Cannabidiol (CBD) for Pain: A Narrative Review of Evidence to Date.

Raffa R.; Pergolizzi J.; Breve F.; Vortsman E.; Varrassi G.; El-Tallawy S. · Cureus · 2026

**Background & Methods** This narrative review synthesized published evidence from PubMed/MEDLINE, PubMed Central, Cochrane Library, and ScienceDirect databases, integrating findings from systematic reviews, meta-analyses, randomized controlled trials, and pharmacology reviews examining cannabidiol (CBD) as a monotherapy for pain conditions of any etiology. The review integrated preclinical mechanistic data, human pharmacokinetic studies, and clinical trial evidence to evaluate efficacy and safety across major pain syndromes. **Key Findings** • Preclinical and mechanistic data support plausible analgesic pathways for CBD, including receptor modulation, indirect enhancement of endocannabinoid tone via fatty-acid-binding-protein (FABP) inhibition, and anti-inflammatory effects; however, translation to clinical benefit has been inconsistent. • The largest meta-analysis of cannabinoids for pain demonstrated that while cannabinoids reduced chronic pain and improved sleep quality, effect sizes fell below predefined minimally important clinical differences, with no benefit observed for acute or cancer pain and increased non-serious adverse events. • Randomized controlled trials in knee osteoarthritis, fibromyalgia, and acute low back pain consistently failed to separate CBD from placebo, whereas smaller/lower-quality trials and observational surveys reported subjective benefit. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Safety data increasingly point to dose-dependent hepatotoxicity risk. Non-serious adverse events were increased in cannabinoid trials. Safety monitoring, particularly of liver enzyme assessment at higher doses, is warranted. **Evidence Quality** This narrative review is limited by reliance on heterogeneous study designs with variable quality. The highest-quality evidence derives from large meta-analyses and randomized controlled trials, which consistently demonstrated failure of CBD to separate from placebo in well-controlled studies. The discrepancy between positive findings in smaller/lower-quality trials and observational surveys versus negative results in rigorous RCTs suggests potential bias and placebo effects in lower-quality evidence. Despite strong biological plausibility and considerable consumer use, the authors conclude that current high-quality evidence does not support CBD monotherapy as an effective analgesic across most pain conditions studied to date. Notably, CBD remains unapproved by regulatory authorities as an analgesic, underscoring the evidence-practice gap.

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