The newly discovered endocannabinoid system (ECS; comprising the . conditions such as hyperproliferative skin diseases (e.g. psoriasis. Findings: Effects of Cannabinoids and CBD on Psoriasis When the endocannabinoid system is disrupted, it can lead to the development of. The endocannabinoid system plays a role in regulating skin cells' life. Research and patients' experience are proving CBD and THC oils and.
the CBD System & in Psoriasis Endocannabinoid
Potential for addiction, however small, is a serious concern when prescribing cannabinoid therapy. Dr Bowling pointed out that drug interactions with cannabinoids remain poorly understood.
Products from state dispensaries may [also] contain contaminants, including pesticides, microbes, mycotoxins, heavy metals, and solvents. Physicians have remained reluctant to use cannabinoids despite evidence of potential benefits in RA, which according to Dr Shoenfeld, can be attributed to 2 key factors: An additional challenge is a lack of physician training in the appropriate use of cannabinoids. Dr Shoenfeld pointed to a survey of American residents and fellows in which Currently only 1 clinical trial examined the efficacy of cannabinoids in pain reduction in [patients with RA].
Researchers examined the frequency of remission and low disease activity in patients with rheumatoid arthritis. Researchers assessed the effect of the introduction of biologic DMARDs on the incidence rate of upper limb joint replacements in patients with RA. This growth inhibition was accompanied by enhanced intra-tumor apoptosis and impaired tumor vascularization altered blood vessel morphology, decreased expression of pro-angiogenic factors such as VEGF, placental growth factor and angiopoietin 2.
Consistently, cannabinoids were also reported to inhibit the in vivo growth of melanomas that express CB 1 and CB 2 by decreasing growth, proliferation, angiogenesis and metastasis formation, while increasing apoptosis [ 39 ]. By contrast, a recent study of Zheng et al. Collectively, these studies suggest that the cutaneous ECS, as in other organs, might act to tonically modulate cell growth, proliferation and death [ 30 , 56 ] Figure 1.
Since the original discovery of the CB 2 receptors in immune cells, much evidence using various CB receptor agonists and antagonists or compounds that enhance the levels of endocannabinoids by decreasing their metabolism suggest that the ECS has numerous important immune modulatory effects e. Although some controversies do exist in the field, it is generally recognized that the ECS exerts protective functions in large number of acute and chronic inflammatory diseases [ 13 , 17 ].
A recent study by Karsak et al. Using an animal model for cutaneous contact allergic hypersensitivity, Karsak et al. They also found that mice lacking both CB 1 and CB 2 or treated with antagonists of these receptors displayed exacerbated allergic inflammatory response.
The existence of the ECS-mediated protection was also supported by a reduced allergic response in the skin of FAAH-deficient mice, which have increased levels of the endocannabinioid AEA. Moreover, the skin inflammation was suppressed by locally administered THC [ 40 ]. Similarly, in a murine model of passive IgE-induced cutaneous anaphylaxis, both synthetic non-selective CB agonists and saturated N -acylethanolamine derivatives homologues of N -palmitoyl ethanolamine, PEA exerted marked anti-inflammatory properties in vivo [ 57 ].
By contrast, using different animal models for acute and chronic contact dermatitis, Oka et al. The symptoms of skin inflammation were markedly attenuated by CB 2 but not CB 1 antagonists [ 61 ]. Likewise, others using different animal models Table 1 to induce allergic contact dermatitis reported a decrease in the cutaneous inflammation of CB 2 -deficient mice [ 62 ], and similar suppression of the inflammatory response by orally administered CB 2 antagonists was also observed [ 62 , 63 ].
Consistently, Zheng et al. In a recent study Akhmetshina et al. The phenotype of knockouts was mimicked by transplantation of knockout bone marrow into control mice, whereas CB 2 knockouts transplanted with bone marrow from wide-type mice did not display an increased sensitivity to bleomycin-induced fibrosis, indicating that leukocyte expression of CB 2 critically influences experimental fibrosis [ 64 ].
Decreased dermal fibrosis and inflammation was observed upon treatment with the CB 2 agonist, suggesting a potential therapeutic utility of selective CB 2 agonists for the treatment of early inflammatory stages of systemic sclerosis. The ECS has a crucial role in central and peripheral processing, and in the control of such skin-derived sensory phenomena as pain and itch. However, the detailed discussion of these effects is beyond the scope of this article and we would like to refer readers to overviews on this subject [ 31 , 65 — 67 ].
The aformentioned preclinical data encourage one to systematically explore whether ECS-modulating drugs can be exploited in the management of common skin disorders.
However, the pleiotropic nature and strong cell-type dependence of the cutaneous ECS-mediated functions will require careful judgment for patient selection and indications. In this section, we review preliminary data and discuss the possible applications of ECS-targeted therapies Figure 2 ; Table 2.
ECS-targeted approaches in skin diseases. Modulations of the fine-tuned tone of the cutaneous endocannabinoid system ECS could have therapeutic values in the management of a large variety of human skin diseases.
For example, suppression of the skin ECS tone using e. Conversely, augmentation of the tone of the cutaneous ECS using e. Data showing that the cutaneous ECS tonically inhibits cell growth and angiogenesis and induces apoptosis in most of the skin cell types, and that both human non-melanoma and melanoma tumors express considerable amounts of CB 1 and CB 2 [ 36 , 39 , 41 , 42 , 45 , 53 ], now warrant proof-of-principle studies to test the therapeutic value of cannabinoid agonists in the clinical management of hyperproliferative skin disease e.
Furthermore, these interventions as detailed later might also suppress skin inflammation seen in psoriasis. The novel concept that human HFs are both targets and sources of endocannabinoids, which, via CB 1 establish an autocrine—paracrine system for negatively regulating hair growth, invites careful investigation of the growth-inhibitory effects of CB 1 agonists in the putative management of unwanted hair growth such as hirsutism.
Likewise, future exploitation of CB 1 -antagonist-based adjuvant treatment options in the clinical management of alopecia areata and effluvium is also of potential interest.
Acne and seborrhea, the most common dermatological diseases, are characterized by highly elevated lipid sebum production of the SGs. Furthermore, transdermal penetration of cannabinoids is well established [ 68 , 69 ], raising the possibility that these agents could be efficiently applied topically to the skin in the form of a cream.
Therefore, such cannabinoid-containing creams could also be beneficial under these conditions. With respect to the possible treatment of itching, it is most promising that Stander et al. Therefore, it can be hypothesized that the fat-production-promoting actions of cannabinoids might, at least in part, contribute to the beneficial effects seen in these patients.
Topical formulations that contain cannabinoid ligands or that enhance the cutaneous ECS tone could have therapeutic values in skin inflammations. A recent experimental study has suggested that CB 2 agonists could represent a promising approach for the treatment of early inflammatory stages of systemic sclerosis scleroderma [ 64 ].
As detailed elsewhere, various cannabinoid agonists in addition to agents that increase the cutaneous levels of endocannabinoids have been effectively used in various models of pain and itch [ 13 , 31 , 65 — 67 ]. Pathological alterations in the activity of the fine-tuned cutaneous ECS might promote or lead to the development of certain skin diseases.
Therefore, it is envisaged this is also strongly supported by pilot studies that the targeted manipulation of the ECS aiming to normalize the unwanted skin cell growth, sebum production and skin inflammation might be beneficial in a multitude of human skin diseases. However, to predict the real therapeutic potential and translate the exciting preclinical observations discussed earlier into clinical practice, numerous important questions should carefully be addressed Box 2.
Nevertheless, targeting the cutaneous ECS for therapeutic gain remains an intriguing and provocative possibility warranting future studies. National Center for Biotechnology Information , U. Author manuscript; available in PMC Oct 5. Author information Copyright and License information Disclaimer. The publisher's final edited version of this article is available at Trends Pharmacol Sci. See other articles in PMC that cite the published article. Abstract The newly discovered endocannabinoid system ECS; comprising the endogenous lipid mediators endocannabinoids present in virtually all tissues, their G-protein-coupled cannabinoid receptors, biosynthetic pathways and metabolizing enzymes has been implicated in multiple regulatory functions both in health and disease.
Introduction to skin biology The skin is the largest organ of the integumentary system the organ system that protects the body from damage and is composed of multiple layers and cell types: Epidermis made of keratinocytes which provide waterproofing and serve as a barrier to infection , Merkel cells which function as mechanoreceptors for the sensation of touch and pressure , melanocytes whose activity of melanogenesis defines skin color and Langerhans cells which function as professional antigen-presenting cells of the skin immune system.
Dermis a dense connective tissue composed of collagen, elastic and reticular fibers produced mainly by dermal fibroblasts. Hypodermis or subcutis made of adipocytes, fibroblasts and macrophages part of the skin immune system. Selected functions of the skin involve: Barrier functions waterproof anatomical protection barrier against, for example, physical environmental challenges e.
Sensory functions sensation of heat and cold, touch, pressure, vibration as well as pain and itch related to tissue injury ; release of neuropeptides that regulate local vasoregulatory, immune-inflammatory and trophic functions. Motor functions vasoregulation dilation or constriction of blood vessels and piloerection.
Exocrine functions production and release to the skin surface of sweat and sebum, which exocrine products participate, for example, in thermoregulation, physical barrier formation, anti-microbial activity and so on. Endocrine functions synthesis of a wide-array of hormones e. Open in a separate window. Role of the cutaneous ECS in skin growth control, survival and differentiation Recent intriguing data suggest that the cutaneous ECS is fully functional Figure 1.
Table 1 Functions of the cutaneous ECS. Skin tumorigenesis Accumulating recent evidence also implicates the ECS in the regulation of growth of skin cells in vivo. Role of the cutaneous ECS in allergic, inflammatory and fibrotic functions Since the original discovery of the CB 2 receptors in immune cells, much evidence using various CB receptor agonists and antagonists or compounds that enhance the levels of endocannabinoids by decreasing their metabolism suggest that the ECS has numerous important immune modulatory effects e.
Role of the ECS in cutaneous sensory functions: Perspectives in the ECS-targeted management of skin diseases The aformentioned preclinical data encourage one to systematically explore whether ECS-modulating drugs can be exploited in the management of common skin disorders.
Table 2 Possible ECS-targeted approaches in skin diseases. Psoriasis and skin tumors: Acne and seborrhea Acne and seborrhea, the most common dermatological diseases, are characterized by highly elevated lipid sebum production of the SGs. Dermatitis Topical formulations that contain cannabinoid ligands or that enhance the cutaneous ECS tone could have therapeutic values in skin inflammations. Systemic sclerosis A recent experimental study has suggested that CB 2 agonists could represent a promising approach for the treatment of early inflammatory stages of systemic sclerosis scleroderma [ 64 ].
Pain and itch As detailed elsewhere, various cannabinoid agonists in addition to agents that increase the cutaneous levels of endocannabinoids have been effectively used in various models of pain and itch [ 13 , 31 , 65 — 67 ]. Outstanding questions Are all members of the ECS functionally expressed in the human skin and appendages?
How do various endogenous mechanisms e. Is there any alteration in the expression levels and patterns of elements of the ECS in various human skin diseases? Alopecia a type of pathological hair loss affecting mostly the scalp; most common forms of alopecia: Cannabinoid receptors G-protein-coupled receptors that bind to and mediate the effects of cannabinoids.
Cannabinoids can be divided to various classes: Dermatitis a universal term describing inflammation of the skin; as most skin diseases, dermatitis can be induced by various factors such as, for example, allergens allergic dermatitis , infections, eczema atopic dermatitis , external compounds contact dermatitis and so on. Effluvium or telogen effluvium a form of alopecia characterized by diffuse hair shedding.
Endocannabinoid system ECS it includes endocannabinoids, the enzymes involved in the biosynthesis or metabolism, and their two G-protein-coupled cannabinoid receptors, CB 1 and CB 2 , which are present in virtually all tissues. Endocannabinoids bioactive lipid mediators produced in virtually all cell types and organs of the body, which exert biological effects similar to those of marijuana.
Hair cycle a life-long regeneration program of the hair follicles controlled by various factors; the hair cycle can be divided to three major phases: Hirsutisms is excessive and increased hair growth especially in women on body regions where the occurrence of hair normally is minimal or absent. Orthodromic, antidromic in a neuron, an orthodromic impulse i.
An antidromic impulse in an axon refers to conduction of the action potentials opposite to the normal, orthodromic direction i. Phytocannabinoids cannabinoids that are isolated from the plant Cannabis sativa ; the most known phytocannabinoid is THC and cannabidiol.
Pilosebaceous unit consists of the hair shaft, the hair follicle, the sebaceous gland and the erector pili muscle, which causes the hair to stand up when it contracts. Psoriasis is a chronic, autoimmune skin disease that is characterized by epidermal hyperproliferation and skin inflammation. Seborrhea or seborrhoeic dermatitis an inflammatory skin condition that particularly affects the sebaceous-gland-enriched areas of the skin; similar to acne, multiple factors are listed in its etiology.
Sebum a lipid-enriched, oily exocrine product of the sebaceous glands; sebum has various function such as waterproof-barrier formation, anti-microbial activity, transport, thermoregulation and so on. Systemic sclerosis scleroderma a chronic autoimmune disease characterized by diffuse fibrosis accumulation of connective tissue , degenerative changes, and vascular abnormalities in the skin, joints and internal organs.
THC the main active ingredient of the plant Cannabis sativa , which predominantly exerts its physiological effects via two main G-protein-coupled cannabinoid receptors.
Roosterman D, et al. Neuronal control of skin function: Paus R, et al. These neurons act as a sort of lock, with cannabinoids acting as the key.
Although they have similar sounding names, these two receptors perform very different functions in the human body. CB1 receptors first discovered in exist in high numbers in the brain especially the hypothalamus, hippocampus, and amygdala , central nervous system CNS , intestines, connective tissues, gonads, and various other glands.
While these are desirable effects for most people, CB1 receptor activation does not come without risks. Please note that these are most often side effects associated with chronic consumption of a potent CB1 receptor agonist such as THC, and not with a non-psychoactive substance such as CBD. CB2 receptors first discovered in occur most commonly in the spleen, tonsils, thymus, and immune cells such as mast cells, monocytes, macrophages, B and T cells, and microglia; only a small number exist in the brain.
Changes in CB2 receptor function is synonymous with virtually every type of human disease; be it cardiovascular, gastrointestinal, neurodegenerative, psychiatric, and autoimmune. It even plays a role in liver and kidney function, bone and skin health, cancer, and even pain-related illnesses.
The human body does produce cannabinoids. Endogenous Cannabinoids are neurotransmitters produced within our bodies that bind to cannabinoid receptors in the brain, immune system, and elsewhere. Endocannabinoids perform differently to the more well-known neurotransmitters like serotonin, dopamine, and norepinephrine. Dopamine, for example, is synthesized in advance, stored in the vesicle, and in response to stimuli, is released from the presynaptic cell, where it crosses the synapse, lands on the postsynaptic cell, and causes activation.
Endocannabinoids, on the other hand, are key components of cellular membranes that we manufacture on demand. Since endocannabinoids are hydrophobic, they cannot travel very far in the body and so their effects are localized. Endocannabinoids also travel in the opposite direction to other neurotransmitters.
They first leave the postsynaptic cell and end at the presynaptic cell where there are high concentrations of axons.
CBD for Psoriasis
Psoriasis, Eczema, and Acne. NO DISCLOSURES or enter the bloodstream. • Besides CBD, hemp oil contains vitamins A, B,C, D, and E The skin has an endocannabinoid system of its own, helping to regulate the production of various . Cannabinoids may be useful for psoriasis, as THC, cannabidiol, cannabinol, . demonstrating that the endogenous cannabinoid system did not. 60 Second Summary. Recent science has found that the endocannabinoid system does not just respond to the endocannabinoids produced in the body, but .