Cannabinoids & skin: Human body produces chemical similar to active ingredient in marijuana

Key Points

National report - A recent study shows that the human body produces chemical compounds similar to the active ingredient in marijuana, and these compounds, called endocannabinoids, play an important part in maintaining healthy skin.

The study's findings, first published online in July 2008, and scheduled for the October 2008 print issue of The Federation of American Societies for Experiment Biology (FASEB) Journal, could lead to new drugs that treat skin conditions ranging from acne to dry skin, and even skin-related tumors.

"Our pre-clinical data encourage one to explore whether endocannabinoid system-acting agents can be exploited in the management of common skin disorders," says Tamás Biró, M.D., Ph.D., lead author and senior scientist involved in the research.

Gerald Weissmann, M.D., editor-in-chief of the FASEB Journal, professor emeritus of medicine and director of the Biotechnology Study Center at New York University School of Medicine, New York, believes these early clinical findings hold promise.

"This research shows that we may have something in common with the marijuana plant," Dr. Weissmann says.

"Just as THC (tetrahydrocannabinol) is believed to protect the marijuana plants from pathogens, our own cannabinoids may be necessary for us to maintain healthy skin and to protect us from pathogens," Dr. Weissmann tells Dermatology Times.

The study

Dr. Biró and colleagues treated cell cultures from human sebaceous glands with various concentrations of endocannabinoids. Then, they measured the production of lipids (fat cells, such as those in skin oil), cell survival and death, and changes in gene expression, and compared these outcomes to those in an untreated control group.

Previously, studies have shown that both locally produced endocannabinoids and exocannabinoids, via cannabinoid receptor-1 (CB1), are powerful inhibitors of human hair growth.

"Therefore, to further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology, using human SZ95 sebocytes as cell culture model," Dr. Biró says.

In the study, the researchers provide the first evidence that SZ95 sebocytes express CB2, but not CB1. They also found that prototypic endocannabinoids (arachidonoyl ethanolamide/anandamide, 2-arachidonoyl glycerol) are present in SZ95 sebocytes, and dose-dependently induce lipid production and (chiefly apoptosis-driven) cell death.

They also found that endocannabinoids upregulate the expression of key genes involved in lipid synthesis (e.g., PPAR transcription factors and some of their target genes). These actions are selectively mediated by CB2-coupled signaling involving the MAPK pathway, as revealed by specific agonists/antagonists and by RNA interference.

"Because cells with 'silenced' CB2 exhibited significantly suppressed basal lipid production, our results collectively suggest that human sebocytes utilize a paracrine-autocrine, endogenously active, CB2-mediated endocannabinoid signaling system for positively regulating lipid production and cell death.

"CB2 antagonists or agonists, therefore, deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions, including acne vulgaris, seborrhea and dry skin," Dr. Biró says.

For example, the observed enhancement of lipid synthesis induced by endocannabinoids strikingly resembles that seen in acne vulgaris, the common, multifactorial pilosebaceous inflammatory skin disease in which differentiation and, hence, lipid synthesis of sebocytes are pathologically increased.

"This, and the finding in CB2-silenced SZ95 sebocytes that both AEA-stimulated and basal lipid synthesis, were suppressed may be interpreted to indicate a role of enhanced CB2 signaling in acne pathogenesis.

"Proof-of-principle studies are now warranted to test the therapeutic value of CB2 blockade in the clinical management, e.g., of acne and seborrhea," he says.