Abstract Background While retinol is known to reduce the appearance of fine lines and wrinkles, it is associated with irritating effects. However, when combined with water soluble cannabidiol (CBD; CR Topical), CBD may act to reduce oxidative stress and inflammation, mitigating irritation from retinol and further improving the skin’s appearance through independent anti-aging mechanisms. Objectives To assess the efficacy and tolerability of CR-Topical for improving facial skin. Methods In this prospective, single-center pilot study, 9 female patients and one male patient aged 20 to 53 years who presented with facial skin imperfections (visible pores, dehydration, roughness, and/or static/dynamic wrinkles) applied CR-Topical to the entire face once daily for 42 days. Outcomes were measured on days 1, 21, and 42 using the Global Ranking Scale (GRS) with Comprehensive Skin Analysis by the patient and senior investigator as well as by a blinded reviewer (board-certified plastic surgeon). Dynamic videos and static imagery were taken before and after treatment, and patient satisfaction surveys were completed. Results Global improvement across all 13 domains was observed, with the greatest mean differences for visible pores (2.0; 95% CI, 1.5-2.5), dehydration (2.0; 95% CI, 1.4-2.6), surface roughness (1.8; 95% CI, 1.2-2.4), static wrinkles (1.8; 95% CI, 1.1-2.5), and dynamic wrinkles (1.6; 95% CI, 0.8-2.3). Patient satisfaction (100%) and willingness to recommend the product to others (90%) were high, and tolerability of CR-Topical was excellent. Conclusions CR-Topical is effective at improving global skin quality, including static and dynamic wrinkles. This study also used 4-dimensional analysis in the evaluation, a novel and developing method. Level of Evidence: 4