Good Morning All. Doctor Eric I. Mitchell sent this essay this morning, and after careful reading I can tell you that while it may be over the heads of many, the information provided is profound. Please take the time to read every word. Much of this people may not fully understand, but what they do comprehend may just blow many away.
The Endocannabinoid System’s Part in Aging and Depression
Nrf2 and its Role in Attacking Inflammation
81 Years of scientific suppression and now the truth be told. And No, I am not talking about global warming, but there are some intersecting points where politics and ideology were selected for the few over the masses. I am talking about a system that has been the victim of willful blindness and now with 7 billion aging people on a warming plant, now has our attention. I am talking about the Endocannabinoid System (ECS) and why we need to learn about our chief biological system.
The ECS is an important molecular system responsible for controlling our body’s homeostasis and is becoming an increasingly popular target of pharmacotherapy. Endocannabinoids made within our own bodies make are ester, ether, and amide derivatives of long chain polyunsaturated fatty acids (PUFAs), such as arachidonic acid, and they act mainly as cannabinoid receptor ligands, like the Cb1 and Cb2 receptors.
Endocannabinoids belong to a large group of compounds with a similar structure and biological activity called cannabinoids. In fact, Cannabinoids found in cannabis now number 114 known, and more are being discovered nearly every day. THC, CBD and CBC are our top three Cannabinoids and are now all the rage. Although cannabinoids will not cure everything, people need to know what it does do!
Cannabidiol (CBD) the second most common Cannabinoid is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L and NO it does not cure everything! CBD is a non-psychoactive Cannabinoid unlike THC, the deemed bad boy, which exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties.
The chemistry and pharmacology of CBD, as well as various molecular targets, includes Cb1 and Cb2 cannabinoid receptors which serve as target opportunity for treatment in our homeostatic ECS system. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential that CBD has for many diseases, including diseases associated with oxidative stress, free radicals and chronic inflammation, all of which are related to cellular aging.
Inflammation is a stereotypical response to tissue damage. Our most powerful detoxification from chronic inflammation lies deep within, a master antioxidant switch that is inside every cell of our body. It is called Nrf2 (pronounced Nurf-2, and short for nuclear factor [erythroid-2]–related factor 2) and it is so important that it is found in all mammalian species. Nrf2 is an exquisitely sensitive cellular switch that, when turned on, regulates the activity of over 200 genes, almost all of them involved in either antioxidant defense or detoxification.
Because Nrf2 participates in inflammation ablation, we hypothesized that Nrf2 could play a role in mitigating depressive disorders. Side note, a causative relationship between inflammation and depression is gradually gaining consistency. Nrf2 is capable of activating powerful protective genes and signaling molecules that are critical for our processing of drugs and toxins, for dampening inflammation, removing damaged proteins, and helping repair DNA.
Monitoring inflammation is now possible with techniques such as microdialysis and has been extensively documented in experimental and clinical traumatic brain injury (TBI). Altering of the acute inflammatory response may be neuroprotective. Nrf2 is an essential transcription factor that regulates an array of detoxifying and antioxidant defense gene expression in the liver. It is activated in response to oxidative stress and induces the expression of its target genes by binding to the antioxidant response element (ARE).
When injury or inflammation occurs, a number of biochemical mediators, including prostaglandins, cytokines, chemokines, neuropeptides, and nerve growth factor (NGF), are released. In conditions related to chronic musculoskeletal pain, such as osteoarthritis (OA), rheumatoid arthritis (RA), tendinitis, and chronic low back pain (CLBP), these mediators have been identified as key drivers for chronic pain. In conclusion, our results indicate that chronic inflammation due to a deletion of Nrf2 can lead to a depressive-like phenotype while induction of Nrf2 could become a new and interesting target to develop novel anti-depressive drugs.
A review of the recent science shows evidence indicating that Nrf2, as the master regulator of multiple cytoprotective responses and a key molecular node within a particular cluster of diseases. This provides a new strategy for drug development and repurposing, the antioxidant activity of CBD through Nrf2 activation. Chronic diseases in the elderly are most likely characterized by the loss of homeostasis during aging or as a result of environmental factors, all of them leading to low-grade stress by pathologic formation of reactive oxygen species (ROS), chronic inflammation, and metabolic imbalance.
Oxidative stress resulting from overproduction of ROS is a key element of the immune system’s response to combatting pathogens and initiating tissue repair. However, metabolic modifications resulting from overproduction of ROS also have many negative aspects and lead to the development and/or exacerbation of many diseases. It is believed that the endocannabinoid system, which includes G-protein coupled receptors and their endogenous lipid ligands, may be responsible for the therapeutic modulation of oxidative stress in various diseases. In this context, the phytocannabinoid, CBD, which was identified several decades ago and may interact with the cannabinoid system, is a promising molecule for pharmacotherapy.
During post‐traumatic inflammation, metabolic products of arachidonic acid, known as prostanoids (prostaglandins and thromboxanes) are released and aggravate the injury process. Neural injury leads to inflammation and activation of microglia that in turn may participate in progression of neurodegeneration.
Prostanoid synthesis is regulated by the enzyme cyclo‐oxygenase (COX), which is present in at least two isoforms, COX‐1 (the constitutive form) and COX‐2 (the inducible form). These two isoforms have been shown to have an adverse effect on brain tissue from several days to several weeks after TBI. Animal studies indicate that blocking the COX reactions results in faster recovery faster to the TBI brain and with better motor outcomes.
The therapeutic potential of CBD has been evaluated in cardiovascular, neurodegenerative, cancer, and metabolic diseases, which are usually accompanied by oxidative stress and inflammation. The production of many antioxidant enzymes is regulated at the transcriptional level by the transcription of (Nrf2). Although evidence is accumulating that activation of the Nrf2 pathway represents a promising therapeutic approach to restore the Central Nervous System (CNS) redox balance by reducing ROS-mediated neuronal damage in experimental models of neurodegenerative disorders, only a few Nrf2-activating compounds have been tested in a clinical setting. Why is this important? This is the future and the future is right NOW!
Authored by
Eric I. Mitchell, MD MA FACPE CPE
The Endocannabinoid System’s Part in Aging and Depression
Nrf2 and its Role in Attacking Inflammation
81 Years of scientific suppression and now the truth be told. And No, I am not talking about global warming, but there are some intersecting points where politics and ideology were selected for the few over the masses. I am talking about a system that has been the victim of willful blindness and now with 7 billion aging people on a warming plant, now has our attention. I am talking about the Endocannabinoid System (ECS) and why we need to learn about our chief biological system.
The ECS is an important molecular system responsible for controlling our body’s homeostasis and is becoming an increasingly popular target of pharmacotherapy. Endocannabinoids made within our own bodies make are ester, ether, and amide derivatives of long chain polyunsaturated fatty acids (PUFAs), such as arachidonic acid, and they act mainly as cannabinoid receptor ligands, like the Cb1 and Cb2 receptors.
Endocannabinoids belong to a large group of compounds with a similar structure and biological activity called cannabinoids. In fact, Cannabinoids found in cannabis now number 114 known, and more are being discovered nearly every day. THC, CBD and CBC are our top three Cannabinoids and are now all the rage. Although cannabinoids will not cure everything, people need to know what it does do!
Cannabidiol (CBD) the second most common Cannabinoid is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L and NO it does not cure everything! CBD is a non-psychoactive Cannabinoid unlike THC, the deemed bad boy, which exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties.
The chemistry and pharmacology of CBD, as well as various molecular targets, includes Cb1 and Cb2 cannabinoid receptors which serve as target opportunity for treatment in our homeostatic ECS system. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential that CBD has for many diseases, including diseases associated with oxidative stress, free radicals and chronic inflammation, all of which are related to cellular aging.
Inflammation is a stereotypical response to tissue damage. Our most powerful detoxification from chronic inflammation lies deep within, a master antioxidant switch that is inside every cell of our body. It is called Nrf2 (pronounced Nurf-2, and short for nuclear factor [erythroid-2]–related factor 2) and it is so important that it is found in all mammalian species. Nrf2 is an exquisitely sensitive cellular switch that, when turned on, regulates the activity of over 200 genes, almost all of them involved in either antioxidant defense or detoxification.
Because Nrf2 participates in inflammation ablation, we hypothesized that Nrf2 could play a role in mitigating depressive disorders. Side note, a causative relationship between inflammation and depression is gradually gaining consistency. Nrf2 is capable of activating powerful protective genes and signaling molecules that are critical for our processing of drugs and toxins, for dampening inflammation, removing damaged proteins, and helping repair DNA.
Monitoring inflammation is now possible with techniques such as microdialysis and has been extensively documented in experimental and clinical traumatic brain injury (TBI). Altering of the acute inflammatory response may be neuroprotective. Nrf2 is an essential transcription factor that regulates an array of detoxifying and antioxidant defense gene expression in the liver. It is activated in response to oxidative stress and induces the expression of its target genes by binding to the antioxidant response element (ARE).
When injury or inflammation occurs, a number of biochemical mediators, including prostaglandins, cytokines, chemokines, neuropeptides, and nerve growth factor (NGF), are released. In conditions related to chronic musculoskeletal pain, such as osteoarthritis (OA), rheumatoid arthritis (RA), tendinitis, and chronic low back pain (CLBP), these mediators have been identified as key drivers for chronic pain. In conclusion, our results indicate that chronic inflammation due to a deletion of Nrf2 can lead to a depressive-like phenotype while induction of Nrf2 could become a new and interesting target to develop novel anti-depressive drugs.
A review of the recent science shows evidence indicating that Nrf2, as the master regulator of multiple cytoprotective responses and a key molecular node within a particular cluster of diseases. This provides a new strategy for drug development and repurposing, the antioxidant activity of CBD through Nrf2 activation. Chronic diseases in the elderly are most likely characterized by the loss of homeostasis during aging or as a result of environmental factors, all of them leading to low-grade stress by pathologic formation of reactive oxygen species (ROS), chronic inflammation, and metabolic imbalance.
Oxidative stress resulting from overproduction of ROS is a key element of the immune system’s response to combatting pathogens and initiating tissue repair. However, metabolic modifications resulting from overproduction of ROS also have many negative aspects and lead to the development and/or exacerbation of many diseases. It is believed that the endocannabinoid system, which includes G-protein coupled receptors and their endogenous lipid ligands, may be responsible for the therapeutic modulation of oxidative stress in various diseases. In this context, the phytocannabinoid, CBD, which was identified several decades ago and may interact with the cannabinoid system, is a promising molecule for pharmacotherapy.
During post‐traumatic inflammation, metabolic products of arachidonic acid, known as prostanoids (prostaglandins and thromboxanes) are released and aggravate the injury process. Neural injury leads to inflammation and activation of microglia that in turn may participate in progression of neurodegeneration.
Prostanoid synthesis is regulated by the enzyme cyclo‐oxygenase (COX), which is present in at least two isoforms, COX‐1 (the constitutive form) and COX‐2 (the inducible form). These two isoforms have been shown to have an adverse effect on brain tissue from several days to several weeks after TBI. Animal studies indicate that blocking the COX reactions results in faster recovery faster to the TBI brain and with better motor outcomes.
The therapeutic potential of CBD has been evaluated in cardiovascular, neurodegenerative, cancer, and metabolic diseases, which are usually accompanied by oxidative stress and inflammation. The production of many antioxidant enzymes is regulated at the transcriptional level by the transcription of (Nrf2). Although evidence is accumulating that activation of the Nrf2 pathway represents a promising therapeutic approach to restore the Central Nervous System (CNS) redox balance by reducing ROS-mediated neuronal damage in experimental models of neurodegenerative disorders, only a few Nrf2-activating compounds have been tested in a clinical setting. Why is this important? This is the future and the future is right NOW!
Authored by
Eric I. Mitchell, MD MA FACPE CPE
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