Alzheimer's Disease

[EDDIEKIRK]

Can marijuana help treat Alzheimer's disease?

General Reference (not clearly pro or con)



The National Institute on Aging stated in its Mar. 2006 booklet Understanding Alzheimer's Disease: "Alzheimer's disease is an illness of the brain. It causes large numbers of nerve cells in the brain to die. This affects your ability to remember things and think clearly. Doctors don't know what causes the disease. They do know that it usually begins after age 60 and nearly half of people age 85 and older may have Alzheimer's. However, it is not a normal part of aging...



There are medicines that can treat the symptoms of Alzheimer's. However, there is no cure. Some medicines keep your memory loss and other symptoms from getting worse for a time. These medicines work best if Alzheimer's disease is found early. Other medicines work to help you sleep better or feel less worried and depressed. These medicines don't directly treat the disease. They do help you feel more comfortable."





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Stimulation of cannabinoid receptor 2 (CB₂) suppresses microglial activation





Background

Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB₂).





Methods

In this study, we investigated the effects of a cannabinoid agonist on CD40 exp<b></b>ression and function by cultured microglial cells activated by IFN- using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB₂small interfering RNA (siRNA) analyses. Furthermore, we examined if the stimulation of CB₂could modulate the capacity of microglial cells to phagocytise Ab₁₄₂peptide using a phagocytosis assay.





Results

We found that the selective stimulation of cannabinoid receptor CB₂by JWH-015 suppressed IFN--induced CD40 exp<b></b>ression. In addition, this CB₂agonist markedly inhibited IFN--induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-a and nitric oxide production induced either by IFN- or Ab peptide challenge in the presence of CD40 ligation. Finally, we showed that CB₂activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Ab₁₄₂peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB₂modulation in neurodegenerative diseases, particularly AD.





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List of abbreviations

Ab : Amyloid-b peptide



CD40: CD40 receptor



CD40L: CD40 ligand



CNS: Central nervous system



HIV: Human immunodeficiency virus



IFN- : Interferon-gamma



JAK: Janus kinase



MHC II: Major histocompatibility complex II



STAT1: Signal transducer and activator of transcription 1



TNF-a : Tumor necrosis factor-alpha









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J Immunol 2003, 171:2216-2224. PubMed Abstract | Publisher Full Text OpenURL







Monsonego A, Weiner HL: Immunotherapeutic approaches to Alzheimer's disease.



Science 2003, 302:834-838. PubMed Abstract | Publisher Full Text OpenURL







Berdyshev EV: Cannabinoid receptors and the regulation of immune response.



Chem Phys Lipids 2000, 108:169-190. PubMed Abstract | Publisher Full Text OpenURL







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Arterioscler Thromb Vasc Biol 2002, 22:1784-1789. PubMed Abstract | Publisher Full Text OpenURL







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J Exp Med 2001, 193:967-974. PubMed Abstract | Publisher Full Text OpenURL







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Calingasan NY, Erdely HA, Altar CA: Identification of CD40 ligand in Alzheimer's disease and in animal models of Alzheimer's disease and brain injury.



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Benveniste EN, Nguyen VT, Wesemann DR: Molecular regulation of CD40 gene exp<b></b>ression in macrophages and microglia.



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[EDDIEKIRK]

Alzheimers, Mom and Cannabis

Posted by Skunk Pharm Research,LLC.

It is Skunk PharmResearchs policy to let patients tell their own story, but in the case of mom, as her daughter and 24/7 caregiver, I will speak for her. She is in the late seventh and final stage of Alzheimers and would want her story told.

Mom was diagnosed as late stage six when she came to me from Seattle four years ago. She was given six more months to live. She began displaying symptoms before 1998, but she wasnt diagnosed until 2001, following her first husbands death. It took that long to resolve other health issues and get her to a neurologist.



Just the thought of Alzheimers frightened her so, that we eventually had to trick her, to get her to a doctor for testing. Once tested and diagnosed, they put her on Aricept, which brought back cognitive skills, with slow decline for the next seven years while my step brother cared for her in her own home. Along with other western meds, this was her medical course.



When Moms Alzheimers progressed to the point that she became combative and personal hygiene became an issue, my brother planned to put her in a nursing home, but I quit my job to look after her. I moved her to Portland with me and took over her care, to focus on the quality of her remaining life.



For five months prior to her arrival, I immersed myself into learning as much about Alzheimers as possible, researching and joining The Alzheimers Association, as well as the Online Alzheimers Support Group, spending as much time as possible conversing with patients and caregivers alike, to prepare myself for the task.



When Mom arrived, besides being on five over the counter drugs, she was on three inhalers and a pill for asthma, blood pressure meds, allergy meds, anti psychotics that made her angry, anti seizure meds that made her delusional, plus three others I have no idea what they were used to combat.



We got her an OMMP card immediately upon her arrival. She had smoked cannabis recreationally with me for over thirty years, but never medically until she came toOregon. Cannabis was my only means of mitigating her despicable behavior (psychotic).



Her physical health was also poor, so I changed her diet, eliminated dairy, wheat and gluten. I prepared and feed her home cooked meals, using whole organic ingredients, supplemented with quality vitamins and minerals.



Ive continued to work with her doctor to straighten out her mishmash of meds. He started with large doses of anti psychotics to combat the behavioral issues (with potential seizure/death side effect), and we systematically took her off as many of the other drugs as possible. Meanwhile, I started trying the different forms of cannabis concentrates.



The first extractions were cannabis essential oils using hot grape seed oil, but she didnt like the flavor and refused to ingest it.



Given that unused meds are 100% ineffective, I next tried honey elixir, thinking she might go for the sweetness of the honey, but no luck.



No luck with fudge either, even though she loves chocolate.



I quickly determined that the only way to get substantial doses into mom would be via concentrates, so after experimenting with bubble hash combined with coconut oil as a menstruum, I focused on hash oil in an effort to improve consistency and homogeneity for consistency in dosing.



More specifically I began to experiment on my version of the Holy Anointing Oil from Exodus, using coconut oil instead of olive oil, and brewed from essential oils, as opposed to using the biblical perfumers extraction practices.



More on that medication at: http://skunkpharmresearch.com/holy-anoin...holy-shit/



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[url=http://skunkpharmresearch.com/holy-anointing-oil-and-holy-shit/]

[eloquentsolution]

ty, kirk! this picture was taken at age 28 at a fashion show luncheon. it was published in the entertainment section of the seattle times. they sent her a copy of the pic. beautiful, wasn't she!!!

[EDDIEKIRK]

ty, kirk! this picture was taken at age 28 at a fashion show luncheon. it was published in the entertainment section of the seattle times. they sent her a copy of the pic. beautiful, wasn't she!!!

She is Model quality beautiful. Like a movie star.

[Lady Strider]

ty, kirk! this picture was taken at age 28 at a fashion show luncheon. it was published in the entertainment section of the seattle times. they sent her a copy of the pic. beautiful, wasn't she!!!

and she still is!!! [img]<fileStore.core_Emoticons>/smile.png[/img]/emoticons/smile@2x.png 2x" width="20" height="20">

[eloquentsolution]

now she is a beautiful old lady. then she was a strikingly beautiful young woman!



my father on the other hand, was a heavy set, scarred, bald headed, freckle faced, marine who loved her dearly to the day he died. in many ways i take after him.

[EDDIEKIRK]

Alzheimers Prevention Research to Target Group With Rare Form

A team of researchers will soon try out an experimental drug that could prevent Alzheimers disease in a group of people who have a genetic mutation that makes it likely they will develop the debilitating disease.



Scientists will begin a clinical trial of crenezumab in about 300 Colombians whose genes predispose them to a rare form of Alzheimers that hits very early usually in the 40s or 50s and can affect multiple members of the same family. Funding for the study has been provided by the National Institutes of Health, Genentech and Banner Health System. Genentech is the developer of the experimental drug.

My link

[EDDIEKIRK]

http://abcnews.go.co...08#.T7HjoVJr12B



More at the bottom of page like this one

http://clinicaltrial...how/NCT00736775



This one is better, longer with more on cognitive disorders



Another study of the same story from Columbia

crenezumab

ACI-01-Ab7; ACI-01-Ab7 (intravenous); ACI-01-Ab7 (subcutaneous); Alzheimer's MAb (intravenous), AC Immune/Genentech; Alzheimer's MAb (subcutaneous), AC Immune/Genentech; Alzheimer's MAb, AC Immune; Alzheimer's MAb, AC Immune/Genentech; Alzheimer's MAb, Genentech; Anti-Abeta; anti-Abeta (intravenous), AC Immune/Genentech; anti-Abeta (subcutaneous), AC Immune/Genentech; anti-Abeta, AC Immune; crenezumab; crenezumab (intravenous); crenezumab (subcutaneous); MABT-5012A; MABT-5012A (intravenous); MABT-5012A (subcutaneous); MABT5102A; MABT5102A (intravenous); MABT5102A (subcutaneous); RG-7412; RG-7412 (intravenous); RG-7412 (subcutaneous); RG7412; RG7412 (intravenous); RG7412 (subcutaneous) crenezumab (MABT-5012A; ACI-01-Ab7; RG-7412) is a humanized anti-Abeta (-amyloid) MAb, under development by AC Immune for the passive immunotherapy of Alzheimer's disease (AD) (Company Web Page, AC Immune, 7 Jun 2005 & 1 Sep 2008; Company Web Page, Genentech, 11 Apr 2008).



OriginatorAC ImmunePhase II Clinical Trial

LicenseeHoffmann-La RochePhase II Clinical Trial

DiseasesAlzheimer's diseasePhase II Clinical Trial Latest Change03 Feb 2012: Ongoing Phase II development and filing plans updated History12 May 2011 Names GrantedMABT-5012A10 May 2011 Change in Global StatusPhase II Clinical trial 15 Aug 2008 Change in Global StatusPhase I Clinical Trial11 Dec 2006 Development Continuing 07 Dec 2006 New LicenseesGenentech, Worldwide18 Sep 2006 No Development Reported 07 Jun 2005 New Product Therapeutic ClassMonoclonal antibody, humanizedPhase II Clinical Trial Cognition enhancerPhase II Clinical Trial Mechanism of ActionBeta amyloid protein antagonist DeliveryRoute:Injectable

Injectable, intravenous

Injectable, subcutaneous Biological Targetamyloid beta (A4) precursor protein

Entrez Gene ID: 351

Target Families: Enzyme > Protease/peptidase Chemical DataOrigin: Biological, protein, antibody

NCE: No

CAS registry number: 1095207-05-8

Chemical Name: Immunoglobulin G4, anti-(human 1-40--amyloid/human 1-42--amyloid) (human-mouse monoclonal MABT5102A heavy chain), disulfide with human-mouse monoclonal MABT5102A light chain, dimer Major Market Information Country DataCountryStatusLicensing AvailabilityArgentina- NoAustralia- NoAustria- NoBelgium- NoBrazil- NoCanadaPhase II Clinical Trial NoChile- NoChina- NoColombia- NoDenmark- NoFinland- NoFrance- NoGermany- NoGreece- NoHong Kong- NoIndia- NoIreland- NoIsrael- NoItaly- NoJapan- NoLuxembourg- NoMalaysia- NoMexico- NoNetherlands- NoNew Zealand- NoNorway- NoPeru- NoPhilippines- NoPortugal- NoRussian Federation- NoSouth Africa- NoSouth Korea- NoSpain- NoSweden- NoSwitzerlandPreclinical NoThailand- NoTurkey- NoUKPhase II Clinical Trial NoUSAPhase II Clinical Trial NoVenezuela- No MarketingFilings

________________



AC Immune; Hoffmann-La Roche

Alzheimer's disease

Worldwide; a registration filing for AD is expected after 2016 (Company pipeline, Roche, 1 Feb 2012, http://www.roche.com...ma_pipeline.htm).



AC Immune

USA; fast-track status for mild-to-moderate AD (Press release, AC Immune, 4 Dec 2008). LicensingAgreements

________________



Hoffmann-La Roche

Worldwide; it is exclusively licensed to Genentech (Hoffmann-La Roche) for development and commercialization. Genentech will pay AC Immune a royalty on sales, upfront and regulatory milestone fees, and will fund a multi-year collaborative research programme, covering all clinical development costs (Press release, AC Immune, 7 Dec 2006; Scrip Daily Online, 11 Dec 2006, S00943102). Roche has the right to opt into development (Company pipeline, Roche, 10 Feb 2009). Key Clinical Information Phase IIAlzheimer's disease

AC Immune; Hoffmann-La Roche

It is in a Phase II, randomized, double-blind, placebo controlled, parallel-group, multicenter, biomarker Phase II study (BLAZE, ABE4955g) of crenezumab iv and sc in 72 patients with mild to moderate AD in the US. Primary endpoint includes change in brain amyloid load from baseline to 69wk (ClinicalTrials.gov, 3 Feb 2012, http://clinicaltrial...how/NCT01397578; Company presentation, Roche, 1 Feb 2012, Slide 140, http://www.roche.com...120201_full.pdf).



It is in a Phase II, randomized, double-blind, placebo controlled, parallel-group, multicenter, cognition study (ABBY) to evaluate the efficacy and safety of crenezumab iv and sc in 372 subjects with mild to moderate AD in Canada, the UK and the US. Primary endpoint includes change in cognition (ADAS-cog) and CDR-SOB score from baseline to 73wk (ClinicalTrials.gov, 29 Apr 2011, http://clinicaltrial...how/NCT01343966; Company Web Page, AC Immune, 10 May 2011, http://www.acimmune.com/content/?p=41; Company presentation, Roche, 1 Feb 2012, Slide 140, http://www.roche.com...120201_full.pdf). Phase IGenentech (Hoffmann-La Roche)

A US Phase I, single-dose, randomized, parallel-group, open-label study (ABE4662g) of the safety, tolerability, pharmacokinetics, and bioavailability of crenezumab iv and sc in 22 healthy volunteers is complete. It was well tolerated and showed a favorable pharmacokinetics/pharmacodynamics profile (ClinicalTrials.gov, 18 Oct 2010, http://clinicaltrial...how/NCT00997919; Company Web Page, AC Immune, http://www.acimmune.com/content/?p=41).



Alzheimer's disease

Genentech (Hoffmann-La Roche)

A randomized, placebo-controlled, double-blind, US Phase I trial (ABACUS) in 56 patients with mild-to-moderate AD to assess safety, tolerability, pharmacokinetics and immunogenicity is complete (ClinicalTrials.gov, 28 Oct 2010, http://clinicaltrial...how/NCT00736775; Company Web Page, Roche, 8 Feb 2010; Half Year Res, Roche, 23 Jul 2009).

PreclinicalIn vivo

It was active in animal models of AD, and induced the transition of insoluble -amyloid to the soluble form (Press release, AC Immune, 7 Dec 2006; Scrip Daily Online, 11 Dec 2006, S00943102). Supporting URLs<li class="ListItem">http://www.roche.com/research_and_development/pipeline/roche_pharma_pipeline.htm?ta=%25&Ph...

<li class="ListItem">http://www.roche.com/irp3q10e.pdf

<li class="ListItem">http://www.acimmune.com/content/?p=41

<li class="ListItem">http://clinicaltrials.gov/ct2/show/NCT00736775

<li class="ListItem">http://www.roche.com/irp110202.pdf

<li class="ListItem">http://www.roche.com/irp1q11e.pdf

<li class="ListItem">http://www.gene.com/gene/pipeline/status/neuroscience/anti-abeta/

<li class="ListItem">http://clinicaltrials.gov/ct2/show/NCT01343966

<li class="ListItem">http://clinicaltrials.gov/ct2/show/NCT01397578

<li class="ListItem">http://www.roche.com/irp2q11e.pdf

<li class="ListItem">http://www.roche.com/irp120201_full.pdf

[EDDIEKIRK]

Today, we now see the vast majority of complaints of food side effects sent to the FDA being caused by aspartame. Aspartame is an excitotoxin, that is, a neurotoxic chemical, and it breaks down in your body into both formic acid and formaldehyde. Now, would you like to go out and drink some formaldehyde? Well, you might do that if you were a biological specimen that needed to be preserved for dissection, but if you're a normal, healthy, sane human being, you'd never drink formaldehyde. Unless, of course, they put it in an artificial sweetener compound and added it to cans of your favorite carbonated soft drink, in which case Americans will gladly drink formaldehyde in can after can, poisoning their nervous systems, going half blind, experiencing epilepsy and increasing the onset of neurodegenerative disorders such as Alzheimer's disease.

Learn more: http://www.naturalnews.com/008511_medica...z1vXd9VsqO

[EDDIEKIRK]

Posted on April 30, 2012 by Tom and Karen Brenner



When we began creating short stories for people living with dementia to read aloud, we were surprised by the journey that this simple exercise created. As people began reading our prepared stories, they started telling us stories from their own lives. These stories really grabbed us, and we began writing them down. It is often said that everyone has at least one good story in them, and we have found this to be true.

We are not talking about autobiography and we are not discussing life histories, but rather we are talking about incidents, fleeting moments from a persons life that they share with us. For example, there was Virginias story about how she met her husband. He was the brother of a girl that Virginia worked with in a factory during WWII. He was in the Navy and was home on leave when Virginia went to her friends house for dinner. Virginia told us,



We took one look at each other and it was bif, bam boom! They were married before his leave was over and he had to go back to the Navy and to the war. He survived the war and they were married until his death, some forty years later. This was just a brief moment in Virginias long life, but of course, a seminal one for her and for her husband.



We asked Virginia if she would like to film her story about how she met her husband. She agreed and we made a very short film of Virginia telling us this story. Then, as we always do, we showed Virginia her movie. At first, we were alarmed because when Virginia saw herself on the television screen, she asked us,



Who is that old woman? How does she know all that stuff about my life? Virginia began to grow agitated and we thought that perhaps this was a mistake. But then, as she began to listen to the old woman talking on the TV, Virginia became engrossed in the story. She began to agree with the old woman, and shake her head yes, that was right. She laughed out loud when the old woman on the TV said that it was bif, bam boom, when Virginia met her husband.



She clapped heartily when the film ended and was very much awake when she went to lunch that day. We were not sure if Virginia understood that the old woman talking on TV was actually her, but then we overheard her talking to her lunch companions and saying, You are not going to believe this, but I was on TV today. I had my own show on TV!



When we realized that some people who have dementia can still tell stories from their lives, we began documenting these stories in print and on film. We learned that it was very important to first give people something to hold in their hands in order to prime the pump of memory. For Virginia, we happened to be visiting on Veterans Day and we just happened to give her a little flag that had the Navy insignia on it. She recognized the flag and that was the prompt that opened the gates to her story of how she met her husband. Now, we deliberately bring in meaningful objects or photographs from peoples lives to help give them some context for sharing stories from their lives.



Finally, there was the love story that was told to us by a highly regarded scientist. He had taught in a major university and conducted important research that had an impact on world wide crop development. Knowing his life work, we brought in small galvanized buckets of different types of grains for him to put his hands into, to feel the grain again, to prime his memory of the years that he researched and worked with arable crops.







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