, et al. Effects of pre-operative recreational smoked cannabis use on opioid consumption following inflammatory bowel disease surgery. A historical cohort study. Eur J Anaesthesiol 2019; 36:705–715. Patient's pre-operative characteristics including severe pre-operative pain (at the surgery site or elsewhere) and its treatment may strongly influence postoperative recovery. In relation to the ‘opioid crisis’, pre-operative opioid intake in particular has been studied, and is implicated in poor early and late postoperative outcomes after various surgical procedures, particularly orthopaedic surgery.1,2 Cannabis sativa has been used for both recreational and medical purposes for almost 12 000 years.3 The actual use of cannabis (marijuana) and cannabinoids is increasing in the developed countries due to societal acceptance and a more relaxed legal attitude. For example, the self-reported prevalence of cannabis consumption in the Canadian population has increased from 5.6% in 1985 to 12.3% in 2015.4 A trend which deserves to be questioned in the European and US populations. A recent prospective population survey underlines that patients generally believe that marijuana and cannabinoid compounds could be somewhat effective for pain management,5 a belief which mostly relies on the ability of cannabis to modulate the negative affect of pain. However, the impact of pre-operative cannabis consumption on postoperative outcomes has not raised much interest among healthcare providers until recently. In the current issue of the European Journal of Anaesthesiology, Jamal et al.6 report some observations made by their postoperative pain service regarding the effects of recreational cannabis smoking (prevalence, 11.9%) on the first 24-h postoperative pain management after abdominal surgery. Cannabis users required a higher dose of postoperative morphine, more or less extrapolated to a 23% increased dose requirement in a model taking into account variables like age, pre-operative morphine use and other comorbidities. The authors conclude that peri-operative cannabis use may complicate postoperative pain management and that the topic deserves further research.6 Significantly, the aforementioned findings go along with those of a recent study4 assessing the impact of pre-operative cannabinoid use (for both recreational or medical indications) on the first 36-h recovery after major orthopaedic surgery. In this large retrospective study including 3793 patients, the authors performed propensity score matching to reduce the risk of bias due to nonrandom assignment of exposure. Here, patient-reported postoperative outcomes of 155 cannabinoid users (prevalence, 4.1%) were compared with those of 155 nonusers. Pre-operative cannabinoid users had higher pain scores at rest and on movement but did not consume more postoperative opioid analgesics. The cannabinoid users also reported a higher incidence of postoperative sleep impairment. Again, the conclusion was that cannabis and cannabinoid intake complicates postoperative pain management.4 Cannabinoid and opioid receptors colocalise in sites of the central nervous system involved in pain processing. In addition to the modulation of nociceptive transmission, the endocannabinoid system regulates various physiological functions such as motor function, thermoregulation, memory, motivation and emotion.3 The cloning of the genes encoding the cannabinoid-1 receptors in 1990 and cannabinoid-2 receptors in 1993 has made it possible to exploit the nonpsychotropic therapeutic properties of the cannabinoids. Indeed, the psychotropic effects and dependence were mainly attributed to the cannabinoid-1 receptor while the modulation of the immune system, inflammation and nociceptive transmission may be associated with cannabinoid-2 receptor activation. As current pain treatment still remains far from optimal, we need drugs with alternative mechanisms of action. Thereby, the analgesic efficacy of cannabinoids has been assessed both in chronic pain conditions (specifically associated with spasticity)7 and in acute pain situations.8 However, in contrast to experimental studies, results of clinical trials have been disappointing showing only moderate-quality evidence for the relief of chronic pain,7 and analgesic effects not superior to placebo in acute pain.8 According to the observations made in the aforementioned studies of Jamal et al.6 and Liu et al.4 pre-operative and peri-operative cannabis use may also impair early postoperative recovery, increasing perceived pain and decreasing sleep quality. Both studies are retrospective and suffer limitations. Moreover, Jamal et al.,6 although only considering recreational cannabis use, have tried to quantify patients’ intake. Liu et al.4 have considered both recreational and medical cannabis use but did not measure the level of exposure, and the latter affects the patients’ physiology as discussed in a recent comprehensive review.9 In addition to common adverse effects like dry mouth, anxiety, dizziness and paranoia, chronic cannabis exposure may also cause severe cardiovascular complications (e.g. arrhythmia, stroke, coronary spasm), bronchial hyper-reactivity, as well as recurrent abdominal pain and paradoxical hyperemetic effects.9 Increased pain, despite higher opioid consumption and sleep disturbances argue for a state of withdrawal and perhaps hyperalgesia4 which deserve further studies. Finally, the impact of cannabis use on delayed outcomes should not be neglected. Although nothing is known about a potential effect on persistent postsurgical pain, cannabis use is associated with a greater incidence of opioid misuse9 that should not be neglected in the context of the ‘opioid crisis’, and with a higher risk of infection as reported after knee arthroplasty.10 In conclusion, some very recent clinical reports invite us to consider the growing impact of cannabis and cannabinoid use on patients’ peri-operative anaesthetic and analgesic management. Until now, this addiction phenomenon has often been minimised by users, who may be reluctant to report it, and by healthcare providers. Prospective studies including adequate pre-operative screening regarding the level of exposure should be correlated with early and late outcomes. Acknowledgements relating to this article Assistance with the commentary: none. Financial support and sponsorship: none. Conflicts of interest: none. Comment from the Editor: this article was checked and accepted by the editors, but was not sent for external peer-review. PL is an Associate Editor of the European Journal of Anaesthesiology.

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