Cannabis Medicine 2.0: Nanotechnology-Based Delivery Systems for Synthetic and Chemically Modified Cannabinoids for Enhanced Therapeutic Performance

Cannabinoid medicine is increasingly moving beyond conventional oils, capsules and extracts toward advanced drug-delivery technologies designed to improve how these compounds reach their targets in the body. This 2025 review examines how nanotechnology-based delivery systems may improve the solubility, stability, bioavailability and targeted delivery of synthetic and chemically modified cannabinoids.

Researchers reviewed nanoparticles, lipid-based carriers, micelles, nanoemulsions and other nanoengineered systems being developed for cannabinoid-related therapies. These technologies have been investigated in preclinical research involving conditions including neuropathic pain, depression and cancer, with some formulations producing longer-lasting or more targeted effects while reducing systemic exposure.

The authors conclude that combining cannabinoid pharmacology with nanotechnology could help create a new generation of more precise cannabinoid medicines, although most of these approaches remain in the preclinical stage and will require additional testing and regulatory development before widespread clinical use.

“The therapeutic potential of cannabinoids and other ligands of cannabinoid receptors attracts considerable attention due to their diverse pharmacological effects and utility in various medical applications. However, challenges such as low solubility, limited bioavailability, and potential side effects hinder their broad clinical use. Nanoformulation techniques offer a promising approach to address these issues and optimize the therapeutic effectiveness of cannabinoids and other cannabinoid receptor ligands.

This comprehensive review explores the advancements in nanoformulation strategies to enhance the therapeutic efficacy and safety of synthetic cannabinoids and related compounds, such as CB13, rimonabant, and HU-211, which have been studied in a range of preclinical models addressing conditions such as neuropathic pain, depression, and cancer.

The review discusses various nanocarriers employed in this field, including lipid-based, polymeric, and hybrid nanoparticles, micelles, emulsions, and other nanoengineered carriers. In addition to formulation approaches, this review provides an in-depth analysis of chemical structures and their effect on compound activity, especially in the context of the affinity for the cannabinoid type 1 receptor in the brain, which is chiefly responsible for the psychoactive effects.

The provided summary of research concerning either chemical modifications of existing cannabinoids or the creation of new compounds that interact with cannabinoid receptors, followed by the development of nanoformulations for these agents, allows for the identification of new research directions and future perspectives for Cannabis-based medicine.

In conclusion, the combination of nanotechnology and cannabinoid pharmacology holds promise for delivering more effective and safer therapeutic solutions for a broad spectrum of medical conditions, making this an exciting area of research with profound implications for the healthcare and pharmaceutical industries.”

“Nanotechnology-enabled delivery of synthetic and chemically modified cannabinoids offers a promising approach to overcome the intrinsic limitations of these compounds, positioning them as candidates for future precision therapeutics. Preclinical evidence supports their enhanced stability, bioavailability, and site-specific activity; however, translating these findings into clinical applications will require coordinated advances in innovation, manufacturing, and regulatory science. Nanoformulated cannabinoids have the potential to transform therapeutic strategies, but their clinical impact will depend on harmonized regulations, standardized testing, and robust translational research. With sustained international collaboration, these next-generation formulations may become a key component of personalized medicine in the coming decade.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC12388155/

Nanotechnology for the Efficacious Delivery of Medicinal Cannabis and Pharmaceutical Medicines

Nanotechnology is creating new possibilities for the delivery of medicinal cannabis and pharmaceutical medicines. This 2025 narrative review examines how nanoscale delivery systems may help overcome common problems such as poor solubility, inconsistent absorption, low bioavailability, gastrointestinal degradation, and first-pass metabolism.

These challenges are especially relevant to cannabinoids such as THC and CBD because they are highly lipophilic compounds. The review discusses how nanoparticle systems may improve cannabinoid stability, targeting, controlled release, selectivity, and overall delivery while exploring alternative routes including oro-buccal, nasal, ocular, and transdermal administration.

The paper directly discusses THC, CBD, dronabinol, nabilone, nabiximols, high-THC cannabis, and NanoCelle™ formulations designed to deliver THC and CBD through the oral mucosa. The authors emphasize that nanotechnology may allow cannabinoid medicines to be delivered more precisely, with improved absorption and reduced loss through first-pass metabolism.

“The application of nanoparticles as nanomedicines, particularly for the targeted and efficacious delivery of drugs is an expanding platform in the field of cannabinoid and pharmaceutical drug delivery. By refocusing the route of drug administration beyond the oral gut pathway, this technology provides significant advancements that are especially relevant for cancer treatments. Orally administered drugs face significant challenges as they traverse the gastrointestinal tract (GIT) and are subject to first-pass GIT metabolism. Physiological conditions encountered in the GIT such as food effects, hormones, gastric pH, emptying time, and intestinal transit time vary widely across individuals. Fluid composition and enzymatic activity in the small intestine and large bowel also influence drug dissolution and absorption. These factors in conjunction with the intestinal cohort of bacteria can metabolize drugs before absorption, contributing to poor and variable drug bioavailability, which can be exacerbated by gut dysbiosis. Drug delivery that bypasses the oral-GIT route and hence first-pass metabolism offers a plausible solution for enhanced safety and drug efficacy.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC12472836