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~ Alzheimer's ~
Patents
US6630507 Neurological & Autoimmune Disorders; Cannabiniods as antioxidants & neuroprotectants
US6410588B1 1998-04-14 2002-06-25 anti-inflammatory agents The Mathilda And Terence Kennedy Institute Of Rheumatology Use of cannabinoids as anti-inflammatory agents
US6630507 Neurological & Autoimmune Disorders; Cannabiniods as antioxidants & neuroprotectants
US6410588B1 1998-04-14 2002-06-25 anti-inflammatory agents The Mathilda And Terence Kennedy Institute Of Rheumatology Use of cannabinoids as anti-inflammatory agents
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Preferred Strains
Preferred Methods to Medicate
Raw Kief/Greens
Ideally one should be eating Raw Kief/Greens for the A molecule THCA, CBDA etc, Over and above the preferred method of medicating, each cannabinoid & Terpenes plays a roll in healing.
Medicating
Ideally one should be eating Raw Kief/Greens for the A molecule THCA, CBDA etc, Over and above the preferred method of medicating, each cannabinoid & Terpenes plays a roll in healing.
Medicating
- Drops/Oil Dropped under tongue for faster absorption (Soft membrane tissue).
- Sprays, if for internal best applied through nasal sprays for soft tissue. (If Issue is eye's or ear's, apply to correlation)
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Ted Talk Must Watch
11 Yr Old Twins childhood Alzheimer's Treated with Cannabis Now they are bright eyed and happpy |
Preclinical Study
Dr finds cannabis (THC) reverses beta-Amyloid Plaque Dose Dependent treatment shows promising results |
KAOT News
Cannabis Treating Alzheimer's & Dementia's Despite Growing evidence They still want more |
Alzheimer's, Overview:
Alzheimer's disease (AD), also referred to simply as Alzheimer's, is a chronic neurodegenerative disease that usually starts slowly and worsens over time.[1][2] It is the cause of 60% to 70% of cases of dementia.[1][2] The most common early symptom is difficulty in remembering recent events (short-term memory loss).[1] As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, not managing self care, and behavioural issues.[1][2] As a person's condition declines, they often withdraw from family and society.[1] Gradually, bodily functions are lost, ultimately leading to death.[10] Although the speed of progression can vary, the average life expectancy following diagnosis is three to nine years.[7][11]
The cause of Alzheimer's disease is poorly understood.[1] About 70% of the risk is believed to be genetic with many genes usually involved.[4] Other risk factors include a history of head injuries, depression, or hypertension.[1] The disease process is associated with plaques, inflammation, tangles in the brain & the collapse of the neuron's transport system.[68] .[4] A probable diagnosis is based on the history of the illness and cognitive testing with medical imaging and blood tests to rule out other possible causes.[5] Initial symptoms are often mistaken for normal ageing.[1]
The cause of Alzheimer's disease is poorly understood.[1] About 70% of the risk is believed to be genetic with many genes usually involved.[4] Other risk factors include a history of head injuries, depression, or hypertension.[1] The disease process is associated with plaques, inflammation, tangles in the brain & the collapse of the neuron's transport system.[68] .[4] A probable diagnosis is based on the history of the illness and cognitive testing with medical imaging and blood tests to rule out other possible causes.[5] Initial symptoms are often mistaken for normal ageing.[1]
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A Breakdown of Alzheimer's, finding Beta-Amyloid & Tau Protein correlation. Although they reference a GMO medication Cannabis will always have less side affects.
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Cholinergic Correlation/hypothesis
The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis,[52] which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective.[53] Suggesting that the Cholinergic role is likely more a result, rather then the cause. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid,[54] leading to generalised neuroinflammation.[55]
The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis,[52] which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective.[53] Suggesting that the Cholinergic role is likely more a result, rather then the cause. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid,[54] leading to generalised neuroinflammation.[55]
Amyloid Correlation/hypothesis
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In 1991, the amyloid hypothesis postulated that extracellular amyloid beta (Aβ) deposits are the fundamental cause of the disease.[56][57] Support for this postulate comes from the location of the gene for the amyloid precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down Syndrome) who have an extra gene copy almost universally exhibit at least the earliest symptoms of AD by 40 years of age.[58][59] Also, a specific isoform of apolipoprotein, APOE4, is a major genetic risk factor for AD. While apolipoproteins enhance the breakdown of beta amyloid, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in the brain.[60] Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer's-like brain pathology with spatial learning deficits.[61]
In 1991, the amyloid hypothesis postulated that extracellular amyloid beta (Aβ) deposits are the fundamental cause of the disease.[56][57] Support for this postulate comes from the location of the gene for the amyloid precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down Syndrome) who have an extra gene copy almost universally exhibit at least the earliest symptoms of AD by 40 years of age.[58][59] Also, a specific isoform of apolipoprotein, APOE4, is a major genetic risk factor for AD. While apolipoproteins enhance the breakdown of beta amyloid, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in the brain.[60] Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer's-like brain pathology with spatial learning deficits.[61]
These toxic oligomers, also referred to as amyloid-derived diffusible ligands (ADDLs), bind to a surface receptor on neurons and change the structure of the synapse, thereby disrupting neuronal communication.[63] One receptor for Aβ oligomers may be the prion protein, the same protein that has been linked to mad cow disease and the related human condition, Creutzfeldt–Jakob disease, thus potentially linking the underlying mechanism of these neurodegenerative disorders with that of Alzheimer's disease.[64]
Tau Correlation/hypothesis
In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells. The over-release of astroglial-derived neurotrophin actively exacerbates the pro-inflammatory cytokine loop fuelled by Aβ stimulation, & massively accelerates amyloidogenicity by promoting cleavage of APP to Aβ and induces tau protein hyperphosphorylation, by disrupting the Wnt pathway [22]–[24].
The tau hypothesis proposes that tau protein abnormalities initiate the disease cascade.[57] In this model, hyperphosphorylated tau begins to pair with other threads of tau. Eventually, they form neurofibrillary tangles inside nerve cell bodies.[67] When this occurs, the microtubules disintegrate, destroying the structure of the cell's cytoskeleton which collapses the neuron's transport system.[68] This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells.[69]
Neurovascular Correlation/Hypothesis
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A neurovascular hypothesis has been proposed which states that poor functioning of the blood–brain barrier may be involved.[70]
The cellular homeostasis of biometals such as ionic copper, iron, and zinc is disrupted in AD, (One highly suspected cause is from Aluminum poisoning) though it remains unclear whether cellular homeostasis of biometals is produced by or causes the changes in proteins. These ions affect and are affected by tau, APP, and APOE,[71](and directly correlate with the nervous system, potentially facilitating neural inflammation and over production of Beta-Amyloid (AB)) and their dysregulation may cause oxidative stress that may contribute to the pathology.[72][73][74][75][76] Ions/Ionic System is also directly connected with the nervous system, potentially facilitating neural inflammation and over production of Beta-Amyloid (AB). The quality of some of these studies has been criticised,[77][78] and the link remains controversial.[79] The majority of researchers do not support a connection with aluminium,[80] Although there seems to be a persistant theme continually arising related to the aluminum connection. And big pharma has a habit of shrugging off the true cause, promoting more sales. |
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Deficiency Syndromes/Endo-cannabinoid system Correlation/Hypothesis
Although cannabinoid deficiency syndromes have not yet been clearly defined in humans, there is some pre-clinical evidence and some human evidence that dysregulation of the endocannabinoid system is associated with several conditions. Endocannabinoid deficiencies have been implicated in schizophrenia, migraine, multiple sclerosis, Huntington’s, and Parkinson’s, irritable bowel syndrome, anorexia, motion sickness, fibromyalgia, menstrual symptoms, and other conditions that involve hyperalgesia and abnormal sensitization to pain. Several polymorphisms [differing forms] have been identified in the genes that code for the cannabinoid receptors. And some of these polymorphisms have been associated with clinical outcomes, such as a tendency towards happiness or depression, and the likelihood of developing a post-traumatic stress disorder. Therefore if your coding ( gene transcription is off, Phytocannabiniods supplemented (which are mimics to the cannabinoids proper form & Cannabiniods/Phytocannabiniods have gene transcription modulation properties, potentially aiding in the correction of the improper coding
Inflammation
AD neuroinflammation is a highly important feature that has been considered responsible for the progressive worsening of the disease. Given the tremendous complexity of AD, however, it appears to be oversimplified reasoning to consider only reactive astrogliosis and neuronal degeneration as the unique factors at the basis of the functional decline provoked by the course of the illness.
Chronic neuroinflammation implicates protracted activation of both microglial and astroglial cells, with the consequent sustained release of pro-inflammatory molecules [15], [16], that act in an autocrine way to self-perpetuate reactive gliosis and in a paracrine way to kill neighboring neurons, Astrocytes represent the most abundant glial cells type in the CNS. Once these cells undergo reactive activation, they produce cytokines and other molecules involved in inflammatory response, which are thought to significantly contribute to expand brain damage. Interestingly astrocytes express the highest level of PPARγ in the CNS [27], as well it has been observed that there is changes in the actions of beta-amyloid in the function of the delivery to the cells creating a plaque build up, promoting miss fire & more inflammation thus creating more inflammation and expanding the neuropathological damage. Once started, neuroinflammation promotes neuronal death, powering a vicious cycle responsible for the progression of the pathology [17].
Chronic neuroinflammation implicates protracted activation of both microglial and astroglial cells, with the consequent sustained release of pro-inflammatory molecules [15], [16], that act in an autocrine way to self-perpetuate reactive gliosis and in a paracrine way to kill neighboring neurons, Astrocytes represent the most abundant glial cells type in the CNS. Once these cells undergo reactive activation, they produce cytokines and other molecules involved in inflammatory response, which are thought to significantly contribute to expand brain damage. Interestingly astrocytes express the highest level of PPARγ in the CNS [27], as well it has been observed that there is changes in the actions of beta-amyloid in the function of the delivery to the cells creating a plaque build up, promoting miss fire & more inflammation thus creating more inflammation and expanding the neuropathological damage. Once started, neuroinflammation promotes neuronal death, powering a vicious cycle responsible for the progression of the pathology [17].
Neurological
evidence that in AD brains progressive neuronal loss is NOT accompanied by a new neuronal replacement while alterations in neurogenesis have been reported to occur [33]. As well the collapse of the collapse of microtubules, obstructing the neuron transport system, blocking Neurological messages. Such aspects are considered to be important in contributing to the long-term development of disease. Therefore the disease symptoms could partly be due to the impaired replacement of new hippocampal neurons from endogenous neuronal stem cells [34], [35], which is believed to promote learning and memory.
evidence that in AD brains progressive neuronal loss is NOT accompanied by a new neuronal replacement while alterations in neurogenesis have been reported to occur [33]. As well the collapse of the collapse of microtubules, obstructing the neuron transport system, blocking Neurological messages. Such aspects are considered to be important in contributing to the long-term development of disease. Therefore the disease symptoms could partly be due to the impaired replacement of new hippocampal neurons from endogenous neuronal stem cells [34], [35], which is believed to promote learning and memory.
AD Breakdown
The beta amyloid (Aβ) and other aggregating proteins in the brain increase with age and are frequently found within neurons. The mechanistic relationship between intracellular amyloid, aging and neurodegeneration is not, however, well understood. using a proteotoxicity model based upon the inducible expression of Aβ in a human central nervous system nerve cell line to characterize a distinct form of nerve cell death caused by intracellular Aβ. It is shown that intracellular Aβ initiates a toxic inflammatory response leading to the cell's demise. Aβ induces the expression of multiple proinflammatory genes, Aβ accumulation in a human CNS nerve cell line leads to the synthesis of proinflammatory cytokines and chemokines, elevated eicosanoid synthesis and the activation of inflammatory pathways. Age and chronic systemic inflammation are risk factors for many CNS diseases, including depression and Alzheimer’s,26 and the elevation of peripheral inflammation in old individuals frequently leads to cognitive decline.27 It follows that there is a complex interrelationship between nerve cell proteotoxicity, inflammation, aging and CNS disease.
Among CNS cytokines elevated in AD,28 all except IL6 are highly expressed in MC65 cells following Aβ induction. However, while there is an elevated inflammatory response within the AD brain, it has generally been assumed to result from the activation of microglia and astrocytes.29,30
data shows that there is a complex and likely autocatalytic inflammatory response within nerve cells caused by the accumulation of intracellular Aβ, and that this early form of proteotoxicity can be blocked by the activation of cannabinoid receptors.
Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves, and with recent studies showing a increase in CB2 receptors in the brain, (which is largely found in the immune system & major organs) suggesting the Immune system is playing some role in AD, as well showing the body/brains need for more cannabinoids for the CB2 receptor, by the increase in receptors.
That being said when it was identified that the molecular basis of the inflammatory response to Amyloid-beta. it became clear, that not only, is a major part of the inflammation from the nerve cells directly (not only the immune system) in the production, and function of beta-amyloid, creating cellular inflammation increasingthe rate of neuron death cascading to the Tao proteins and further deterioration, plaque build up of Tau, & Beta-Amyloid . As well the it's clear the THC-like compounds, nerve cells make themselves are involved in protecting the cells from dying, ” Therefore it is fair to postulate with recent trials supporting such evidence Phyto/endocannabiniods aid in AD.
~ How Cannabis Aids ~
Inflammation
Correlation between AD, Inflammation & Cannabis
Correlation between AD, Inflammation & Cannabis
Several recent findings show that targeting the endogenous cannabinoid system can be considered as a potential therapeutic approach to treat Alzheimer's disease (AD). CBD was already reported to exert a marked anti-inflammatory effect through the A2A and 5HT1A receptors [18], [19], as well as to improve brain function [20]. In addition, it has been already demonstrated that CBD markedly downregulate reactive gliosis by reducing pro-inflammatory molecules and cytokine release that strongly occurs in Aβ neurotoxicity. This activity was linked to its ability to act as a potent inhibitor of NFκB activation induced by Aβ challenge [21]. The present findings, confirming the formerly obtained results and extending our knowledge about CBD pharmacology, indicate that a selective PPARγ activation occurs upstream to CBD-mediated NFκB inhibition. Such activation appears to be responsible for a large plethora of CBD effects. Indeed, the interaction of CBD at the PPARγ site results in a profound inhibition of reactive gliosis as showed by the reduction of both GFAP and S100B protein expression together with a marked decline of pro-inflammatory molecules and cytokine release observed in Aβ challenged astrocytes.
CBD through the activation of PPARγ provoked a marked reduction of NO, TNFα, and IL-1β release in association with a parallel decline of GFAP, S100B, and iNOS protein expression. The observation that in the hippocampus the selective activation of PPARγ caused a decrease in p50 and p65 protein expression, further reinforces the importance of the sequence of events PPARγ activation/NFκB inhibition as responsible for the CBD anti-inflammatory effect in this case. which in turn prevents the over-release of this astroglial-derived neurotrophin actively which exacerbates the pro-inflammatory cytokine loop fuelled by Aβ stimulation, massively accelerates amyloidogenicity by promoting cleavage of APP to Aβ and induces tau protein hyperphosphorylation, by disrupting the Wnt pathway [22]–[24]. The PPARγ mediated inhibition of S100B induced by CBD represents a crucial step in interrupting self-perpetuation of the reactive gliosis cycle. Notably, both in vivo and in vitro, the neuroprotective and anti-gliotic effect of CBD
Neurological
Correlation between AD, Neurological Issue's & Cannabis
Correlation between AD, Neurological Issue's & Cannabis
It has been recently demonstrated that CBD promotes cerebral neurogenesis , and even more specifically related CBD promotes CNS & hippocampal neurogenesis by activating CB1 receptors [39](As dose THC by also activating the CB 1 receptor. Such an assumption was supported by the observation that the CBD neurogenic effect was lost in mice with the CB1 receptor knocked-out, suggesting that the pro-neurogenic action of this phytocannabinoid was clearly dependent on the interaction at the CB1 receptor, which shows a wide expression over the entire DG, including the neuronal precursor cells. Trials are also showing that on top of the healing properties of CBD. CBD-mediated activation of PPARγ is associated with a significant neurogenic activity in the granule cell layer of the hippocampal DG. Moreover, CBD mediated activation of PPARγ has been reported to promote neurogenesis and agonists at these receptors regulate neuronal stem cell proliferation and differentiation as well [37]. In addition PPARγ activation promotes neurite outgrowth in mature neurons, significantly contributing to a proper neuronal connectivity in neuronal networks [38]. Moreover, with CBD regulating the immune system, through the suppressing of pro-inflammatory proteins and the suppression of the fat protein Beta-Amyloid which in itself promotes cellular inflammation and neurological miss-fire in the brain & nervous system, directly aid in AD.
Neuro Expression & gene Transcription:
Cannabis Facilitating gene & Neurogenesis & Plasticity
Cannabis Facilitating gene & Neurogenesis & Plasticity
Endogenous cannabinoid (eg. THC, CBD) ligand interaction with cannabinoid type 1 receptor is highly expressed in the cortex, substantia nigra pars reticulata, globus pallidus, cerebellum, hippocampus, and brainstem, thereby modulating a wide range of neural functions, making the activation of the type 1 receptors directly aid in the areas in question for AD, PD, Autism, bipolar, MS, Tourette's, etc. such as motor activity, learning, and memory. CB1R, located presynaptically on GABA and glutamate neurons, decreases their release by inhibition of presynaptic Ca2+ influx through voltage-gated Ca2+ channels (VGCCs). CB1R activation is coupled with inhibition of adenylyl cyclase, downregulation of the cAMP/PKA pathway, and activation of the MAP kinase/ERK pathway, thereby regulating expression of genes through gene modulation transcription, recoding the potentially missing coded genetic script. eCBs are the best characterized retrograde messenger for carrying out neurological actions of endocannabinoids. Cannabinoids activate the enzyme phospholipase Cb (PLCb), which triggers short and long term plasticity aiding in the repair of damaged neurons, common within a neuropsychiatric disorder (Hashimotodani et al., 2007). eCBs interaction with CB1R is capable of inducing presynapsis forms (eCB-LTD) at both excitatory and inhibitory synapses. A buildup of neurotoxins that the body cannot eliminate is believed to contribute to AD, Parkinson’s and more. Studies have found that cannabis can aid cells in the elimination of toxins and other waste products. Ingested cannabinoids support and improve mitochondrial function, which is responsible for cellular respiration, the metabolizing of carbohydrates into energy, and the excretion of waste products.
changes in dendritic spine density, and changes in neurotransmitter pathways. It gives rise to all types of adaptive learning, including recovering from a stroke, the conscious act of gaining a new skill, and the unconscious acquisition of a new emotional response. It is also involved in pathological processes such as central sensitization to pain. There are multiple mechanisms by which cannabinoids modulate neural plasticity, including neurogenesis (the formation of new neurons), aiding in long-term potentiation and long-term depression. Research in humans has shown that the administration of exogenous cannabinoids can cause neuroplastic changes.
changes in dendritic spine density, and changes in neurotransmitter pathways. It gives rise to all types of adaptive learning, including recovering from a stroke, the conscious act of gaining a new skill, and the unconscious acquisition of a new emotional response. It is also involved in pathological processes such as central sensitization to pain. There are multiple mechanisms by which cannabinoids modulate neural plasticity, including neurogenesis (the formation of new neurons), aiding in long-term potentiation and long-term depression. Research in humans has shown that the administration of exogenous cannabinoids can cause neuroplastic changes.
"Cannabis Promoting Cerebral Circulation through, Arterioles Dilation & Plaque Reduction"
Cerebral Circulation
Cannabis promoting blood & Oxygen distribution
Anandamide (AN, arachidonyl ethanolamide) has been isolated from the brain and shown to be an endogenous ligand for the delta 9-tetrahydrocannabinol (delta 9-THC) receptor. The purpose of these studies was to determine whether AN or delta 9-THC can affect the cerebral circulation. With the use of the closed cranial window AN and delta 9-THC (10(-13)-10(-3) M) were topically applied to rabbit cerebral arterioles and effects on diameter were measured with a microscope. AN and delta 9-THC similarly induced a dose-dependent dilation starting at concentrations as low as 10(-12) M. Maximum dilation for AN was 25% and that for delta 9-THC 22%, Creating better blood floe throughout the brain, in turn transporting more oxygen to specific sites improving AD symptoms. Add this function with the suppression of beta-amyloid production and the reduction of the plaque build up from beta-amyloid, creating even more improvement of blood and oxygen delivery within the brain.
Cannabis promoting blood & Oxygen distribution
Anandamide (AN, arachidonyl ethanolamide) has been isolated from the brain and shown to be an endogenous ligand for the delta 9-tetrahydrocannabinol (delta 9-THC) receptor. The purpose of these studies was to determine whether AN or delta 9-THC can affect the cerebral circulation. With the use of the closed cranial window AN and delta 9-THC (10(-13)-10(-3) M) were topically applied to rabbit cerebral arterioles and effects on diameter were measured with a microscope. AN and delta 9-THC similarly induced a dose-dependent dilation starting at concentrations as low as 10(-12) M. Maximum dilation for AN was 25% and that for delta 9-THC 22%, Creating better blood floe throughout the brain, in turn transporting more oxygen to specific sites improving AD symptoms. Add this function with the suppression of beta-amyloid production and the reduction of the plaque build up from beta-amyloid, creating even more improvement of blood and oxygen delivery within the brain.
~How Cannabis Aids correlations/Hypothesis~
Beta-Amyloid/Cannabis Correlation
Cannabis Regulating Beta-Amyloid
Cannabis Regulating Beta-Amyloid
It is a well-known fact that most neurodegenerative diseases can be attributed to the accumulation of proteins and in the case of Alzheimer’s disease, that protein is called beta amyloid.
Endocannabinoids are lipid molecules produced by the body and can activate cannabinoid receptors, CB1 and CB2. The researchers found that upon activation of these receptors by an endocannabinoid, neuronal cell survival was increased and beta amyloid accumulation was blocked. Conversely, the activation of cannabinoid receptors prevents Aβ accumulation and toxicity. Both intracellular Aβ accumulation and nerve cell death are potentiated by 5-LOX metabolites and proinflammatory cytokines. they found that deactivation of CB1 and CB2 had the opposite effect and increased toxicity and beta amyloid accumulation. Thus establishing the regulatory properties of the CB receptors. Endocannabinoids can be produced in response to stress,44,45 and in AD models cannabinoids reduce Aβ accumulation and improve memory.46,47 THC also reduces inducible huntingtin overexpression in PC12 cells,48 and both THC, CBD and endocannabinoids reduce inflammation.49,50 Several synthetic, plant derived and endogenous cannabinoids are able to prevent the accumulation of intraneuronal Aβ, reduce the production of eicosanoids, and block nerve cell death. Therefore, it is reasonable to conclude that there is a therapeutic potential of cannabinoids for the treatment of AD. In summary, the accumulation of intraneuronal Aβ and inflammation precede plaque formation and nerve cell death in AD. It is shown here that intracellular Aβ activates a broad spectrum of inflammatory signaling pathways. There is clearly a dynamic interplay between these pathways that may lead to either cell survival or death (Figure 5). Cell death can only be completely prevented by 5-LOX inhibitors, cannabinoids and caspase inhibitors. However, once the cell death process is underway, death can be reduced through the above mentioned proteins/inhibitors. Interestingly, of all the compounds tested, tetrahydrocannabinol (THC) was the most effective (but not exclusively, as CBD shows similar properties, which is why it is more therapeutic to utilize nature's remedy ie all cannabinoids & Terpenes, not any one molecule soley) at activating the CB1 receptor and stimulated the removal of beta amyloid proteins, blocked the inflammatory response and had a protective effect on neuron cells. Through gene transcription modulation properties regulating the transcription code, of genes, and specifically the beta-amyloid gene which in turn expresses/ activates other pro-inflammatory genes, making the suppression of beta-amyloid very beneficial for AD. As well it has been observed that cannabinoids change the structure of beta-amyloid plaque build up facilitating the function if dissolving. Cannabinoids remove intraneuronal Aβ and completely eliminates the elevated eicosanoid production in induced MC65 cells.
Endocannabinoids are lipid molecules produced by the body and can activate cannabinoid receptors, CB1 and CB2. The researchers found that upon activation of these receptors by an endocannabinoid, neuronal cell survival was increased and beta amyloid accumulation was blocked. Conversely, the activation of cannabinoid receptors prevents Aβ accumulation and toxicity. Both intracellular Aβ accumulation and nerve cell death are potentiated by 5-LOX metabolites and proinflammatory cytokines. they found that deactivation of CB1 and CB2 had the opposite effect and increased toxicity and beta amyloid accumulation. Thus establishing the regulatory properties of the CB receptors. Endocannabinoids can be produced in response to stress,44,45 and in AD models cannabinoids reduce Aβ accumulation and improve memory.46,47 THC also reduces inducible huntingtin overexpression in PC12 cells,48 and both THC, CBD and endocannabinoids reduce inflammation.49,50 Several synthetic, plant derived and endogenous cannabinoids are able to prevent the accumulation of intraneuronal Aβ, reduce the production of eicosanoids, and block nerve cell death. Therefore, it is reasonable to conclude that there is a therapeutic potential of cannabinoids for the treatment of AD. In summary, the accumulation of intraneuronal Aβ and inflammation precede plaque formation and nerve cell death in AD. It is shown here that intracellular Aβ activates a broad spectrum of inflammatory signaling pathways. There is clearly a dynamic interplay between these pathways that may lead to either cell survival or death (Figure 5). Cell death can only be completely prevented by 5-LOX inhibitors, cannabinoids and caspase inhibitors. However, once the cell death process is underway, death can be reduced through the above mentioned proteins/inhibitors. Interestingly, of all the compounds tested, tetrahydrocannabinol (THC) was the most effective (but not exclusively, as CBD shows similar properties, which is why it is more therapeutic to utilize nature's remedy ie all cannabinoids & Terpenes, not any one molecule soley) at activating the CB1 receptor and stimulated the removal of beta amyloid proteins, blocked the inflammatory response and had a protective effect on neuron cells. Through gene transcription modulation properties regulating the transcription code, of genes, and specifically the beta-amyloid gene which in turn expresses/ activates other pro-inflammatory genes, making the suppression of beta-amyloid very beneficial for AD. As well it has been observed that cannabinoids change the structure of beta-amyloid plaque build up facilitating the function if dissolving. Cannabinoids remove intraneuronal Aβ and completely eliminates the elevated eicosanoid production in induced MC65 cells.
Tau/Cannabis correlation
Cannabis Regulating Tau Strands Stabilizing Microtubules & Neuro Pathways
Cannabis Regulating Tau Strands Stabilizing Microtubules & Neuro Pathways
changes in tau protein lead to the disintegration of microtubules in brain cells. which collapses the neuron's transport system.[68] This results first in malfunctions in biochemical communication between neurons and later in the death of the cells.[69] This is facilitated through the over-release of astroglial-derived neurotrophin actively exacerbates the pro-inflammatory cytokine loop fuelled by Aβ stimulation, & massively accelerates amyloidogenicity by promoting cleavage of APP to Aβ and induces tau protein hyperphosphorylation, by disrupting the Wnt pathway [22]–[24]. Trial observations suggest, supplementing cannabinoids, facilitates the suppression of beta-amyloid, preventing cleavage of APP to AB and preventing induction of tau protein hyperphosphorylation, & disruption of Wnt pathway [22]–[24]. by means of the cannabinoids & terpenes themselves and through the medium via CB 1 receptors and PPARy sites. In turn reducing even more inflammation & aiding in the functions of biochemical communication between neurons and prevention of cell death, reducing AD symptoms.
Neurovascular/Cannabis Correlation
Cannabis Strengthening BBB & Detoxifying Unwanted metals (ie. Aluminum)
Cannabis Strengthening BBB & Detoxifying Unwanted metals (ie. Aluminum)
The cellular homeostasis of biometals and the Ionic system are directly regulated by the endo-cannabinoid system, which ironically regulates the nervous system as well. as the Ionic system is directly linked to the nervous system Cannabiniods are a obvious form of regulating both systems. When the blood brain barrier is week not only can a irregular Ion system create a cascade of inflammatory & neurological effects. but if the aluminum hypothesis plays a role, a weakened blood brain barrier would allow for disaster. Ironically clinical trials have demonstrated cannabis having detox properties, aiding in the removal of aluminum, and more, as well cannabis has properties in which promote strengthening of the blood brain barrier, again making cannabis the best choice to date.
Cholinergic/Cannabis Connection
Cannabis regulating & Promoting Homeostasis in neurotransmitters Including Acetylcholine
Cannabis regulating & Promoting Homeostasis in neurotransmitters Including Acetylcholine
In the case of reduced synthesis of the neurotransmitter acetylcholine. Although there is less known of the reduced function of acetylcholine, the endo-cannabinoid system is the bodies regulatory system regulating proteins, hormones, and the nervous system as well promoting neurogenesis & neuroprotective, facilitating homeostatic synthesization of the neurotransmitter acetylcholine.
Clinical Studies