THC Nanoemulsion Mouth Spray Shows Promise for Chronic Pain

Medical cannabis has become an important treatment option for many people living with chronic pain, but delivering cannabinoids consistently remains a major pharmaceutical challenge. While THC has demonstrated therapeutic potential, traditional cannabis oils dissolve poorly in water, produce inconsistent absorption after swallowing, and lose a significant portion of the dose through the first-pass metabolism. Conventional alcohol-based mouth sprays can bypass some of these issues, but their high ethanol content may irritate the lining of the mouth and limit long-term comfort for some patients.

Emerging research published in the European Journal of Pharmaceutics and Biopharmaceutics suggests that nanotechnology could offer a more practical solution. Researchers developed a THC nanoemulsion spray designed specifically for buccal (inside the cheek) delivery, creating a formulation that improved THC solubility, adhered to the oral mucosa, and demonstrated encouraging early results in patients with treatment-resistant chronic pain. Let’s dive into the study and what it could mean for patients with chronic pain.

Why THC Delivery Has Been Difficult

THC presents several formulation challenges that complicate medical use. Because it is highly lipophilic, meaning it dissolves poorly in water, it is difficult to formulate products that deliver predictable doses. Traditional cannabis oils often produce delayed and inconsistent absorption that varies considerably between patients depending on food intake, digestion, and individual metabolism. Even after absorption through the digestive tract, much of the THC undergoes first-pass metabolism in the liver before reaching systemic circulation. This process can reduce bioavailability while also contributing to delayed onset and variable therapeutic effects.

Buccal delivery, where the product is absorbed through the cheek, offers an attractive alternative because medication absorbed through the lining of the cheek can enter the bloodstream directly, bypassing much of the liver’s first-pass metabolism. Existing cannabis mouth sprays have demonstrated this concept, but many rely on high concentrations of ethanol that can cause burning or irritation with repeated use.

How a Nanoemulsion Improves Buccal Delivery

To address these limitations, researchers formulated a nanoemulsion containing a Cannabis sativa extract derived from Bedrocan®. Instead of suspending THC in larger oil droplets, the formulation disperses the cannabinoid into nanoscale droplets measuring approximately 72.84 nanometers in diameter.

These extremely small droplets increase the surface area available for absorption while remaining evenly dispersed throughout the formulation. Laboratory testing showed that the nanoemulsion maintained a narrow droplet size distribution, contained THC concentrations consistent with the intended formulation, and remained physically stable for at least 90 days when refrigerated. The formulation was also designed using pharmaceutically acceptable ingredients with properties intended to support buccal administration.

Better Contact with the Oral Mucosa

One of the most important characteristics of the formulation was its ability to adhere to the buccal mucosa. Good mucoadhesion allows the spray to remain in contact with the cheek lining longer, increasing the opportunity for THC to permeate through the tissue before being washed away by saliva.

Together, these findings suggest that converting THC into a nanoemulsion may improve both solubility and controlled delivery across the oral mucosa.

Early Clinical Results in Chronic Pain Patients

Once the nanoemulsion spray was formulated, the researchers conducted an observational clinical study involving 18 patients with refractory chronic pain whose symptoms had not responded adequately to standard treatments.

• Significant Pain Reduction: Average self-reported patient pain scores dropped significantly from 8.6 to 5.4 out of 10 over a median follow-up of 189 days.
• High Response Rate: A notable 83% of chronic pain participants achieved a clinically meaningful pain reduction of 20% or greater.
• Substantial Benefit for Responders: Among the patients who responded well to the treatment, the average pain severity scores decreased by 45%.
• Strong Long-Term Adherence: Treatment persistence remained high, with 64% of responding patients choosing to stay on the therapy after six months.
• Manageable Safety Profile: Side effects were generally mild-to-moderate and temporary (most commonly dry mouth and dizziness), completely resolving shortly after treatment suspension.

As with many cannabinoid therapies, side effects occurred but were generally manageable. Researchers reported 17 adverse events among 11 patients, with most classified as mild to moderate and temporary. Three participants discontinued treatment because of adverse events, three others stopped because they experienced insufficient benefit, and two discontinued for logistical reasons unrelated to the medication itself.

What the Findings Mean

The study highlights how advances in pharmaceutical formulation may improve cannabinoid therapies without changing the active ingredient itself. By engineering THC into nanoscale droplets that spread across and adhere to the buccal mucosa, researchers were able to improve laboratory measures of solubility, tissue permeation, and controlled release while also observing meaningful reductions in pain in an early patient study.

Importantly, the clinical portion of the research was observational rather than a randomized, placebo-controlled trial. The study included only 18 participants and did not compare the nanoemulsion directly against existing cannabis formulations or standard therapies. Because of these limitations, the improvements observed cannot yet be attributed solely to the nanoemulsion with the same level of confidence that larger controlled trials would provide.

Looking Ahead

As cannabinoid medicine continues to mature, innovation is increasingly focused on drug delivery rather than simply developing new cannabis products. Improving how cannabinoids are absorbed may help clinicians achieve more consistent dosing while reducing the variability that has historically complicated medical cannabis treatment. Advances in pharmaceutical technologies such as nanoemulsions, controlled-release formulations, and targeted delivery systems are shifting the conversation from simply what cannabinoids are used to how they are delivered to achieve the greatest therapeutic benefit.

This THC nanoemulsion study represents an encouraging example of that evolution. Its laboratory performance and early clinical findings suggest that buccal nanoemulsion delivery could become a more patient-friendly option for individuals living with refractory chronic pain. However, the clinical evidence remains preliminary. Larger randomized controlled trials will be essential to determine whether these promising early results can be consistently reproduced across broader and more diverse patient populations.

However, one thing is becoming increasingly clear, that the future of cannabinoid pain management will likely be defined not only by discovering new therapies, but also by delivering existing ones more precisely. As researchers continue refining cannabinoid formulations and delivery technologies, medical cannabis may become a more predictable, personalized, and clinically reliable tool for managing chronic pain. For patients and healthcare providers alike, that could mark an important step toward treatments that are both more effective and easier to integrate into everyday clinical care.

References:

^{1. A. Spirito, R. Provenzano, A. Vitiello, N.A. Di Spirito, L. Izzo, A. Lombardi, P. Maiolino, C. Pane, F. Ungaro, F. Saccà, I. d’Angelo, A. Miro, Development and clinical evaluation of a nanoemulsion for buccal delivery of cannabis extract in refractory chronic pain, European Journal of Pharmaceutics and Biopharmaceutics (2026), doi: https://doi.org/10.1016/j.ejpb.2026.115162}