Cannabidiol and Epigenetic Regulation of Hair Follicle Cycling: Receptor Crosstalk and Transcriptional Control in Alopecia

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid with increasingly recognized effects on cutaneous and hair follicle (HF) biology. This narrative review evaluates CBD-responsive signaling and its intersection with transcriptional, epigenetic, and post-transcriptional mechanisms relevant to HF cycling and alopecia, with particular emphasis on the hierarchy of experimental evidence. Available data indicate that CBD does not exert a uniformly pro-growth effect, but instead produces concentration-, compartment-, and context-dependent responses. In human HFs, submicromolar CBD primarily demonstrates anti-inflammatory activity, whereas micromolar exposure suppresses hair shaft production and promotes catagen through TRPV4-dependent Ca2+ signaling. CBD also modulates adenosine and Wnt/β-catenin pathways and can restore β-catenin expression in human dermal papilla cells under inhibitory conditions. Beyond acute receptor signaling, CBD influences DNA methylation, histone modifications, miRNA networks, and transcriptional regulators including PPARγ and AhR. However, most of this evidence derives from non-follicular systems, and direct CBD-induced epigenetic remodeling of human HFs has not been demonstrated. Among alopecia subtypes, AGA has the strongest mechanistic and preliminary clinical rationale, whereas evidence in AA and scarring alopecia remains largely indirect. Translation is further limited by uncertain intrafollicular CBD exposure, formulation-dependent delivery, and the absence of controlled clinical efficacy data. CBD should therefore be viewed as a context-dependent regulator of follicular signaling rather than an established hair growth treatment. Future studies should define follicular pharmacokinetics, establish concentration–response relationships, and test pathway causality in intact human HFs and disease-specific models.