Systematic Review: CBD and Ketamine Are the Only Drugs Tested Across All Three Major Chronic Pain Conditions

Among novel drug development approaches for fibromyalgia, CRPS, and chronic low back pain (2014-2024), only CBD and esketamine have been tested across all three conditions. The most promising therapeutic targets include cannabinoid, glutamate, GABAergic, neuroinflammatory, and immune mechanisms. No breakthrough pharmacotherapy has been achieved for any of these conditions.

Systematic review of Phase 1-3 clinical trials from clinicaltrials.gov, clinicaltrialsregister.eu, and PubMed (January 2014-July 2024) for fibromyalgia, CRPS, and chronic low back pain. Assessed both novel drug development and repurposing approaches.

Chronic primary pain affects millions worldwide and remains an unmet medical need. The fact that cannabinoid mechanisms are identified among the most promising targets — and CBD is one of only two drugs tested across all major CPP conditions — positions cannabinoid research as central to future pain treatment.

The lack of breakthrough treatments after a decade of clinical trials underscores how challenging chronic primary pain is. The convergence of evidence on cannabinoid mechanisms across multiple pain conditions supports continued investment in cannabinoid-based therapies.

Registered trials may not represent completed or published results. Heterogeneous patient populations complicate cross-condition comparisons. Many trials are industry-sponsored with potential bias. Review captures registrations but not all outcomes.