ALZHEIMER'S DISEASE - 15 MEDICAL MARIJUANA RESEARCH PAPERS

Alzheimer's Disease - Medical Marijuana Research Findings

Alzheimer's Disease - Medical Marijuana Research Findings

 

By now, there is a wealth of clinical evidence that marijuana - the high THC variety - works to alleviate the symptoms of Alzheimer's disease in many, but certainly not all cases,   It appears that CBD or THC with CBD may work on average even better.  Little studied Cannabinoids such as THC-V and unheated forms of both THC and CBD (their acids) now show efficacy in the clinic as well.

 

Cannabinoids work in a variety of ways, and there is some evidence that marijuana can treat the symptoms of Alzheimer's and even the disease itself.

Though one prominent researcher's research showed the effectiveness of cannabis in treating Alzheimer's, he warned its THC could make some symptoms worse.  However, because of the very low toxicity of cannabis components, cannabis based medicines of various sorts can be experimented with greater safety than most pharmaceutical medicines.  In any case, Alzheimer's patients should be closely monitored by a capable health professional.  

Researhers know that cannabinoids can dial up and dial down different cellular functions almost immediately upon vapor intake - to affect the receptors that control nerves and their support cells.  When the body's own cannabinoids - called endocannabinoids - are in chronic short supply, the cells don't perform properly and a variety of symptoms results, and is especially evident in nervous and cerebral dysfunction.  In the case of Alzheimer's, cannabiniods seem to restore more normal brain chemistry, which results in the normalization of cognitive function.

Despite all this good news, we're not seeing a miracle cure here, but in many cases, Alzheimer's patients quality of life has been restored from a state of unacceptable to acceptable, from non-coherence to somewhat normal.  Provided that current researchers are permitted to explore the vast array of natural and synthetic cannabinoids, the future appears bright indeed.

 

“Mom transformed from aggressive to cheerful, the woman I knew in childhood. The isolation switched to humor.  From weird, frantic shuffling and hiding of objects, she began offering them to others.  Instead of kicking, biting and hitting, she became happily and cooperative.  She literally turned into a social butterfly!“ - The  Best Case Scenario

 

Note: * denotes a synthetic cannabinoid.

 

1 Prevention of Alzheimer's - AD disease pathology by cannabinoids. Ramirez et-al the year of 2005. The Journal of Neuroscience 25: 1904-1913.

1 Alzheimer's - AD is characterized by enhanced β-amyloid peptide -βA - deposition along with glial (brain cell support) activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity (impairment by excessive excitation) in vitro (cellular)  and acute brain impairment in vivo (whole organism).

1 This review prompted us to inquire into the localization, expression, and behavior of cannabinoid receptors in AD and the possible protective role of cannabinoids after βA treatment, both in vivo (whole organism)  and in vitro (cellular) . Here, we show that senile plaques in AD subjects express cannabinoid receptors CB1 and CB2, together with markers of microglial (brain cell support) activation, and that CB1-positive neurons, present in high amounts in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly dialed down in AD brains.

1 In addition, in AD brains, protein nitration is dialed up, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular (into veins) dose of the synthetic cannabinoid *Win 552122 to rats prevent βA-induced microglial (brain cell support) activation, cognitive impairment, and loss of neuronal markers. Cannabinoids -*HU210, *Win 552122, and *JWH 133 - block βA-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-α release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist (binds to receptor).

1 Furthermore, cannabinoids abrogate (halt) microglia-mediated neurotoxicity after βA addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the condition.

 

"CANNABINOIDS REMOVE PLAQUE-FORMING ALZHEIMER’S PROTEINS FROM BRAIN CELLS" - RESEARCH HIGHLIGHT

 

2 israeli research shows cannabidiol may slow Alzheimer's - AD disease. Israel National News. December 16, the year of 2010.

2 Professor Raphael Mechoulam and a team led by Dr. Maria de Ceballos at the Cajal Institute in Madrid, Spain, mice were injected with a molecule found in the brain of humans suffering from Alzheimer’s disease, and then treated for 7 days with cannabidiol. Following the treatment, their learning ability was assessed by measuring the length of time needed for them to find a hidden platform in a maze.

2 Those mice injected with cannabidiol successfully performed the task within half a minute, compared to mice in the control group who had not been treated with cannabidiol, who took almost double the amount of time, three quarters of a minute, to complete the task.

2 Mechoulam presented the findings this week at the Cannabis Medicines Symposium in London, hosted by the Royal Pharmaceutical Society of Great Britain and said that human trials will hopefully follow in the near future.

2 Although the findings look promising, Professor Mechoulam warned that Alzheimer’s subjects should not use marijuana high in THC, the psychoactive ingredient in marijuana, because it could have the opposite effect and have a damaging effects on the memory.

 

Editor's note:  Unfortunately, Dr Mechoulam did not comment precisely the use of on high CBD strains.

 

 

3 A molecular link between the active component of cannabis and Alzheimer's disease pathology. Eubanks et-al the year of 2006. Molecular Pharmaceutics 3: 773-777.

3 Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next fifty years. Consequently, the development of treatments that slow or halt the condition progression have become imperative to both help the quality of life for subjects and reduce the health care costs attributable to Alzheimer's - AD disease.

3 We demonstrate that the active component of cannabis,d9THC , competitively inhibits the enzyme acetylcholinesterase -AChE (neuro-transmitter) - as well as prevents AChE-induced amyloid β-peptide -Aβ - aggregation, the key pathological marker of Alzheimer's - AD disease. Computational modeling of the THC−AChE (neuro-transmitter) interaction revealed that THC binds in the peripheral anionic site of AChE (neuro-transmitter), the critical region involved in amyloidogenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's - AD disease,

3 THC is a considerably superior inhibitor of Aβ aggregation, and this enquiry provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating condition.

 

4 Phyto-cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells Salk News. June 27, the year of 2016.

4 Salk Institute scientists have found preliminary evidence that d9THC and other compounds found in cannabis may promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer's - AD disease.  While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer's - AD disease and could provide clues to developing new medicinals for the disorder.

4 “Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer’s, we believe our enquiry is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells,” says Salk Professor David Schubert, the senior author of the paper.

4 Alzheimer's - AD disease is a progressive brain disorder that leads to memory loss and may seriously impair a person’s ability to carry out daily tasks. It affects more than five million Americans, according to the National Institutes of Health, and is a leading cause of death. It is also the most common cause of dementia and its incidence is expected to triple during the next fifty years.

4 It has long been known that amyloid beta accumulates within the nerve cells of the aging brain well before the appearance of Alzheimer's - AD disease symptoms and plaques. Amyloid beta is a major component of the plaque deposits that are a hallmark of the condition. But the precise role of amyloid beta and the plaques it forms in the conditioning process remains unclear.

 

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5 Anti-inflammatory property of the cannabinoid agonist (binds to receptor) *Win-55212-2 in a rats and mice model of chronic brain inflammation. Marchaland et-al the year of 2007.  Neuroscience 144: 1516-1522.

5 The antioxidative properties of cannabinoids suggest a medicinal use as neuroprotective agents, and the particular properties of cannabidiol make it a good candidate for such development. Although cannabidiol was similar in neuroprotective capacity to BHT, cannabidiol has no known tumor-promoting effects [unlike BHT. The lack of psychoactivity associated with cannabidiol allows it to be administered in higher doses than would be possible with psychotropic cannabinoids such as THC.

5 Furthermore, the ability of cannabidiol to protect against neuronal injury without inhibiting NMDAr may reduce the occurrence of toxicity or side effects associated with NMDAr antagonists (blockers). Previous studies have indicated that cannabidiol is not toxic, even when chronically administered to humans or given in large acute doses.

5 In vivo (whole organism) studies to examine the efficacy of cannabidiol as a treatment for experimentally induced ischemic stroke are currently in progress.receptors -CB1-2 - stimulation induces numerous central and peripheral effects. A growing interest in the beneficial properties of manipulating the endocannabinoid system has led to the possible involvement of CB1-2 in the control of brain inflammation. In the present enquiry we examined the effect of the CB1-2 agonist (binds to receptor),

5 Our results emphasize the potential use of CB1-2 agonists in the regulation of inflammatory processes within the brain; this knowledge may lead to the use of CB1-2 agonists in the treatment of neurodegenerative conditions associated with chronic neuroinflammation, such as Alzheimer disease.

 

6 Cannabidiol and d9-THC are neuroprotective antioxidants Hampson et-al the year of 1998.  .Proceedings of the National Academy of Sciences 95: 8268-8273.

6 The antioxidative properties of cannabinoids suggest a medicinal use as neuroprotective agents, and the particular properties of cannabidiol make it a good candidate for such development. Although cannabidiol was similar in neuroprotective capacity to BHT, cannabidiol has no known tumor-promoting effects.

6 The lack of psychoactivity associated with cannabidiol allows it to be administered in higher doses than would be possible with psychotropic cannabinoids such as THC. Furthermore, the ability of cannabidiol to protect against neuronal injury without inhibiting NMDAr may reduce the occurrence of toxicity or side effects associated with NMDAr antagonists (blockers). Previous studies have indicated that cannabidiol is not toxic, even when chronically administered to humans or given in large acute doses.. in vivo (whole organism) studies to examine the efficacy of cannabidiol as a treatment for experimentally induced ischemic stroke are currently in progress.

 

7 Alzheimer's - AD disease; taking the edge off with cannabinoids? Campbell and Gowran. the year of 2007. British Journal of Pharmacology 152: 655-662.

7 Alzheimer's - AD disease is a devastating illness for which there is no cure. Current AD drugs, which serve as AChE (neuro-transmitter) inhibitors, have an amount of unpleasant side effects such as hepatotoxicity and gastrointestinal disturbances.

7 While the NMDA receptor antagonist (blockers), memantine, may modify the condition, it cannot reverse the process of neurodegeneration. Manipulation of the cannabinoid pathway offers a new pharmacological approach for the treatment of AD that may be more efficacious than current treatment regimes. Phyto-cannabinoids may reduce the oxidative stress, neuroinflammation and apoptosis that are evoked by Aβ, while promoting the brain's intrinsic repair mechanisms.

7 Certain cannabinoids, such as d9-THC, may also increase ACh availability and reduce amyloidogenesis, although potential psychoactive side effects may hinder its clinical effectiveness. Phyto-cannabinoids clearly offer a multifaceted approach for the treatment of AD and future studies should focus on examining the efficacy of phyto-cannabinoids in the array of animal models that exhibit AD-like pathology and cognitive decline.

7 Targeting the CB2 receptor to reduce neuroinflammation while stimulating neurogenesis is likely to be of particular interest, given the reduced risk of psychoactive activity and the close association of the CB2 receptor with the senile plaque, thus limiting drug effects to the region of pathology and sparing the potential for widespread effects on normal neurophysiological processes. In conclusion, manipulation of the cannabinoid system offers the potential to upregulate neuroprotective mechanisms while dampening neuroinflammation.

7 Whether these properties will be beneficial in the treatment of AD in the future is an exciting topic that undoubtedly warrants further investigation.

 

8 .International Journal of Geriatric Psychiatry 12: 913-919.

 

8 WHY CONDUCT THE STUDY:Nighttime agitation occurs frequently in subjects with dementia and represents the number one burden on caregivers currently. Today's treatment options are few and limited due to substantial side effects.
 

8 AIM: The aim of the enquiry was to measure the effect of the cannabinoid *dronabinol - synthetic THC on nocturnal motor activity.
 

8 PROTOCOL: In an open-label pilot study, six consecutive subjects in the late stages of dementia and suffering from circadian and behavioral disturbances-five subjects with Alzheimer's - AD disease and one patient with vascular dementia-were treated with 2.5 milligram *dronabinol - synthetic THC daily for two weeks. Motor activity was measured objectively using actigraphy.
 

8 DATA: Compared to baseline, *dronabinol - synthetic THC led to a reduction in nocturnal motor activity. These findings were corroborated by improvements in Neuropsychiatric Inventory total score as well as in subscores for agitation, aberrant motor, and nighttime behaviors. No side effects were observed.
 

8- FINDINGS: The study suggests that *dronabinol - synthetic THC was able to reduce nocturnal motor activity and agitation in severely demented subjects. Thus, it appears that *dronabinol - synthetic THC may be a safe new treatment option for behavioral and circadian disturbances in dementia.

8  Effects of *dronabinol - synthetic THC on anorexia and disturbed behavior in subjects with Alzheimer's - AD disease Volicer et-al the year of 1997.

 


9 Cannabis lifts Alzheimer's appetite. BBC News. August 21, the year of 2003.  

9 In the latest US trial, forty-eight subjects with an average age of seventy-seven who had experienced problems with agitation and had been diagnosed with anorexia were studied.

9 All lived in a dementia unit or a care home. Researchers assessed their cognitive skills and looked at how they coped with daily life. They were then given daily doses of five milligrams of *dronabinol - synthetic THC per day, which was gradually dialed up to ten milligrams a day. They were also given anti-psychotic drugs, which reduce delusions and have a calming effect, and at least four other medications to control behaviour.

9 After a month, it was found all the subjects had gained weight. Two thirds experienced a significant improvement in agitation. No adverse events such as falls, seizures or depressions were reported.
'Upsetting and stressful' Dr Joshua Shua-Haim, medical director at the Meridian Institute for Aging, who led the enquiry, said: "Our research suggests *dronabinol - synthetic THC may reduce agitation and help appetite in subjects with Alzheimer's - AD disease, when traditional therapies are not successful.

9 "It's important to look at all the aspects of Alzheimer's - AD disease that contribute to quality of life for subjects, family members and caregivers. Agitation and weight loss are upsetting and stressful as the patient's needs become ever more demanding."


 

10 The Effects of Medical Marijuana on Alzheimer’s Treatment

10 “It’s important to keep in mind that just because a drug may be effective doesn’t mean it may be safely used by anyone. However, these findings may lead to the development of related compounds that are safe, legal, and effective in the treatment of Alzheimer's - AD disease.”

10 “Although other studies have offered evidence that phyto-cannabinoids might be neuroprotective against the symptoms of Alzheimer’s, we believe our study is the first to demonstrate that phyto-cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells.”


10 In the study, researchers found that by exposing beta amyloid proteins to d9THC, it reduced the levels of beta amyloid, halted the inflammatory response from the nerve cells caused by beta amyloid and allowed the nerve cells to survive. Antonio Currais, a postdoctoral researcher and first author on the paper noted:
 

10 “Inflammation within the brain is a major component of the impairment associated with Alzheimer's - AD disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves. When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that d9THC-like compounds that the nerve cells make themselves may be involved in protecting the cells from dying.”
 

10 Researchers caution that their findings were conducted in a laboratory model and that further research needs to be done in a clinical trial before any conclusive evidence may be produced.

 

 

11 Alzheimer's - AD disease – Medical Marijuana Research Overview

11 Studies have determined that two of the major phyto-cannabinoids found in marijuana,  d9THC and cannabidiol - CBD, reduce the buildup of plaques and tangles, and therefore show viable potential as treatment options for Alzheimer’s disease.

11 Cannabis’ potential efficacy for Alzheimer’s disease has been linked to its interaction with the endocannabinoid system, which modulates several pathological processes associated with the neurodegenerative disorder, including neuroinflammation, excitotoxicity (impairment by excessive excitation), mitochondrial dysfunction, and oxidative stress. The endocannabinoid system’s CB1 receptors have shown to regulate the neurotransmitters involved in excitotoxic neurodegenerative processes, while its CB2 receptors have shown to reduce the inflammation associated with Alzheimer’s disease..

11 THC has been shown to be effective at lowering amyloid-beta levels and enhancing mitochondrial behavior, therefore causing the researchers to conclude “that d9THC could be a potential medicinal treatment option for Alzheimer’s through multiple behaviors and pathways”.

11 An earlier study also found d9THC to be effective at preventing amyloid beta aggregation, indicating it could impact the progression of the condition.  Another showed d9THC to reduce nocturnal motor activity and agitation in subjects with dementia, suggesting it could be beneficial for treating behavioral and circadian disturbances.

11 The brains of Alzheimer’s subjects experience an over-activation of microglia -cells that form myelin -, which contributes to excessive tau buildup and eventually tangles. However, Cannabidiol - CBD has been shown to modulate microglial (brain cell support) function and control neuroinflammation.

11 In addition, Cannabidiol - CBD has been shown to help the survival rate of cells through a combination of neuroprotective, anti-oxidative, anti-inflammatory and anti-apoptotic effects against the toxicity caused by beta-amyloid, therefore showing potential as a medicinal option for Alzheimer's. One inquiry that found Cannabidiol - CBD is neuroprotective effects and its ability to promote the regeneration of brain cells was effective for reversing the cognitive deficits caused by Alzheimer’s.

 

12 A Molecular Link Between the Active Component of Marijuana and Alzheimer's Pathology

12 Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both help the quality of life for subjects as well as reduce the health care costs attributable to Alzheimer's disease.

12 Here, we demonstrate that the active component of cannabis,d9THC, competitively inhibits the enzyme acetylcholinesterase -AChE (neuro-transmitter) - as well as prevents AChE-induced amyloid β-peptide -Aβ - aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the d9THC-AChE (neuro-transmitter) interaction revealed that d9THC binds in the peripheral anionic site of AChE (neuro-transmitter), the critical region involved in amyloidogenesis.

12 Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, d9THC is a considerably superior inhibitor of Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

 

13 Alzheimer’s, Mom and Cannabis

13 Mom transformed from aggressive and angry to the cheerful woman I knew from childhood.  Instead of slapping my cheeks, she caressed them tenderly and moved my hair from my face as she told me she loved me.  From her isolation came the interaction and humor required to joke with us.   From frantic shuffling and hiding of objects she began offering them for my use.  Rather then kicking, biting and hitting, she became happily compliant, even cooperative.  She literally became a social butterfly!

13 Mom also suffered extensively from muscle spasms, particularly in her legs, typically relieved by dancing the night away together. But one night I thinned some HAO oral with coconut oil, to reduce the cinnamon oil below topical TLV as an irritant and to help penetration.  After slathering her leg with the modified HAO, the cramps went away, allowing her to go back to sleep.  She woke 20 minutes later complaining of the other leg.  Again, HAO topical and back to sleep! HAOT was born.

13 It took nearly two years working with her physician to get her medical care stabilized and a permanent “Primary Care Practitioner" established.  We were able to get her off of most of the original drug regimen, and determined that her psychotic episodes were directly related to urinary tract infections, for which she is susceptible.

 

14 Medical Marijuana and Alzheimer's What Every Caregiver Should Know

14 Low-dose d9THC was effective in reducing the production of the amyloid beta plaques that most experts believe ultimately cause Alzheimer's. The results from in vitro (cellular)  studies showed that d9THC boosts the behavior of mitochondria, the "energy factories" of cells, suggesting d9THC might aid brain activity.

14 "Dialed down levels of amyloid beta means less aggregation, which may protect against the progression of Alzheimer's disease," said lead researcher Chuanhai Cao, a neuroscientist at the University of South Florida's Byrd Alzheimer's - AD Institute. "Since d9THC is a natural and relatively safe amyloid inhibitor, d9THC or its analogs may help us develop an effective treatment in the future."

 

 

15 EFFECTS OF DRONABINOL ON ANOREXIA AND DISTURBED subjects WITH ALZHEIMER'S

15 A placebo-controlled crossover design, with each treatment period lasting six weeks, was used to investigate e?ects of *dronabinol - synthetic THC in fifteen subjects with a diagnosis of probable Alzheimer's - AD disease who were refusing food. Eleven subjects completed both study periods; one patient who died of a heart attack two weeks before the end of the study was also included in the analysis.

15 The study was terminated in three subjects: one developed a grand mal seizure and two developed serious intercurrent infections. Body weight of study subjects dialed up more during the *dronabinol - synthetic THC treatment than during the placebo periods.

15 *Dronabinol - synthetic THC - treatments dialed down severity of disturbed behavior and this e?ect persisted during the placebo period in subjects who received *dronabinol - synthetic THC. Adverse reactions observed more commonly during the *dronabinol - synthetic THC treatment than during placebo periods included euphoria, somnolence and tiredness, but did not require discontinuation of therapy. These results indicate that *dronabinol - synthetic THC - synthetic THC is a promising new medicinal agent which may be effective not only for treatment of anorexia, but Alzheimer's as well.

 

Labels: ALZHEIMER'S DEMENTIA Alzheimer's - AD DISEASE MEMORY LOSS cannabinoid receptors inflammation spatial memory

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