Chronic non-cancer pain is estimated to affect around 20% of the global population and is associated with reduced quality of life as well as disability and considerable socioeconomic and personal burden. Chronic pain often co-occurs with morbidities such as depression, anxiety, and insomnia, adding to the burden of the condition. While opioids are the most commonly prescribed pharmaceutical for chronic pain conditions, they can be associated with unwanted side effects and significant harms in certain individuals. For this reason, many patients and clinicians are becoming increasingly interested in alternative therapies for managing their pain and improving physical functioning.
In recent years, medical cannabis has become increasingly popular among patients with chronic non-cancer pain. According to recent figures, two-thirds of medical cannabis users endorse the products for the management of chronic pain; however, clinical evidence of the safety and efficacy of medical cannabis in this setting is still underdeveloped. In 2019, the National Institute of Health and Care Excellence (NICE) published guidelines on the prescription of cannabis-based medical products (CBMPs) in the UK with strong recommendations against their use for chronic pain. The International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia found the evidence on medical cannabis’ efficacy across acute and chronic pain to be equivocal. Other sources, including a 2021 BMJ Rapid Recommendation and the European Pain Federation have since recommended the conditional use of some medical cannabis preparations. Nonetheless, the use of medical cannabis in the treatment and management of chronic pain remains a controversial issue.
A recent systematic review aimed to review the current evidence gathered by randomised controlled trials (RCTs) to explore the comparative benefits and harms of medical cannabis and opioids for chronic non-cancer pain.
Design and Methods of the Study
The researchers searched several databases from inception to March 2021 to identify eligible studies as well as relevant reviews and guidelines of identify further studies. Eligible studies were RCTs that enrolled ≥20 patients with chronic non-cancer pain (pain lasting ≥3 months), randomised them to any type of cannabis for therapeutic use, an opioid or placebo and followed them for ≥4 weeks to allow for sufficient time for functional outcomes to manifest among treatment responders. Trials including patients with chronic cancer and non-cancer pain were included if outcome data were reported separately.
Instruments used in the RCTs mostly consisted of either a Visual Analogue Scale (VAS) and a Numerical Rating Scale for pain intensity and sleep quality, and the Short Form-36 for other important patient outcomes (such as physical and social functioning). The researchers converted continuous measures to common scales on a domain-by-domain basis when other instruments were used. For studies that reported outcomes at several time points, data from the longest follow-up were used.
Results of the Study
A total of 90 studies from 89 publications (22,028 patients) were included in the final review. No trials of inhaled cannabis were eligible for the current review due to inadequate duration of follow-up (<4 weeks). Sixty-six trials compared opioids to placebo, 23 compared medical cannabis to placebo, and one trial randomised patients to nabilone (a synthetic mimic of tetrahydrocannabinol) or dihydrocodeine. Twenty-nine studies enrolled patients with neuropathic pain, 60 with non-neuropathic pain, and one trial enrolled patients with mixed pain.
Patient Outcomes: Medical Cannabis vs Opioids
Moderate certainty evidence showed that, compared with placebo, opioids provide small changes in pain, physical functioning, and sleep quality. Low to moderate certainty evidence showed similar effects for patients prescribed medical cannabis; however, neither treatment option was more effective than placebo for role, social or emotional functioning.
Low certainty evidence from 82 RCTs (19,693 patients) suggest that there may be little to no difference in changes in pain severity associated with medical cannabis and opioid treatment. Furthermore, moderate certainty evidence from 44 RCTs (12,727 patients) show there is probably little to no difference in physical functioning improvements and low certainty evidence from 32 RCTs (8,201 patients) suggest little to no difference in sleep quality when comparing medical cannabis with opioids. There were insufficient data to construct networks for health-related quality of life.
Discontinuation due to Adverse Events
Among enrichment trials (n = 22), low certainty evidence suggests that there may be little to no difference in discontinuations due to adverse events between medical cannabis and opioids. However, moderate certainty evidence shows that in non-enriched studies (n = 51), discontinuations due to adverse events are probably less for cannabis for medical use versus opioids, while moderate and high certainty evidence showed that, compared with placebo, opioids and medical cannabis, respectively, result in higher discontinuations.
The findings of the present study, which is the first network meta-analysis exploring the comparative effectiveness of medical cannabis and opioids for chronic non-cancer pain suggest that both opioids and medical cannabis have similar effects in changing pain intensity in chronic non-cancer pain (compared with placebo). The authors note that reviews of patient values and preferences show that people living with chronic pain place a high value on the possibility of achieving small but important pain relief.
Furthermore, the findings from this review indicate that fewer people are likely to discontinue medical cannabis due to adverse events compared to opioids. The authors recommend that future research “directly compare the effectiveness of opioids versus cannabis for chronic pain and follow patients sufficiently to inform long-term benefits and harms.”