Current Challenges and Opportunities for Improved Cannabidiol Solubility

Abstract

Cannabidiol (CBD), derived from the cannabis plant, has gained significant attention due to its potential therapeutic benefits. However, one of the challenges associated with CBD administration is its low bioavailability, which refers to the fraction of an administered dose that reaches systemic circulation. This limitation necessitates the exploration of various approaches to enhance the bioavailability of CBD, thus helping to maximize its therapeutic potential. A variety of approaches are now emerging, including nanoemulsion-based systems, lipid-based formulations, prodrugs, nanocarriers, and alternative routes of administration, which hold promise for improving the bioavailability of CBD and pave the way for novel formulations that maximize the therapeutic potential of CBD in various medical conditions. This opinion piece presents the current understanding surrounding CBD bioavailability and considers strategies aimed at improving both its absorption and its bioavailability.

Modulation of Oxidative Stress and Neuroinflammation by Cannabidiol (CBD): Promising Targets for the Treatment of Alzheimer’s Disease

“…Although preclinical studies support CBD's promise as a potential treatment for AD, there are several limitations and areas for future research to address. First, despite encouraging results from preclinical studies, to date, no human randomized control trials (RCTs) have investigated the efficacy and safety of CBD in treating AD [2,11,26,[156][157][158][159][160][161][162][163][164][165][166][167][168]. Second, the optimal dosage, administration route, formulation, and treatment duration of CBD for achieving effective management of AD is unclear, and determining this remains challenging [38,[158][159][160]162,164,165,[169][170][171].…”

“…First, despite encouraging results from preclinical studies, to date, no human randomized control trials (RCTs) have investigated the efficacy and safety of CBD in treating AD [2,11,26,[156][157][158][159][160][161][162][163][164][165][166][167][168]. Second, the optimal dosage, administration route, formulation, and treatment duration of CBD for achieving effective management of AD is unclear, and determining this remains challenging [38,[158][159][160]162,164,165,[169][170][171]. Individual variability in responses to CBD and factors like age, sex, and genetic predisposition complicate establishing optimal treatment protocols [2,159,166].…”

“…Additionally, there are legal and regulatory restrictions that exist in some countries, creating barriers to CBD research and access [156,157,[159][160][161]163]. Lastly, CBD is a relatively recent topic of investigation in the context of AD, and our understanding of its mechanisms of action, therapeutic potential, long-term effects, and drug-drug interactions is still evolving [2,11,26,[156][157][158][159][160][161][162][163][164][165][166][167][168]171].…”

Cannabidiol-Loaded Solid Lipid Nanoparticles Ameliorate the Inhibition of Proinflammatory Cytokines and Free Radicals in an In Vitro Inflammation-Induced Cell Model

“…We have optimized the encapsulation efficiency (EE) and drug loading (DL) parameters of our SLNs through meticulous formulation strategies to address these challenges. Our approach involves a comprehensive analysis to enhance CBD's bioavailability and minimize degradation, resulting in an efficient delivery system that maximizes its therapeutic benefits [31,33]. By leveraging CBD's pharmacological advantages, we aim to extend its applicability in treating chronic conditions, underscoring the importance of advanced drug delivery systems in overcoming the pharmacokinetic limitations associated with hydrophobic compounds.…”

Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo

“…One challenge has concerned its hydrophobic nature, with poor water solubility posing difficulties in formulating CBD into aqueous solutions, limiting its options for oral delivery. 12 , 13 Another disadvantage has been the low oral bioavailability of CBD. CBD undergoes extensive first-pass metabolism in the liver when taken orally, significantly reducing its bioavailability.…”