1. In this updated systematic review, cannabis-based products with a comparable or high tetrahydrocannabinol (THC)-to-cannabidiol (CBD) ratio may provide a small reduction in chronic pain severity.
2. However, these products are also associated with an increased risk of common adverse events, including dizziness, sedation, and nausea.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Although opioids are commonly used to treat chronic pain, they offer only modest benefit and are associated with serious harms, including opioid use disorder and overdose. Cannabinoids have been proposed as alternative treatments. This study synthesized recent evidence on cannabis-based products for chronic pain, updating a 2022 living systematic review. Products containing synthetic or purified THC alone may slightly reduce short-term pain severity compared with placebo, with stratified analyses suggesting a moderate benefit for nabilone. Evidence was insufficient to assess pain response outcomes for THC-only products. However, THC-containing products were associated with a moderate to large increase in adverse events compared with placebo. Products with a comparable THC-to-CBD ratio, particularly nabiximols, may also slightly reduce short-term pain severity but have shown little effect on pain response or physical function. Nabiximols were associated with increased risk of dizziness, sedation, and nausea. In contrast, products with a low THC-to-CBD ratio, especially oral synthetic or purified CBD-only formulations, did not meaningfully improve short-term pain severity, pain response, or function compared with placebo, although they may slightly reduce the risk of dizziness. Combined oral purified THC and synthetic CBD products showed little effect on pain or function, with imprecise estimates, and were associated with increased nausea, dizziness, and sedation. Generalizability is limited by inconsistent reporting of cannabis products, limited evidence on pain response, psychosis, cannabis use disorder, and long-term outcomes, imprecision of estimates, and heterogeneity across product categories. Overall, cannabinoid products with comparable or high THC-to-CBD ratios may provide small improvements in chronic pain, most notably with nabilone, but these benefits must be weighed against an increased risk of common adverse events.
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Relevant Reading: Cannabis-Based Products for Chronic Pain: A Systematic Review
In-Depth [systematic review]: This systematic review synthesized evidence from randomized controlled trials (RCTs) evaluating cannabis-based products for chronic pain. Searches of Ovid MEDLINE, PsycInfo, Embase, the Cochrane Library, and Scopus from inception to July 2025 identified English-language, placebo-controlled RCTs lasting at least four weeks. Primary outcomes included pain severity, pain response, physical function, and adverse events. Twenty-five RCTs were included, comprising 2,303 participants with mean ages of 24–68 years and baseline pain scores of 2.5–8.5/10. Risk of bias was low in 6 trials, moderate in 14, and high in 5. High THC-to-CBD ratio products were evaluated in 10 RCTs. Oral synthetic or purified THC products (8 RCTs, n = 507) probably slightly reduced short-term pain severity compared with placebo (0 to 10 scale mean difference [MD], −0.78; 95% confidence interval [CI], −1.59 to −0.08), though results were heterogeneous. Stratified analyses showed a moderate effect for nabilone (4 RCTs, n = 100; MD, −1.59; 95% CI, −2.49 to −0.82) and no significant effect for dronabinol (4 RCTs, n = 407; MD, −0.23; 95% CI, −0.82 to 0.54), with a statistically significant difference between agents (p = 0.027). THC products increased risk of adverse events, including withdrawals (14.0% vs. 6.5%; RR, 1.92), dizziness (33.4% vs. 14.6%; RR, 2.30), sedation (24.2% vs. 15.6%; RR, 1.57), and nausea (12.2% vs. 6.1%; RR, 2.12). Comparable THC-to-CBD ratio products (nabiximols; 7 RCTs, n = 702) probably slightly reduced short-term pain severity (MD, −0.54; 95% CI, −0.95 to −0.19) with little effect on pain response or function, but increased dizziness (31.0% vs. 8.0%; risk ratio [RR], 3.57), sedation (8.0% vs. 1.2%; RR, 5.04), and nausea (13.9% vs. 7.5%; RR, 1.79). Low THC-to-CBD ratio products, mainly CBD-only formulations, showed minimal effect on pain or function and no increase in adverse events. Overall, cannabis products with high or comparable THC-to-CBD ratios may provide small reductions in chronic pain but carry increased risk of common adverse events.
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