Aviram J, Samuelly-Leichtag G Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain Physician. 2017 Sep;20(6):E755-E796.
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BACKGROUND: The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field.

OBJECTIVES: This study's aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians' and researchers' knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment.

STUDY DESIGN: A systematic review and meta-analysis.

METHODS: An electronic search was conducted using Medline/Pubmed and Google Scholar with the use of Medical Subject Heading (MeSH) terms on all literature published up to July 2015. A follow-up manual search was conducted and included a complete cross-check of the relevant studies. The included studies were RCTs which compared the analgesic effects of CBMs to placebo. Hedges's g scores were calculated for each of the studies. A study quality assessment was performed utilizing the Jadad scale. A meta-analysis was performed utilizing random-effects models and heterogeneity between studies was statistically computed using I² statistic and tau² test.

RESULTS: The results of 43 RCTs (a total of 2,437 patients) were included in this review, of which 24 RCTs (a total of 1,334 patients) were eligible for meta-analysis. This analysis showed limited evidence showing more pain reduction in chronic pain -0.61 (-0.78 to -0.43, P < 0.0001), especially by inhalation -0.93 (-1.51 to -0.35, P = 0.001) compared to placebo. Moreover, even though this review consisted of some RCTs that showed a clinically significant improvement with a decrease of pain scores of 2 points or more, 30% or 50% or more, the majority of the studies did not show an effect. Consequently, although the primary analysis showed that the results were favorable to CBMs over placebo, the clinical significance of these findings is uncertain. The most prominent AEs were related to the central nervous and the gastrointestinal (GI) systems.

LIMITATIONS: Publication limitation could have been present due to the inclusion of English-only published studies. Additionally, the included studies were extremely heterogeneous. Only 7 studies reported on the patients' history of prior consumption of CBMs. Furthermore, since cannabinoids are surrounded by considerable controversy in the media and society, cannabinoids have marked effects, so that inadequate blinding of the placebo could constitute an important source of limitation in these types of studies.

CONCLUSIONS: The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.Key words: Cannabis, CBMs, chronic pain, postoperative pain, review, meta-analysis.

Comments from MORE raters

Nurse rater

This review is timely given current issues with chronic pain and opiate use disorders and deaths from overdose. Medical cannabis should be considered as adjunct therapy for those patients with chronic pain from neuropathy that is refractory to usual treatment modalities.

Physician rater

The fact that the evidence is scanty will, I suspect, have little impact on those who are pro- or anti- these drugs. This will have no impact on my practice.

Physician rater

We need yet more primary well done studies con cannabinoids, but this reviews show that marihuana is not miracle.

Physician rater

The theme is definitely worth of summarizing the obtainable opinions and researches. However, the collected studies are as disproportionate as usual in this kind of topic. There are so many factors like statistical and subject heterogeneity, different cannabinoid derivatives, different treatment indications, different administration routes, differences in doses, unreliable naiveness to medication of each patient and, so on, make the trustworthiness limited. We might at most keep in mind that the majority of the collected studies did not show an effect, and only limited trials showed distinct potency.

Physician rater

The current review was very comprehensive yet could have been more concise and informative. Also, the criteria for study selection for inclusion was inconsistent: for example, the authors aimed to searched for double-blind placebo-controlled RCTs but at the end also included some RCTs that did not fulfill this criterion (so they listed a lack of masking in the limitation section).
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