Phytochemical Modulators of Nociception: A Review of Cannabis Terpenes in Chronic Pain Syndromes

Cannabis sativa L. is a phytochemically rich plant with therapeutic potential across various clinical domains, including pain, inflammation, and neurological disorders. Among its constituents, terpenes are gaining recognition for their capacity to modulate the pathophysiological processes underlying chronic pain syndromes. Traditionally valued for their aromatic qualities, terpenes such as myrcene, β-caryophyllene (BCP), limonene, pinene, linalool, and humulene have demonstrated a broad spectrum of biological activities. Beyond their observable analgesic, anti-inflammatory, and anxiolytic outcomes, these compounds exert their actions through distinct molecular mechanisms. These include the activation of cannabinoid receptor type 2 (CB₂), the modulation of transient receptor potential (TRP) and adenosine receptors, and the inhibition of pro-inflammatory signalling pathways such as Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Cyclooxygenase-2 (COX-2). This narrative review synthesizes the current preclinical and emerging clinical data on terpene-mediated analgesia, highlighting both monoterpenes and sesquiterpenes, and discusses their potential for synergistic interaction with cannabinoids, the so-called entourage effect. Although preclinical findings are promising, clinical translation is limited by methodological variability, the lack of standardized formulations, and insufficient pharmacokinetic characterization. Further human studies are essential to clarify their therapeutic potential.