Cannabinoids: Potential Role in Inflammatory and Neoplastic Skin Diseases

Rose Milando; Adam Friedman

Disclosures

Am J Clin Dermatol. 2019;20(2):167-180. 

In This Article

Abstract and Introduction

Abstract

The endocannabinoid system is a complex and nearly ubiquitous network of endogenous ligands, enzymes, and receptors that can also be stimulated by exogenous compounds such as those derived from the marijuana plant, Cannabis sativa. Recent data have shown that the endocannabinoid system is fully functional in the skin and is responsible for maintaining many aspects of skin homeostasis, such as proliferation, differentiation, and release of inflammatory mediators. Because of its role in regulating these key processes, the endocannabinoid system has been studied for its modulating effects on both inflammatory disorders of the skin and skin cancer. Although legal restrictions on marijuana as a Schedule I drug in the USA have made studying cannabinoid compounds unfavorable, an increasing number of studies and clinical trials have focused on the therapeutic uses of cannabinoids. This review seeks to summarize the current, and rapidly expanding field of research on the broad potential uses of cannabinoids in inflammatory and neoplastic diseases of the skin.

Introduction

For centuries, components of the marijuana plant Cannabis sativa have been incorporated into medicinal therapies for a broad range of clinical indications. However, in the USA, marijuana is currently classified by the US Drug Enforcement Administration as a Schedule I drug, alongside heroin, as a substance "with no currently accepted medical use and a high potential for abuse".[1] Because of this classification as strictly non-medicinal and illegal, marijuana and its derivatives have not always been ideal study subjects. Nonetheless, in the 1990s, scientists discovered the human endocannabinoid system—a set of receptors, enzymes, and ligands that exogenous cannabinoids, such as marijuana derivatives, utilize to impart their physiologic effects.[2] Since the discovery of the human endocannabinoid system, there has been a surge of interest in the scientific community to better understand its role in health, disease, and as a target for therapeutic intervention. Until recently, the US FDA had only approved synthetic delta9-tetrahydrocannabinol (THC) (Marinol, Syndros) and a related compound, Cesamet, for the treatment of anorexia in patients with AIDS and for nausea caused by chemotherapy treatment.[3] However, in June 2018, the FDA approved the first-ever cannabidiol treatment for two rare forms of epilepsy. This represents the first time the FDA has approved a purified derivative of marijuana.[4]

Although marijuana is widely known for its psychoactive effects, recent studies have proven that cannabinoids are actively involved in peripheral systems such as the innate and adaptive immune response and in regulation of the cell cycle.[5,6] The endocannabinoid system has been described in tissues throughout the body, from neuronal cells to hepatocytes.[7] In the skin, the endocannabinoid system is fully functional and responsible for regulating many aspects of skin homeostasis.[8] We provide an overview of the current understanding of the endocannabinoid system and the potential therapeutic use of cannabinoids in chronic inflammatory and neoplastic diseases of the skin.

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