HEMP
The first known hemp rope was created before the last Ice Age! Archaeologists have found that the relics made of hemp fabric are over 10,000 years old.
The oldest known records of cannabis cultivation in China date back 5,000 years.
Hemp is the most important industry for thousands of products and enterprises producing most fibers, fabrics, incense, glass fiber substitutes, lightweight sandwich panels, composite wood, cat litter, potting mix, diapers, skincare products, etc.
WHAT ARE CANNABINOIDS?
Cannabinoids are compounds that fall into three categories:
Endocannabinoids (ECB) – cannabinoid compounds biosynthesized in the human body,
Phytocannabinoids (PCBs) – obtained from plants, are abundant in the resin-producing the Cannabis sativa L. (C. sativa) plant,
Synthetic cannabinoids (SC) – synthetically produced using various chemical processes (e.g., Dronabinol, Nabilone).
ENDOCANNABINOID SYSTEM ECS
The ECS is a molecular signaling network that plays a role in the body’s homeostasis. The ECS consists of (a) signaling molecules called endocannabinoids, (b) specific receptors, and (c) enzymes that synthesize and decompose endocannabinoids and endocannabinoid transporters.
The most studied functions of the ECS are related to central nervous system (CNS) modulation and the body’s immune function. Research indicates a key role for the ECS in maintaining skin homeostasis and barrier function, and its dysregulation is associated with various skin diseases such as atopic dermatitis, pruritus, acne, hair growth/loss, and hyper/hypopigmentation.
Endocannabinoids present in the skin
Of all endocannabinoids in the skin, Anandamide (N-arachidonoylethanolamide, AEA) and 2-arachidonoyl glycerol (2-AG) are the most widely studied. Anandamide and 2-AG have been detected in both keratinocytes and fibroblast cells.
Cannabinoid receptors
CB 1 cannabinoid receptors are found in the central nervous system (brain and spinal cord), and CB2 receptors are located in the peripheral nervous system (nerves in the extremities), the digestive system, and the immune system.
Both CB1 and CB2 receptors are also found in epidermal keratinocytes, dermal nerve fibers, dermal cells, melanocytes, eccrine sweat glands, and hair follicles.
Endocannabinoids also bind to TRP (Transient Receptor Potential) receptors present in various skin cells and are involved in multiple functions such as skin barrier formation and maintenance, cell growth, cell differentiation, immune and inflammatory processes.
In addition, ECBs interact with peroxisome proliferator-activated receptors (PPARs) through either direct (endocannabinoid) or indirect (secondary endocannabinoid metabolite) signaling pathways. Activation of PPAR (α and γ) partially mediates neuroprotective, anti-inflammatory, and analgesic effects.
PHYTOCANNABINOIDS
Dried medical cannabis is the so-called medical marijuana. Its main ingredients are phytocannabinoids: THC (Δ9-tetrahydrocannabinol) and CBD (cannabidiol). Phytocannabinoids affect the ECS, showing several health properties, including: hypnotic, muscle-relaxing, analgesic, anti-inflammatory, and neuroprotective. The main difference between THC and CBD is the psychoactive effect displayed by THC.
CBD has a low molecular weight (314.46 Da), but its high log P (Partition Coefficient lipid/water) of ~ 6.3 is a challenge for its transdermal delivery. This problem can be resolved by using appropriate supports. There are reports of successful transdermal delivery of CBD using ethosomal carriers (ethosomes). Topical application of CBD (1-10%) as a gel has also been effective, especially for reducing inflammation.
Currently, there are no clinical studies to assess the local absorption capacity in humans. Further work is required to understand better the appropriate dosages and delivery methods for therapeutic applications of CBD on the skin.
THERAPEUTIC POTENTIAL OF CANNABIDIOL
Oxidative stress
CBD penetrates the cells and balances the response to oxidative stress from UVB radiation and hydrogen peroxide. CBD protects against the reduction of polyunsaturated fatty acids in the cell membrane, positively influencing the integrity of the membrane. CBD can also activate PPAR-γ receptors with cytoprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects. Treatments regulating the expression of these receptors may be beneficial in the skin with inflammation and keratin disorders such as eczema or atopic dermatitis.
Eczema and atopic dermatitis
Phytocannabinoids modulate inflammatory responses by regulating several basic mechanisms in atopic dermatitis. Researches have shown that Adelmidrol effectively treats mild AD in the pediatric population.
Hemp oil shows antimicrobial and anti-biofilm efficacy against S. aureus bacteria. The oil can disrupt and eliminate the mature biofilm of S. aureus, hence its therapeutic potential in preventing skin diseases such as atopic dermatitis has been suggested.
Wound healing
There is little clinical evidence for the use of CBD in wound healing. One study showed that in patients suffering from blistering epidermal detachment, wounds healed faster, blistering decreased, and the pain was relieved after topical application of cannabidiol. Despite the lack of clinical evidence, the preclinical models show an optimistic outlook. Studies using Cannabis Sativa Extract (CSE, standardized to 5% CBD) indicate that additional components of the CSE extract, such as other cannabinoids, flavonoids, and terpenes, may exert a synergistic anti-inflammatory effect more significant than CBD alone. Clinical studies are needed to conclude the cutaneous wound healing response to CBD and its related compounds.
Acne
The endocannabinoid AEA (N-arachidonoyl ethanolamide) in low concentrations has been shown to stimulate lipid production in human sebaceous cells but induce apoptosis in higher concentrations. CBD can inhibit the lipogenic effect in a dose-dependent manner. CBD can also inhibit external lipid synthesis induced by lipogenic compounds such as arachidonic acid, linoleic acid, and testosterone. CBD can normalize lipogenesis in an imbalanced state. CBD does not reduce the number of viable cells, but it significantly minimizes overall cell proliferation at doses of 1-10 µM. Higher doses of CBD (50 μM) or prolonged use (6 days) result in apoptosis-induced cytotoxicity and an overall reduced number of viable cells. CBD can prevent the expression of tumor necrosis factor TNF-α (an inflammatory cytokine) from being upregulated by acne mediators. CBD normalizes lipopolysaccharide-induced expression of pro-inflammatory interleukins IL-1B and IL6. So CBD has an anti-inflammatory effect.
The antimicrobial effect of CBD
In vitro studies have shown that hemp seed hexane extract HSHE has antimicrobial activity against C. acnes while inducing inflammation and lipogenesis in the sebaceous glands at the molecular and cellular levels. Treatment with 20% HSHE showed complete inactivation of C. acnes. These studies did not consider the CBD content of HSHE, so it is difficult to attribute the contribution of CBD alone to the inactivation of C. acnes. A clinical trial using a 3% cannabis seed cream resulted in a reduction in sebum and redness. Hemp seed extract contains minimal CBD, so its use in treating acne and seborrhea is more theoretical. Similarly, besides CBD, hemp oil contains many terpenes that have antimicrobial effects against C. acnes. No large-scale in vivo studies have investigated the role of CBD in treating acne. Research is needed to help understand how CBD may affect acne at the clinical level.
Modulation of the hair growth cycle
Human skin is characterized by differential expression of CB1 and CB2 receptors in hair follicles. CB1 is found in the funnel and inner root sheath, and CB2 is located in the outer root sheath and hair bulb. The facial hair follicles produce the ECB: Anandamide AEA and 2-arachidonyl glycerol 2-AG. These ECBs inhibit hair follicle growth and induce the catagen cycle. Studies have shown that CB1 agonists can help deal with unwanted hair growth, while CB1 antagonists stimulate hair growth in mice but have no effect when applied topically.
The anandamide metabolite, bimatoprost, is a topical prostamide (a lipid-like substance related to prostaglandins) used to treat eyebrow and eyelash hypotrichosis.
Human scalp hair follicles have selected prostamide receptors in the dermal papilla. Clinical studies have shown that bimatoprost accelerated hair regrowth in patients with alopecia areata to a greater extent than in patients treated with topical steroids.
Systemic use of CBD has a dose-dependent, opposing effect on the hair growth cycle. At the dose of 0.1 µM and 1.0 µM, the hair shaft grew similar to the control, while at 10 µM, there was a significant hair growth inhibition and induction of catagen. As the dose of CBD increases, the proliferation of keratinocytes decreases.
Scientists suggest: low doses may benefit hair growth pathways, while high doses inhibit cell proliferation.
Given the complexity of hair growth dynamics, additional research, including clinical trials, is needed to determine whether phytocannabinoids such as CBD can be effective topical interventions for treating hair loss or excessive hair growth.
Melanogenesis
Due to the limited number of studies, the role of the ECS system in the cascades of the melanogenesis process is not clear.
One study found that CB1 receptor agonists inhibited basal melanogenesis upon exposure to UVB radiation, while inhibition could be reversed by supplying a CB1 antagonist. Another study documented that cannabinoids had no significant effect on hair pigmentation.
The involvement of the ECS pathways in melanocytes is very complex and unclear, requiring additional studies in various in vitro and in vivo models.
To sum up the above, despite many theoretical applications of phytocannabinoids, their action in many skin diseases has not been clinically confirmed. The fad for cosmetics with CBD is based on potential properties rather than confirmed results of in vivo tests.
