Enhancing Cannabinoid Bioavailability in Pain Management: The Role of Cyclodextrins

Chronic pain (CP), including pain related to cancer, affects approximately 2 billion people worldwide, significantly diminishing quality of life and imposing socio-economic burdens. Current treatments often provide limited relief and may cause adverse effects, demanding more effective alternatives. Natural compounds from Cannabis sativa L., particularly cannabinoids like THC and CBD, exhibit analgesic and anti-inflammatory properties, but their therapeutic use is restricted by poor solubility and low bioavailability. Cyclodextrins (CDs) and cyclic oligosaccharides may encapsulate hydrophobic drugs in order to enhance their solubility and stability, offering a promising solution to these challenges. This study explores the formation of CD inclusion complexes with cannabinoids and specific terpenes, such as D-limonene (LIM), beta-caryophyllene (BCP), and gamma-terpinene (γ-TPN), aiming to improve pharmacokinetic profiles and therapeutic efficacy. We discuss analytical techniques for characterizing these complexes and their mechanisms of action, highlighting the potential of CDs to optimize drug formulations. The integration of CDs in cannabinoid therapies may enhance patient compliance and treatment outcomes in CP management. Future research should focus on innovative formulations and delivery systems to maximize the clinical applications of those compounds.