Background: The management of chronic pain is a complex challenge worldwide. Cannabisbased medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topicremains highly controversial in this field.Objectives: This study’s aim is to conduct a conclusive review and meta-analysis, whichincorporates 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 postoperativepain treatment.Study Design: A systematic review and meta-analysis.Methods: An electronic search was conducted using Medline/Pubmed and Google Scholar withthe use of Medical Subject Heading (MeSH) terms on all literature published up to July 2015. Afollow-up manual search was conducted and included a complete cross-check of the relevantstudies. 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 performedutilizing the Jadad scale. A meta-analysis was performed utilizing random-effects models andheterogeneity 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 which24 RCTs (a total of 1,334 patients) were eligible for meta-analysis. This analysis showed limitedevidence showing more pain reduction in chronic pain -0.61 (-0.78 to -0.43, P < 0.0001), especiallyby inhalation -0.93 (-1.51 to -0.35, P = 0.001) compared to placebo. Moreover, even though thisreview consisted of some RCTs that showed a clinically significant improvement with a decrease ofpain scores of 2 points or more, 30% or 50% or more, the majority of the studies did not showan effect. Consequently, although the primary analysis showed that the results were favorable toCBMs over placebo, the clinical significance of these findings is uncertain. The most prominent AEswere related to the central nervous and the gastrointestinal (GI) systems.Limitations: Publication limitation could have been present due to the inclusion of Englishonly published studies. Additionally, the included studies were extremely heterogeneous. Only7 studies reported on the patients’ history of prior consumption of CBMs. Furthermore, sincecannabinoids are surrounded by considerable controversy in the media and society, cannabinoidshave marked effects, so that inadequate blinding of the placebo could constitute an importantsource of limitation in these types of studies.Conclusions: The current systematic review suggests that CBMs might be effective for chronicpain 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 thanby inhalation