A systematic review of clinical trials for chronic primary pain found no breakthrough drugs in a decade, but CBD and esketamine are the only compounds tested across fibromyalgia, CRPS, and chronic low back pain, with cannabinoid mechanisms among the most promising targets.
pain medicine specialists, rheumatologists, pharmaceutical researchers, chronic pain patients
What the researchers found
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.
Why it matters
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 numbers in context
10-year review period (2014-2024). Three CPP conditions: fibromyalgia, CRPS, chronic low back pain. Only CBD and esketamine tested across all three. Most promising targets: cannabinoid, glutamate, GABAergic, neuroinflammatory, immune mechanisms.
How the study worked
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.
What this study cannot tell us
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.
How to read the evidence
Comprehensive systematic review of registered clinical trials, but the evidence base for individual treatments remains limited by trial heterogeneity and lack of breakthrough results.
When this study was published
2025 publication reviewing 2014-2024 trials.
The bigger picture
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.
Questions still open
- Why has drug development for chronic primary pain failed so consistently?
- Could combination cannabinoid therapies succeed where monotherapies have not?
Common questions
Can CBD help with chronic pain?
Why is chronic pain so hard to treat?
Read the original research
Novel approaches for drug development against chronic primary pain: A systematic review.
British journal of pharmacology
Citation
Tékus, Valéria; Borbély, Éva; Goebel, Andreas; Baron, Ralf; Hajna, Zsófia; Helyes, Zsuzsanna. (2025). Novel approaches for drug development against chronic primary pain: A systematic review.. British journal of pharmacology. https://doi.org/10.1111/bph.70228
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