cbd oil topically for acne

Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders

Though there is limited research confirming the purported topical benefits of cannabinoids, it is certain that cutaneous biology is modulated by the human endocannabinoid system (ECS). Receptors from the ECS have been identified in the skin and systemic abuse of synthetic cannabinoids, and their analogs, have also been associated with the manifestation of dermatological disorders, indicating the effects of the ECS on cutaneous biology. In particular, cannabidiol (CBD), a non-psychoactive compound from the cannabis plant, has garnered significant attention in recent years for its anecdotal therapeutic potential for various pathologies, including skin and cosmetic disorders. Though a body of preclinical evidence suggests topical application of CBD may be efficacious for some skin disorders, such as eczema, psoriasis, pruritis, and inflammatory conditions, confirmed clinical efficacy and elucidation of underlying molecular mechanisms have yet to be fully identified. This article provides an update on the advances in CBD research to date and the potential areas of future exploration.

Introduction

The Endocannabinoid System in Skin

The ECS is an evolutionarily conserved network of molecular signaling that plays a role in bodily homeostasis. 1–3 The ECS is made up of multiple components: (a) signaling molecules called endocannabinoids, (b) specific receptors, and (c) enzymes that synthesize and breakdown endocannabinoids and transporters of endocannabinoids. The most well-researched functions of the ECS are related to modulation of the central nervous system (CNS) and immune function in the body. Recent research has indicated the critical role of the ECS in maintaining skin homeostasis and barrier function, and its dysregulation has been implicated in various skin disorders like atopic dermatitis, itch, acne, hair growth/loss, and hyper/hypopigmentation. 4–7

Endocannabinoids

The existence of an endogenous ECS ligand was first reported by Devane et al in 1988 when they showed that N-arachidonoylethanolamine glycerol (AEA/Anandamide) binds to the cannabinoid brain receptor in a murine model. 8 , 9 Since then, detection of numerous endocannabinoids has also been reported in the human body including the peripheral organs like skin. 10 Amongst all endocannabinoids present in skin, anandamide (N-arachidonoyl ethanolamide, AEA) and 2-arachidonoyl glycerol (2-AG) are the most widely studied. 11 , 12 Anandamide and 2-AG were detected and quantified in the femtomolar range in both keratinocytes and fibroblast cells by Gegotek et al. 13 The biosynthesis pathways and cellular uptake of these two lipid mediators are described in multiple review articles. 2 , 14 , 15 Other less know endocannabinoids detected in skin by Kendall et al are N-palmitoyl ethanolamide (PEA), N-alpha-linolenoyl ethanolamide (ALEA) N-linoleoyl ethanolamide (LEA), N-oleoyl ethanolamide (OEA), N-stearoyl ethanolamide (SEA), N-eicosapentaenoyl ethanolamide (EPEA), and, N-docosahexaenoyl ethanolamide (DHEA).

Receptors

Cannabinoid (CB) 1 receptors are generally present in abundance in the central nervous system (brain and spinal cord) and CB2 receptors are present in the peripheral nervous system (nerves in extremities), the digestive system, and immune system. Research indicates that both CB1 and CB2 receptors are also found in epidermal keratinocytes, cutaneous nerve fibers, dermal cells, melanocytes, eccrine sweat glands and hair follicles. 13 , 16 , 17 , 19 – 21 , 22 While cannabinoid receptors remain the primary targets for endocannabinoids, they have also been shown to bind to Transient Receptor Potential (TRP) receptors present in various types of skin cells ( Figure 1 ) and are involved in different functions like formation and maintenance of the skin barrier, cell growth, cell differentiation, immunological and inflammatory processes. 23

Schematic representation of the key components of the ECS in different cellular compartments of the skin.

In addition, endocannabinoids also interact with peroxisome proliferator-activated receptors (PPAR) via direct (endocannabinoid) or indirect (secondary metabolite of endocannabinoids) signaling pathways. PPAR (α and γ) activation partially mediates major biological functions of endocannabinoids like neuroprotection, antiinflammation, and analgesic actions. The ECS and some other non-cannabinoid (indirect) targets influencing the ECS in different cellular compartments of the skin are also shown in Figure 1 . A simplistic mechanism of action of endocannabinoids like AEA and 2-AG on CB1 and CB2 receptors in presynaptic neurons in the central and peripheral nervous systems is shown in Figure 2 , which also shows the modulation of the ECS by phytocannabinoids (PCBs) by direct activation of CB1 (like THC). Indirect mechanisms of the ECS (not shown in the figure) include inhibition of enzymatic breakdown of endocannabinoids (ECBs) and/or receptor modulation.

Modulation of the ECS by endocannabinoids and phytocannabinoids in presynaptic neurons in the central and peripheral nervous systems.

Enzymes and Transporters

The synthesis of endocannabinoid AEA is mediated by Phospholipase D while diacylglycerol lipase (DAGL) regulates the synthesis of 2-AG. 24 , 25 The degradation of AEA and 2-AG primarily is regulated by two enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. 2 The biological signaling of endocannabinoids via interaction with their receptors is inhibited by a two-step mechanism. The endocannabinoids are first removed from the intracellular space by a membrane transporter known as anandamide membrane transporter (AMT) and then, after reuptake, the endocannabinoids entering the cells are metabolized by enzymes like FAAH and MAGL. 26

Types of Cannabinoids

Cannabinoids can be broken into three general categories based on where they are produced. Endocannabinoids (ECBs) are the cannabinoids compounds biosynthesized within the human body. Figure 3 represents the chemical structures of nine endocannabinoids found in human skin by Kendall et al. 10 Phytocannabinoids (PCBs) are the cannabinoids obtained from plants while synthetic cannabinoids (SCs) are generated synthetically using various chemical processes (e.g., Dronabinol, Nabilone). Phytocannabinoids are found in abundance in the resin-producing trichomes of the Cannabis sativa L. plant (C. sativa). While there are many cultivars of C. sativa, regulatory bodies typically segment them into one of two different chemotypes. Industrial hemp is the chemotype with a minimal amount of tetrahydrocannabinol (THC) and higher levels of CBD, while the marijuana chemotype contains high levels of THC (e.g., above 0.3% w/w by dry weight). Figure 4 represents the most common phytocannabinoids found in hemp.

Chemical Structures of 9 endocannabinoids found in human skin.

Chemical structures of the most common phytocannabinoids found in the hemp plant.

Historically, hemp has been cultivated for its fiber, which can be used to produce paper or clothing, or for its nutritious seeds. More recently, hemp has gained popularity for its beneficial cannabinoid constituents including CBD. While the flowering tops and leaves of hemp have significant levels of CBD, the hemp stems/stalks and seeds have little to none. Hemp seeds contain nutritious omega-3 fatty acids and are high in protein, but only contain trace amounts of PCBs and no terpenoids. 27 Steam distillation of hemp flowering tops and leaves is commonly used to produce an essential oil containing terpenoids such as myrcene, α-pinene, and β-caryophyllene. 28 However, the volatile fraction produced from steam distillation will not contain appreciable amounts of PCBs. 29 Ethanolic and supercritical CO2 extracts of whole hemp plant or flowering tops and leaves can have significant levels of CBD. 30 These extracts have various commonly known nomenclatures like full spectrum hemp extract, broad spectrum hemp extract, hemp oil, and, phytocannabinoid-rich hemp oil/extract.

Potential of Cannabidiol for Skin Health and Dermatological Conditions

Because the ECS plays an important regulatory function in the skin, it is plausible that treatment with topical cannabinoids could be efficacious for certain disorders or skin health in general. However, most of the clinical evidence to date has focused on the effects of CBD and other cannabinoids when consumed, inhaled, or injected. There is limited research investigating the therapeutic potential for topical applications. Yet, there is evidence to suggest applying cannabinoids, and specifically CBD, topically may be a viable route of administration for certain conditions. Although CBD has a reasonable molecular weight (314.46 Da), its high log P value (lipid/water partitioning) of

6.3, poses unique challenges to its transdermal delivery. 31 However, this challenge may be overcome if appropriate carrier systems are used, as seen with CBD being absorbed transcutaneously in preclinical models. In 2003, Lodzki et al reported successful transdermal delivery of CBD in a murine model by using ethosomal carriers. 32 Similarly, Hammel et al investigated the efficacy of topically applied CBD (1–10%) in a gel format, specifically for reduction of inflammation-associated symptoms in a monoarthritic rat model, and found that it was well-absorbed, as the plasma concentration showed a linear relationship with the dose applied. 33 In vitro diffusion studies using human tissue have demonstrated CBD’s permeation potential. 34 However, at present no clinical trials investigating the topical absorptive capability in humans have been identified. Further work is warranted to better understand the appropriate doses and delivery methods for therapeutic CBD skin applications.

Skin Protection | Barrier Function

Skin serves as a protective barrier against environmental insults which can lead to the generation of reactive oxygen species (ROS). 35 , 36 Oxidative stress induces cell damage and can result in chronic inflammation if left unchecked. It is also implicated in skin disorders and skin aging. 36 Keratinocytes are the main cell type in the epidermis and are particularly sensitive to environmental stressors. 37

The harmful accumulation of ROS is countered in healthy skin by activation of numerous defense mechanisms. Many of these systems are controlled by the master regulator of cellular antioxidant defense system, NRF2 (nuclear factor erythroid 2-like 2) and PPAR-γ. 38 The stress-induced enzyme Hemeoxygenase1 (HMOX1) is one of the key NRF2 target genes and exhibits antioxidant and anti-inflammatory properties. 39 In in vitro studies, CBD has demonstrated the ability to induce expression of HMOX1 and other NRF2-regulated genes. 40 , 41 One study done in Normal Human Epidermal Keratinocytes (NHEK), reported that CBD induced the expression of several NRF2 target genes, with HMOX1 being the most upregulated by CBD. 42 In the same study, increased levels of HMOX1 and expression of proliferation and wound repair keratins 16 and 17 were observed in mice epidermis after topical application of CBD. In another in vitro study using human keratinocytes, researchers showed that CBD was able to penetrate the cells and balance the oxidative stress response resulting from UVB irradiation and hydrogen peroxide. They also demonstrated that CBD had a protective effect against the peroxide-induced reduction of polyunsaturated fatty acids in the cell membrane, helping to protect membrane integrity. 43 There is evidence to suggest CBD can activate PPAR-γ, as well. Treating 2D and 3D fibroblast cells with CBD resulted in activation of PPAR-γ with a corresponding decrease in levels of NF-kB. 44 Since HMOX1 and PPAR-γ play strong cytoprotective roles with anti-inflammatory, antioxidant, and anti-apoptotic properties, treatments regulating their expression could be beneficial for skin conditions characterized by inflammation and keratin disorders, such as eczema or atopic dermatitis.

Pain and Muscle Relief

Tissue damage typically triggers an inflammatory response in the body which could result in irritation, ulcers, sensitization of peripheral tissues, neuropathies, and chronic wounds. 45 If left unresolved, a chronic inflammatory state in the body leads to increased tissue damage and pain. 46 Current therapies (cannabinoids, antidepressants, NSAIDs and anticonvulsants) for chronic pain management target the peripheral and central nervous system often producing undesirable side effects. 47 , 48 Preclinical and clinical models have shown that targeting peripheral inflammation by topical therapy (e.g., clonidine 49 , 50 capsaicin) 51 , 52 is not only effective in reducing pain for specific conditions but also circumvents the CNS, thereby reducing the negative side effects, ie, respiratory depression, sedation, and tolerance. While preclinical models strongly indicate that ingestible cannabinoids may produce antinociceptive effects in neuropathic and inflammatory pain models 53 , 54 and a moderate level of clinical evidence supports the use of ingestible cannabinoids for chronic pain (primarily THC and combination of THC+ CBD + lower levels of other cannabinoids) 18 , 55 , 56  the clinical application of topically applied CBD for pain management has not yet been validated by robust scientific and clinical studies.

Eczema or Atopic Dermatitis

Atopic Dermatitis (AD) is a chronic inflammatory skin disorder associated with multifactorial causes like environmental triggers, damaged skin barrier function, microbiome imbalance, genetic predisposition, and an altered immune response. 57 Phytocannabinoids have been shown to modulate inflammatory responses by regulating more than one underlying mechanism. Adelmidrol, a PEA derivative, has been shown to be effective in treating mild AD in a pediatric population. 58 Though the efficacy of CBD is yet to be clinically validated, in a recent study by Petrosino et al, CBD was shown to exhibit anti-inflammatory properties in an experimental, allergic contact dermatitis model. 59

The influence of microbiome imbalance, especially due to colonization and biofilm formation of Staphylococcus aureus (S. aureus), has also emerged as an influencing factor which can contribute towards the severity of dermatitis. 60 , 61 The preliminary data indicating the antimicrobial and antibiofilm activity of hemp come from the essential oil (steam distillate) fraction of hemp which is composed mainly of terpenoids such as myrcene, α-pinene, β-caryophyllene and other terpenes, but no significant levels of CBD. 28 , 62 Zengin et al evaluated the antimicrobial and antibiofilm efficacy of hemp essential oil (EO) against a reference strain (S. aureus American Type Culture Collection (ATCC) 29,213) and three clinical strains (S. aureus 101 TV, S. aureus 104, and S. aureus 105). The effective Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), and the Minimum Biofilm Eradication Concentration (MBEC) hemp EO values against all S. aureus strain types were reported as 8, 16 and 24 mg/mL, respectively, which indicated the hemp EO may disrupt and eradicate a mature biofilm of S. aureus. Thus, the antimicrobial and antibiofilm activities of hemp EO against S. aureus suggest its therapeutic potential to prevent skin disorders like atopic dermatitis. 63

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Itch (Pruritis)

When it becomes chronic, itch or pruritis can severely affect one’s quality of life. The pathogenesis of pruritis is well researched and is described comprehensively in various recent review articles. 64–66 Though most of the ECS research indicates that the itch response is primarily modulated through CB1 receptors in the CNS, 67–69 some reports argue the involvement of peripheral CB1 receptors could also be a potent contributor to itch. 70 , 71 The available data thus far for the involvement of peripheral CB2 receptors are conflicting and more research is needed to conclusively determine its role in pruritis. 72 , 73 It has also been shown that all ionotropic cannabinoid responsive receptors (e.g., TRPV1−4, TRPA1 and TRPM8) play a vital role in the complex cutaneous communication between keratinocytes, immune (Mast) cells and the sensory nerves which leads to an itch sensation. 74–78 Thus, inhibiting the activity of such ionotropic channels by selective PCBs may be helpful in alleviating pruritis.

FAAH and MAGL inhibitors, which can increase the levels of endocannabinoids and modulate cannabinoid and non-cannabinoid receptor responses, were found to demonstrate anti-pruritic effects on murine models when administered via intraperitoneal and intrathecal routes. 79–81 Though cannabinoids like THC and PEA have been shown to reduce itching in murine models, 82 the human clinical data for testing the antipruritic potential of PEA have resulted in conflicting results. 83 , 84 To add to the dilemma, a study by Spradley et al indicated that peripheral endocannabinoids have opposite effects on itching behavior in spinally versus trigeminally innervated skin of mice, and therapeutic treatment of itch might be more relevant for treating the lower body than itch arising from trigeminal innervated skin of the face or scalp. 85 Since CBD is a FAAH inhibitor, a CB2 inverse agonist 86 (antagonist of CB2 agonists) and TRPV1 agonist, it could potentially play a role in modulating itch response, but the scientific evidence remains scarce for this application to-date.

Wound Healing

Wound healing is an intricate process which includes three overlapping phases – inflammation, proliferation, and maturation/tissue remodeling. 87–89 It is plausible that the complex process of wound healing is influenced by ECS signaling, as it modulates epidermal proliferation and differentiation, fibroblast functions, and cutaneous inflammation. CB1 and CB2 receptor involvement during the wound healing process in various immune and fibroblast cells are based on murine models. 90–92 In these models, various cannabinoid analogs have generated a wound healing response possibly associated with activation of CB1 and/or CB2 receptors, upregulation of anti-inflammatory factors, indirect activation of TRPV1 and epidermal growth factor receptors, and inhibition of the FAAH enzyme. 91 , 93 , 94 The evidence of the clinical application of PCBs, especially CBD, for wound healing is scarce. A single study reported three patients suffering from Epidermolysis bullosa (a rare skin disorder characterized by pain and blistering) had faster wound healing, less blistering and amelioration of pain with self-reported topical use of cannabidiol. 95 , 96

Though there is a dearth of clinical evidence, the pre-clinical models indicate an optimistic outlook. A study by Sangiovanni et al reported the effects of CBD and Cannabis Sativa Extract (CSE, standardized to 5% CBD) on human keratinocytes (HaCaT cells) and human dermal fibroblast (HDF) cells. 97 In keratinocytes, TNF-α (Tumor Necrosis Factor alpha) treatment resulted in upregulated expression of 26 genes involved in inflammatory pathways and included chemokines like CXCL8 and CXCL10, interleukins like IL−17C and IL−1B, and VEGF-A. Treatment with CSE downregulated all 26 inflammatory related genes, and CBD alone downregulated 15 genes. In HDF cells, TNF-α treatment upregulated 16 genes involved in the process of wound healing. While CSE was again able to downregulate all genes, CBD only downregulated 11 genes and did not exhibit any inhibitory effects on genes playing a role in inflammation and matrix remodeling, including IL−6 and MMP−9. These results indicate that the additional components within the complex cannabinoid extract, such as the other cannabinoids, flavonoids, and terpenes, may exert a synergistic anti-inflammatory effect greater than that of CBD alone. More robust preclinical and clinical studies are needed to draw a conclusion on the cutaneous wound healing response of the CBD and its related compounds.

Acne/Seborrhea

The major factors involved in acne onset are sebum overproduction, unwanted sebocyte proliferation, and inflammation. It is known that the ECS plays a key role in homeostasis of the skin, and specifically in lipogenesis. The endocannabinoid AEA, has been shown to stimulate lipid production in human sebocytes at low concentrations but induces apoptosis at higher levels. 98 Although current research is limited, several in-vitro studies indicate that CBD could be a novel therapeutic in the management of acne by acting on pathways relating to sebum production, sebocyte proliferation, and inflammation. One notable study performed by Oláh et al addresses CBD’s potential effects on several of these outcomes. First, researchers investigated the effects of CBD on sebaceous gland function in human SZ95 cells. They found that a 24-hour treatment of CBD (1–10 μM) alone caused no changes in cellular lipid synthesis; however, when cells were first treated with AEA, CBD was able to quell the lipogenic actions in a dose-dependent manner. The researchers went on to test other lipogenic substances, including arachidonic acid and a mixture of linoleic acid and testosterone, and found that CBD was able to inhibit extraneous lipid synthesis induced by those compounds, as well. This finding suggests that CBD’s effect is a universal action and is not limited to direct ECS interaction. 99 Also, it is important to note that CBD does not simply reduce lipid production but rather it is able to normalize lipogenesis in a state of imbalance. The same researchers went on to investigate the anti-proliferation abilities of CBD in-vitro. They found that CBD did not suppress cell counts beyond the starting number (did not reduce the number of viable cells) but did significantly reduce the overall proliferation of cells at 1−10 μM doses. Higher doses of CBD (50 μM) or elongated application (6 days) did result in apoptosis-driven cytotoxicity and overall viable cell count was reduced.

Finally, Oláh’s research group examined CBDs anti-inflammatory actions and found that it was able to prevent pro-acne mediators from elevating TNF-α mRNA expression. It also was able to normalize the LPS-induced expression of IL−1B and IL6. This data provided further evidence for CBD’s substantial anti-inflammatory actions. Notably, it is believed the control of sebocyte proliferation and lipid production was mediated through TRPV4 signaling, while the anti-inflammatory effects of CBD application were not. 99

In addition to previously mentioned factors, imbalance in the skin microbiome may also contribute to the pathogenesis of acne. Specifically, Cutibacterium acnes (C. acnes) overgrowth has been linked to the establishment of acne for over 100 years. 100 Therefore, the known anti-microbial effects of CBD may also prove effective in acne treatment. In an in-vitro study by Jin et al, a hemp seed hexane extract (HSHE) exhibited anti-microbial activity on C. acnes while inducing inflammation, and lipogenesis in sebocytes at the molecular and cellular level. 101 With 20% HSHE treatment, complete inactivation of C. acnes was observed. In this study, the content of CBD in HSHE was not reported; hence, it is difficult to attribute the contribution of CBD alone towards inactivation of C. acnes. Similarly, in a small clinical study involving men with buccal facial acne, a 3% Cannabis seed extract containing cream led to decreased sebum content and erythema. As cannabis seed extract contains minimal CBD content, it limits our understanding of application of CBD for acne and seborrhea therapy. 102 Likewise, hemp essential oil contains many terpenes which were shown to have anti-microbial effects against C. acnes (formerly known as Propionibacterium acnes). 103 , 104

We speculate that Hemp seed extract or hemp EO could also have potential for treating acne vulgaris because of its anti-lipogenic, anti-proliferative, anti-inflammatory, and anti-microbial, properties, which may target similar or independent mechanisms than that of CBD. Unfortunately, no large-scale human trials have investigated the role of CBD for the management of acne. Larger studies will help to understand how CBD may impact acne at the clinical level.

Modulation of Hair Growth

The human hair follicle is an immune-privileged miniaturized organ consisting of epithelial and mesenchymal tissue. As part of the pilosebaceous complex, the hair follicle is extensively regulated, the extent of which is still not completely understood. Human scalp hair growth is a complex and dynamic process including a period of keratinocyte proliferation and hair fiber growth (anagen), followed by a stage of apoptotic follicle regression (catagen) and a semi-quiescent stage (telogen). 105 Hair growth abnormalities include lack of hair growth (alopecia), and excessive hair growth (hirsutism and hypertrichosis). Given the success of topically applied compounds to treat hair loss 106 coupled with the detection of major cannabinoid compounds in hair fibers, including CBD, following cannabis consumption 107 and topical application of hemp oil 108 further understanding of how cannabinoid compounds can potentially benefit hair-related issues is needed. 109–111

Immunohistochemical analysis of human skin revealed differential expression of CB1 and CB2 receptors within the hair follicle. CB1 was detected in portions of the infundibulum and the inner root sheath, but absent from the outer root sheath, the bugle, hair bulb, and arrector pili muscle. CB2 was present in the outer root sheath and hair bulb, but absent in the inner root sheath, bulge, and arrector pili muscle. 19 Surgically isolated facial hair follicle cultures showed production of ECBs – AEA and 2-AG. Intriguingly, AEA, and ∆ 9 -THC suppressed hair follicle growth and induced the catagen cycle. The effects of these endo-exo cannabinoids were ameliorated by the addition of a CB1 antagonist. 2-AG treatment, however, resulted in comparable follicle growth compared to vehicle control-treated follicles. 112

An orally administered synthetic antagonist of CB1 promoted hair growth stimulation in obese mice but had no effect when applied topically. Whether oral administration of the CB1 antagonist specifically targeted CB1 to induce hair growth was not discussed by Srivastava et al. 113 Bodo et al identified the expression of TRPV1 in human hair follicles and outer root sheath keratinocytes. 114 Activation of TRPV1 in follicle organ cultures leads to inhibition of cell proliferation, while inducing apoptosis and catagen entry. Hair growth activators, HGF, IGF1, and SCF, were also suppressed with TRPV1 stimulation. TRPV3 and TRPV4 were also detected in human hair follicles and outer root sheath keratinocytes, and receptor activation, though not exclusively by cannabinoids, resulted in suppression of hair follicle elongation. 115 , 116 A metabolite of the endocannabinoid anandamide, bimatoprost, is recognized as a topical prostamide treatment for eyebrow hypotrichosis. 117 Khidhir et al also showed human scalp hair follicles possess select prostamide receptors within the dermal papilla. Working with human scalp, organ-cultured hair follicles, bimatoprost treatment resulted in follicle growth and it stimulated hair regrowth when applied to mouse skin. 118 A limited clinical study showed bimatoprost application also accelerated hair regrowth in alopecia areata patients to a greater extent than a topical steroid treatment. 119 Szabo et al in a pilot study using ex vivo human hair follicles and primary outer root sheath keratinocytes found systemic-like application of CBD had dose-dependent opposing effects on hair growth dynamics. 116 At the 0.1 µM and 1.0 µM doses, the hair shafts grew similar to controls, while at the 10 µM dose, growth was significantly suppressed and follicle catagen was induced. As CBD dosage increased, keratinocyte proliferation decreased. The researchers proposed that CBD concentration may lead to differential receptor activation, with low doses favorably affecting hair growth pathways and higher doses activating suppression targets such as TRPV4.

As the hair follicle contains ECS and cannabinoid-responsive receptors, coupled with the evidence of cannabinoid deposition within the fiber followed by cannabis consumption and topical application, there may be potential to use compounds like CBD to treat certain hair disorders. However, given the complexity of hair growth dynamics, research conducted employing hair follicle organ culture and systemic-like treatment, and the potential of pleiotropic effects of certain cannabinoids seen to date, additional research is needed, including clinical trials, to determine if phytocannabinoids like CBD can be effective topical interventions to treat hair loss or excessive hair growth conditions.

Skin and Hair Pigmentation

The pigmentation of human skin is the manifestation of synthesis of dark pigment, melanin, which is regulated by a melanogenesis process in melanocytes. 120 , 121 Melanogenesis is a complex process regulated by more than 250 genes. 122 Microphthalmia Transcription Factor (MITF) acts as a master regulator of melanogenesis, directly controlling the transcription of key genes involved in pigmentation such as tyrosinase (TYR), tyrosinase-related protein (TYRP)-1, and TYRP-2. 123

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Due to a limited number of studies, the involvement of the ECS in the cascades of the melanogenesis process is not clear. In 2012, Pucci et al showed that a fully functional ECS was present in normal human primary epidermal melanocytes. Lower concentrations of AEA, as well as other endocannabinoids like Arachidonoyl-2′-chloroethylamide (ACEA), and 2-AG, demonstrated induction of melanogenesis in a dose-dependent manner via the CB1 receptor. 21 However, other studies demonstrated contrasting results with CB1 agonism inhibiting melanogenesis or having no influence. Zhou et al demonstrated that OEA acts as an inhibitor of melanin synthesis and MITF production in α-MSH stimulated B16 cells via activation of ERK, Akt, and p38 pathways and inhibition of the CREB pathway. 124 Another study by Magina et al demonstrated that CB1 agonism, under UVB exposure in a co-culture model using HaCat and SK-mel-1 cells, inhibited basal melanogenesis, whereas the inhibition was reversed when a CB1 antagonist was introduced. 125 Kim et al demonstrated that a major metabolite from JWH-073, a synthetic cannabinoid, had no significant effect on hair pigmentation. 126 Unfortunately, there are limited studies regarding the effect of phytocannabinoids, such as CBD, on melanogenesis. Hwang and colleagues demonstrated that CBD stimulated both melanin content and tyrosinase activity, mediated by the CB1 receptors in human epidermal melanocytes. The melanogenic effects of CBD occur primarily through MITF upregulation, which is mediated by the activation of p42/44 MAPK and p38 MAPK signaling. 127

Involvement of ECS pathways in melanocytes is very complex and unclear, thus requiring additional research with various in vitro and in vivo models. Although endocannabinoids are potential mediators for healthy and diseased skin, it is believed to be premature to target pigmentation disorders using cannabinoids. 124

Potential Applications in Oral Care

There is little published about the use of CBD in oral care. In the 1950s, the topical preparations from C. sativa were found to contain antiseptic properties against several oral cavities and skin lesions. 128 , 129 In 2012, Ali et al studied the effect of C. sativa seed oil, and petroleum ether and methanol extracts of the whole plant, on two Gram-positive bacteria (B. subtilis, S. aureus), two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and two fungi (Aspergillus and Candida albicans). The seed oil exhibited pronounced antibacterial activity against the Gram-positive bacteria, moderate to high activity against Gram-negative bacteria, but was ineffective against the fungi. 130 Rashid et al tested ethanol and methanol extracts of cannabis leaves and stem against different microorganisms. A significant inhibitory effect was observed in the ethanol leaf extracts of C. sativa, with 13.8 and 21.33 mm zones of inhibition against S. aureus and K. pneumoniae, respectively. 131 At 4 µg/mL and 10 µg/mL concentrations, the aqueous and acetone extracts of C. sativa cannabinoids demonstrated a high antimicrobial activity by showing clear zones of inhibition against the bacteria Pseudomonas aeruginosa (3–8 mm), and Vibrio cholerae (4–10 mm) and the fungi Cryptococcus neoformans (4–10 mm), and Candida albicans (4–12 mm). 132 It must be noted that hemp seeds and stalks barely contain CBD content, whereas other parts of the hemp plant contain significant amounts of CBD and other cannabinoids.

Dental plaque is associated with several dental diseases and should be regularly removed using mechanical (toothbrushes, floss) and chemical (mouthwashes) oral regimens. Dental plaque is the complex biofilm that acts as a reservoir of several microbes adhering to the tooth surface and gum line. An antimicrobial treatment can be used as an effective aid for plaque control and to improve the inflamed tissues of gums and bones. 130 Microorganisms forming the biofilm of the dental plaque are Gram-positive bacteria, such as Streptococcus mutans, Gram-negative bacteria, and several other anaerobes such as Fusobacterium and Actinobacteria. In 2019, Stahl et al assessed the efficacy of cannabinoids (BGA, cannabigerolic acid; CBN, cannabinol; CBG, cannabigerol; CBD; and CBC, cannabichromene) in comparison to commercial oral care products. Cannabinoids were more effective in reducing the bacterial content of the dental plaque compared to the commercially available synthetic oral care products. Therefore, natural cannabinoids may have the potential to be used as an effective treatment to remove dental plaque associated oral bacteria and provide a safer alternative to synthetic antibiotics. 129

Other Skin Disorders

Skin Infections

CBD and CBG have been reported to have potent activity against a variety of Gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) strains. 133 Likewise, an antimicrobial effect of CBD against Listeria monocytogenes, Enterococcus faecalis and Methicillin-resistant Staphylococcus epidermidis (MRSE) was reported with Minimum Inhibitory Concentration (MIC) values of 4 µg/mL for MRSA and L. monocytogenes and 8 µg/mL for E. faecalis and MRSE. 134 This study also characterized CBD as a helper compound that potentiates the effect of Bacitracin (BAC), a skin antibiotic. The MIC value of BAC was remarkably reduced to at least a 64-fold reduction for MRSA, MRSE and E. faecalis, when combined with ½ MIC of CBD as compared to MIC of BAC alone.

Furthermore, to assess the potentiating and synergistic effect against MRSA, growth curve and time kill assay results showed the combined activity of CBD and BAC reduced bacterial viability by 6-log10 cfu/mL as compared to CBD or BAC alone. Interestingly, CBD was able to potentiate the effects of BAC against MRSA (S. aureus USA300) and other Gram-positive bacteria. The spectrum of use of CBD and BAC on growth of Gram-negative bacteria, including Pseudomonas aeruginosa, Salmonella typhimurium, Klebsiella pneumoniae, and Escherichia coli, was also measured. The results obtained from the combined effect of CBD and BAC against these Gram-negative bacteria concluded that the combined activity of CBD and BAC was considered ineffective against Gram-negative bacteria. Due to potent antibacterial properties against Gram-positive bacteria, cannabinoids can be used as an effective helper compound when combined with known antimicrobial actives to fight antibiotic resistant Gram-positive bacteria which cause skin disorders and other infections. 134

Psoriatic Plaques

Some anecdotal information suggests the use of CBD for treating psoriatic plaques which are characterized by keratinocyte hyperproliferation and chronic inflammation. NF-kB plays a significant role in skin inflammatory conditions like psoriasis, and its expression is strongly induced by TNF-α. 135 Sangiovanni et al demonstrated that CBD and C. sativa extract (CSE, standardized to 5% CBD) inhibited TNF-α induced NF-kB transcription in a dose-dependent manner in HaCaT cells. 97 However, in HDF cells, only CSE exhibited NF-kB inhibitory effects. In other cell types, CBD has been reported to have the ability to impair the NF-kB pathway both in-vitro and in-vivo. 136 , 137 Though CBD has shown to have anti-inflammatory properties, its role in keratinocyte differentiation and proliferation is not clear. Some in vitro studies have shown that CBD inhibits differentiation in immortalized HaCaT cells 138 and also exerts antiproliferative actions on transformed human keratinocytes (HPV16). 139 On the contrary, a study by Casares et al indicated that the role of CBD in treating psoriasis should be approached with caution due to its proliferative effects for keratins 16 and 17. 42 Thus, more robust experimentation is needed to determine the use of treatment for psoriatic lesions.

Cutaneous Malignancies

The therapeutic potential of targeting the ECS for cutaneous malignancies such as melanoma and non-melanoma skin tumors is described at length in an excellent review article by Toth et al and is beyond the scope of this article. 4 Cannabinoids such as ∆ 9 -THC and AEA have better scientific research for this application. Though some preclinical studies have shown that CBD inhibits transporter proteins involved in breast cancer 140 the application of CBD for treating cutaneous malignancies has yet to be explored in detail.

Open Questions and Future Research

The significance of the ECS in maintaining skin homeostasis and the resulting dermatological conditions from its imbalance has garnered scientific attention. Despite promising research on the topical therapeutic potential targeting the ECS, much remains unknown on the complexity of interactions of cannabinoids with other systems of the human body. A good example of this is the unintended interaction of BIA 10–2474 (a FAAH inhibitor intended for treating pain and anxiety) with the lipid network in human cortical neurons resulting in metabolic dysregulation of the nervous system. 141 , 142 Though the outcomes of this study are stemming from oral treatment at higher doses, it does have sound advice to treat any topical application of cannabinoids with due diligence. While many topical CBD products appear to be relatively well tolerated, topical safety studies are underway, and the evidence is still emerging.

The authors conclude that while the therapeutic potential of CBD for acne, seborrhea, eczema/dermatitis, and skin barrier function is promising, more robust studies are needed to fully validate its efficacy. The therapeutic potential of CBD should also be balanced with largely unknown/contrasting early studies in modulating pigmentation and hair growth. Thus, there is an underlying need for intense fundamental scientific research as any speculative science could lead to unwanted effects like hair growth/loss or hyper/hypopigmentation issues. Looking beyond the horizon of the buzzword CBD, the therapeutic benefits of hemp phytocannabinoids and other botanicals with phytocannabinoid-like activity ( Table 1 ), will most likely be the focus of future research.

Table 1

Examples of Phytochemicals Targeting the ECS with Phytocannabinoid-Like Activity

Ingredient Chemical Classification Plant Source(s) Mechanism of Actions Potential Therapeutic Actions
Limonene Terpene Citrus fruits Glutathione upregulation 143 Antioxidant, antitumor activity 143
β-Carophyllene (BCP) Sesquiterpene Hops, Copaiba, black pepper, rosemary, hemp essential oil 144 CB2 receptor agonism 145 , 146 Anxiolytic, antinociceptive 144 , 146–148
Echinacea Alkylamides Echinacea, Sichuan pepper CB2 receptor agonism 149–151 Anti-inflammatory 152 , antimicrobial 153 , antioxidant 154
Turmeric Curcuminoids Turmeric CB1 receptor agonism 155 Anti-inflammatory and antinociceptive properties 156
Boswellic acids Triterpenes Frankincense Inhibition of PGE2 (Prostaglandin E2) synthase 157 Anti-inflammatory 157
Magnolia Polyphenols Magnolia bark CB2 receptor agonism 158 Antioxidant, anti-inflammatory 159
Ashwagandha Lactones and steroidal alkaloids Withania somnifera Potential GABA mimetic action 160 Immuno-modulatory, stress reduction 160

Disclosure

All the authors are employees of Amway Corporation which has commercial offerings in the wellness space. The authors report no other potential conflicts of interest for this work.

CBD Oil for Skin

Many people do not recognize that the cannabis plant has a male and female part. While marijuana is classified as the female version of the cannabis plant, hemp is considered to be the male version of the plant. The hemp plant contains a higher amount of cannabidiol with low amounts of THC whereas the marijuana plants contains high amounts of THC with low amounts of CBD. It is important to note the difference when determining which type of CBD will be most beneficial to you.

There are several variations of CBD oils including:

  • CBD isolate means pure CBD, no other cannabinoids or other naturally occurring substances like flavonoids or terpenes can be detected.
  • Full spectrum CBD includes all contents of the hemp plant alongside the CBD, including trace amounts of THC and other cannabinoids such as CBG (cannabigerol) and antioxidant compounds.
  • Broad spectrum CBD means no THC is detectable. Trace amounts of THC can be detected in full spectrum CBD, but must fall below 0.3% in order to not be considered active.

CBD oil is not the same thing as hemp seed oil, which is another great ingredient for skin. The two are often marketed interchangeably, but CBD oil is richly concentrated in cannabidiol, whereas hemp seed oil only contains trace amounts of cannabidiol, if any.

The body produces endocannabinoids, which are neurotransmitters that bind to cannabinoid receptors in your nervous system. Studies have shown that CBD may help reduce inflammation through endocannabinoid receptor activity by leveraging CB1 and CB2 receptors.

CAN CBD BE ABSORBED THROUGH SKIN?

CBD can be absorbed in the skin. However, it is important to understand that this technique is much different than ingesting CBD sublingually or via inhalation. When CBD is absorbed topically it does not enter the bloodstream but rather connects with nearby cannabinoid receptors through the skin pores.

It is important to note that human skin is generally highly resistant, meaning the immune system will attempt to block many substances from entering. Research recommends that CBD topical application is potent enough to overcome the resistibility of our immune system.

The potency required is typically determined by the case being treated as well as the bodyweight of the subject. All in all, CBD is permeable to the skin through its pores and can be used for several different reasons.

IS CBD OIL GOOD FOR YOUR SKIN?

The emergence of CBD research suggests that CBD oil for skin can provide many health benefits by leveraging the cannabinoid receptors that are accessible beneath the pores of the skin. Overtime products such as CBD lotions and oils have been recommended to many for several different skin ailments.

CBD FOR ACNE

Acne is a skin condition that occurs when hair follicles are plugged with excess sebum oil and dead skin cells. This blockage causes white heads, black heads or pimples.

Research can prove that CBD is considered to be an effective all natural anti-inflammatory.

CBD for acne is well known for its ability to reduce the visibility of breakouts especially acne related redness. By reducing inflammation and redness CBD oil for skin is able to improve the look and feel of acne prone skin.

In addition, CBD acts as a hormonal balancer, this suggests that CBD can potentially decrease excess sebum oil production; helping reduce the likelihood of future breakouts.

CBD FOR WRINKLES AND AGING

CBD is well known for its antioxidant properties. An antioxidant can be defined by a substance such as vitamin C or E that removes potentially damaging oxidizing agents in a living organism.

By offsetting free-radical damage; free radicals cause collagen to break down faster, so ultimately antioxidants are also helping to slow down the process of collagen loss

visibly reducing the look of wrinkles, skin dullness and deterioration overtime related to ageing.

In this case, research suggests that CBD is ingested sublingually in order to receive its full benefit.

CBD FOR SENSITIVE SKIN

Sensitive skin can be described as easily irritable or reactive. CBD is known for its soothing properties. CBD oil for skin can help reduce redness, inflammation and reactivity that may be related to skin sensitivity or environmental stressors.

CBD AND PSORIASIS

Psoriasis is a chronic autoimmune disease where the life cycle of skin cells are accelerated. Psoriasis is considered to be very similar to eczema in its physical appearance while appears red or pink with a silver lining.

By leveraging the endocannabinoid system we can help the human body find balance again, CBD also known as cannabidiol can interact with this system in order to regulate skin pathogenesis.

Although Psoriasis doesn’t have a cure, CBD oil for skin is becoming a popular natural anti-inflammatory that can help reduce the effects of this disease while providing relief from itchiness/irritation.

CBD AND ECZEMA

Similarly to Psoriasis, Eczema can be characterized by rashes that are painful, itchy and inflamed. Research suggests that these responses are modulated by the endocannabinoid system, insinuating that CBD can potentially provide relief. According to Mary’s Nutritionals’ Chief Scientist, Jeremy Riggle, Ph.D., CBD “CBD interacts with this system and may help the skin re-establish or maintain homeostasis, the result, in this case, being a reduction in symptoms associated with eczema.” When CBD is applied topically to the affected area it avoids dilution and targets the dermal cellular level of the skin allowing this method to be most effective.

Conclusion

Although the research relating to CBD and its health benefits is in its infancy stages. CBD research continues to suggest that CBD can be beneficial in several ways. However it is important to assess the quality of CBD products by paying close attention to how it was supplied and manufactured. We recommend using a CBD isolate; meaning it is completely absent of ingredients that can potentially cause CBD to be ineffective. Prior to purchasing CBD ensure that you are taking the necessary steps finding the correct potency for your case, taking into account your body weight, tolerance and health issue.

As CBD research continues to become more prevalent, holistic wellness strategies are proven to have a lower amount of side effects suggesting that natural techniques could potentially present a better approach to health ailments in the near future.

What to Know About CBD Skin-Care Products

Research on this trendy skin-care ingredient is limited. Read this comprehensive guide before you buy.

Few ingredients have taken skin care by storm quite like CBD. And if you look carefully, it’s everywhere: in sunscreens, masks, lip balms, moisturizers, and more. The question is: Should you really be slathering this stuff on your skin?

First, let’s talk about what CBD is. Cannabidiol (CBD) is an active ingredient in the cannabis plant, according to Harvard Health Publishing. CBD can be derived from either medical marijuana or hemp. Although marijuana contains CBD, CBD doesn’t have psychoactive effects. (THC, tetrahydrocannabinol, is the chemical that causes the high.) All that said, CBD won’t lead to any mind-altering effects.

The Proposed Benefits of Skin-Care Products With CBD

Experts attribute the popularity of CBD to its “do anything” reputation. In fact, many people turn to CBD in the hope of treating various ailments, including anxiety, insomnia, pain conditions, and now — increasingly, it seems — skin problems.

In general, manufacturers add CBD to their products to give them a boost. “CBD is a very cost-effective way to enhance products,” says Austin Katz, cofounder of Sheabrand in Brooklyn, New York. CBD is in a range of products — those that claim to treat acne, dry skin, and eczema — because of its versatility. “I think we’re living in an era where people want to feel empowered to address their needs on their own,” he says.

CBD Skincare

Potentially Helps Inflammation, Eczema, and Psoriasis

One of the touted functions of CBD is controlling inflammation. “The body has two CBD receptors that we know of: CB1 and CB2,” says Robert Dellavalle, MD, PhD, adjunct professor of epidemiology at the Colorado School of Public Health in Aurora. When applied to skin, CBD interacts with these receptors to turn down the inflammatory response. This happens by “decreasing the interleukins, which are chemicals that are like the immune system’s fire alarm that calls the fire department in an emergency. CBD may decrease the loudness of that fire alarm,” he explains.

In short, you may see less redness overall, and in skin diseases, including eczema and psoriasis, it may also be effective in tamping down itch, possibly because CBD creams may help reduce dryness, per a review published in July 2017 in the Journal of the American Academy of Dermatology. (Dr. Dellavalle was a coauthor of that report.) Keep in mind, though, that the review included only three studies: two in humans but with small sample sizes and one in mice, which doesn’t necessarily translate to human health. Therefore, more studies on the potential benefits of CBD for reducing skin redness are needed.

Additionally, a small study published in the March-April 2019 issue of the Italian journal Clinical Therapeutics looked at 20 participants with either psoriasis, eczema, or scarring and found that a specific CBD ointment improved measures of skin hydration (by moisturizing and preventing water loss), boosted elasticity in the skin, and in general bettered their quality of life. This could have been due to the fatty acids in the ointment but was also likely in part because of the anti-inflammatory effect of CBD, the researchers say. Yet more research in a larger human population is needed to know for sure.

For many skin diseases, dermatologists often prescribe topical steroid creams, which act as anti-inflammatory medicines. “These are very safe for most people, and they’re effective, but some people don’t want to use steroids in any way. CBD could be a nonsteroidal therapy to fill that gap,” says Dellavalle. Side effects of topical steroids include thinning of the skin if overused or used long term, but you can help avoid these risks when using them correctly, notes the National Eczema Association. Working with your dermatologist to ensure that you have the right medication at the right dosage can help with this.

Indeed, Mona Gohara, MD, a dermatologist in Hamden, Connecticut, and associate clinical professor of dermatology at Yale University in New Haven, Connecticut, prefers to use CBD “in inflammatory skin conditions as they’re fizzling out.” She adds, “I recommend generally using a medication to put out the fire and then using CBD to clean up the carnage.”

Beyond that, though, is the potential to use CBD as a tool to delay early signs of aging. “Inflammation is the basis of all skin disease, including aging,” she says. But while there’s a lot of hype surrounding CBD in skin care — and health in general — there is no cure-all. “Everything has its advantages and disadvantages or limitations,” says Dr. Gohara.

Possibly Plays a Role in Treating Acne

Along with being a potential therapy for inflammatory skin diseases, CBD is also featured in some anti-acne products. For instance, Mantra Mask's CBD Blemish Mask combines CBD and pimple-fighting tea tree oil. “There are CB2 receptors on sebaceous glands, which produce oil. According to research, CBD influences the sebum production of cells and has an anti-inflammatory component,” says Jeanette Jacknin, MD, a board-certified dermatologist in Solana Beach, California, who specializes in CBD skin care. This echoes findings outlined in articles previously published in The Journal of Clinical Investigation and Experimental Dermatology.

Dr. Jacknin also points to preliminary research presented in June 2019 at the annual meeting of the American Society for Microbiology that found topical CBD may help kill a range of gram-positive bacteria. “This bacteria is one cause of acne,” she says. (For the study, researchers collaborated with Botanix Pharmaceuticals, a company that develops products to treat skin diseases like acne and psoriasis.)

May Decrease Inflammation From Sunburns

Finally, one of the newest uses for CBD skin care is in sunscreen. Dellavalle notes that it does make sense to add CBD to sunscreen, as its anti-inflammatory properties may help reduce the effects of a sunburn, such as redness. Of course, the idea is to apply sunscreen correctly (following guidelines from the American Academy of Dermatology), but in real life, many people miss areas, and applying a CBD-infused SPF may supply more general absorption and temper the reaction of sunburned spots, he says.

What Scientific Evidence Doesn’t Yet Tell Us About CBD for Skin Care

If CBD sounds like the answer to your skin woes, it’s helpful to take a step back and look at the bigger picture. “What we don’t have in CBD is a lot of research. [CBD has] been illegal federally for so long, and it’s been difficult to do research on something that’s previously been considered on par with cocaine or heroin,” says Dellavalle. That’s starting to change, though. The 2018 Farm Bill removed hemp from the definition of marijuana, which meant that CBD products were no longer considered like marijuana. This has paved the way for researchers to conduct more studies on CBD, and for product manufacturers to create and sell CBD products legally, though per the Food and Drug Administration (FDA), it is still illegal to market CBD as a supplement.

A review published in June 2018 in the Dermatology Online Journal, which Dellavalle coauthored, pointed out that while CBD may “have shown some initial promise as therapy for a variety of skin diseases,” there is a need for large, high-quality, randomized, controlled trials, a sentiment echoed in an article published in December 2020 in Cannabis and Cannabinoid Research. Another paper, published in the May-June 2019 issue of Clinics in Dermatology, urges people and their doctors to approach these products with the same caution. Finally, though topical CBD tends to be well tolerated and may have a role in addressing various skin issues (including acne, dryness, and irritation), there’s still ongoing research on the safety of CBD treatment, notes an article published in 2020 in Clinical, Cosmetic, and Investigational Dermatology.

Unknowns About CBD Dosage

Scientists still don’t know the ideal dose of CBD for treating skin conditions or promoting general health. Some companies, like Sheabrand, formulate with different doses depending on the area of skin the product is designed for — the body or the face, for instance — for maximum penetration. Scientists also don’t know where CBD stands in relation to proven topical therapies, like retinoids, vitamin C, or alpha hydroxy acids.

Questions About Cannabinoid Combinations

There are hundreds of other chemicals in the cannabis plant, and researchers don’t know what combinations are best. For instance, terpenes, the essential oils in plants (including cannabis), may exert synergistic benefits, suggests the Clinical Therapeutics study. “So much research needs to be done. We’ll be sorting this out for the next 25 years,” says Dellavalle. On the horizon with more research from universities and companies, says Jackin, may be more targeted and efficacious therapies for conditions like eczema and acne.

8 Steps to Take Before Trying a CBD Skin-Care Product

For now, know that CBD products are safe in general, and early research suggests that they may make a difference in how your skin looks and feels. Just don’t count on it as a cure-all for any skin condition. In other words, talk to your dermatologist before replacing products they have recommended with ones containing CBD, and don’t treat any new skin conditions with CBD products until you speak to your dermatologist. If you’re interested in venturing into CBD skin care, here’s what you need to know before you buy and try:

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