Encapsulating cannabinoids in lipid nanoparticles may improve their stability, absorption and pain-relieving effects, according to a new review published in the journal Pharmaceutics.

Researchers from the Federal University of Rio Grande do Norte and the Federal University of Uberlândia in Brazil reviewed the available evidence on nanoencapsulated cannabinoids, particularly cannabidiol (CBD), for managing acute, chronic and neuropathic pain.

“This review compiled and analyzed the available evidence regarding the antinociceptive effects of nanoencapsulated cannabinoids compared to free compounds,” the researchers state.

Researchers note that cannabinoids such as CBD and THC are highly lipophilic, meaning they dissolve poorly in water. They are also vulnerable to degradation from oxygen, light, humidity and temperature. These characteristics can limit their stability, absorption and effectiveness when administered in conventional formulations.

Lipid-based nanocarriers are designed to protect cannabinoids and improve their delivery through systems such as nanoemulsions, liposomes and nanostructured lipid carriers.

“The findings indicated that cannabinoids exhibited promising analgesic effects, while nanoencapsulation could enhance its stability and bioavailability,” the researchers state.

The review highlighted four published formulations intended for human pain management, although the biological testing was conducted primarily in animals and other preclinical models.

In one study, an intrathecal CBD nanoemulsion remained stable for 70 days and produced a pronounced pain-relieving effect in rats while largely remaining concentrated in the spinal cord rather than spreading to the liver, spleen or bloodstream.

Another study examined a mucoadhesive CBD nanoparticle formulation administered through the nose. The formulation achieved nearly 100% encapsulation efficiency, improved retention in the nasal tissue and produced a stronger and longer-lasting antinociceptive effect in mice.

A separate CBD lipid nanoparticle formulation remained physically stable for one year. It showed no detectable toxicity at certain concentrations in a chicken embryo model and produced significant antinociceptive effects in fruit flies.

Researchers also reviewed a transdermal liposomal formulation containing CBD and lidocaine. The system increased skin penetration and retention, provided sustained CBD release and produced greater therapeutic activity at a CBD concentration of 0.2% than commercial formulations containing between 5% and 10%.

The authors said particle size, formulation composition and the route of administration can directly influence how cannabinoid nanocarriers affect pain.

Despite the promising findings, the review found that research remains limited and is dominated by preclinical studies. Many studies also failed to provide sufficient information about formulation structure, stability, drug-release profiles and quality-control testing.

The researchers found no published studies examining the nanoencapsulation of full-spectrum cannabis oils or whole cannabis extracts for pain management, describing this as a significant gap in the literature.

“Although the number of works that investigated nanoencapsulated cannabidiol pain management are scarce, the available evidence demonstrated important physicochemical and pharmacological advantages of these delivery systems, including enhanced stability, sustained release profile, improved bioavailability and optimized efficacy,” the authors conclude.

They said additional research, standardized testing methods and stronger regulatory frameworks are needed before cannabinoid-based nanomedicines can be widely translated into clinical treatment.

“Overall, advances in the nanoencapsulation of cannabinoids and other cannabis-derived products can significantly contribute to the development of stable, safe, effective and cost-effective pain therapies, particularly for chronic and neuropathic pain conditions,” the researchers state.