Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse Effects and Legal Challenges
Aleksandar Sič, C. George, Dani O. Gonzalez, Vasilis‐Spyridon Tseriotis, Nebojša Nick Knežević
Abstract
Cannabinoids have gained increasing attention as potential therapeutic agents in chronic pain management. Their mechanisms of action, mediated through CB1 and CB2 receptors, provide a pharmacological alternative to conventional analgesics. The evidence is strongest for neuropathic pain and multiple sclerosis-related spasticity, while the results for fibromyalgia, osteoarthritis, and musculoskeletal pain remain inconsistent. The average pain reduction is modest, often not exceeding 0.5-1.0 points on a 10-point scale, and therapeutic gains are offset by safety concerns. Quantitative data show that discontinuation rates range from 4.3% at low-dose CBD to 12.9% at high-dose CBD, compared with 3.5% on placebo, while nabiximols (THC + CBD spray) are associated with dizziness in 25% of patients, somnolence in 8%, and treatment discontinuation in 12%. High-dose CBD also carries a measurable risk of hepatotoxicity. Regulatory heterogeneity further constrains trial feasibility, scalability, and patient access, with disparities evident across the United States, Europe, Canada, and Australia. Overall, cannabinoids provide modest, condition-specific analgesia and should be considered adjunctive rather than first-line options, reserved for patients unresponsive to conventional therapy. Future progress requires standardized formulations, harmonized international regulations, long-term safety data, and large-scale randomized controlled trials to clarify their role in evidence-based pain management.