Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

[LALucia]

For the last several years I've been taking a very small dose for sleep (with a prescription in California). I've been a serious insomniac my whole life, and it's the best sleep aid I've ever found. It's always seemed like it couldn't be that bad for me, especially compared to the Ambien and Ativan doctors have prescribed for me. I've found articles/studies saying it's good for Alzheimer's and others saying it's bad, but I decided that getting a good night's sleep was important enough for my health to take the risk. I'm very glad to know about this study!

[Tincup]

Oh...it's legit right????

In 2000, medical marijuana was legalized in Colorado. A patient needed a script from a doc to get a medical marijuana card. Amazingly, a high number of cardholders were young men in their early 20's... However it does seem to help a lot of people with legitimate pain, migraines and seizures. My ex and her sister use edibles to dramatically help with lifelong (or at least since puberty) migraines. My ex also uses non-THC CBD oil for sleep. Recreational use was legalized in 2014. They are the same, except medical requires a card and is taxed less.

[TheresaB]

I’ve been doing some research on CBD, cannabidiol, which is derived from both cannabis and hemp plants. I have learned A LOT and thought I’d share.

While my ApoE4 status is always a consideration, my motivation for this came from struggles with foot pain. Since 2013, I’ve had three surgeries, tried numerous physical therapy/exercise approaches, and used various joint/inflammation supplementation strategies, but I’m still experiencing issues which impact my life in many ways.

Although I live in Colorado, which has had medical marijuana for a while (2000) and was one of two states to first legalize recreational marijuana, (2014) until recently I have been reluctant to consider this option for multiple reasons. But the anecdotes I was hearing were success stories, perhaps I’ve heard more stories than most because of our legal status, so my interest was piqued. Besides, after following the discussions on this APOE4.info website, I’ve learned that traditional medicine isn’t necessarily going to provide good answers.

When I heard that there was this “form of marijuana” called CBD which is effective at addressing pain/inflammation without “getting high” and that CBD can come in cream/balm form that can be applied directly to an affected area, I became seriously interested. But I didn’t want to adapt a practice that would contradict my ApoE4/health strategies. For example, unless necessary, I avoid NSAIDS even though they can reduce pain/inflammation because they also interfere with a healthy gut biome which is critical for clear cognition. I since learned CBD is not strictly a marijuana product that has to be purchased at a marijuana dispensary.

Some terminology:
Cannabis – also known as marijuana, a plant that is used for its psychoactive drug qualities (to get high) or for medicinal purposes. Illegal in all 50 states per federal law, regardless of the state’s law. Recognized as legal for medical purposes (medical marijuana card required) in over half the 50 states (28 plus DC as of April 2017). State law recognized as legal for recreational purposes in 8 states plus DC (as of April 2017). Even in states where it is legal recreationally, there are laws as to where it can be smoked/consumed, specifically public consumption is illegal. Landlords, hotels, etc. can restrict usage within their abodes. A person needs to be careful with cannabis products in the home around pets and children. A state’s legal recognition does not circumvent what an employer may dictate for employment. A person can still be charged with driving under the influence of marijuana. Even if bought in a state that recognizes legal recreational marijuana, it’s illegal to transport to any another state. If you have a medical marijuana card, states that allow medical marijuana do tend to reciprocally respect that, but recognize that if you are flying, TSA cannot allow people to bring any marijuana on airplanes. I’m sure there are other “prickly” issues.

Hemp -- A variety of the cannabis sativa plant species that is generally grown for commercial and industrial uses. Although cannabis and industrial hemp are both members of the species cannabis sativa and both contain tetrahydrocannabinol (THC), they are distinct strains. Hemp has lower concentrations of THC and higher concentrations of cannabidiol (CBD). Hemp products for consumption (hemp protein powder, hemp seed oil, hemp lotion, hemp hearts, etc.) can be purchased without legal restrictions in the U.S.

THC -- Tetrahydrocannabinol -- the principal psychoactive constituent of cannabis (what makes a person high)

CBD -- Cannabidiol - one of at least 113 active cannabinoids in cannabis (don't know about hemp). CBD does not have the intoxicating effects as THC and can actually counteract the psychoactivity of THC. In 2013, CNN produced a segment that featured “Charlotte's Web” a high CBD, low THC cannabis extract that does not induce a high (it was was originally called "Hippie's Disappointment" ). Charlotte’s Web was named after a 10 year old girl, Charlotte, who experienced a reduction of her epilectic seizures after her first dose of medical marijuana. That 2013 CNN segment resulted in increased demand for CBD-dominant cannabis and led to some changes to U.S. legislation. CBD products derived from marijuana plants must be purchased from marijuana dispensaries, even if they are sold for their medicinal not psychoactive effects. CBD derived from hemp is considered a food and dietary supplement, not a medication. There are no restrictions on the production, sale, and consumption of hemp oil in the U.S.

I have also learned there are various products cannabis/CBD can come in, I was personally stunned. There’s the traditional marijuana “joint” which is smoked, but there’s also vaping oil, edibles, drinks, creams, tinctures, powders, crumbles, patches, capsules, and probably more! There are hemp products for your pet too. Gracious! The different forms allow for varying degrees of discretion but also come with varying degrees of time until a response is felt. I’ve also learned that the cream I’m interested in for direct application to the constantly inflamed area of my foot can also be applied to certain areas of the body where veins are closest to the skin for general, systemic use.

Since it is not considered a medication, CBD products have not been evaluated by the FDA. If you visit a website which features the sale of CBD products you will likely notice they claim to help a LONG list of ailments. FYI, anyone can go online to read about CBD products that contain THC, purchasing them on-line, however, is a different story. There are no restrictions to purchasing CBD products that don’t contain THC, although if purchasing out of country, there may be customs restrictions.

Most (if not all) of the beneficial claims on these websites cannot be backed by rigorous research. Growing hemp has been restricted in the US and universities in this country have only been allowed to grow hemp for research purposes since 2014. When it comes to research on medical marijuana, scientists in the U.S. have to get approval from the Drug Enforcement Agency (DEA) and the FDA. So there are many unknowns as far as benefits and negative risks/side effects.

There are many ailments CBD claims to help. This was taken from the literature of a company that sells CBD oil products from hemp (no THC):

Health benefits in every drop of CBD oil
• Reduces small intestine contractions
• Reduces risk of artery blockage
• Reduces vomiting and nausea
• Suppresses muscle spasms
• Reduces blood sugar levels
• Inhibits cancer cell growth
• Supports immune system
• Protects nervous system
• Promotes bone growth
• Reduces inflammation
• Relieves pain
• Antibacterial
• Vasorelaxant
• Treats psoriasis

Their literature also says:

Recent studies have shown that CBD has a wide range of therapeutic properties that may help manage and even prevent certain diseases. Although further clinical research is still needed to determine the potential long-term effects of CBD on the human body, experiential evidences show that it has indeed a positive impact in various organ systems.
Brain

• Antipsychotic
  Anti-Depressant
  Anti-Anxiety
  Anti-Oxidant
  Neuroprotective

Eyes

• Vasorelaxant for glaucoma

Heart

• Artherosclocrosis
  Anti-ischemic
  Anti-inflammatory

Stomach

• Anti-emetic
  Appetite control

Intestines

• Anti-prokinetic

Bones

• Analgesic for rheumatoid arthritis
  Stimulates new bone growth and strengthens bones affected by osteoporosis

Like I said, a long list of ailments, but even the brochure admits more clinical research is needed.

I didn’t spend too much time researching, but here are some studies I found of interest to ApoE4s:

In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease. Published 2017
https://www.ncbi.nlm.nih.gov/pubmed/28217094
“Thus, it is investigated as a potential multifunctional treatment option for AD. Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD. The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models. Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone.”

Cannabidiol Modulates the Expression of Alzheimer's Disease-Related Genes in Mesenchymal Stem Cells. Published 2016
https://www.ncbi.nlm.nih.gov/pubmed/28025562
“In conclusion, we have found that pre-treatment with CBD prevented the expression of proteins potentially involved in tau phosphorylation and Aβ production in GMSCs. Therefore, we suggested that GMSCs preconditioned with CBD possess a molecular profile that might be more beneficial for the treatment of AD.”
GMSCs: gingiva

Delineating the Efficacy of a Cannabis-Based Medicine at Advanced Stages of Dementia in a Murine Model. Published 2016
https://www.ncbi.nlm.nih.gov/pubmed/27567873
“Here, we provide evidence that such natural cannabinoids are still effective in reducing memory impairment in AβPP/PS1 mice at advanced stages of the disease but are not effective in modifying the Aβ processing or in reducing the glial reactivity associated with aberrant Aβ deposition as occurs when administered at early stages of the disease. The present study also demonstrates that natural cannabinoids do not affect cognitive impairment associated with healthy aging in wild-type mice. The positive effects induced by Δ9-THC and CBD in aged AβPP/PS1 mice are associated with reduced GluR2/3 and increased levels of GABA-A Rα1 in cannabinoid-treated animals when compared with animals treated with vehicle alone.

Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer's disease transgenic mice. Published 2014.
https://www.ncbi.nlm.nih.gov/pubmed/25024347
“Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.”

Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement. Published 2014
https://www.ncbi.nlm.nih.gov/pubmed/24288245
“Cannabidiol (CBD), a Cannabis derivative devoid of psychotropic effects, has attracted much attention because it may beneficially interfere with several Aβ-triggered neurodegenerative pathways, even though the mechanism responsible for such actions remains unknown…..Results indicated the CBD capability to induce the ubiquitination of APP protein which led to a substantial decrease in APP full length protein levels in SHSY5Y(APP+) with the consequent decrease in Aβ production. Moreover, CBD promoted an increased survival of SHSY5Y(APP+) neurons, by reducing their long-term apoptotic rate. Obtained results also showed that all, here observed, CBD effects were dependent on the selective activation of PPARγ.”

Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets. Published 2008
https://www.ncbi.nlm.nih.gov/pubmed/18679164
“In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits.”
HI: temporary occlusion of both carotid arteries plus hypoxia

How does CBD works? According tohttp://www.medicalnewstoday.com/articles/317221.php

All cannabinoids, including CBD, attach themselves to certain receptors in the body to produce their effects.
The human body produces certain cannabinoids on its own. It has two receptors for cannabinoids, called CB1 receptors and CB2 receptors.
CB1 receptors are found all around the body, but many of them are in the brain.
The CB1 receptors in the brain deal with coordination and movement, pain, emotions and mood, thinking, appetite, and memories, among others. THC attaches to these receptors.
CB2 receptors are more common in the immune system. They have an effect on inflammation and pain.
It used to be thought that CBD acts on these CB2 receptors, but it appears now that CBD does not act on either receptor directly. Instead, it seems to influence the body to use more of its own cannabinoids.

[karelena]

Very interesting, although it looks like there have been no human studies so far. There is a drug that is FDA approved and prescribed by doctors, "Marinol", generic name Dronabinol, which is THC and is used for nausea from chemo and anorexia due to AIDS and other conditions. It is a specific and regulated dose of THC, as opposed to medical and recreational marijuana which can vary greatly in THC content. I have teenage daughters and every year at their school, there is a "freedom from chemical dependence" program where we are warned about the unpredictable and frequently high potency products that are currently available. Apparently the marijuana growers have been cultivating potency and the marijuana of today is much more potent than ever before. So if you decide to experiment, you could consider asking your doctor about a trial of Marinol off-label.

[TheresaB]

So if you decide to experiment, you could consider asking your doctor about a trial of Marinol off-label.

I briefly came across Marinol in my research, it along with Cesamet are man-made versions of THC, to treat nausea and lack of appetite. These are two of only three FDA approved drugs made from marijuana.

Since Marinol is man-made THC, I’m not sure it contains any CBD. I think it depends what you are trying to accomplish whether you want to introduce THC into your system.

THC does seem to help in areas of appetite, nausea, and pain. Maybe my stereotypical conceptualization of a “dazed and confused” stoner is getting in the way, but I’m not so sure about dementia or ApoE4 utility. Perhaps in very small doses. That’s what this article posits.

http://www.alzheimers.net/6-15-15-effec ... lzheimers/

A preclinical study published in the Journal of Alzheimer’s Disease found that very small doses of tetrahydrocannabinol (THC), a chemical found in marijuana, can slow the production of beta-amyloid proteins, thought to be a hallmark characteristic and key contributor to the progression of Alzheimer’s.
The study, published in 2014, is among others to support the effectiveness of THC in prohibiting the growth of toxic amyloid plagues.

I may be reading too much into this, but I keyed into the “very small doses” of THC part.

I admit, nobody really knows, and the totality of my research consists of visiting various sites on internet over the past week, and most of that research was on CBD not THC.

Oh by the way, just FYI, the third FDA approved marijuana derived drug is Epidiolex which treats children’s epilepsy. It received FDA approval in 2013. Its use is highly restricted. A 4th drug, Sativex, is in clinical trials in the U.S. for pain with breast cancer. Sativex is already approved in more than 20 countries to treat muscle spasms from MS and cancer pain.

[Tincup]

Apparently the marijuana growers have been cultivating potency and the marijuana of today is much more potent than ever before.

The buzz on the street in Colorado is this is certainly correct for the products where the intention is to get high. However on the true medical side, the products list how much THC & CBD are in each dose. One friend who uses THC for her migraines takes a very small THC dose before bed. She says she does not get "high." She says it has been a huge blessing for treating her migraines. I was riding up a ski life with a gentleman who had prostate issues and interrupted sleep due to waking to urinate. One of his son's insisted he consume some medical marijuana for it. He said hes been getting the best sleep he's had in a long time.

Another issue is pesticide use. Because of the federal legal status, the USDA will not certify marijuana as organic, however industrial hemp (which can be used to make CBD oil) can be certified as organic by the USDA. There are third parties taking on the certification role for marijuana.

As for me, I tried some CBD oil as sleep aid with no benefit.

[TheBrain]

Theresa, thanks for sharing your research with us.

Personally, I enjoy using marijuana, though I'm careful with dosing because what karelena said is true. Marijuana is more potent than ever, and the quality control in terms of dosing in the marijuana industry is nowhere near that of the pharmaceutical industry.

For me, marijuana (especially the sativa varieties) is an anti-depressant. I am one of those wound-too-tight people who has a hard time relaxing. Marijuana helps me chill, and I never get a hangover the next day. So I'm less inclined to drink alcohol, which is a good thing. I only use marijuana at home and would never drive while high.

And let me just briefly add that marijuana brings out my intuition (which is enormously illuminating and helpful), and it greatly enhances sex.

However, if I had a chronic pain condition, I would not want to be high all day. I'd definitely look into CBD oil (which I've never used).

[TheresaB]

Another consideration if deciding to experiment: industrial hemp can be USDA certified as organic, marijuana products cannot.

Edit: Ooops, didn't see GeorgeN's post, apologize for the redundancy.

[TheresaB]

However on the true medical side, the products list how much THC & CBD are in each dose.

But how much is a dose? Ahhh, once again, the internet has the answer :
5 Helpful Tips For Getting The Correct Dose Of Medical Cannabis http://herb.co/2017/04/27/dose-medical-cannabis/

[TheBrain]

Theresa, thanks for the link to the article about dosing. In my experience as a medical marijuana patient in Colorado for three years, I have to say that just because a certain dose is listed on a product doesn't mean that it's accurate. But I left Colorado at the end of 2013. Maybe it's better now. George's comment about marijuana being certified by third parties is certainly a positive sign.

Have you tried finding a cannabis-savvy doctor? If not, perhaps you could call around to various dispensaries and ask if they could recommend a doctor who is particularly knowledgeable about chronic pain conditions. You might want to get a medical marijuana card anyway. As we know, the prices are much cheaper if you have a card.

I'm sorry to hear about your foot pain. Did it all begin with an injury of some kind?

A therapy called Hellerwork lifted me out of seven years of disability from a repetitive strain injury to my hands. It's an adaptation of the more commonly known Rolfing, and both are great. Previously, I tried many therapies, including four months-long rounds of physical therapy with different therapists, and none of those helped.

The Rolf Institute of Structural Integration is in Boulder. And I believe another form of structural integration is also taught in Boulder (can't recall the name of it). I found that Boulder and surrounding areas have a lot of Rolfers (but only one Hellerworker, based on my possibly dated knowledge). It's Rolfing haven out there.