Information on the use of cannabinoids for chronic pain comes from trials, systematic reviews (SR), meta-analyses (MA) and organisational reports. The outcomes vary, and are limited by factors including study design, moderate to high risk of bias (Hauser et al. 2018a), limited participants (most recent SR/MA (Stockings et al. 2018a) identified 104 studies, 21 with > 100 participants), short duration of exposure to the cannabinoid (median eight weeks (Stockings et al. 2018a)) and varying definitions of “chronic pain”. Many studies within these systematic reviews are notable for high withdrawal rates in the treatment arms (Stockings et al. 2018a; Mucke et al. 2018).

The most recent SR concluded that the number needed to harm (NNTH) for cannabinoid use in chronic pain was 6 (opioids NNTH = 5) (Stockings et al. 2018a) with a number needed to treat (NNT) of 24 (30% reduction in pain). This compares unfavourably with opioids (NNT 4.3), pregabalin (7.7) and tricyclics (NNT 3.6) (Stockings et al. 2018a). When the pain intensity reduction (versus placebo) was pooled, it was equivalent to a 3 mm reduction on a 100 mm visual analogue scale. Taken with a higher risk of an adverse event and trial withdrawal (Stockings et al. 2018a), the authors suggested that whilst there was moderate evidence for pain reduction with cannabinoids compared with placebo (higher quality evidence for MS and neuropathic related pain), it seemed unlikely that cannabinoids are highly effective for chronic non-cancer pain.

Other SR/MAs make varying comments on the strength of the evidence, including weak recommendations (Meng et al. 2017), low strength (Rodríguez-Muñoz et al. 2016), moderate (Therapeutic Goods Administration 2017; Mucke et al. 2018; Whiting et al. 2015) (30% reduction pain relief), moderate to high (Aviram and Samuelly-Leichtag 2017), strong or “conclusive” (Abrams 2018) evidence for the use of cannabinoids in chronic pain. Others suggest a moderate to high risk of bias, concluding the evidence base is insufficient to make well found conclusions about the use of CBMs for cancer and non-cancer pain (Hauser et al. 2018b). Additionally, a large observational cohort study in Australia disputed cannabis use as an adjunct to reduce opiate consumption (Sánchez-Blázquez et al. 2014).

Globally, regulatory bodies have come to different conclusions. The Health Products Regulatory Authority (HPRA) of Ireland does not support CBMs as a treatment in chronic pain (Health Products Regualtory Authority 2017). The European Pain Federations recent position paper recommended CBMs be considered for chronic neuropathic pain, but as a third line agent, and stated there was insufficient evidence for CBMs for non-neuropathic chronic non-cancer pain (Hauser et al. 2018a). This is in direct contrast to the National Academies of Science Engineering and Medicine (NASEM) review on the health effects of cannabis and cannabinoids (National Academies of Sciences Engineering and Medicine 2017) which concluded that there was conclusive or substantial evidence for the use cannabis or cannabinoids for the treatment of pain in adults.

In summary, CBMs have a higher NNT than opioids, pregabalin or TCA, with a clinically insignificant pooled pain reduction of 3 mm on 100 mm VAS, and are thus unlikely to be effective in chronic, non-cancer pain, non-neuropathic pain. Additionally, other problems include study design and high withdrawal rates in intervention arms, with Cannabinoids demonstrating a higher risk of adverse events.