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Introduction to the Skin’s Endocannabinoid System

The skin at a glance

The skin is one of the largest organs of the body. Alongside its role in protecting us from various environmental challenges, it is a highly active structure in itself. For example, the skin is both the source and target of several hormones, has its own immune system, is our largest sensory organ, and so on. Without this remarkable organ, human life as we know it would be impossible.

Epidermis

The outermost part of the skin is the epidermis, which is formed by several layers of epithelial cells called keratinocytes. This compact sheet provides the body’s waterproof, physical protection barrier against UV irradiation, microbial invasion, extreme heat and cold, allergens, chemicals, and more.

Hair follicle, sebaceous gland, sweat gland

The next layer of the skin is the home of several “mini-organs” that we call appendages. Constantly-rejuvenating follicles produce hair, while sebaceous glands supply oily sebum to the skin’s surface, reinforcing the waterproof barrier of the epidermis. Glands secrete sweat to help regulate the body’s temperature. These “mini-organs” also produce various hormones, such as steroids and Vitamin D, and play a role in the skin’s immune defense.

Immune cells

The skin has its own immune system that constantly protects against bacteria, viruses, allergens and other external factors. This system is composed of various immune cell types which either live inside the skin or invade it when danger is sensed. Most importantly, all other skin cell types can join the skin’s immune system to protect and heal the organ when necessary.

Sensory nerves

Each part of the skin is supplied by a huge, dense network of nerve fibers. Sensory nerve endings recognize practically all types of stimuli, which result in the tactile sensations of heat, cold, pressure, vibration, pain and itch. Because of these versatile functions, the skin is considered the largest sensory organ.

Endocannabinoids

The skin produces endocannabinoid molecules such as anandamide (AEA) and 2-AG. These endocannabinoids are constantly released in specific amounts, depending on the “healthy need” of the organ, resulting in the skin’s cannabinoid tone. Endocannabinoid molecules are synthesized by several cell types in the epidermis, hair follicles and sebaceous glands.

The skin’s cannabinoid tone constantly affects all compartments of the skin, as endocannabinoids act on various cell types and contribute to their healthy physiological function.

CB1 & CB2

Endocannabinoids may act on various receptors in the body. The “classic” CB1 and CB2 receptors are present in practically all cell types of the skin.

Effects of ECS on the epidermis

Activation of cannabinoid receptors by endocannabinoids on epidermal cells regulates normal function of the skin as a barrier. When CB1 or CB2 are engaged, these functions of epidermal cells are modified – whether through proliferation, differentiation or apoptosis – which are all important processes for the healthy physical defense of the body. Endocannabinoids also suppress inflammation in the epidermis.

Effects of ECS on immune cells

The ECS’ role in skin’s immunity is to constantly control the activity of the skin’s immune and inflammatory system. This happens in two ways:

  • Endocannabinoids exert anti-inflammatory effects
  • The skin’s ECS prevents the activation of the immune system when it is not needed

Novel drugs that increase the activity of the skin’s ECS may hold promise for treating inflammatory and immune-related diseases in the skin.

Effects of ECS on hair follicles

Hair follicles exhibit a lifelong cycle of growth, regression and resting phases. When the hair follicle’s CB1 receptors are activated, the cell division, or proliferation, of the “mini-organ” stops and several cells die; this results in inhibited hair growth and a longer regression phase, also known as catagen. Modulation of ECS activity in the hair follicle may be therapeutically promising for hair growth disorders, such as unwanted hair growth or baldness.

Effects of ECS on sebaceous glands

The physiological cannabinoid tone is also key to the healthy biology of the sebaceous glands. When endocannabinoids or their receptors are not properly produced or functioning, the glands are unable to secrete enough lipid-containing sebum and the waterproof skin barrier may be weakened, increasing the potential for microbes to invade the body. If the cannabinoid tone of the glands is kept in balance, it contributes to homeostasis and healthy skin.

Effects of ECS on sweat glands

The ECS is also expressed in sweat glands. Though CB1 and CB2 receptors were found to regulate the life cycle of sweat gland cells, more research is needed to clarify how endocannabinoids affect their function, for example, in sweat production.

Effects of ECS on sensory nerves

Activation of cannabinoid receptors on certain sensory nerve endings can hinder the function of these structures. Most importantly, when painful stimuli touch the skin, its “cannabinoid tone” can inhibit the development and spread of pain, thereby easing the body’s suffering. The skin’s ECS effectively suppresses the unpleasant sensation of itch, which is the most-frequently diagnosed symptom in dermatology practice. These effects provide a solid base for the development of new, ECS-targeted, analgesic and anti-itch drugs.

ECS in skin diseases

Endocannabinoid deficiency and dysregulation are thought to contribute to a wide array of human diseases. In the skin, we need more studies to precisely describe the role of the ECS in various conditions. It can be inferred that unhealthy activity of the skin’s cannabinoid tone likely contributes to the development of highly-prevalent conditions including acne, dry skin, inflammation and eczema.

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by Artwork by John Karapelou, Text by Phytecs is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License

Introduction to the Skin’s Endocannabinoid System

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The skin at a glance

The skin is one of the largest organs of the body. Alongside its role in protecting us from various environmental challenges, it is a highly active structure in itself. For example, the skin is both the source and target of several hormones, has its own immune system, is our largest sensory organ, and so on. Without this remarkable organ, human life as we know it would be impossible.

Epidermis

The outermost part of the skin is the epidermis, which is formed by several layers of epithelial cells called keratinocytes. This compact sheet provides the body’s waterproof, physical protection barrier against UV irradiation, microbial invasion, extreme heat and cold, allergens, chemicals, and more.

Hair follicle, sebaceous gland, sweat gland

The next layer of the skin is the home of several “mini-organs” that we call appendages. Constantly-rejuvenating follicles produce hair, while sebaceous glands supply oily sebum to the skin’s surface, reinforcing the waterproof barrier of the epidermis. Glands secrete sweat to help regulate the body’s temperature. These “mini-organs” also produce various hormones, such as steroids and Vitamin D, and play a role in the skin’s immune defense.

Immune cells

The skin has its own immune system that constantly protects against bacteria, viruses, allergens and other external factors. This system is composed of various immune cell types which either live inside the skin or invade it when danger is sensed. Most importantly, all other skin cell types can join the skin’s immune system to protect and heal the organ when necessary.

Sensory nerves

Each part of the skin is supplied by a huge, dense network of nerve fibers. Sensory nerve endings recognize practically all types of stimuli, which result in the tactile sensations of heat, cold, pressure, vibration, pain and itch. Because of these versatile functions, the skin is considered the largest sensory organ.

Endocannabinoids

The skin produces endocannabinoid molecules such as anandamide (AEA) and 2-AG. These endocannabinoids are constantly released in specific amounts, depending on the “healthy need” of the organ, resulting in the skin’s cannabinoid tone. Endocannabinoid molecules are synthesized by several cell types in the epidermis, hair follicles and sebaceous glands.

The skin’s cannabinoid tone constantly affects all compartments of the skin, as endocannabinoids act on various cell types and contribute to their healthy physiological function.

CB1 & CB2

Endocannabinoids may act on various receptors in the body. The “classic” CB1 and CB2 receptors are present in practically all cell types of the skin.

Effects of ECS on the epidermis

Activation of cannabinoid receptors by endocannabinoids on epidermal cells regulates normal function of the skin as a barrier. When CB1 or CB2 are engaged, these functions of epidermal cells are modified – whether through proliferation, differentiation or apoptosis – which are all important processes for the healthy physical defense of the body. Endocannabinoids also suppress inflammation in the epidermis.

Effects of ECS on immune cells

The ECS’ role in skin’s immunity is to constantly control the activity of the skin’s immune and inflammatory system. This happens in two ways:

  • Endocannabinoids exert anti-inflammatory effects
  • The skin’s ECS prevents the activation of the immune system when it is not needed

Novel drugs that increase the activity of the skin’s ECS may hold promise for treating inflammatory and immune-related diseases in the skin.

Effects of ECS on hair follicles

Hair follicles exhibit a lifelong cycle of growth, regression and resting phases. When the hair follicle’s CB1 receptors are activated, the cell division, or proliferation, of the “mini-organ” stops and several cells die; this results in inhibited hair growth and a longer regression phase, also known as catagen. Modulation of ECS activity in the hair follicle may be therapeutically promising for hair growth disorders, such as unwanted hair growth or baldness.

Effects of ECS on sebaceous glands

The physiological cannabinoid tone is also key to the healthy biology of the sebaceous glands. When endocannabinoids or their receptors are not properly produced or functioning, the glands are unable to secrete enough lipid-containing sebum and the waterproof skin barrier may be weakened, increasing the potential for microbes to invade the body. If the cannabinoid tone of the glands is kept in balance, it contributes to homeostasis and healthy skin.

Effects of ECS on sweat glands

The ECS is also expressed in sweat glands. Though CB1 and CB2 receptors were found to regulate the life cycle of sweat gland cells, more research is needed to clarify how endocannabinoids affect their function, for example, in sweat production.

Effects of ECS on sensory nerves

Activation of cannabinoid receptors on certain sensory nerve endings can hinder the function of these structures. Most importantly, when painful stimuli touch the skin, its “cannabinoid tone” can inhibit the development and spread of pain, thereby easing the body’s suffering. The skin’s ECS effectively suppresses the unpleasant sensation of itch, which is the most-frequently diagnosed symptom in dermatology practice. These effects provide a solid base for the development of new, ECS-targeted, analgesic and anti-itch drugs.

ECS in skin diseases

Endocannabinoid deficiency and dysregulation are thought to contribute to a wide array of human diseases. In the skin, we need more studies to precisely describe the role of the ECS in various conditions. It can be inferred that unhealthy activity of the skin’s cannabinoid tone likely contributes to the development of highly-prevalent conditions including acne, dry skin, inflammation and eczema.

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