Review
doi: 10.1002/prp2.70304.
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Review
Pharmacol Res Perspect.
2026 Aug.
Abstract
Despite advances in targeted and immunotherapy for melanoma, resistance to treatment and severe adverse effects pose significant challenges. This necessitates the development of new treatment strategies, and cannabinoids, because of the extensive preclinical evidence for their cytotoxic action on carcinoma cells in a variety of cancers, can offer a novel therapeutic option when used appropriately. Indeed, the potential therapeutic benefits of cannabinoids were formally recognized in the world and much more recently in the United Kingdom when cannabis-based medicinal products were moved from Schedule 1 of the Misuse of Drugs Regulations 2001 to Schedule 2 in 2018. This move further encouraged scientists to look at more applications of cannabinoids in different disorders. Although the potential psychoactivity of cannabis as a Schedule 1 drug hinders research, more research could focus on non-psychoactive components such as cannabidiol (CBD) and cannabigerol (CBG). This review summarizes some past and current research on the relationship between the cannabinoid system and the microbiome in patients with metastatic melanoma who undergo immunotherapy. The review also provides a comprehensive background on the function of the cannabinoid system in normal and diseased skin, as well as future directions in using cannabinoids as an adjunct to chemotherapeutics in the treatment of the disease.
Keywords:
cannabinoids; gut microbiome; melanoma; skin cancer.
© 2026 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and John Wiley & Sons Ltd.
Conflict of interest statement
The authors declare no conflicts of interest.
Figures
FIGURE 1
Cannabinoid and non‐cannabinoid receptors in human skin. Physiological functions of the endocannabinoid system. This figure illustrates the key components of the endocannabinoid system in human skin, highlighting CB and non‐CB receptors in different skin compartments, such as sebocytes derived from keratinocytes, epidermal, and sebaceous glands. Anandamide in human keratinocytes can induce an inhibition of epidermal cell differentiation by inhibiting protein kinase C activation via CB1 receptors.
FIGURE 2
Relationship between cannabinoids and gut microbiome. This figure illustrates how cannabinoids influence the composition of the intestinal microbiota, promoting beneficial bacterial strains such as Akkermansia muciniphila. Changes in the intestinal microbiota can regulate the activity of the endocannabinoid system by modulating CB1 and CB2 receptors in the gastrointestinal tract. A higher number of Bacteroides species is related to metabolic problems and intestinal inflammation.
References
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PubMed
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