Long-term observational studies with cannabis-based medicines for chronic non-cancer pain- A systematic review and meta-analysis of effectiveness and safety

Abstract
Background and Objective
This systematic review evaluated the effectiveness, tolerability and safety of cannabis-based medicines (CbMs) for chronic non-cancer pain (CNCP) in long-term observational studies.

Databases and Data Treatment
CENTRAL, EMBASE and MEDLINE were searched until December 2021. We included prospective observational studies with a study duration ≥26 weeks. Pooled estimates of event rates of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model.

Results
Six studies were included with 2686 participants, with study duration ranging between 26 and 52 weeks. Pain conditions included nociceptive, nociplastic, neuropathic and mixed pain mechanisms. The certainty of evidence for every outcome was very low. The weighted mean difference of mean pain reduction was 1.75 (95% confidence interval [CI] 0.72 to 2.78) on a 0–10 scale. 20.8% (95% CI 10.2% to 34.0%) of patients reported pain relief of 50% or greater. The effect size for sleep problems was moderate and for depression and anxiety was low. Study completions was reported for 53.3% (95% CI 26.8% to 79.9%) of patients, with dropouts of 6.8% (95% CI 4.3% to 9.7%) due to adverse events. Serious adverse events occurred in 3.0% (95 CI 0.02% to 12.8%) and 0.3% (95% CI 0.1% to 0.6%) of patients died.

Conclusions
Information included in observational studies should be regarded with caution. Within the context of observational studies. CbMs had positive effects on multiple symptoms for some CNCP patients and were generally well tolerated and safe.

Significance
There is very low quality evidence for the long-term effectiveness (pain, sleep, mood, health-related quality of life), tolerability and safety of medical cannabis for chronic non-cancer pain (CNCP) according to reports of prospective observational studies. Predefined criteria of a large magnitude of effect size in these types of studies were not met. Nevertheless, long-term medical cannabis therapy can be considered in some carefully selected and monitored patients with CNCP.