Atopic dermatitis (AD) is a chronic skin disorder characterized by pruritus, erythema and excoriation. While AD has a multifactorial etiology, neuro-signaling pathways are now recognized to play an essential role in the pathogenesis of AD, particularly pruritus. Neuromodulators, such as topical naltrexone, are being utilized in AD treatment. Another class of neuromodulator, Palmitoylethanolamide (PEA), has demonstrated effectiveness in the treatment of itch, excoriation and erythema in AD patients. Phytocannabinoids including cannabidiol (CBD) are becoming increasingly accessible to the public and continue to be advertised for their efficacy to treat inflammatory skin disorders such as eczema. However, no human studies have been conducted to support the claim. Therefore, this study aimed to explore the effects of CBD in individuals with self-reported eczema. Twenty individuals consented to participate and 16 completed a 28-item online questionnaire assessing subjects’ disease severity using Patient Oriented Eczema Measure (POEM) and psychosocial burden of their disease through the emotional domain of Quality of Life Hand Eczema Questionnaire (QOLHEQ). Findings demonstrated a significant reduction in the mean score of POEM from baseline (mean ±SE: 16±1.35) and at a two weeks interval (8.25 ±1.80), P<0.0007. Similar reduction was seen in emotional domain of QOLHEQ from a mean score of 20.9±2.06 to 8.375 ±1.609 at 2 week-interval, P<0.004. 67% of subjects reported a decrease in itch and 50% perceived an improvement in their eczema by more than 60%. This observational study shed light on the potential clinical utility of topical CBD in the treatment of atopic dermatitis. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5464.