A Summary of Pre-Clinical and Clinical Evidence for Cannabinoid Hair Follicle Effects

Abstract

The endocannabinoid system (ECS), discovered in the 1990s, is a system involved with maintaining cellular homoeostasis by down-regulating the damaging inflammatory responses and upregulating regenerative processes. Tetrahydrocannabinol (THC), Cannabidiol (CBD), tetrahydrocannabivarin (THCV) and cannabidivarin (CBDV) are all phytocannabinoids that have novel therapeutic effects on hair growth through the ECS receptors on hair follicles. These cannabinoids are fat-soluble and poorly absorbed past the epidermis, but topical application easily reaches hair follicles where CBDV, THCV and CBD act as partial or full CB1 antagonists and agonists of vanilloid receptor-1 (TRPV1) and vanilloid receptor-4 (TRPV4). All these ECS receptors relate to hair follicle function. THC on the other hand has the opposite effects decreasing hair shaft elongation and matrix production. A summary of the pre-clinical and clinical cannabinoid research is reviewed. The studies confirm that for androgenetic alopecia (AGA) the method of action is different from and synergistic with current hair regrowth therapies. Blocking the CB1 receptor on the hair follicle has been shown to result in hair shaft elongation and matrix production via keratinocytes, in addition, the hair follicle cycle (anagen, catagen, and telogen phases) is controlled by TRPV1. The effects of CBD on hair growth are dose dependent and higher doses may result in premature entry into the catagen phase via a different receptor known as TRPV4. CBD has also been shown to increase Wnt signaling, which causes dermal progenitor cells to differentiate into new hair follicles and maintains anagen phase of the hair cycle. Two recent six-month duration clinical trials of adults with androgenetic alopecia (AGA) have revealed an average 93.5% increased hair count with CBD alone, and 164% increased hair count with hemp extract high in CBD, THCV, CBDV and menthol. A current study is underway to look at punch biopsies of the areas of hair regrowth in patients treated with a combination of CBD, THCV isolate, menthol and caffeine. Another study is underway looking at using hexahydrocannabinol (HHC) a hydrogenated version of THC to decrease facial hair growth as a cosmetic effect