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Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse Effects and Legal Challenges
Aleksandar Sic1, Conor George1,2, Daniela Ferrer Gonzalez1
1Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA.
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.
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