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October 28, 2021The endocannabinoid system
The endocannabinoid system is formed by cannabinoid receptors, endocannabinoids, metabolizing enzymes, and the membrane transporter. With the elucidation of cannabinoid receptors, scientists have heightened curiosity regarding the existence of endogenous ligands and have been trying to understand how to intervene in the modulation of the system, whether using synthetic cannabinoids or phytocannabinoids (extracted from cannabis).
The discovery of the endocannabinoid system begins in 1964, when Professor Mechoulam transported five kilos of Lebanese hash on a bus, seized by the police and made available for research at the Weitzmann Institute, in Rehovot, Israel. Raphael Mechoulam is an organic chemical, of Bulgarian origin, based in Israel, known worldwide for the isolation, structural definition and synthesis of Δ-9-Tetrahydrocannabinol (THC). It is also responsible for identifying the endocannabinoid system.
While working with that seized hashish, he discovered the psychoactive component of Cannabis: THC, a substance passed unnoticed for decades. Twenty years later, the scientist found that THC interacts with the largest receptor system in the human body, the endocannabinoid system mentioned above.
He also discovered that the human brain produces its own Cannabis – a chemical they symbolically named Anandamide, a word derived from the “Sanskrit Ananda”, which means inner calm, bringer of peace, inner happiness.
The system is a set of receptors and enzymes that work as signalers between our cells and body processes.
Scientific evidence has shown that there is dysfunction in the endocannabinoid system in pathological conditions of the central nervous system. Cannabidiol (CBD) – which has no psychoactive effect – and Δ-9-Tetrahydrocannabinol (THC), found in Cannabis sativa, are the main phytocannabinoids that have been studied over the last few years.
Through several studies, it was possible to identify three key elements that make up the endocannabinoid system: endocannabinoids, cannabinoid receptors and enzymes. Endocannabinoids are synthesized in the body and act as signaling molecules that bind to receptors in the endocannabinoid system. "Endo" means "inside" and "cannabinoid" refers to any molecule that activates these receptors. The two main endocannabinoids in the body are anandamide and 2-AG.
The endocannabinoid system has two main types of receptors: CB1 and CB2. These binding sites appear on many cell types throughout the body. Different cannabinoids bind to, block, or shape the activity of these receptors. These include endocannabinoids as well as phytocannabinoids (those found in plants) and synthetic laboratory-produced cannabinoids. The researchers also consider that TRPV1 (vanilloid-type transient potential receptor 1) is part of the network, as it serves as a binding site for CBD, THC and anandamide.
Cannabinoid CB1 and CB2 receptors
CB1 receptors are preferentially located in the central nervous system and mediate the psychotropic effects of cannabinoids. These receptors influence the behavior of different neurotransmitters such as GABA, glutamate, norepinephrine, serotonin and dopamine, and may influence cognition, perception, motor functioning, appetite, sleep, neuroprotection, neurodevelopment and hormone release. They are densely expressed in the pars reticulata of the substantia nigra, cerebellum, hippocampus, striatum and frontal cortex, and distributed in low density in the peripheral nervous system.
So far, CB1 receptors have been observed in the following areas of the body: Brain, Spinal Cord, Fat Cells, Liver, Pancreas, Skeletal Muscles, Gastrointestinal Tract and Reproductive System.
CB2 receptors are preferably located in the immune and hematopoietic system. Also, they have already been found in some areas of the central nervous system. There is an increased expression of them in some pathologies, such as chronic pain or in response to neuro-inflammation and cerebral hypoxia-ischemia events. CB2 receptors have been found in the following areas of the body: immune cells, gastrointestinal tract, liver, fat cells, bone and reproductive system.
Enzymes are proteins that catalyze chemical reactions. The endocannabinoid system has enzymes that produce and break down endocannabinoids. As one of the main enzymes in the system, the hydrolysis of fatty acid amides (FAAH) breaks down anandamide.
Cannabinoid receptors play a key role in the operations of the endocannabinoid system. It helps transmit endocannabinoid messages from cell to cell, and from outer to inner cells.
Cannabinoid receptors exist on the membranes of numerous types of cells throughout the body. On the one hand there is the extracellular space and on the other there is the interior of the cell. The membrane acts as a protective barrier where receptors respond to chemicals found outside the cell.
The endocannabinoid system plays a modulating role
When a cannabinoid attaches to a cannabinoid receptor, it sends a signal into the cell that causes a temporary change in cell function. The location of the receiver often indicates which processes it influences.
Cannabinoid receptors act as the intermediary between the extracellular space and the interior of the cell. Once activated, cannabinoid receptors trigger a cascade, causing cells to change their activity and trigger a collective shift to a balanced state.
The cannabinoid system is known to act as a homeostatic regulator. This means that it helps to ensure that other processes run smoothly. Neurons even send cannabinoids to receptors back through the synaptic space to govern which chemical they want to receive.
We can think of body temperature as an example of homeostasis. If it reaches a very low value or a very high peak, the physical functions will no longer operate correctly. Our body works constantly to keep us at a safe 36–37 °C.
All of our other corporeal systems exist in a constant state of physiological equilibrium, and endocannabinoids help mediate this state as needed. The endocannabinoid system plays a modulating role in the following systems: central and peripheral nervous systems, endocrine system, immune tissues and our metabolism.
When cannabinoid receptors are stimulated, a variety of physiological mechanisms take place.
The endocannabinoid system is responsible for regulating physiological processes such as appetite, pain, inflammation, thermoregulation, intraocular pressure, sensation, muscle control, energy balance, metabolism, sleep quality, stress response, motivation/reward, mood and memory.
The endocannabinoid system exists for the organism to remain balanced. It is a kind of intermediary system, acting as a bridge between cells of different types.
Elmo Resende, Ph.D
Director of R&D
Piauhy Labs
References
Avraham, Y; Israeli, E.; Gabbay, E.; Okun, A.; Zolotarev, O., et al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiol. Dis. 1:237–245, 2006.
Baker, D. and Pryce, G. The therapeutic potential of cannabis in multiple sclerosis. Expert Opin Invest Drugs 12:561–567, 2003.
Barratt, E. S.; Beaver, W. and White, R. The effects of marijuana on human sleep patterns. Biol. Psychiatry 8:47–54, 1974.
Basavarajappa, B. S. and Hungund, B. L. Neuromodulatory role of the endocannabinoid signaling system in alcoholism: an overview. Prostaglandins Leukotrienes Essent. Fatty Acids 66:287–299, 2002.
Berry, E. M. and Mechoulam, R. Tetrahydrocannabinol and endocannabinoids in feeding and appetite. Pharmacol. Ther. 95:185–190, 2002.
Centonze, D., Finazzi Agrò, A., Bernardi, G., and Maccarrone, M. The endocannabinoid system in targeting inflammatory neurodegenerative diseases. Trends Pharmacol. Sci. 28, 180–187, 2007.
COSTA, J. L. G. P. et al. Neurobiologia da Cannabis: do sistema endocanabinoide aos transtornos por uso de Cannabis. Revisão de literatura. J. Bras. Psiquiatr. Rio de Janeiro. v.60,n.2, p.111-122,2011.
Dewey, W. L. Cannabinoid pharmacology. Pharmacol. Rev. 38:151–178, 1986.
Di, S., Boudaba, C., Popescu, R. et al. Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus. J. Physiol. (London) 569:751–760, 2005.
IUVONE, T. et al. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J. Neurochem. v. 89, n.1, p.134–41, 2004.
The endocannabinoid system
The endocannabinoid system is formed by cannabinoid receptors, endocannabinoids, metabolizing enzymes, and the membrane transporter. With the elucidation of cannabinoid receptors, scientists have heightened curiosity regarding the existence of endogenous ligands and have been trying to understand how to intervene in the modulation of the system, whether using synthetic cannabinoids or phytocannabinoids (extracted from cannabis).
The discovery of the endocannabinoid system begins in 1964, when Professor Mechoulam transported five kilos of Lebanese hash on a bus, seized by the police and made available for research at the Weitzmann Institute, in Rehovot, Israel. Raphael Mechoulam is an organic chemical, of Bulgarian origin, based in Israel, known worldwide for the isolation, structural definition and synthesis of Δ-9-Tetrahydrocannabinol (THC). It is also responsible for identifying the endocannabinoid system.
While working with that seized hashish, he discovered the psychoactive component of Cannabis: THC, a substance passed unnoticed for decades. Twenty years later, the scientist found that THC interacts with the largest receptor system in the human body, the endocannabinoid system mentioned above.
He also discovered that the human brain produces its own Cannabis – a chemical they symbolically named Anandamide, a word derived from the “Sanskrit Ananda”, which means inner calm, bringer of peace, inner happiness.
The system is a set of receptors and enzymes that work as signalers between our cells and body processes.
Scientific evidence has shown that there is dysfunction in the endocannabinoid system in pathological conditions of the central nervous system. Cannabidiol (CBD) – which has no psychoactive effect – and Δ-9-Tetrahydrocannabinol (THC), found in Cannabis sativa, are the main phytocannabinoids that have been studied over the last few years.
Through several studies, it was possible to identify three key elements that make up the endocannabinoid system: endocannabinoids, cannabinoid receptors and enzymes. Endocannabinoids are synthesized in the body and act as signaling molecules that bind to receptors in the endocannabinoid system. "Endo" means "inside" and "cannabinoid" refers to any molecule that activates these receptors. The two main endocannabinoids in the body are anandamide and 2-AG.
The endocannabinoid system has two main types of receptors: CB1 and CB2. These binding sites appear on many cell types throughout the body. Different cannabinoids bind to, block, or shape the activity of these receptors. These include endocannabinoids as well as phytocannabinoids (those found in plants) and synthetic laboratory-produced cannabinoids. The researchers also consider that TRPV1 (vanilloid-type transient potential receptor 1) is part of the network, as it serves as a binding site for CBD, THC and anandamide.
Cannabinoid CB1 and CB2 receptors
CB1 receptors are preferentially located in the central nervous system and mediate the psychotropic effects of cannabinoids. These receptors influence the behavior of different neurotransmitters such as GABA, glutamate, norepinephrine, serotonin and dopamine, and may influence cognition, perception, motor functioning, appetite, sleep, neuroprotection, neurodevelopment and hormone release. They are densely expressed in the pars reticulata of the substantia nigra, cerebellum, hippocampus, striatum and frontal cortex, and distributed in low density in the peripheral nervous system.
So far, CB1 receptors have been observed in the following areas of the body: Brain, Spinal Cord, Fat Cells, Liver, Pancreas, Skeletal Muscles, Gastrointestinal Tract and Reproductive System.
CB2 receptors are preferably located in the immune and hematopoietic system. Also, they have already been found in some areas of the central nervous system. There is an increased expression of them in some pathologies, such as chronic pain or in response to neuro-inflammation and cerebral hypoxia-ischemia events. CB2 receptors have been found in the following areas of the body: immune cells, gastrointestinal tract, liver, fat cells, bone and reproductive system.
Enzymes are proteins that catalyze chemical reactions. The endocannabinoid system has enzymes that produce and break down endocannabinoids. As one of the main enzymes in the system, the hydrolysis of fatty acid amides (FAAH) breaks down anandamide.
Cannabinoid receptors play a key role in the operations of the endocannabinoid system. It helps transmit endocannabinoid messages from cell to cell, and from outer to inner cells.
Cannabinoid receptors exist on the membranes of numerous types of cells throughout the body. On the one hand there is the extracellular space and on the other there is the interior of the cell. The membrane acts as a protective barrier where receptors respond to chemicals found outside the cell.
The endocannabinoid system plays a modulating role
When a cannabinoid attaches to a cannabinoid receptor, it sends a signal into the cell that causes a temporary change in cell function. The location of the receiver often indicates which processes it influences.
Cannabinoid receptors act as the intermediary between the extracellular space and the interior of the cell. Once activated, cannabinoid receptors trigger a cascade, causing cells to change their activity and trigger a collective shift to a balanced state.
The cannabinoid system is known to act as a homeostatic regulator. This means that it helps to ensure that other processes run smoothly. Neurons even send cannabinoids to receptors back through the synaptic space to govern which chemical they want to receive.
We can think of body temperature as an example of homeostasis. If it reaches a very low value or a very high peak, the physical functions will no longer operate correctly. Our body works constantly to keep us at a safe 36–37 °C.
All of our other corporeal systems exist in a constant state of physiological equilibrium, and endocannabinoids help mediate this state as needed. The endocannabinoid system plays a modulating role in the following systems: central and peripheral nervous systems, endocrine system, immune tissues and our metabolism.
When cannabinoid receptors are stimulated, a variety of physiological mechanisms take place.
The endocannabinoid system is responsible for regulating physiological processes such as appetite, pain, inflammation, thermoregulation, intraocular pressure, sensation, muscle control, energy balance, metabolism, sleep quality, stress response, motivation/reward, mood and memory.
The endocannabinoid system exists for the organism to remain balanced. It is a kind of intermediary system, acting as a bridge between cells of different types.
Elmo Resende, Ph.D
Director of R&D
Piauhy Labs
References
Avraham, Y; Israeli, E.; Gabbay, E.; Okun, A.; Zolotarev, O., et al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiol. Dis. 1:237–245, 2006.
Baker, D. and Pryce, G. The therapeutic potential of cannabis in multiple sclerosis. Expert Opin Invest Drugs 12:561–567, 2003.
Barratt, E. S.; Beaver, W. and White, R. The effects of marijuana on human sleep patterns. Biol. Psychiatry 8:47–54, 1974.
Basavarajappa, B. S. and Hungund, B. L. Neuromodulatory role of the endocannabinoid signaling system in alcoholism: an overview. Prostaglandins Leukotrienes Essent. Fatty Acids 66:287–299, 2002.
Berry, E. M. and Mechoulam, R. Tetrahydrocannabinol and endocannabinoids in feeding and appetite. Pharmacol. Ther. 95:185–190, 2002.
Centonze, D., Finazzi Agrò, A., Bernardi, G., and Maccarrone, M. The endocannabinoid system in targeting inflammatory neurodegenerative diseases. Trends Pharmacol. Sci. 28, 180–187, 2007.
COSTA, J. L. G. P. et al. Neurobiologia da Cannabis: do sistema endocanabinoide aos transtornos por uso de Cannabis. Revisão de literatura. J. Bras. Psiquiatr. Rio de Janeiro. v.60,n.2, p.111-122,2011.
Dewey, W. L. Cannabinoid pharmacology. Pharmacol. Rev. 38:151–178, 1986.
Di, S., Boudaba, C., Popescu, R. et al. Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus. J. Physiol. (London) 569:751–760, 2005.
IUVONE, T. et al. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J. Neurochem. v. 89, n.1, p.134–41, 2004.
