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 noncancer 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.

The Utility of Cannabis-Based Medicine in Chronic Pain Management: A Case Report

“…Although these results support the efficacy and safety of medical cannabis therapy as an alternative to opioid management, more studies are needed to determine the appropriate dosage, timing, and method of administration. Recent systematic reviews investigating the safety and efficacy of medical cannabinoid therapy for chronic pain have found that the certainty of evidence is low [ 17 , 18 ]. Of these reviews, one study stated that 20.8% of the patients reported a reduction in half or more of their pain and 3% of patients reported serious adverse events [ 17 ].…”

“…Recent systematic reviews investigating the safety and efficacy of medical cannabinoid therapy for chronic pain have found that the certainty of evidence is low [ 17 , 18 ]. Of these reviews, one study stated that 20.8% of the patients reported a reduction in half or more of their pain and 3% of patients reported serious adverse events [ 17 ]. In the study, serious adverse events were defined as an event leading to hospitalization or death [ 17 ].…”

“…Of these reviews, one study stated that 20.8% of the patients reported a reduction in half or more of their pain and 3% of patients reported serious adverse events [ 17 ]. In the study, serious adverse events were defined as an event leading to hospitalization or death [ 17 ]. The other review found that chronic cannabinoid use, occurring for 24 weeks or longer, was associated with a higher rate of adverse events, which were defined as including nausea, vomiting, headache, drowsiness, and dizziness [ 18 ].…”

Systematic Review and Meta-analysis Seem to Indicate that Cannabinoids for Chronic Primary Pain Treatment Have Limited Benefit

“…However, the analgesic effect was small and with limited clinical significance, while the efficacy in pain reduction was similar between patients affected by neuropathic or non-neuropathic chronic pain. Moreover, the evidence was in general moderate to low, and meta-analyses included both CPP and chronic secondary pain, without differentiating these different conditions, with the majority of included studies having enrolled patients with the latter condition [11][12][13][14][15][16][17][18]. Also, other systematic reviews evaluated and included studies without comparators [17,19], which may limit the possibility to evaluate the presence of the placebo effect and thus estimate the real efficacy or effectiveness of cannabinoids.…”

“…Moreover, the evidence was in general moderate to low, and meta-analyses included both CPP and chronic secondary pain, without differentiating these different conditions, with the majority of included studies having enrolled patients with the latter condition [11][12][13][14][15][16][17][18]. Also, other systematic reviews evaluated and included studies without comparators [17,19], which may limit the possibility to evaluate the presence of the placebo effect and thus estimate the real efficacy or effectiveness of cannabinoids. Albeit limited by some clinical and methodological constraints, recent studies and systematic reviews on fibromyalgia suggested that cannabinoids might be useful and safe in the treatment of CPP [20][21][22].…”