Cannabinoids in Psoriasis: From Cutaneous Endocannabinoid Biology to Emerging Clinical Evidence

Psoriasis is a chronic, immune-mediated inflammatory disease whose management remains limited by treatment costs, routes of administration, and suboptimal adherence, despite major advances in biologic therapies targeting the interleukin-23 (IL-23)/T helper 17 (Th17) axis. In this context, the cutaneous endocannabinoid system has emerged as a promising therapeutic target because of its involvement in keratinocyte proliferation and differentiation, local immune regulation, inflammation, pruritus, and neuroimmune signaling. This narrative review synthesizes evidence retrieved from PubMed, Scopus, and Web of Science regarding the role of the cutaneous endocannabinoid system in psoriasis and the therapeutic potential of phytocannabinoids derived from Cannabis sativa. Preclinical studies indicate that cannabinoids can exert anti-inflammatory, antiproliferative, antipruritic, and neuroimmunomodulatory effects through multiple molecular targets relevant to psoriatic pathophysiology. However, these compelling biological findings have not yet been consistently translated into clinical efficacy. The available randomized controlled trials are limited by small sample sizes, heterogeneous formulations and routes of administration, and divergent findings concerning objective disease severity, although potential benefits for symptoms such as pruritus and sleep disturbances have been reported. Overall, cannabinoid-based interventions represent a biologically plausible therapeutic strategy under investigation for psoriasis, particularly as adjunctive or symptom-oriented interventions. Nevertheless, adequately powered clinical trials using standardized formulations, well-defined cannabinoid compositions and dosing regimens, clinically appropriate routes of administration, and longer follow-up periods are urgently needed to establish their efficacy, safety, and role in clinical practice.