Tolerability Profile of Topical Cannabidiol and Palmitoylethanolamide: A Compilation of Single-Center Randomized Evaluator-Blinded Clinical and In Vitro Studies in Normal Skin

Introduction: While an increasing number of studies have investigated the side effect profile of oral cannabinoids, few studies have provided sufficient data on the tolerability of topical cannabinoids in human subjects.

Objective: To assess the tolerability profile of several commercial topical formulations containing cannabidiol (CBD) and palmitoylethanolamide (PEA) on the skin of healthy human subjects.

Methods: Three human clinical trials and one in vitro study were conducted. Skin irritation, sensitization, and phototoxic potential of products including two formulations containing CBD and PEA, one containing hemp seed oil, and four concentrations of CBD alone, were assessed via patch testing on healthy human skin. Ocular toxicity was tested using a traditional hen’s egg chorioallantoic membrane model, with three CBD, PEA and hemp seed oil formulations.

Findings: There was no irritation or sensitization of the products evident via patch testing on healthy subjects. Additionally, mild phototoxicity of a hemp seed oil product was found at the 48-hour time point compared to negative control. The in vitro experiment demonstrated comparable effects of cannabinoid products to historically non-irritating products.

Limitations: External validity may be limited as formulations from a single manufacturer were used for this study, while vast heterogeneity exists across non-regulated, commercial CBD products on the market. Product was assessed only on normal, non-diseased human skin; therefore, extrapolation to those with dermatologic diseases cannot be assumed.

Conclusion: These specific formulations of CBD and PEA containing products are non-irritating and non-sensitizing in healthy adults and further encourage similar research assessing long-term safety and efficacy in human subjects with dermatologic diseases.