Exploring the potential benefits of combining cannabidiol and beta-caryophyllene for neuropathic and inflammatory pain: A systematic review.

Benamar K. · Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026

**Background & Methods** This systematic review examined the analgesic efficacy of combined cannabidiol (CBD) and beta-caryophyllene (BCP) across pain conditions, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Literature searches spanning 2009-2026 were conducted across PubMed, Web of Science, and Google Scholar, identifying 31 records with 5 studies meeting final inclusion criteria. **Key Findings** - The CBD and BCP combination demonstrated consistent analgesic effects in reducing both neuropathic and inflammatory pain across rodent models studied - Synergistic pain reduction was achieved without triggering adverse effects associated with cannabinoid receptor 1 (CB1) activation, suggesting a mechanistic advantage over traditional cannabinoid therapies - The combination appears to produce analgesia through alternative pathways beyond CB1-dependent mechanisms, supporting potential for chronic pain management without central cannabinoid-related side effects **Dosage & Administration** Not reported. The review does not specify doses, routes of administration, or treatment schedules used in the included studies. **Safety & Adverse Effects** The review explicitly notes that the CBD and BCP combination does not produce adverse outcomes associated with CB1 receptor activity. No other specific adverse effects or safety concerns were reported in the available literature. However, comprehensive safety data from clinical trials are not yet available. **Evidence Quality** This systematic review has significant limitations. The evidence base is restricted to preclinical studies in rodent models only, with only 5 studies meeting inclusion criteria from an initial 31 records identified. This represents a narrow, early-stage evidence base without any human clinical trials. The review itself acknowledges these findings are "preclinical" and explicitly calls for future preclinical and clinical studies, indicating the current evidence is insufficient for clinical recommendations. The mechanisms of synergistic action are discussed theoretically but require further investigation. Applicability to human pain conditions remains unestablished, and optimal dosing, long-term safety profiles, and efficacy in clinical populations await investigation.

More recent cannabis research