**Background:** The Cannabis plant has been used for millennia for therapeutic purposes, including skin disorders. Phytocannabinoids (pCBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD) exhibit anti-inflammatory, antioxidant, anti-acne, and antimicrobial properties. The endocannabinoid system (ECS), present in the skin, modulates cell growth, immune responses, and sensory phenomena. Skin conditions like psoriasis, atopic dermatitis (AD), allergic contact dermatitis (ACD), asteatotic eczema, acne, and seborrhea affect 30–70% of people worldwide, and current treatments have limitations including poor efficacy, side effects, and high costs. This review aims to bridge traditional use with modern science regarding formulation, route of administration, dosage, and frequency of cannabinoids in dermatology.
**Methods:** This is a narrative review of recent scientific literature on topical and transdermal cannabinoids. It covers the skin as a therapeutic target, the role of the ECS, and specific skin disorders. The review also examines pharmacokinetics, formulation strategies (e.g., nanoemulsions, liposomes, solid lipid nanoparticles), and challenges such as high lipophilicity (logP 5–7) and low oral bioavailability (CBD 13–19%, THC 6%).
**Key Results:** Cannabinoids show promise in multiple skin conditions. For psoriasis, THC inhibits keratinocyte proliferation via PPARγ and CB1 activation, while JWH-133 reduces inflammatory cytokines and angiogenic factors. In AD, a cream with palmitoylethanolamide (PEA) improved itching severity and sleep quality by 60% in one study, and a topical cannabinoid emulsion led to clinical resolution in 80% of patients. For ACD, THC reduced inflammation in rodent models by inhibiting keratinocyte-derived proinflammatory mediators. In acne, CBD normalizes sebocyte lipogenesis and decreases pro-inflammatory cytokines; a single-blind study with 3% cannabis seed extract cream significantly improved sebum production over 12 weeks. For pruritus, PEA reduced itching by 86.4% in 22 patients. In wound healing, topical cannabis-based medications combined with compression therapy achieved complete wound closure in 79% of patients with nonhealing venous leg ulcers (median 34 days). Transdermal delivery avoids first-pass metabolism, but cannabinoids' high lipophilicity requires enhancers like oleic acid and ethanol or nanocarriers (e.g., liposomes, nanoemulsions) to improve skin penetration. For example, nanoemulsions improved skin penetration of THCA and CBDA, and liposomal CBD provided sustained plasma levels in a canine model over 28 days.
**Clinical Implications:** Topical cannabinoids offer a safer alternative to conventional treatments (e.g., corticosteroids, calcineurin inhibitors) with fewer side effects like skin atrophy, hypertension, or immunosuppression. They are effective for localized symptoms (itching, inflammation, pain) and may improve quality of life. Transdermal formulations could enable systemic delivery for conditions like chronic pain or epilepsy, avoiding hepatic metabolism. However, challenges remain: standardization of extracts, stability (CBD degrades at pH 6–7), psychotropic effects of THC, and high production costs. Future research should focus on optimizing nanocarriers, developing non-psychoactive compounds, and conducting rigorous clinical trials to establish efficacy and safety.