Studies have shown that women are more susceptible to adverse effects (AEs) from conventional drugs. This study aimed to investigate the differences of medical cannabis (MC)-related AEs between women and men in patients with chronic noncancer pain (CNCP). This is a cross-sectional study of adult patients licensed for MC treatment who were also diagnosed as patients with CNCP by a physician. Data included self-reported questionnaires and comprehensive MC treatment information. Simultaneously, identification and quantification of phytocannabinoids and terpenoids from the MC cultivars were performed. Comparative statistics were used to evaluate differences between men and women. Four hundred twenty-nine patients with CNCP (64% males) reported fully on their MC treatment. Subgrouping by sex demonstrated that the weight-adjusted doses were similar between men and women (0.48 [0.33-0.6] gr for men and 0.47 [0.34-0.66] gr for women). Nonetheless, women reported more than men on MC-related AEs. Further analysis revealed that women consumed different MC cultivar combinations than men, with significantly higher monthly doses of the phytocannabinoids CBD and CBC and significantly lower monthly doses of the phytocannabinoid 373-15c and the terpenoid linalool. Our findings demonstrate sex differences in MC-related AEs among patients with CNCP. Women are more susceptible to MC-related AEs, presumably because of both the inherent sex effect and the consumption of specific phytocannabinoid compositions in the MC cultivar(s). The understanding of these differences may be crucial for planning MC treatments with safer phytocannabinoid and terpenoid compositions and to better inform patients of expected AEs.

The cannabidiol (CBD)-rich cannabis extract CAN296 shows anti-inflammatory and anticancer activity relevant to oral lichen planus (OLP), oral graft-versus-host disease (oGVHD), and oral squamous cell carcinoma (OSCC), but its high lipophilicity limits aqueous dispersion. This study developed a stable Tween-based nanoemulsion optimized for oral mucosal delivery. Ethanol-dissolved CAN296 was nanoemulsified using a 1% Tween/Span system. Physical stability was visually assessed; droplet size and morphology were examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM); and wettability was measured by static contact angle (SCA). Additional evaluations included temperature stability (25 °C vs. 4 °C), in vitro release using a dialysis membrane, and scanning electron microscopy (SEM) of membrane-associated droplets. Nanoemulsions with ≥80% Tween 80 incorporated CAN296 up to 800 µg/mL, clear at 400 µg/mL, and uniformly turbid at 800 µg/mL. DLS and TEM confirmed spherical nanoscale droplets, and SCA indicated favorable cohesion and wettability. Stability was maintained for 30 days at 4 °C. Dialysis studies demonstrated strong membrane association with limited diffusion, supported by SEM visualization of membrane-bound droplets. The Tween-dominant (≥80%) nanoemulsion stably incorporated CAN296 up to 800 µg/mL, demonstrated nanoscale uniformity, improved 4 °C stability, and strong membrane retention under static conditions, suggesting potential for localized oral delivery.

Background/Objectives: The cannabidiol (CBD)-rich cannabis extract (CAN296) exhibits potent anti-inflammatory and anticancer activity with a favorable safety profile, making it a promising candidate for the management of inflammatory, precancerous, and malignant conditions, particularly for diseases with limited treatment options such as oral lichen planus (OLP), oral manifestations of graft-versus-host disease (oGVHD), and oral squamous cell carcinoma (OSCC). However, cannabis extracts in general, including CAN296, are characterized by high lipophilicity and poor aqueous solubility, which pose significant challenges to formulation stability and bioavailability. This study aimed to develop a stable Tween-based nanoemulsion of cannabis extract optimized for oral mucosal delivery. Methods: Ethanol-dissolved cannabis extract was nanoemulsified with Tween 80/Span 80 surfactant blends at varying concentrations up to 4000 µg/mL and 1% total surfactant. Formulations were visually inspected for physical stability over an 8-week period. Selected emulsions were analyzed by dynamic light scattering (DLS) for droplet size and polydispersity and by transmission electron microscopy (TEM) for morphology. Additional assays included static contact angle (SCA) measurements for wettability, temperature-dependent stability testing (at 25 °C vs. 4 °C for 30 days), and an in vitro release study using a dialysis membrane, complemented by scanning electron microscopy (SEM) to visualize droplet deposition on the membrane surface. Results: Nanoemulsions containing ≥80% Tween 80 (1% surfactant) successfully incorporated cannabis extract up to 800 µg/mL, clear at 400 µg/mL, and turbid but homogeneous at 800 µg/mL, forming stable dispersions with improved nanoscale uniformity. DLS and TEM confirmed uniform spherical morphology, while SCA analysis indicated optimal droplet cohesion and wettability. Storage stability was maintained for 30 days at 4 °C, and in vitro dialysis studies revealed strong membrane association with limited diffusion, further supported by SEM visualization of membrane-bound aggregates. These findings suggest a favorable mucoadhesive potential for oral application. Conclusion: A Tween-dominant (≥80%) nanoemulsion stably incorporated CBD-rich extracts up to 800 µg/mL, well above therapeutic levels. The optimized system showed nanoscale uniformity, improved stability at 4 °C, and significant membrane retention, supporting its potential as a mucoadhesive platform for targeted oral delivery in immune-mediated and precancerous conditions.