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Turned-Off Cannabinoid Receptor Turns on Colorectal Tumor Growth

  • October 18, 2012 4:55 pm

HOUSTON, Aug. 1, 2008 – New preclinical research shows that cannabinoid cell surface receptor CB1 plays a tumor-suppressing role in human colorectal cancer, scientists report in the Aug. 1 edition of the journal Cancer Research.

CB1 is well-established for relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. It now may serve as a new path for cancer prevention or treatment.

“We’ve found that CB1 expression is lost in most colorectal cancers, and when that happens a cancer-promoting protein is free to inhibit cell death,” said senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president of The University of Texas M. D. Anderson Cancer Center.

DuBois and collaborators from Vanderbilt-Ingram Cancer Center also show that CB1 expression can be restored with an existing drug, decitabine. They found that mice prone to developing intestinal tumors that also have functioning CB1 receptors develop fewer and smaller tumors when treated with a drug that mimics a cannabinoid receptor ligand. Ligands are molecules that function by binding to specific receptors. Agonists are synthetic molecules that mimic the action of a natural molecule.

“Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists are being evaluated now to treat the side-effects of chemotherapy and radiation therapy,” DuBois said. “Turning CB1 back on and then treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention.”

Cannabinoids are a group of ligands that serve a variety of cell-signaling roles. Some are produced by the body internally (endocannabinoids). External cannabinoids include manmade versions and those present in plants, most famously the active ingredient in marijuana (THC).

Receptor shutdown by methylation

Endocannabinoid signaling is important to the normal functioning of the digestive system and has been shown to protect the colon against inflammation. Since chronic inflammation is a known risk factor for colorectal cancer, the researchers decided to look into the role of cannabinoid receptors in a mouse model of colon cancer.

“People have looked at cannabinoids in cancer earlier, mainly in cell culture experiments,” DuBois said. “The molecular mechanisms for loss of the receptor and its effect on cancer have not been previously shown.”

First, the team found that CB1 was largely absent in 18 of 19 human tumor specimens and in 9 of 10 colorectal cancer cell lines. Further experimentation showed that the gene that encodes the CB1 protein was not damaged, but shut down chemically by the attachment of methyl groups – a carbon atom surrounded by three hydrogen atoms – to the gene encoding CB1.

Treating cell lines with decitabine, a demethylating agent approved for some types of leukemia, removed the methyl groups, restoring gene expression in 7 of 8 cell lines and full expression of CB1 protein in three lines.

Next, the group found that deletion of the CB1 gene in a strain of mice that spontaneously develops precancerous polyps resulted in a 2.5-to-3.8-fold increase in the number of polyps and a 10-fold increase in the number of large growths, those most likely to develop into cancer.

Treating mice that had the CB1 receptor with an endocannabinoid agonist resulted in a decline in polyps ranging from 16.7 percent to 50 percent. The reduction was greater for larger polyps.

CB1 thwarts survivin, a protein that protects cancer

Cannabinoids previously had been shown to kill cancer cells in lab experiments by inducing apoptosis – programmed cell death. The team confirmed the role of CB1 in apoptosis, showing that tumor cells with high CB1 expression were sensitive to apoptosis when treated by a cannabinoid agonist. Cell lines with silenced CB1 resisted cell death.

A series of experiments showed that CB1 increases cancer cell death by stifling a protein called survivin. Survivin is overexpressed in nearly every human tumor but is barely detectable in normal tissue, DuBois noted. Overexpression of survivin is associated with poor outcome and reduced apoptosis in colorectal cancer patients. The researchers pinpointed a cell signaling pathway by which activated CB1 cuts down survivin.

“Just increasing the levels of cannabinoids to treat colorectal cancer won’t work if the CB1 receptor is not present,” DuBois said. This suggests that treating first with a demethylating agent, such as decitabine, to reactivate CB1 in the tumor and following up with a cannabinoid might be an effective attack on colorectal cancer.

Scarcity of CB1 also is associated with Huntington’s disease, Alzheimer’s disease and multiple sclerosis. Further investigation, the researchers note, is needed to define its role in those diseases and other types of cancer. The team also analyzed the other main cannabinoid receptor, CB2, and found no role for it in colorectal cancer.

They also treated the mice with a CB1 antagonist, a compound that binds to the receptor but does not activate it. Mice with CB1 blocked in this manner also showed an increase in the number and size of polyps. A CB1 antagonist called rimonabant is currently marketed overseas for weight loss. The researchers note that a patient’s risk for colorectal cancer should be assessed when use of such drugs is being considered.

The study was funded by grants from the National Cancer Institute and the National Colorectal Cancer Research Alliance.

Co-authors with DuBois are first author Dingzhi Wang, Ph.D., Haibin Wang, Ph.D., Wei Ning, Michael Backlund, Ph.D., and Dushansu K. Dey, Ph.D., all of the Vanderbilt-Ingram Cancer Center.

Cannabis use and it’s curing of Cancers

  • October 1, 2012 3:37 pm

Rick Simpsons Site: Phoenixtears.ca

National Cancer Institute – Cannabis and Cannabinoids

Cannabinoids Kill Cancer Cells: “Publius” Deciphers Update from National Cancer Institute

Cannabis oil is a highly efficient natural cancer cure

Cleaned Up Cancer : Peer Reviewed Cannabis and Cancer References

Granny Storm Crow’s List

Cannabis destroys cancer cells

NORML: Cannabinoids As Cancer Hope

How Weed Can Protect Us From Cancer and Alzheimer’s

What Your Government Knows About Cannabis And Cancer — And Isn’t Telling You

Marijuana Found to Kill Cancer Cells – The Marijuana and Cancer Relationship

Can Pot Treat Cancer Without The Devastating Effects of Chemotherapy?

Cannabinoid-associated cell death mechanisms in tumor models (review).

Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233.

Towards the use of non-psychoactive cannabinoids for prostate cancer

Cannabinoids: A new hope for breast cancer therapy?

Role of Lipid Rafts/Caveolae in the Anticancer Effect of Endocannabinoids.

ANNABIDIOL INHIBITS ANGIOGENESIS BY MULTIPLE MECHANISMS

Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy.

The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications.

CANNABIDIOL AS POTENTIAL ANTICANCER DRUG.

Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting.

Role of cannabinoid 2 receptor in the development of bone cancer pain

Cannabis Oil Fights Cancer

Cancer and Medical Cannabis

NORML: Gliomas/Cancer

Cannabis-Derived Substances in Cancer Therapy – An Emerging Anti-Inflammatory Role for the Cannabinoids

Cannabinoids as potential new therapy for the treatment of gliomas

CANNABINOIDS: POTENTIAL ANTICANCER AGENTS

Cannabinoids for Cancer Treatment: Progress and Promise

Turned-Off Cannabinoid Receptor Turns on Colorectal Tumor Growth

Delta9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria.

Study Indicates THC May Eradicate Brain Tumors

 Cannabinoids in pancreatic cancer: Correlation with survival and pain

Unlocking a Cure for Cancer—With pot

Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells.

Cannabinoids and Cancer

The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells

Cannabinoid receptor as a novel target for the treatment of prostate cancer

Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines

Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas

Inhibition of tumor angiogenesis by cannabinoids

Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation

A Population-Based Case-Control Study of Marijuana Use and Head and Neck Squamous Cell Carcinoma

Cannabinoids as a potential new drug therapy for the treatment of gliomas

Δ9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis

Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells

Cannabis and cancer chemotherapy. A comparison of oral delta-9-thc and prochlorperazine

THC From Cannabis Destroys Cancer Cells

Could cannabis be a natural cancer ´cure´?

Cannabis Is “An Effective Treatment” For Cancer Patients, Israeli Study Concludes

Cannabis, cannabinoids and cancer – the evidence so far

At least 800 Scientists say: Cannabis Can Kick Cancer’s Ass

THC (marijuana) helps cure cancer says Harvard study

Does Marijuana Cure Cancer?

CANNABIS CURES CANCERS! | Facebook

Marijuana Cuts Lung Cancer Tumors In Half ,Study Shows

Can Cannabis Cure Cancer?

Marijuana Benefits Cancer: Two Studies You Probably Never Read About

Medicinal Marijuana and Cancer Treatment: How Medicinal Marijuana Can Ease Cancer Treatment Side Effects

Breakthrough Discovered in Medical Marijuana Cancer Treatment

Marijuana As Medicine?: The Science Beyond the Controversy : Institute of Medicine

Pot Shows Promise as Cancer Cure

Can Medical Marijuana Ease the Side Effects of Chemotherapy?

Cannabis and Chemotherapy

Marijuana and Chemotherapy – An Alternative Medicine for Nausea

The Benefits of Medical Marijuana For Cancer Patients

Marijuana cuts nerve pain post chemotherapy

Cannabis and Chemo: How a Patient Uses Medical Marijuana to Cope with Breast Cancer

Two Marijuana Cancer Studies You Probably Never Heard About

How Hemp Oil Cures Cancer And Why No One Knows

U.S. Government Repressed Marijuana-Tumor Research

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

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Cannabis and Cancer Videos

Run From The Cure: The Rick Simpson Story

The OFFICIAL Rick Simpson Cancer Cure/Hemp Oil Channel

How to Make Rick Simpson’s Medicinal Hemp Oil Safely

Cannabis Cured Cancer

Vitamin Cannabis

Clearing the Smoke’: The Benefits, Limits of Medical Marijuana

PBS documentary sheds light on marijuana’s cancer-killing properties

Proof Marijuana CURES Cancer

THC kills cancer – Raw Footage

Cannabinoids Kill Cancer and Our Government Has Known for 36 Years

Marijuana ACTUALLY DOES Cure Cancer!

What if Cannabis Cured Cancer

Marijuana Natural Plant Cures Cancer! Legalize Cannabis! BBC Horizon: UK Medicinal Pharma

Prostate Cancer Cured with Cannabis Oil – Part 1 – Spiral Up with Ava Marie

Prostate Cancer Cured with Cannabis Oil – Part 2 – Sprial Up with Ava Marie

Cannabis For Cancer Patients

Medical Marijuana Stops Spread of Breast Cancer – NBC NEWS

The Cure for Cancer is Cannabis – THC & CBD in Marijuana Cures Cancer !!!

Cannabis and Glaucoma

Medical Marijuana – Cures Brain Cancer

Thomas Orvald, M.D. Discusses Medical Cannabis and Chemotherapy

 

Cancer and Healing aids

  • September 23, 2012 7:40 am

THE KEY TO KILLING CANCER IS 5 THINGS: DETOXIFY, OXYGENATE,
ALKALINIZE, CLEANSE, & IMMUNE SYSTEM SUPPORT

SUPPLEMENTS

CANNABIS OIL -

OXY – DHQ – bought online – buy about 6 bottle – take about 15 to
30 drops per day in real purified water. (This oxygenates the body
for free radicals good PH, can carry the oxygen to the cells which
is vital to kill cancer cells)

SERRAPEPTASE – buy online & some healthfood stores – take
80,000IUs. 2 to 3 times a day. (Do stop a week before surgery if
having it) (this sort of goes in and eats up the bad in your body,
is really the way to explain it, including cancer cells as they die
off)

VITAMIN D3 – Online or any healthfood store – Take 20,000IUs per
day – have periodic blood test every 3 months to see levels. Cancer
with take all your D3 so adjustments can be made to a higher or
lower dose. Keep in mind even if they say you’re within normal
limits, low side normal isn’t ok to stop cancer. You want a high
level. In the above 50′s blood levels for cancer. D3 is vital to
the immune system for all. Deficiency or even low normal allows
cancer & all illness to come. Everyone should take at least
10,000IUs ea day. Sick or not. To stay healthy.

ZEOLITE EBHANCED WITH DHQ – buy about 6 bottles & take about 15 to
30 drops per day in real purified water.
Taken together is a oxygenate, alkalize, & detoxer. (If taking
chemo stop this 3 days before and 3 days after chemo treatment)

CESIUM & DMSO 70% – buy online – take 3grams of cesium mixed in
DMSO TOPICALLY 2 times a day rub on area cancer is located.
or mix with water for ingestion or both.

FLAXSEED OIL/ Omega 3 – online, trader joes, or any health food
store, Take 400mg to 1,000mg once a day. Flax helps Oxygenate,
detox, & immune system as well as cleanse.

POMEGRANATE EXTRACT – online & health food stores – take 375mg per
day – is an antioxidant detoxifier, immune system booster. Powerful
against cancer.

MAGNESIUM – online or health food stores – take 800 to 1,000 mg.
Per day {or optimal health, detoxifier, immune system booster,
magnesium is also known to help detox fluoride. A must!

SPIRULINA – online or trader joes or health food stores -
Take 10grams per day. Is a detoxifier, immune system booster,
protects your thyroid from radiation & other heavy metals. START
WITH 5grams 1 gram 5 times a day or 2 grams 2 times a day then 1
gram & build up to 10grams, when healthier, go down to 3grams per
day taking 1 gram 3 times a day. Or as directed on bottle. Don’t
stay on higher dose for too long. (A must for all)

CHLORELLA – online or trader jos or health food stores.
Take 5grams per day. Start with 2 or 3 grams and build up to
5grams. 1 gram 2 to 3 times a day then up to 5grams. When
healthier, go down to 1gram 2 times a day or as directed on bottle.
Same as Spirulina, Detoxer, immune system booster helps thyroid
from radiation and heavy metals. (A must for all)

GRAVIOLA – online or health food stores- Take 2 grams 3 times a
day. (Buy a formula with the leaves of the plants only) Graviola is
known to stop cancer in its tracks. All of the plant can be used
but there have been problems seen in using other parts of the plant
although it may be a stronger attack I don’t like the risks. The
leaves only are completely safe and very effective.

B COMPLEX 100 – online, trader joes, health food stores – Take 1
per day -  immune system – can reverse thyroid problems & much more
- a must for all, but especially during cancer. The 100 means 100mg
of most B’s.

C-COMPLEX – online or trader joes or healthfood store. The best 1
I’ve seen at trader joes- Take 1,000mg with 500mg bioflaviniods (in
the complex & ok if has rosehips and rutin). Can take many times a
day. Non toxic you can’t take too much. With cancer I’d take 5 to10
times a day. Can be taken 1,000mg an hour. If taken all at once
will just pee out so spread apart by an hour or so. Also know to
help detox fluoride – Immune system booster.

ESSIAC TEA – buy online – take according to box. Drinking thruout
the day. Essiac tea was created to kill cancer. The maker was shut
down as they found it did work. But it is still available. If you
can read a write up on the maker casse, it will give best
instructions on taking during cancer. Essiac is her name spelled
backwards. This is a must!
Id drink more than box says, be sure its the real essiac tea. Her
formula has cured cancer.

TURMERIC EXTRACT – online, health food stores, Take 8 grams per
day. Turmeric is Glutathione a powerful cancer preventor and cure.
Can kill off ovarian, protate, stomach, lung, and work on all
cancers. Purifies the blood and a powerful antioxidant immune
system fighter & detoxer.
All should be taking & eating foods rich in. A super herb.
Turmeric can detox aluminum & other heavy metals helping the
thyroid as well. A Must!

ASTRAGALAS- online or healthfood stores. Take as directed on
botttle. Astragalas is a detox, antioxidant, immmune system booster.

BAKING SODA – Take 1 teasoon before breakfast. This will keep your
PH alkaline levels at a normal place. Just mix it in a real
purified water.

MORINGA – Online, Take 1,000mg 2 to 3 times a day. Use the leaves
of the tree formula. Moringa has been used for Ovarian and all
cancers. Known as the miracle tree. All parts of the tree are used
for something. Moringa is a must for cancer treatment. Also used as
an anti biotc, for staph, to lower blood pressure, and blood sugar,
& so much more
A must!

MANUKA HONEY – online or healthfood stores. Take 1 teaspoon each
day. Manuka honey is from New Zealand & helps so many things. Can
help in cancer treatment with the rest of your regimen. And anti
fugus and anti biotic, antioxidant.

GREEN TEA EXTRACT – online or healthfood stores, Take 70 to 100mg
per day. A powerful antioxidant, immune system. Green tea extract
is also a free radical neutralizer.

GINKO – online or healthfood stores. Take as directed. Ginko can
detox Auminum as well as many other uses. (stop 1 week before
surgery if having it)

CORVIX – Buy 4 to 6 bottles, take about 6 drops per day in real
purified water. This is an immune system booster & a must for
killing cancer cells

BLA – Buy 4 to 6 bottles. Take 15 to 30 drops per day in real
purified water. This is known to kill cancer cells with the others
I’m listing. Take them all. A Must!

LIFE SUPPORT – Herbal formula online, buy 8 bottles, take about 20
to 30 drops per day. Can cure cancer. An Oxygenator

PRUGX – Use 4 to 6 bottles per month. Take 15 to 30 drops per day
in purified water. This formula is known as #1 cancer killer.
Powerful antioxidant, cancer killer. A Must!

ZORMUS – Use 4 to 6 bottle per month Take 15 to 30 drops per day in
purified water. Same as Prugx. Oxygenate. Cancer cell killer. A
Must!

RONUV – buy 4 to 6 bottles per month Take 15 to 20 drops per day in
purified water. Oxygenate. Gets t cells to stop releasing hydrogen
Peroxide. Detox & Immune System.

MC2 – buy 2 bottle a month. Take 6 drops per day in purified water.
PH & Alkalize. Prevention & kills cancer cells left after surgery
and without it as well. Oxygenates thruout the body into cells &
detoxes. Use 2 bottles for 6 months then 1 bottle or 3 drops per
day after.

ZADMOR – buy 4 to 6 bottles. Take 15 to 30 drops per day. Immune
system

QUZU – buy 4 bottles a month. Take 7 to 15 drops per day. Immune
system

CILANTRA EXTRACT – online or healthfood stores. Take as directed on
bottle. Powerful Detoxer & immune system. Cilantra extact can detox
Mercury, Aluminum, Lead, helps Chlorela work better. Also a
fluoride detoxer. Detoxing is vital to rid cancer.

Okay, these are the supplements.
Now, other considerations.

It is vital to stay Alkalized. These supplements will do that but
take your PH strips each morning to check your levels to stay at
best levels to rid cancer. As well as prevent cancer for all.

Stay away from Meat (unless organic & try to stay away anyway)
Also, stay away from, WHEAT, BARLEY, CORN, SORGHUM, PEANUT. These
can not only be GMO but, have a poison called mycotoxin causing and
feeding cancer. Its a fungus. Fungus=cancer.

Eat Organic

Stay away from antibiotics

Get at least 8 to 9 hours sleep per day. Your body rejuvenates
while you sleep. Its said your liver rejuvenates around 2 to 4am.

Overcoming cancer is a process of REVERSING the conditions that
allowed the cancer to develop & going after & killing cancerous
cells. How you got it isn’t as important.

Boosting the Immune System with supplements and detoxing the body
of toxins is vital.

Ridding your body of candida is vital. The supplements should do
this as well. The baking soda helps attack the candida also, as
well as an alkaline diet. Candida fuel cancer.

Detoxing of heavy metals is vital. The supplements will do this is
taken as directed. The chemtrails are feeding us with toxins. Stay
out of the rain and mist as much as possible. Id say always during
cancer.

VERY IMPORTANT
Also, it is CRUCIAL you have a whole house water filter. Tap and
even bottled water has CHLORINE. Chlorine causes cancer, feeds
cancer, and a host of other problems. The water you drink must be
purified. But, chlorine can even be absorbed thru the skin while
showering. It is said cancer risk is 93% higher with chlorinated
water than those using non chlorinated. Therefore a whole house
water filter is crucial to stop the absorption of the heavy metals
and chlorine & FLUORIDE in water. Some of the supplements rid you
of Fluoride, but you must not keep getting more. Also, 60% of
hormone cancers eg: ovarian, prostate, breast, cervical, had high
levels of organ chlorines in their tissues. Bad news stuff!

IMPORTANT:
Fluoride is a killer. Use non Fluoride toothpaste such as Toms. And
non Aluminum deodorants.
Use natural soaps, shampoos, make ups, laundry soaps, dish soaps
etc. These all absorb the toxins thru the skin. Many products have
aluminum, mercury, and junk! FYI: boron or borax is a detoxer of
Fluoride. 1/8th teaspoon to 1 liter of purified water drink thruout
the day. Good for everyone. Fluoride is a killer. Its said if you
eat food that is sprayed, watered with fluoride water, & use
fluoride toothpaste you’re getting a triple wammy, and if you drink
unfiltered water you’re being posioned bad. Its also said fluoride
causes calcification of the pineal gland which in turn stops
melatonin which helps sleep and can cause thyroid problems, as well
as mess with the entire endocrine system. Also if the pineal gland
is clogged the higher chakra, 3rd eye can not be open for intuitive
and spiritual. It also cases problems with your kidneys, liver & IQ
& alzheimers. Its said the government purposely douses us with
fluoride to “dummy us up” as it lowers IQ. Rid yourself from
fluoride. Filter your water in whole house. It can be absorbed thru
the skin in the shower. Use non fluoride toothpaste & buy foods
local unsprayed & organic not watered with fluoride containing
water.

Stay away from MILK. The hormone rBGH in milk causes prostate and
other hormone cancers such as ovarian, breast, cervical. Also, stay
away from Soy milk and soy. Same hormone can be in soy milk and Soy
is usually GMO.

Stay away from GMO. All canola oil is GMO. Use other natural oil
such as a good Olive oil or Coconut oil.

It is good to do a colon cleanse. There are many on the market and
homemade ones you can find online.

Postive thinking is more powerful than anyone can imagine. If you
can tap into your brains positive energy you can heal your body
with your mind. Sounds crazy but I’ve seen it work with my friend.
She should not be here :(

Also, staying happy, laughing, watch comedies that make you laugh.
Sounds silly as well, but many studies show it works to heal the
body. Releases the good chemicals into the body to heal.

Keep all stress to a minimum. A must.

I realize being happy, laughing, positive thinking, and no stress
is a hard one, but a must do nonetheless. You must attack cancer
from all angles to rid it and keep it away. :0)

Lastly, IMPORTANT. You should not be taking any blood thinners
during this protocol. Many are natural blood thinners and can
interfere with the meds.

GOOD LUCK & GOOD HEALTH TO ALL! <3

Written by Shar Williams

The mineral selenium proves itself as powerful anti-cancer medicine

  • September 20, 2012 1:26 am

One of the most effective naturally occurring weapons against cancer is, like most healthy things, something many of us are not getting enough of. The mineral selenium has been shown in multiple studies to be an effective tool in warding off various types of cancer, including breast, esophageal, stomach, prostate, liver and bladder cancers. Not many people get the recommended dose of 200 micrograms a day. Most Americans only get between 60 and 100 micrograms of selenium daily from dietary sources, according to the Life Extension Foundation’s Disease Prevention and Treatment. That means daily supplements might be worth considering.

Selenium was first used in conventional medicine as a treatment for dandruff, but our understanding of the mineral has come a long way since then. Today, research shows selenium, especially when used in conjunction with vitamin C, vitamin E and beta-carotene, works to block chemical reactions that create free radicals in the body (which can damage DNA and cause degenerative change in cells, leading to cancer).

Selenium also helps stop damaged DNA molecules from reproducing. In other words, selenium acts to prevent tumors from developing. “It contributes towards the death of cancerous and pre-cancer cells. Their death appears to occur before they replicate, thus helping stop cancer before it gets started,” says Dr. James Howenstine in A Physician’s Guide to Natural Health Products That Work.

Selenium makes chemotherapy safer, more effective
In addition to preventing the onset of the disease, selenium has also been shown to aid in slowing cancer’s progression in patients that already have it. According to the Life Extension Foundation, the use of selenium during chemotherapy in combination with vitamin A and vitamin E can reduce the toxicity of chemotherapy drugs. The mineral also helps “enhance the effectiveness of chemo, radiation, and hyperthermia while minimizing damage to the patient’s normal cells; thus making therapy more of a ‘selective toxin,’” says Patrick Quillin in Beating Cancer with Nutrition.

A 1996 study by Dr. Larry Clark of the University of Arizona showed just how effective selenium can be in protecting against cancer. In the study of 1,300 older people, the occurrence of cancer among those who took 200 micrograms of selenium daily for about seven years was reduced by 42 percent compared to those given a placebo. Cancer deaths for those taking the selenium were cut almost in half, according to the study that was published in the Journal of the American Medical Association.

While the study concluded the mineral helped protect against all types of cancer, it had particularly powerful impacts on prostate, colorectal and lung cancers. Jean Carper, in Miracle Cures, called Dr. Clark’s findings an “unprecedented cancer intervention study” that “bumped up the respectability of using supplements against cancer several notches.”

Food sources of selenium
Although too much selenium can actually be toxic to the system, research indicates the majority of the population is not getting enough of the essential mineral. So, how can we up our intake of selenium and help our bodies fight cancer? The good news is there are some good dietary sources of selenium: Mushrooms, egg yolks, seafood, poultry and kidney, liver and muscle meats contain the mineral. Vegetables — garlic, onions, broccoli, asparagus, tomatoes and others — as well as whole grains and seeds can also be good sources of selenium.

However, because the amount of selenium in vegetables and grains depends on the selenium content in the soil in which they are grown, it can be hard for average consumers to know how much of the mineral they are actually getting in their diets. “The selenium content of food is largely dependent on the content of volcanic ash in the soil on which the food was grown, with higher volcanic ash content yielding higher selenium levels. Soil that is irrigated by seawater, such as much of California’s cropland, also contains higher levels of selenium,” says Sue Gebo in What’s Left to Eat. Gebo adds that, in general, soil in the western United States is richer in selenium than soil in the eastern part of the country.

Accordingly, geography can have a significant impact on diet. In Antioxidants Against Cancer, author Ralph Moss PhD, says one theory for why cancer rates are so high in Linxian, China, dubbed “the ‘world capital’ of cancer,” is that the soil is deficient in the essential minerals selenium and zinc. In Earl Mindell’s Supplement Bible, Earl Mindell RPh PhD, suggests part of the reason American men are five times more likely than Japanese men to die from prostate cancer could be because, in general, “the Asian diet contains four times the amount of selenium as the average American diet.”

Another reason it seems to be difficult for Americans to get enough selenium is the processing many of our foods go through before they make it onto grocery store shelves. Mindell points out, for example, that processing wheat into white flour strips it of a great deal of its selenium. One way to get more selenium in your diet might be to eat more organically grown foods, which some studies have shown to contain more selenium as well as higher levels of beta carotene and vitamin E. These two work together with selenium in cancer prevention, according to Alternative Medicine author Burton Goldberg.

Perhaps a more surefire way to boost your selenium intake is to add supplements to your diet. Mindell advocates the use of supplements, saying, “To me, taking selenium supplements, in addition to eating selenium-rich foods, is good insurance against disease.” However, for those who oppose taking pills, Dr. Andrew Weil in Ask Dr. Weil says eating just one shelled Brazil nut — grown in the selenium-rich soil of central Brazil — provides 120 micrograms of the mineral, getting you that much closer to the daily target of 200 micrograms.

Although extremely high doses of selenium can have toxic effects, most people are not at risk for such an overdose, and could, in fact, use more of the mineral. Simply adding more selenium-rich foods, such as organically grown vegetables and fruits to your diet, along with supplements, can help reduce your risk of cancer. And another positive side effect of selenium, according to Eat and Heal, by the Editors of FC&A Medical Publishing, is that it can actually improve your mood. Those editors write, “People who don’t eat enough selenium-rich foods tend to be grumpier than people with a high dietary intake, according to recent research.” So, go ahead and crack a Brazil nut open and smile.

The experts speak on selenium and cancer

Selenium Mechanisms
There are several possible mechanisms for the protective effect of selenium. Selenium activates an enzyme in the body called gluthathione peroxidase that protects against the formation of free radicals—those loose molecular cannons that can damage DNA. In this situation, selenium may work interchangeably (and in synergy) with vitamin E. In test tube studies, selenium inhibited tumor growth and regulated the natural life span of cells, ensuring that they died when they were supposed to instead of turning “immortal” and hence malignant. Because of this particular action, the University of Arizona researchers say that selenium could be effective within a fairly short time frame.
Ask Dr Weil by Andrew Weil MD, page 207

Numerous studies suggest that an inverse association exists between selenium levels and cancer incidence (Hocman, 1988; Willett and Stampfer, 1986; Milner, 1985). Associations appear to be particularly strong with cancers that are also associated with high-fat, low-fiber diets (i.e., breast, colon, prostrate, etc.). The mechanism for selenium’s reported protective effects is likely due to its function in antioxidant synthesis. Glutathione peroxidase, the primary enzyme that converts hydrogen peroxide to water (and thus prevents lipid peroxidation) is selenium-dependent. Inhibition of lipid or bile acid oxidation may account for its protective role (reviewed by Linder 1991:496-7). Selenium may also act as an immune stimulant. Selenium deficiency inhibits macrophage-mediated tumor destruction, and inhibits tumor necrosis factor-alpha production in animals (Kiremidjian-Schumacher et al., 1992). Dietary supplementation with selenium produced the opposite effects.
Cancer And Natural Medicine by John Boik, page 146

The safest antioxidants are vitamin C, vitamin E, selenium, and beta-carotene. Together, they block the chemical reactions that create free radicals, which can damage DNA and promote a variety of degenerative changes in cells. Chemotherapy and radiation generate free radicals; that is how they kill dividing cells.
Ask Dr Weil by Andrew Weil MD, page 47

At the Yunnan Tin Corporation in China there is a very high rate of lung cancer among the miners. Forty healthy miners were given selenium supplements for a year. The selenium, which increased in their blood, boosted a key detoxifying enzyme system while simultaneously decreasing dangerous lipid peroxide levels by nearly 75 percent. It also protected against cancer-causing substances and ultraviolet radiation. Doctors at the Chinese Academy of Medical Sciences concluded that selenium supplements were a safe and effective food supplement for people.
Cancer Therapy by Ralph W Moss PhD, page 112

Numerous mechanisms have been explored to explain the modulation of carcinogenesis by selenium (Medina 1986, El-Bayoumy 1991). The best characterized function of selenium in mammalian cells is as a component of the seleno- enzyme, glutathione peroxi-dase. This enzyme is localized in the cytosol and mitochondrial matrix, and it eliminates organic peroxides from the cell (Medina 1986). However, available evidence suggests that the prevention of carcinogenesis by selenium is not related to its function in glutathione peroxidase (Medina 1986). Other seleno- proteins have been identified, but their impact on carcinogenesis is not defined (Medina 1986). There is some evidence that selenium may alter the metabolism of carcinogens or the interaction of chemical carcinogens with DNA, but there is considerable controversy in the literature (Medina 1986). Additional mechanistic studies suggest that selenium may alter cell proliferation and/or immunologic responses (Medina 1986, El-Bayoumy 1991). Further research is needed to understand the mechanisms whereby selenium prevents cancer.
Carcinogens Human Diet by National Research Council, page 100

Selenium is needed to produce glutathione peroxidase, an antioxidant enzyme that protects the body from free radical damage. It is also important in preventing cancer and cardiomegaly an enlargement of the heart that causes premature aging and early death.
Complete Encyclopedia Of Natural Healing by Gary Null PhD, page 11

The best known functions of selenium at nutritionally adequate, but not at excessive, levels are its role as a part of the enzyme glutathione peroxidase and its interaction with heavy metals. Glutathione peroxidase destroys hydroperoxides and lipoperoxides, thereby protecting the constituents of the cells against free radical damage. Ip and Sinha (1981) have shown that selenium, through its function in glutathione peroxidase, could well be involved in protecting against cancer induced by high intakes of fat, especially polyunsaturated fatty acids. Glutathione peroxidase activity in human blood increases with increasing selenium intakes, but reaches a plateau at intakes well below those customary in the United States (Thomson and Robinson, 1980). Thus, if the antitumorigenic effect of selenium is mediated through its function in glutathione peroxidase, attempts to increase the enzyme activity by selenium supplementation, superimposed on an adequate diet in the United States, would not be successful. The second function of selenium is to protect against acute and chronic toxicity of certain heavy metals. Although selenium is known to interact with cadmium and mercury, the mechanism of action is not known. Selenium does not cause an increased elimination of the toxic elements, but, rather, an increased accumulation in some nontoxic form (National Academy of Sciences, 1971). It is conceivable that carcinogenic effects of these, and perhaps other heavy metals, could be counteracted by selenium, in a manner similar to its protection against their general toxicity.
Diet Nutrition Cancer by National Research Council, page 168

Selenium’s main function in the body is to convert hydrogen peroxide to water, which is important for cellular health. Herbal Medicine Healing Cancer by Donald R Yance Jr, page 193 All of the body’s tissues contain selenium, but it is most plentiful in the liver, kidneys, spleen, pancreas, and testes. Selenium works synergistically with vitamin E to protect tissues and cell membranes, aid in the production of antibodies, and help maintain a healthy heart and liver
Prescription For Dietary Wellness by Phyllis A Balch, page 44

Selenium Dosage/Administration
It has been reported that selenium doses of about 250-300 micrograms a day (diet and supplements) would be helpful in preventing cancer. If an average person consumes 125 to 150 micrograms of selenium a day, an additional supplemental amount of 100 micrograms is unlikely to produce any major side effects.
Choices In Healing by Michael Lerner, page 612

Recommendation: Take selenium aspartate in a dose of 100 to 200 micrograms daily..
Doctors Complete Guide Vitamins Minerals by Mary D Eades MD, page 496

Selenium is a mineral with anticancer activity. But the anticancer effects of selenium are greatly reduced when there is an insufficient intake of vitamin E. Rats who receive a normal amount of vitamin E in their diets showed a 45 percent decrease in tumors when they were given selenium. But they only had a 25 percent decrease if their diet was low in vitamin E. In fact, vitamin E was considered more important than selenium in decreasing “oxidant stress” to the fat of the breast.
Cancer Therapy by Ralph W Moss PhD, page 74

In the treatment of cancer the dosage is generally about 10,000 micrograms, still nearly one hundred times the National Academy of Science’s recommended dose. Revici’s treatment is more complicated than just organic selenium. He only uses selenium in patients whom he deems to be in a “catabolic,” as opposed to an “anabolic,” state. He has devised a number of urine tests to find whether a patient is in one condition or the other. Selenium is given when the urine has a low specific gravity, a high surface tension and a pH above 6.0. The alkalinity of the urine is supposed to reflect the state of the body’s defenses against tumors.
Cancer Therapy by Ralph W Moss PhD, page 112

Selenium levels show a U-shaped correlation with prostate cancer. In other words, both low and high blood levels of selenium increase risk. This simply means that we need enough selenium to maintain good health, yet too much can be dangerous. A practical compromise is to use a supplement that provides 100 I.U. of vitamin E (up to 400 I.U. would be fine), and about 50 micrograms of selenium.
20 Natural Ways To Reduce The Risk Of Prostate Cancer By James Scala PHD, page 60

Unlike selenomethionine, which is incorporated into protein in place of methionine, SMSC is not incorporated into any protein, thereby offering a completely bioavailable compound. In animal studies, SMSC has been shown to be 10 times less toxic than any other known form of selenium. The recommended dose of Se-methylselenocysteine (SMSC) is 200-400 mcg a day for cancer patients.
Disease Prevention And Treatment by Life Extension Foundation, page 316

Selenium Sources
You need just three Brazil nuts to get the 200 micro-grams of selenium that studies have shown to have a potent anti-cancer effect. As a bonus, when you eat Brazil nuts, which grow best in the Amazon rain forest, you support the conservation of one of my favorite places on earth. So you’re not only protecting your body, you’re saving the environment.
Anti-Aging Prescriptions by James Duke PhD, page 90

The Garlic Connection. It has long been noted that people who ate garlic, onion, broccoli, and whole grains had a reduced risk of cancer. It turns out that all of these foods are rich in selenium, in fact, selenium is one of the reasons that these particular foods are so healthful for us.
Antioxidants Against Cancer by Ralph Moss PhD, page 77

If you’re not fond of popping pills, you can get 120 micrograms of selenium in just one Brazil nut. Buy the shelled kind—they’re grown in a central region of Brazil where the soil is richest in the mineral. Other good sources are tuna fish, seafood, wheat germ, and bran.
Ask Dr Weil by Andrew Weil MD, page 207

One good food source is Brazil nuts, which happen also to contain at least one other anticancer substance, ellagic acid. One large nut can provide over 50 mcg of selenium. When Cornell scientist Donald J. Lisk and his colleagues ate six Brazil nuts a day for three weeks, their blood levels of selenium rose between 100 and 350 percent.
Cancer Therapy by Ralph W Moss PhD, page 122

Selenium—An essential trace mineral found in fruits and vegetables, selenium helps the body produce functional glutathione peroxidase, an enzyme essential for detoxification. Low dietary levels of selenium have been correlated with a higher incidence of cancer; accordingly, supplementation of this nutrient acts as a deterrent against cancer in general.
Alternative Medicine by Burton Goldberg, page 591

Red clover is also rich in calcium, manganese, and selenium, which is a key cancer-fighting antioxidant. I munch the flower heads, but not everyone likes them. Some people dry the flower heads, turn them into a powder, and add them to soups.
Anti-Aging Prescriptions by James Duke PhD, page 61

The debate continues regarding the active ingredients in garlic, but they may include amino acids (like the branched chain amino acids of leucine and isoleucine), S-allyl cysteine, allicin, and organically-bound selenium…Garlic grown on selenium-rich soil was more effective than selenium supplements at inhibiting carcinogen-induced tumors in animals. A study published in the Journal of the National Medical Association referred to garlic as “..a potent, non-specific biologic response modifier.”
Beating Cancer With Nutrition by Patrick Quillin, page 147

A particularly worthy form of selenium is Se-methylselenocysteine, currently available and attracting positive attention. This is the form of selenium found naturally in plants such as broccoli and garlic. A suggested selenium dosage (as a preventive) is 200 mcg a day. The optimal dose for the cancer patient is unknown at this time, but suggestions have ranged from 200-400 mcg a day. Depending upon the selenium content of the soil, foods considered to be good sources of selenium include Brazil nuts, grains, onions, tomatoes, broccoli, chicken, eggs, garlic, liver, seafood, and wheat germ. Americans typically get from 60-100 mcg of selenium a day from dietary sources.
Disease Prevention And Treatment by Life Extension Foundation, page 243

Stephen Cann, associate researcher at the University of British Columbia, gives advice to women who want to fight breast cancer with diet, “Eat different types of seaweed.” These include wakame, kombu, and the more common nori — sea vegetables that might fight cancer because of their iodine and selenium. “We think it’s very important for the breast,” Cann says about iodine. This mineral, he believes, may prevent and even shrink breast tumors by combining with certain fatty acids and stopping cancerous cells from multiplying. And without the selenium, iodine doesn’t do its job properly.
Eat and Heal by the Editors of FC&A Medical Publishing, page 317

In parts of Europe, pumpkin seeds are the standard treatment for benign prostate enlargement. The seeds are rich in zinc, selenium and other minerals that have been shown to reduce prostate cancer risk. Typical daily dosage: Eat one-quarter cup of the seeds.
Bottom Line Yearbook 2002 by Bottom Line Personnel, page 76

The intake of selenium and other nutrients from plant foods may be influenced by the type of farming practices used. In a preliminary investigation, organically grown foods were, in some cases, nutritionally superior to conventionally grown foods (Smith, 1993).
Cancer And Natural Medicine by John Boik, page 147

The Journal of Nutrition reported that selenium-enriched broccoli is protective against chemically induced mammary and colon cancer in rats (Davis et al. 2002). Note: While selenium is contributing to the lower incidence of malignancy, the anticancer affects of broccoli should also be factored into the defense.
Disease Prevention And Treatment by Life Extension Foundation, page 242

You can find selenium in grains, shellfish, poultry, garlic, and egg yolks.
Natural Cures And Gentle Medicines by The Editors of FC&A Medical Publishing, page 266

Commercial preparations of selenium include inorganic selenium (sodium se-lenite) and various organic compounds of selenium. It has been reported that sodium selenite is not absorbed adequately, whereas organic selenium, including yeast-selenium, is absorbed very well. For this reason, yeast-selenium is considered best for human consumption
Choices In Healing by Michael Lerner, page 612

Throughout history and around the world, people from Mexico to Russia have given mushrooms magical powers. In reality, there’s nothing miraculous about these fungi at all, but they can make you healthier. Although mushrooms are largely made up of water, they are also high in protein, carbohydrates, and fiber. They are a potent source of vitamin D, riboflavin, and niacin, plus minerals like potassium, selenium, and copper.
Eat and Heal by the Editors of FC&A Medical Publishing, page 252

In addition, some foods, such as lima beans, soy beans, and other soy products, seem to have medicinal capabilities because of the presence of isoflavones and phytoestrogens, or plant estrogens. These substances actually curb the activity of the excess estrogen in the body’s tissues. Phytoestrogens can also be found in other vegetables and in fruits, along with useful amounts of nonsoluble fiber, beta-carotene, and selenium.
Complete Encyclopedia Of Natural Healing by Gary Null PhD, page 72

A new approach is now being explored: how to enrich our food with antioxidant and protective agents. The simpler approach is to add antioxidant vitamins to basic foods. Studies address the genetic engineering of food to prevent heart disease and cancer [105], and such measures as growing garlic with selenium fertilization [95]. The authors of these studies state that “in view of the impossible task of persuading the public to eat only those foods that are presumably good for their health . . . the time has come to enrich our foods with known cancer preventive agents so that their benefit can be realized fully over the life span of the individual.”
Every Persons Guide To Antioxidants by John R Smythies MD, page 103

Plentiful in poultry, selenium may help to protect against cancer, cataracts, heart disease, and macular degeneration. Dark-meat turkey is particularly high in this mineral (3 ounces of cooked turkey have 35mcg of selenium, or 50% of the Daily Value).
Fight Back With Food by Readers Digest, page 73

To get more selenium in your diet, try tuna; a three-ounce can serves up a full 99 micrograms. Or treat yourself to an ounce of baked tortilla chips for a whopping 284 micrograms.
Healing With Vitamins by Alice Feinstein, page 64

Selenium comes from the soil, and fruits and vegetables that come from selenium-rich soil are more likely to contain the mineral.
Natures Medicines by Gale Maleskey, page 363

If you eat a normal diet with plenty of unprocessed foods, you should be fine. You’ll find selenium in many grains, nuts, and vegetables; meat, especially organ meats like liver; and seafood.
Natural Cures And Gentle Medicines by The Editors of FC&A Medical Publishing, page 242

A new form of selenium is Se-methylselenocysteine (SeMC), a naturally occurring selenium compound found to be an effective chemopreventive agent. SeMC is a selenoamino acid that is synthesized by plants such as garlic and broccoli.
Disease Prevention And Treatment by Life Extension Foundation, page 277

Essiac formula was given to nurse Rene Caisse more than 80 years ago by a woman whose breast cancer had been healed by this Ojibway Indian herbal preparation. The formula is composed of four herbs (burdock root, slippery elm, sheep sorrel, and Indian rhubarb). The burdock root contains inulin, which improves the function of white blood cells. This root also contains Vitamin A and selenium, which scavenge free radicals and chromium which regulates blood sugar levels.
A Physicians Guide To Natural Health Products That Work By James Howenstine MD, page 156

Selenium Anti-Cancer Effects
Some forms of cancer are the result of free radical oxidation that destroys or damages the part of the DNA that regulates cell multiplication. When that happens, the cells can begin to multiply abnormally, damaging the healthy tissue until your whole body is invaded by these wildly proliferating cells. Since selenium can protect you from free radical oxidation, one way to minimize your risk of developing this type of cancer is to eat selenium-rich foods like whole grains or their products with each meal. If you already have cancer, selenium may be useful in slowing its progression. A way to get it in even more concentrated doses than in foods is to take brewer’s yeast or supplements.
Complete Guide Health Nutrition by Gary Null, page 483

Laboratory studies have shown that selenium can inhibit the growth of breast, cervical, colon, and skin cancer.
Antioxidants Against Cancer by Ralph Moss PhD, page 79

Regular intake of yellow and green vegetables, as well as foods containing calcium, selenium and other micro-nutrients, lowers the risk of colon cancer.
Cancer Therapy by Ralph W Moss PhD, page 197

Selenium is protective against many types of cancers, promotes apoptosis, is a powerful antioxidant, and improves quality of life during aggressive cancer therapies According to P.D. Whanger (professor of agricultural chemistry), nearly 200 animal studies have been conducted to evaluate the effects of supernutritional levels of selenium on experimental carcinogenesis using chemical, viral, and transplantable tumor models. Two thirds of the studies found that high levels of selenium reduced the development of tumors at least moderately (14-35% compared to controls) and, in most cases, significantly (by more than 35%) (Whanger 1998).
Disease Prevention And Treatment by Life Extension Foundation, page 242

Selenium has been used in combination with vitamin A and vitamin E to reduce the toxicity of chemotherapy drugs, particularly Adriamycin (Faure et al. 1996; Vanella et al. 1997). The synergistic effect of vitamin E and selenium together to enhance the immune system is greater than either alone. A new form of selenium is Se-methylselenocysteine (SeMC), a naturally occurring selenium compound found to be an effective chemopreventive agent. SeMC is a selenoamino acid that is synthesized by plants such as garlic and broccoli. SeMC has been shown to induce apoptosis in certain ovarian cancer cells (Yeo et al. 2002) and to be effective against breast cancer cell growth both in vivo and in vitro (Sinha et al. 1999). SeMC has also demonstrated significant anticarcinogenic activity against mammary tumorigenesis (Sinha et al. 1997). Moreover, a study has demonstrated that SeMC is one of the most effective selenium chemopreventive compounds, inducing apoptosis in leukemia HL-60 cell lines (Jung et al. 2001a). Some of the most impressive data suggest that exposure to SeMC blocks clonal expansion of premalignant lesions at an early stage. This is achieved by simultaneously modulating certain molecular pathways that are responsible for inhibiting cell proliferation and enhancing apoptosis (Ip et al. 2001). Unlike selenomethionine, which is incorporated into protein in place of methionine, SeMC is not incorporated into any protein, thereby offering a completely bioavailable compound for preventing cancer. Therefore, 200—400 mcg of SeMC a day is suggested for cancer patients. Please note that selenium also possesses antioxidant properties, so its use before, during, or immediately after chemotherapy could theoretically inhibit the actions of certain chemotherapy drugs.
Disease Prevention And Treatment by Life Extension Foundation, page 277

Scientists have confirmed that vitamins C and E along with the mineral selenium afford some prostate cancer prevention. This is not surprising to anyone who understands diet, biochemistry, and how antioxidants work. Glutathione peroxidase destroys free radicals and superoxides. Its name means that it destroys peroxides (the potent oxidants that form in tissues) and uses glutathione as a helper. Glutathione requires selenium to function; and wherever selenium is at work, vitamin E can’t be far away because they function together.
20 Natural Ways To Reduce The Risk Of Prostate Cancer By James Scala PHD, page 54

For prostate cancer management, stay on a low fat diet, eat tomato products often, take a multivitamin, vitamins C, E and selenium.
A Physicians Guide To Natural Health Products That Work By James Howenstine MD, page 151

Men with higher intakes of antioxi-dants such as vitamin C, vitamin E, and the trace mineral selenium have lower levels of prostate cancer.
Alternative Cures by Bill Gottlieb, page 519

Selenium Statistics
In a December 1996 article in the Journal of the American Medical Association, Dr. Larry Clark presented evidence that supplemental selenium could reduce cancer death rates by as much as 50%. 1,312 patients were given 200 mcg. of selenium daily. The patients receiving selenium had a rise of 67% in their blood selenium level.
A Physicians Guide To Natural Health Products That Work By James Howenstine MD, page 148

The patients receiving selenium had a 67% decrease in cancer of the prostate, a 58 percent decrease in colon or rectal cancer and a 45% decrease in lung cancer. This suggests that possibly up to 100,000 lives a year might be saved in the USA by the simple addition of selenium to the diet.
A Physicians Guide To Natural Health Products That Work By James Howenstine MD, page 149

An article in the Journal of the American Medical Association (JAMA) by Clark et al. (1996) showed that 200 mcg of supplemental selenium a day reduced overall cancer mortality by 50% in humans compared to a placebo group not receiving supplemental selenium. This 9-year study demonstrated that a low-cost mineral supplement could cut the risk of dying from cancer in half in certain individuals.
Disease Prevention And Treatment by Life Extension Foundation, page 1255

In a recent five-year study of nearly 30,000 rural Chinese people, researchers from the NCI found that daily doses of these three nutrients reduced cancer deaths by 13%.
Alternative Medicine by Burton Goldberg, page 590

But what if you already have cancer? Again, the research shows a prolongation of lifespan with proper supplementation. In a study in Cancer Letters (Evangelou et al. 1997), animals with malignant tumors given high doses of vitamins C and E and selenium manifested a significant prolongation of the mean survival time. Complete remission of tumors developed in 16.8% of the animals.
Disease Prevention And Treatment by Life Extension Foundation, page 1256

Dr. Raymond Shamberger was also among the first to discover the link between low selenium content in the soil and increasing numbers of deaths from cancer. In 1976, he pointed out that the cities and states with high selenium content in the soil also had significantly lower rates of cancer, especially of the digestive and urinary systems.
Antioxidants Against Cancer by Ralph Moss PhD, page 77

A Powerful Antioxidant “selenium is a crucial mineral in the battle against prostate cancer,” says Dr. Schachter. In one study of hundreds of men, a daily intake of 200 micrograms of selenium cut the incidence of prostate cancer by 60 percent.
Alternative Cures by Bill Gottlieb, page 518

The statistics for breast cancer are particularly striking. “The higher the selenium, the lower the breast cancer,” said Prof. Ladas. Similar associations have been found with leukemia, as well as cancers of the intestines, rectum, ovary, prostate, lung, pancreas, skin and bladder. In Yugoslavia, scientists studied 33 patients with breast cancer. These women had selenium levels in their bloodstream only half those of healthy volunteers.
Cancer Therapy by Ralph W Moss PhD, page 112

Although the study failed to show the effectiveness of selenium in altering the course of either basal or squamous cell carcinoma, selenium impacted the incidence of other types of malignancies with amazing success (Clark et al. 1996). The overall reduction in cancer incidence was 37% in the selenium-supplemented group; a 50% reduction in cancer mortality was observed over a 10-year period. The following are the site-specific reductions in cancer incidence observed in the study: colon-rectal cancers (58%), lung cancer (46%), and prostate cancer (63%). A selenium deficiency appears to increase the risk of prostate cancer fourfold to fivefold. It was determined that, as the male population ages, selenium levels decrease, paralleling an increase in prostate cancer (Brooks et al. 2001).
Disease Prevention And Treatment by Life Extension Foundation, page 242

In a study published in the journal of the National Cancer Institute, the relationship between serum levels of selenium and the development of upper digestive tract cancer was explored (Mark et al, 2000). The relative risk of esophageal cancer was 0.56 in individuals in the highest quartile of selenium level compared with those in the lowest quartile. The corresponding relative risk of gastric cardia cancer was 0.47. Based on the data, the researchers calculate that 26.4% of esophageal and gastric cardia cancers are attributable to low selenium levels.
Disease Prevention And Treatment by Life Extension Foundation, page 242

Selenium Recommendations
The Recommended Daily Allowance (RDA) is 50 to 100 micrograms (not milligrams) but few people get even that much. Selenium is so important that I believe that practically every adult should take a 200 microgram selenium supplement every day. This is readily available in health food stores at a minimal price. Organic selenium derived from yeast may be better absorbed man the mineral form, sodium selenite. Very high doses of either can be toxic, however, and should only be taken under a doctor’s prescription. To summarize: selenium has a strong ability to prevent cancers, especially of the internal organs. There is no evidence that selenium interferes with chemotherapy, radiation or a combination of both. On the contrary, there is evidence that it decreases the side effects of such treatments
Antioxidants Against Cancer by Ralph Moss PhD, page 81

The supplements that I’d recommend for cancer prevention are the antioxidants: vitamins C and E, beta-carotene, and the mineral selenium.
Anti-Aging Prescriptions by James Duke PhD, page 90

Moderate doses of zinc, beta-carotene, selenium and vitamin E are safe and inexpensive. I believe these results are valid and are an accurate reflection of what antioxidants can do. The finding that two terrible cancers could be prevented by a few pennies worth of supplements received little attention in the mainstream media.
Antioxidants Against Cancer by Ralph Moss PhD, page 83

The National Academy of Sciences advises that no more than 150 micrograms of selenium be taken orally daily. But Revici’s “bivalent negative selenium”— a combination of the mineral with various organic substances, such as the fatty acids of sesame oil—is said to be so non-toxic that huge amounts, up to one million micrograms, have been injected (in the treatment of drug addiction), apparently without any ill effects. In the treatment of cancer the dosage is generally about 10,000 micrograms, still nearly one hundred times the National Academy of Science’s recommended dose.
Cancer Therapy by Ralph W Moss PhD, page 112

But in the meantime, I will continue to take my 200 micrograms of selenium a day—the same dose used in the study—and I suggest that you do, too. Excess selenium has been associated with toxicity, so don’t go overboard. If you’re not fond of popping pills, you can get 120 micrograms of selenium in just one Brazil nut. Buy the shelled kind—they’re grown in a central region of Brazil where the soil is richest in the mineral. Other good sources are tuna fish, seafood, wheat germ, and bran.
Ask Dr Weil by Andrew Weil MD, page 207

While everyone needs selenium on an everyday basis, there are certain situations in which the human need for selenium may be increased, or in which additional selenium may be helpful in the treatment of a disease. If you are a male, your selenium needs are greater than if you are female. If you suffer from heart disease or muscular disorders, additional selenium may help you. The same can be said if you suffer from cataracts, diabetes, cystic fibrosis, liver necrosis, iron deficiency anemia, joint problems, heavy metal poisoning, or cancer.
Complete Guide Health Nutrition by Gary Null, page 479

Now, Dr. Mark A. Nelson, a professor and researcher at the Arizona Cancer Center, says, “The Nutritional Prevention of Cancer (NPC) Trial tripled the intake and suggests that higher levels of selenium may be necessary for cancer prevention.” Until nutritionists conduct more research, though, no one can recommend the best, safest amount you should get. Experts warn selenium is a toxic mineral, which means too much of it, especially from supplements, is unsafe.
Eat and Heal by the Editors of FC&A Medical Publishing, page 98

Doctors at the Chinese Academy of Medical Sciences concluded that selenium supplements were a safe and effective food supplement for people. There have also been a number of reports of selenium’s toxicity or even its alleged ability to cause cancer. There is no question that excess selenium in the soil (in the form of its compounds, selenite or selenate) can kill grazing animals and could probably in sufficiently large doses kill humans as well. The symptoms of selenium poisoning are readily apparent without a doctor’s assistance, according to Dr. Gerhard Schrauzer, a world expert on the topic. These symptoms include a heavy garlic odor, pallor, nervousness, depression, a metallic taste, skin eruptions, irritability, discolored teeth and hair loss. There is some doubt about the carcinogenicity studies. For instance, one study showed toxic effects for inorganic, but not organic, forms of the mineral.
Cancer Therapy by Ralph W Moss PhD, page 112

General / History of Selenium
Selenium (Se) is a metal that is chemically similar to sulfur. It was first discovered in 1817 and because of its silvery color was named for Selene, the ancient goddess of the moon. Selenium is an essential component of two important antioxidant enzymes and is also the helpmate of vitamin E.
Antioxidants Against Cancer by Ralph Moss PhD, page 76

Initially, selenium’s importance in human health was underrated. In fact, its main use in conventional medicine was as a treatment for dandruff!
Antioxidants Against Cancer by Ralph Moss PhD, page 76

Strange as it may seem, toenail levels of selenium are considered a good indicator of long-term selenium intake. They found that the people whose toenails had the highest levels of selenium had half of the rate of lung cancer compared with those whose toe-nails were low in selenium.
Healing With Vitamins by Alice Feinstein, page 143

Emmanuel Revici, MD based his treatment on correcting an imbalance between fatty acids and sterols in the cancer patient; called “biological dualism”. Revici was considered a very dedicated physician and developer of selenium as an anti-cancer agent. -Ewan Cameron, MD, a Scottish surgeon first popularized the use of high dose vitamin C in terminal cancer patients.
Beating Cancer With Nutrition by Patrick Quillin, page 45

Some scientists still do not accept the need for selenium supplements and argue against its protective effect against cancer and other diseases. Others endorse the value of moderate amounts of selenium added to the diet. In the laboratory, selenium has shown a wide range of anticancer effects.
Cancer Therapy by Ralph W Moss PhD, page 109

Aside from Revici’s work, little has been done to investigate the use of this mineral as a cancer treatment. In 1911, Prof. August von Wasserrman achieved growth inhibition, shrinkage and eventually the disappearance of tumors by injecting selenium directly into mouse tumors. Four years later, two doctors caused the shrinkage and the eventual disappearance of small tumors in cancer patients, although larger tumors failed to respond.
Cancer Therapy by Ralph W Moss PhD, page 112

After critically examining this book, I came to the conclusion that Dr. Revici is an innovative medical genius, outstanding chemist and a highly creative thinker [emphasis added]. I also realized that few of his medical colleagues would be able to follow his train of thought and thus would be all too willing to dismiss his work. Because of my own professional interest in selenium, let me merely focus on this aspect of his work. Selenium containing medications were introduced into cancer therapy as early as 1911 by none less than the great physician August von Wasserman. Working with experimental animals, von Wasserman was able to show his selenium compounds produced liquefactive necrosis of solid tumors, an unheard of event at the time, hailed as a major success. However, von Wasserman’s compounds were too toxic and thus could not be employed in the treatment of human cancer. Dr. Revici deserves credit for having discovered pharmacologically active selenium compounds of very low toxicity. The same was achieved years later by one other great physician, Dr. Klaus Schwarz, in collaboration with a leading organic chemist, Dr. Arne Fredga, of Uppsala University. The National Cancer Institute has recognized the importance of selenium only within the past few years. Would one thus not have to conclude that Dr. Revici, in this one instance, was 40 years ahead of his time? The same could be said for many of his other researches which form the basis of his therapy.
Choices In Healing by Michael Lerner, page 614

Dr. Gerbhard Schauzer, a biochemist at the University of California in San Diego, … believes that if every woman in America began taking selenium supplements today or followed a diet high in selenium, the breast cancer rate in this country would decline drastically in a few years.
Miracle Medicine Herbs by Richard M Lucas, page 16

Asia has considerable quantities of selenium in its soil, making the Asian diet rich in the mineral; not surprisingly, cancer and heart disease occur considerably less often in Asian cultures than in the West.
Optimum Health by Stephen T Sinatra MD, page 123

Additional Benefits of Selenium
Antioxidants, like beta carotene, vitamin C, vitamin E, and selenium appear to enhance the effectiveness of chemo, radiation, and hyperthermia while minimizing damage to the patient’s normal cells; thus making therapy more of a “selective toxin.” An optimally nourished cancer patient can better tolerate the rigors of cytotoxic therapy.
Beating Cancer With Nutrition by Patrick Quillin, page 18

Patients with advanced rectal cancer were treated with a combination of selenium, the drug 5-FU, and radiation. Scientists reported a protective effect of selenium on quality of life.
Antioxidants Against Cancer by Ralph Moss PhD, page 80

Selenium-deficient animals have more heart damage from the chemo drug, adriamycin.43 Supplements of selenium and vitamin E in humans did not reduce the efficacy of the chemo drugs against ovarian and cervical cancer. Animals with implanted tumors who were then treated with selenium and cisplatin (chemo drug) had reduced toxicity to the drug with no change in anti-cancer activity. Selenium supplements helped repair DNA damage from a carcinogen in animals. Selenium was selectively toxic to human leukemia cells in culture.
Beating Cancer With Nutrition by Patrick Quillin, page 56

While most nutritionists agree on the importance of growth (proliferative) nutrients, few nutritionists respect the importance for anti-proliferative nutrients. For every force in the body, there must be an opposing force to regulate that mechanism. There are agents that cause fluid loss from the kidneys (diuresis) and other agents that stem this fluid loss when it is excessive (anti-diuretic hormone). Just as there is a need for nutrients to augment growth, there is a need for nutrients to control excessive growth and shut down the process. Selenium, fish oil, garlic, Cat’s claw, Maitake D-fraction, vitamin E succinate, vitamin K, quercetin, genistein, and bovine cartilage all may assist the cancer patient in this manner.
Beating Cancer With Nutrition by Patrick Quillin, page 80

Vitamin E and selenium supplements in animals helped to reduce the heart toxicity from adriamycin. Selenium and vitamin E supplements were given to 41 women undergoing cytotoxic therapy for ovarian and cervical cancers, with a resulting drop in the toxicity-related rise in creatine kinase.
Beating Cancer With Nutrition by Patrick Quillin, page 107

One of the foremost selenium investigators, Gerhard Schrauzer of the University of California at San Diego, says: Apart from its functions as an essential micronutrient, selenium also appears to have other physiological functions in which it acts as a physiological resistance factor [emphasis added]. Its cancer protecting effects fall into this category. In addition, selenium protects against free radicals, mutagens, toxic heavy metals and certain bacterial, fungal and viral pathogens. The selenium requirement increases under stress, just as the requirement for certain vitamins increases during infections. Selenium, according to Schrauzer, is most effective as a form of nutritional cancer prophylaxis. In animal research, its protective effect is greater the earlier in life it is given, and its shielding effect against virally induced cancer disappears if the nutrient is no longer fed to the animal. Nevertheless, selenium does have an effect on slowing the rate of growth of established spontaneous or transplanted breast tumors in animals, and in reversing the development of some malignant cell lines when used at pharmacological levels. Further, selenium has shown a general capacity to stimulate the immune system in several animal models, which may add to its anticancer effects. It is of special relevance to cancer patients undergoing chemotherapy that selenium “has by now been shown to prevent or retard tumorigenesis induced by virtually all the major known carcinogens,” probably, Schrauzer believes, “by modulating the rate of cell division.”
Choices In Healing by Michael Lerner, page 612

Just as selenium protects you against toxic metal poisoning, it can also protect you against radiation, whether you are exposed to it through the environment or more directly through medical treatments. A particularly effective form of selenium for this purpose is selenoaminoacid compounds (selenium plus amino acids). Selenium also protects you against compounds called epoxides, as it breaks them down. What are epoxides? Formed when an enzyme named aryl hydrocarbon hydroxylase binds with a carcinogenic substance, epoxides could be called the immediate cause of cancer. The carcinogens cause your body to produce them, and then cancer may ensue.
Complete Guide Health Nutrition by Gary Null, page 483

Reports from Germany indicate that selenium supplementation in patients undergoing radiation therapy for rectal cancer improved quality of life and reduced the appearance of secondary cancers (Hehr et al. 1997) It appears that selenium acts as an immunologic response modifier, normalizing every component of the immune system (Life Extension Report 1995).
Disease Prevention And Treatment by Life Extension Foundation, page 243

Macrophages—those garbagemen of the bloodstream—are capable of keeping your body clear of tumor cells. Also, since they produce interferon, they can help eliminate the viruses that cause some forms of cancer. But to do their job properly, they need adequate selenium.
Complete Guide Health Nutrition by Gary Null, page 483

Some of the known natural compounds that can reduce insulin resistance include omega-3 fatty acids, curcumin, flavonoids, selenium, and vitamin E. Dietary risk factors must be managed. Therefore, besides restricting dietary sugars, individuals should eat an adequate amount of fruits and vegetables because phytochemicals in fruits and vegetables act as potent anticancer agents.
Disease Prevention And Treatment by Life Extension Foundation, page 598

Selenium can prevent solar damage, pigmentation and dark spots, but because the selenium content of soil varies across the country, not everyone is getting enough to be beneficial,” says Dr. Burke, citing the Southeast in particular as an area deficient in selenium. To quench the free radicals caused by sun exposure and to prevent skin damage, Dr. Burke recommends daily supplements of 50 to 200 micrograms of selenium in the form of 1-selenomethionine, depending on where you live and your family history of cancer. Selenium can be toxic in doses exceeding 100 micrograms, so if you’d like to try this therapy to protect your skin, you should discuss it with your doctor.
Healing With Vitamins by Alice Feinstein, page 64

The importance of selenium to cardiovascular health was demonstrated in the provinces of China where the mineral was deficient. This correlation can be seen throughout the world. Ray Shamberger, M.D., and Charles Willis, M.D., of the Cleveland Clinic in Ohio, reported in 1976 that people who live in low-selenium areas have three times more heart disease than those living in areas where the soil and water are rich in the mineral.
Saturated Fat May Save Your Life by Bruce Fife ND, page 142

Selenium also appears to help stimulate antibody formation in response to vaccines. This immunostimulating effect is also enhanced by vitamin E; the presence of these two nutrients can increase antibody formation by 20-30 times, as shown by research.
Staying Healthy With Nutrition by Elson M Haas MD, page 213

Selenium may also aid in protein synthesis, growth and development, and fertility, especially in the male. It has been shown to improve sperm production and motility. Thus, selenium may prevent male infertility; however, we do not know whether selenium deficiency will actually cause male infertility. These are only some of the conjectures about other selenium functions.
Staying Healthy With Nutrition by Elson M Haas MD, page 213

Selenium Interactions
Certain metals such as lead, cadmium, arsenic, mercury and silver block the action of selenium. . . . Recent laboratory experiments have shown that high doses of zinc block the action of selenium. Therefore, one has to be careful about taking excessive amounts of zinc (over 20 milligrams per day from diet and supplements) while taking selenium [emphasis added].
Choices In Healing by Michael Lerner, page 619

I think the selenium and saffron complement one another. Selensaff, a product made by Scientific Botanicals (see Resources), is used in cancer therapy to create a redox effect—a process of improving cell function by enhancing both oxygen uptake and the excretion of oxygen waste.
Herbal Medicine Healing Cancer by Donald R Yance Jr, page 148 Zinc is important because it is an antagonist to selenium and may in itself enhance or inhibit different tumors. Selenium in minute quantities is essential to human health. According to Prasad, among the minerals, “only selenium has been shown to have a role in cancer prevention”:
Choices In Healing by Michael Lerner, page 619

Vitamin E and selenium protected animals against the potent carcinogenic effects of DMBA from tobacco.
Beating Cancer With Nutrition by Patrick Quillin, page 164

Selenium acts as an antioxidant and strengthens the body’s immune defense system. Thus, many of the effects which are produced by vitamin E deficiency can be reversed or prevented by selenium. Some laboratory experiments have suggested that the combination of vitamin E and selenium is more effective in preventing cancer than either of them alone.
Choices In Healing by Michael Lerner, page 619

However, one experiment has demonstrated increased susceptibility to DMBA-induced tumors when selenium deficiency was aggravated by high dietary levels of polyunsatu-rated fatty acids, and protection by a physiological supplement of selenium (0.1 pg/g) to the diet (Ip and Sinha, 1981). The interpretation of these results is further complicated because of the varied protocols used in these experiments and the knowledge that selenium interacts with many other nutrients, such as heavy metals in the diet.
Diet Nutrition Cancer by National Research Council, page 169

In some experiments, dietary zinc exceeding nutritional requirements has been shown to suppress chemically induced tumors in rats and hamsters, but when given in drinking water it counteracts the protective effect of selenium in mice…While the evidence on the effect of zinc on tumor development is complex, it strongly suggests that, in general, one should be cautious about taking zinc supplements if one has cancer. And since selenium has a wide spectrum of demonstrable anticancer effects, cancer patients should be particularly cautious with zinc, since it is a selenium antagonist. I have seen many cancer patients taking moderately large amounts of zinc as part of a comprehensive megavitamin nutritional supplement program. In view of the available scientific evidence, this is another critical example of an area where uninformed nutritional supplementation may do harm.
Choices In Healing by Michael Lerner, page 612

In addition, statistically significant protection from high levels of selenium and alpha-tocopherol occurred only when gamma- tocopherol concentrations were also high (Helzl-sourer et al. 2000).
Disease Prevention And Treatment by Life Extension Foundation, page 258

Selenium and co-enzyme Q-10. Exhibits anticancer activity especially in blocking development of colon cancer and spread of breast cancer.
Food Your Miracle Medicine by Jean Carper, page 481

Source: naturalnews.com

Cannabindiol: United States Patent 6,630,507

  • August 25, 2012 5:28 pm
United States Patent 6,630,507
Hampson ,   et al. October 7, 2003

Cannabinoids as antioxidants and neuroprotectants

Abstract
Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting of H, CH.sub.3, and COCH.sub.3. ##STR1##


Inventors: Hampson; Aidan J. (Irvine, CA), Axelrod; Julius (Rockville, MD), Grimaldi; Maurizio (Bethesda, MD)
Assignee: The United States of America as represented by the Department of Health and Human Services (Washington, DC)
Appl. No.: 09/674,028
Filed: February 2, 2001
PCT Filed: April 21, 1999
PCT No.: PCT/US99/08769
PCT Pub. No.: WO99/53917
PCT Pub. Date: October 28, 1999

 

Current U.S. Class: 514/454
Current International Class: A61K 31/35 (20060101); A61K 031/35 ()
Field of Search: 514/454

 

Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In Vivo

  • August 24, 2012 3:53 am
  1. Nicholas A. Jones,
  2. Andrew J. Hill,
  3. Imogen Smith,
  4. Sarah A. Bevan,
  5. Claire M. Williams,
  6. Benjamin J. Whalley and
  7. Gary J. Stephens

+ Author Affiliations


  1. School of Pharmacy (N.A.J., A.J.H., I.S., S.A.B., B.J.W., G.J.S.) and School of Psychology (N.A.J., A.J.H., C.M.W.), University of Reading, Whiteknights, Reading, United Kingdom
  1. Address correspondence to:
    Dr. Gary Stephens,
    School of Pharmacy, University of Reading, Whiteknights, P.O. Box 228, Reading RG6 6AJ, UK.

    E-mail: g.j.stephens@reading.ac.uk

Abstract

Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the antiepileptiform and antiseizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model, respectively. CBD (0.01–100 μM) effects were assessed in vitro using the Mg2+-free and 4-aminopyridine (4-AP) models of epileptiform activity in hippocampal brain slices via multielectrode array recordings. In the Mg2+-free model, CBD decreased epileptiform local field potential (LFP) burst amplitude [in CA1 and dentate gyrus (DG) regions] and burst duration (in all regions) and increased burst frequency (in all regions). In the 4-AP model, CBD decreased LFP burst amplitude (in CA1 only at 100 μM CBD), burst duration (in CA3 and DG), and burst frequency (in all regions). CBD (1, 10, and 100 mg/kg) effects were also examined in vivo using the pentylenetetrazole model of generalized seizures. CBD (100 mg/kg) exerted clear anticonvulsant effects with significant decreases in incidence of severe seizures and mortality compared with vehicle-treated animals. Finally, CBD acted with only low affinity at cannabinoid CB1 receptors and displayed no agonist activity in [35S]guanosine 5′-O-(3-thio)triphosphate assays in cortical membranes. These findings suggest that CBD acts, potentially in a CB1 receptor-independent manner, to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel antiepileptic drug in the unmet clinical need associated with generalized seizures.

A growing number of phytocannabinoids have been shown to possess biological activity (Pertwee, 2008) and, in particular, to affect neuronal excitability in the CNS. Phytocannabinoid actions are reported to be mediated by G protein-coupled cannabinoid CB1 and CB2 receptors and potentially by other non-CB receptor targets (Howlett et al., 2004; Pertwee, 2008). CB1 receptors are highly expressed in the hippocampus (Herkenham et al., 1990; Tsou et al., 1998) and are well known to modulate epileptiform and seizure activity (Shen and Thayer, 1999; Wallace et al., 2001). Moreover, the endocannabinoid (eCB) system has been shown to be a key determinant of hippocampal epileptiform activity (Wallace et al., 2002; Monory et al., 2006; Ludányi et al., 2008). The major psychoactive compound Δ9-THC was the first phytocannabinoid reported to affect epileptiform activity; Δ9-THC, a partial agonist at CB1 receptors, was shown to inhibit excitatory glutamatergic neurotransmission in hippocampal neurons under low Mg2+ conditions (Shen and Thayer, 1999; but see Straiker and Mackie, 2005).

CBD is the major nonpsychoactive component of Cannabis sativa whose structure was first described by Mechoulam and Shvo (1963); CBD has recently attracted renewed interest for its therapeutic potential in a number of disease states (Pertwee, 2008). CBD has been proposed to possess anticonvulsive, neuroprotective, and anti-inflammatory properties in humans. Thus, within the CNS, CBD has been proposed to be protective against epilepsy, anxiety, and psychosis and to ameliorate diseases of the basal ganglia, such as parkinsonism and Huntington’s disease (Iuvone et al., 2009; Scuderi et al., 2009). CBD neuroprotective effects may be augmented by reported antioxidant properties (Hampson et al., 1998; Sagredo et al., 2007). Early studies suggested that CBD had anticonvulsant potential in one small-scale phase I clinical trial (Cunha et al., 1980). In this regard, there is a significant unmet clinical need for epilepsy, with ∼30% of epileptic patients experiencing intractable seizures regardless of conventional AED treatment (Kwan and Brodie, 2007). CBD is extremely well tolerated in humans; for example, CBD at doses of 600 mg does not precipitate any of the psychotic symptoms associated with Δ9-THC (Bhattacharyya et al., 2009). At present, CBD is used therapeutically in Sativex (1:1 Δ9-THC/CBD; GW Pharmaceuticals, Porton Down, UK) to alleviate pain symptoms in multiple sclerosis and cancer pain. CBD has anticonvulsant effects in animal models of maximal electroshock (Karler et al., 1974; Consroe and Wolkin, 1977; Consroe et al., 1982); however, CBD remains untested in other animal seizure models (Gordon and Devinsky, 2001) and so has yet to fulfill its potential indications as a clinical anticonvulsant.

In the present study, we demonstrate the potential of CBD as an AED. We show that CBD caused concentration-related and region-dependent attenuation of chemically induced epileptiform activity in hippocampal brain slices using in vitro MEA electrophysiological recordings. Furthermore, CBD reduced seizure severity and mortality in an in vivo model of generalized seizures. We also investigated the specific role of CB1 receptors in CBD action and found only a low-affinity interaction and lack of clear agonist effects. Overall, these data are consistent with CBD acting to mediate antiepileptiform and antiseizure effects in vitro and in vivo, respectively, potentially by CB1 receptor-independent mechanisms.

Materials and Methods

In Vitro Electrophysiology

Tissue Preparation and Solutions.

All experiments were performed in accordance with Home Office regulations [Animals (Scientific Procedures) Act 1986]. Acute transverse hippocampal brain slices (∼450 μm thick) were prepared from male and female (postnatal day ≥21) Wistar Kyoto rats using a Vibroslice 725M (Campden Instruments Ltd., Loughborough, Leicestershire, UK). Slices were produced and maintained in continuously carboxygenated (95% O2-5% CO2) artificial cerebrospinal fluid (aCSF) composed of 124 mM NaCl, 3 mM KCl, 1.25 mM KH2PO4, 1 mM MgSO4 · 6H2O, 36 mM NaHCO3, 2 mM CaCl2, and 10 mM d-glucose, pH 7.4. Spontaneous epileptiform activity was induced either by exchange of the standard aCSF perfusion media for aCSF with MgSO4 · 6H2O removed (Mg2+-free aCSF) or by addition of the K+ channel blocker 4-AP (100 μM; 4-AP aCSF).

MEA Electrophysiological Recording.

Substrate-integrated MEAs (Multi Channel Systems, Reutlingen, Germany) (Egert et al., 2002a; Stett et al., 2003) were used to record spontaneous neuronal activity as described previously (Ma et al., 2008). MEAs were composed of 60 electrodes (including reference ground) of 30 μm diameter, arranged in an ∼8 × 8 array with 200 μm spacing between electrodes.

MEAs were cleaned before each recording by immersion in 5% w/v Terg-A-Zyme (Cole-Palmer, London, UK) in distilled H2O, followed by methanol, and, finally, distilled H2O before air drying. Hippocampal sections immersed in aCSF were gently microdissected away from surrounding slice tissue using fine forceps under a WILD M8 binocular microscope (Leica AG, Solms, Germany). Dissected hippocampi were then adhered to the cleaned MEA surface using an applied and evaporated cellulose nitrate solution in methanol (∼4 μl, 0.24% w/v; Thermo Fisher Scientific, Leicestershire, UK) to ensure maximum contact between the tissue and recording electrodes and to avoid any physical stress on the tissue during recordings. Slices were observed at 4× magnification with a Nikon TS-51 inverted microscope (Nikon, Tokyo, Japan) and imaged via a Mikro-Okular camera (Bresser, Rhede, Germany) to map electrode positions to hippocampal regions. Slices were maintained at 25°C, continuously superfused (∼2 ml/min) with carboxygenated aCSF, and allowed to stabilize for at least 10 min before recordings. Signals were amplified (1200× gain), band pass-filtered (2–3200 Hz) by a 60-channel amplifier (MEA60 System, Multi Channel Systems), and simultaneously sampled at 10 kHz per channel on all 60 channels. Data were transferred to PC using MC_Rack software (Multi Channel Systems). Offline analysis of CBD effects upon burst amplitude, duration, and frequency was performed using MC_Rack, MATLAB 7.0.4. (Mathworks Inc., Natick, MA) and in-house analysis scripts. Animated contour plots of MEA-wide neuronal activity (Supplemental Fig. 1) were constructed from raw data files processed in MATLAB 6.5 using in-house code with functions adapted from MEA Tools and interpolated using a five-point Savitzky-Golay filter in MATLAB (Egert et al., 2002b). These data are displayed as peak source and peak sink animation frames. Burst propagation speeds were calculated by determining burst peak times at electrode positions closest to burst initiation (CA3) and termination (CA1) sites using MC_Rack and ImageJ software (Abramoff et al., 2004).

Data Presentation and Statistics.

Application of Mg2+-free and 4-AP aCSF induced spontaneous epileptiform activity characterized by recurrent status epilepticus-like local field potential (LFP) events (Figs. 2, A and B, and 4, A and B). We have recently characterized and validated the use of MEA technology to screen candidate AEDs in the Mg2+-free and 4-AP models using reference compounds, felbamate and phenobarbital (Hill et al., 2009). A discrete burst was defined as an LFP with both positive and negative components of greater than 2 S.D. from baseline noise. In each model, LFPs were abolished by the addition of the non-NMDA glutamate receptor antagonist 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2–3-dione (5 μM) and tetrodotoxin (TTX, 1 μM) (n = 3 per model), indicating that epileptiform activity was due to firing of hippocampal neurons. After an initial 30-min control period, CBD was added cumulatively in increasing concentrations (30 min each concentration). Burst parameters (amplitude, duration, and frequency) were determined from the final 10 bursts of the control period or of each drug concentration. Increases in burst amplitude and decreases in frequency inherent to both in vitro models were observed over time in recordings in the absence of CBD (n = 4 per model). These changes required appropriate compensation to allow accurate assessment of CBD effects and have been rigorously modeled by us recently (Hill et al., 2009). Thus, burst frequency and amplitude from control recordings were normalized to the values observed after 30 min of epileptiform activity, then pooled to give mean values. Curves were fitted to resultant data, and derived equations were used to adjust values obtained from recordings in the presence of CBD. For amplitude; y = 0.8493 × e(x×−0.009295) + 0.4216 for Mg2+-free-induced bursting (r2 = 0.98) and y = 0.87 × e(−x/83.32) + 0.45 for 4-AP-induced bursting (r2 = 0.99), where x = time and y = burst amplitude. Frequency changes were more complex and required fifth-order polynomial equations: y = −9e−14x4 + 7e−10x3 − 3e−06x2 + 0.006x − 3.594 for Mg2+-free-induced bursting (r2 = 0.818); and y = 5−14x4 − 5e−10x3 + 2e−06x2 − 0.004x + 3.965 for 4-AP-induced bursting (r2 = 0.915), where x = time and y = frequency (Hill et al., 2009). Inevitable dead cell debris on the slice surface produced slice-to-slice variability in signal strength. Consequently, drug-induced changes are presented as changes to the stated measure versus control per experiment to provide normalized measures for pooled data. Statistical significance was determined by a nonparametric two-tailed Mann-Whitney U test. Mean propagation speeds (meters per second) were derived from pooled data and the significance of drug effects was tested using a two-tailed Student’s t test. In all cases, P ≤ 0.05 was considered significant.

Pharmacology.

The following agents were used: 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2-3-dione (Tocris Cookson, Bristol, UK), tetrodotoxin (Alomone, Jerusalem, Israel), and 4-AP (Sigma-Aldrich, Poole, UK). CBD was kindly provided by GW Pharmaceuticals. CBD was made up as a 1000-fold stock solution in dimethylsulfoxide (Thermo Fisher Scientific, Leicestershire, UK) and stored at −20°C. Individual aliquots were thawed and dissolved in carboxygenated aCSF immediately before use. In all experiments, drugs were bath-applied (2 ml/min) for 30 min to achieve steady-state effects after the induction of epileptiform activity.

Pentylenetetrazole in Vivo Seizure Model

PTZ (80 mg/kg; Sigma-Aldrich) was used to induce seizures in 60 adult (postnatal day >21, 70–110 g) male Wistar Kyoto rats. In the days before seizure induction, animals were habituated to handling, experimental procedures, and the test environment. Before placement in their observation arenas, animals were injected intraperitoneally with CBD (1, 10, or 100 mg/kg); vehicle was a 1:1:18 solution of ethanol, Cremophor (Sigma-Aldrich), and 0.9% w/v NaCl. CBD is known to penetrate the blood-brain barrier such that 120 mg/kg delivered intraperitoneally in rats provides Cmax = 6.8 μg/g at Tmax = 120 min and, at the same dosage, no major toxicity, genotoxicity, or mutagenicity was observed (personal communication via GW Pharmaceuticals Ltd; Study Report UNA-REP-02). A group of animals that received volume-matched doses of vehicle alone served as a negative control. Sixty minutes after CBD or vehicle administration, animals were injected with 80 mg/kg PTZ i.p. to induce seizures. An observation system using closed-circuit television cameras (Farrimond et al., 2009) was used to monitor the behavior of up to five animals simultaneously from CBD/vehicle administration until 30 min after seizure induction. Input from closed-circuit TV cameras was managed and recorded by Zoneminder (version 1.2.3; Triornis Ltd., Bristol, UK) software and then was processed to yield complete videos for each animal.

Seizure Analysis.

Videos of PTZ-induced seizures were scored offline with a standard seizure severity scale appropriate for generalized seizures (Pohl and Mares, 1987) using Observer Video-Pro software (Noldus, Wageningen, The Netherlands). The seizure scoring scale was divided into stages as follows: 0, no change in behavior; 0.5, abnormal behavior (sniffing, excessive washing, and orientation); 1, isolated myoclonic jerks; 2, atypical clonic seizure; 3, fully developed bilateral forelimb clonus; 3.5, forelimb clonus with tonic component and body twist; 4, tonic-clonic seizure with suppressed tonic phase with loss of righting reflex; and 5, fully developed tonic-clonic seizure with loss of righting reflex (Pohl and Mares, 1987).

Specific markers of seizure behavior and development were assessed and compared between vehicle control and CBD groups. For each animal the latency (in seconds) from PTZ administration to the first sign of a seizure, development of a clonic seizure, development of tonic-clonic seizures, and severity of the seizure were recorded. In addition, the median severity, percentage of animals that experienced the highest seizure score (stage 5: tonic-clonic seizure), and percent mortality for each group were determined. Mean latency ± S.E.M. are presented for each group, together with the median value for seizure severity. Differences in latency and seizure duration values were assessed using one-way analysis of variance with a post hoc Tukey test; Mann-Whitney U tests were performed when replicant (n) numbers were insufficient to support post hoc testing. Differences in seizure incidence and mortality (percentage) were assessed by a nonparametric binomial test. In all cases, P ≤ 0.05 was considered to be significant.

Receptor Binding Assays

Membrane Preparation.

Cortical tissue was dissected from the brains of adult (postnatal day >21) male and female Wistar Kyoto rats and stored separately at −80°C until use. Tissue was suspended in a membrane buffer, containing 50 mM Tris-HCl, 5 mM MgCl2, 2 mM EDTA, and 0.5 mg/ml fatty acid-free bovine serum albumin (BSA) and complete protease inhibitor (Roche, Mannheim, Germany), pH 7.4, and was then homogenized using an Ultra-Turrax blender (Labo Moderne, Paris, France). Homogenates were centrifuged at 1000g at 4°C for 10 min, and supernatants were decanted and retained. Resulting pellets were rehomogenized and centrifugation was repeated as before. Supernatants were combined and then centrifuged at 39,00g at 4°C for 30 min in a high-speed Sorvall centrifuge; remaining pellets were resuspended in membrane buffer, and protein content was determined by the method of Lowry et al. (1951). All procedures were carried out on ice.

Radioligand Binding Assays.

Competition binding assays against the CB1 receptor antagonist [3H]SR141716A rimonabant were performed in triplicate in assay buffer containing 20 mM HEPES, 1 mM EDTA, 1 mM EGTA, and 5 mg/ml fatty acid-free BSA, pH 7.4. All stock solutions of drugs and membrane preparations were diluted in assay buffer and stored on ice immediately before incubation. Assay tubes contained 0.5 nM [3H]SR141716A (Kd = 0.53 ± 0.01 nM, n = 3, determined from saturation assay curves) together with drugs at the desired final concentration and were made up to a final volume of 1 ml with assay buffer. Nonspecific binding was determined in the presence of the CB1 receptor antagonist AM251 (10 μM). Assays were initiated by addition of 50 μg of membrane protein. Assay tubes were incubated for 90 min at 25°C, and the assay was terminated by rapid filtration through Whatman GF/C filters using a Brandell cell harvester, followed by three washes with ice-cold phosphate-buffered saline to remove unbound radioactivity. Filters were incubated overnight in 2 ml of scintillation fluid, and radioactivity was quantified by liquid scintillation spectrometry.

[35S]GTPγS Binding Assays.

Assays were performed in triplicate in assay buffer containing 20 mM HEPES, 3 mM MgCl2, 60 mM NaCl, 1 mM EGTA, and 0.5 mg/ml fatty acid-free BSA, pH 7.4. All stock solutions of drugs and membrane preparations were diluted in assay buffer and stored on ice immediately before use. Assay tubes contained GDP at a final concentration of 10 mM, together with drugs at the desired final concentration and were made up to a final volume of 1 ml with assay buffer. Assays were initiated by addition of 10 μg of membrane protein. Assays were incubated for 30 min at 30°C before addition of [35S]GTPγS (final concentration 0.1 nM). Assays were terminated after a further 30-min incubation at 30°C by rapid filtration through Whatman GF/C filters using a Brandell cell harvester, followed by three washes with ice-cold phosphate-buffered saline to remove unbound radioactivity. Filters were incubated for a minimum of 2 h in 2 ml of scintillation fluid, and radioactivity was quantified by liquid scintillation spectrometry.

Data Analysis and Statistical Procedures.

Data analyses were performed using GraphPad Prism (version 4.03; GraphPad Software Inc., San Diego, CA). Saturation experiments were performed to determine Kd and Bmax (picomoles per milligram) values; the free radioligand concentration was determined by subtraction of total bound radioligand from the added radioligand concentration. Data for specific radioligand binding and free radioligand concentration were fitted to equations describing one- or two-binding site models, and the best fit was determined using an F test. Saturation analyses best fit a one-binding site model. Competition experiments were fitted to one- and two-binding site models, and the best fit was determined using an F test. Data for the best fits are expressed as Ki values, with the respective percentage of high-affinity sites (percent Rh) given for two-binding site models (Vivo et al., 2006). The Hill slope for competition experiments was determined using a sigmoidal concentration-response model (variable slope). [35S]GTPγS concentration-response data were analyzed using a sigmoidal concentration-response model (variable slope) or linear regression and compared using an F test to select the appropriate model. No other constraints were applied. [35S]GTPγS binding is expressed as percentage increase in radioactivity as described previously (Dennis et al., 2008). All data are expressed as mean ± S.E.M.

Pharmacology.

The following agents were used: AM251, WIN55,212-2 (Tocris-Cookson, Bristol, UK), CBD (GW Pharmaceuticals), and [3H]SR141716A and [35S]GTPγS (GE Healthcare, Chalfont St. Giles, Buckinghamshire, UK). All other reagents were from Sigma-Aldrich.

Results

Characterization of Mg2+-Free and 4-AP Models of Epileptiform Activity Using MEA Electrophysiology.

To investigate neuronal excitability in vitro, we used both the Mg2+-free and 4-AP models of epileptiform activity in acute hippocampal brain slices, as measured using MEA electrophysiology. Two separate models of epileptiform activity were used to provide a broader analysis of drug effects (Hill et al., 2009; Whalley et al., 2009). Hippocampal slices have a well defined architecture (Fig. 1A), exhibited no spontaneous LFP events in control aCSF, and proved readily amenable to MEA recording (Fig. 1B). We sought to take advantage of the ability of MEAs to record spatiotemporal activity at multiple discrete, identifiable regions by investigating activity at CA1, CA3, and DG regions within the hippocampus. Application of Mg2+-free aCSF (Fig. 1C) or 4-AP aCSF (Fig. 1D) to hippocampal slices resulted in the appearance of robust spontaneous epileptiform LFPs across the preparation. LFPs were consistent with status epilepticus-like activity and were reliably recorded using the multisite MEA technique (Table 1). Slice-to-slice variability and electrode contact variability resulted in substantial variation in signal strength (Table 1); therefore, subsequent drug-induced changes in burst characteristics were normalized to control bursts before drug application (these analyses are fully characterized in Hill et al., 2009).

Fig. 1.

View larger version:

Fig. 1.

Hippocampal slices are amenable to MEA recording. A, schematic representation of hippocampal slice showing the position of CA1, CA3, and DG regions, together with major pathways: Schaffer collateral (SC), mossy fiber (MF), and perforant pathway (PP). B, micrograph showing a hippocampal brain slice (stained with pontamine blue) mounted onto a substrate-integrated MEA (60 electrodes of 30 μm diameter, spaced 200 μm apart in an ∼8 × 8 arrangement). Scale bar, 400 μm. Representative LFP burst activity was recorded at 60 electrodes across a hippocampal slice in (C) Mg2+-free aCSF and (D) 4-AP aCSF. Traces were high pass-filtered in an MC_rack at 2 Hz.

Table 1

Characterization measures for the Mg2+-free and 4-AP (100 μM) aCSF-induced LFP epileptiform activity in the CA1, CA3, and DG regions of the hippocampus

LFP peak burst amplitude values are presented as a minimum and maximum range and mean ± S.E.M. LFP burst duration and frequencies are presented as mean ± S.E.M. A minimum of six separate hippocampal slices were used in the characterisation of each in vitro model.

Effects of CBD in the Mg2+-Free Model of in Vitro Epileptiform Activity.

We first examined the effects of CBD in the Mg2+-free model to assess CBD effects on a receptor-dependent model of epileptiform activity. The Mg2+-free model removes the Mg2+-dependent block of NMDA glutamate receptors, rendering them more responsive to synaptically released glutamate at resting membrane potentials. In Mg2+-free aCSF, CBD significantly decreased LFP burst amplitude in the CA1 (1–100 μM CBD) and DG (10–100 μM CBD) regions (Fig. 2, A, B, and Ci). In contrast, CBD (0.01–100 μM) effects on LFP burst amplitude in CA3 failed to reach significance. CBD decreased burst duration in CA1 (0.01–100 μM CBD), CA3 (0.01–100 μM CBD), and DG (0.1–100 μM CBD) regions (Fig. 2, A, B, and Cii). CBD (0.01–10 μM) also caused an increase in burst frequency in all regions tested (Fig. 2Ciii; however, this effect was lost at 100 μM CBD. To correlate these data with information on LFP burst initiation and spread across the hippocampal brain slice, we constructed contour plots (Fig. 3A) and associated video animations (Supplemental Fig. 1). Such plots spatiotemporally visualize the “8 × 8” MEA configuration (Fig. 1, B and C) and the individual LFP activity shown in raw data traces (Fig. 2, A and B). In these experiments, Mg2+-free aCSF-induced bursts typically originated in the CA3 region of the hippocampal slice preparation and propagated along the principal cell layer toward CA1. LFP events induced by Mg2+-free aCSF had a mean propagation speed of 0.229 ± 0.048 m/s (n = 6). CBD (100 μM) caused a clear suppression of Mg2+-free-induced LFP burst amplitude peak source and peak sink values across the hippocampal slice (Fig. 3A; Supplemental Fig. 1). Propagation speed across the brain slice in Mg2+-free aCSF was not affected by 100 μM CBD (0.232 ± 0.076 m/s; n = 6; P > 0.5). Taken together, these data suggest that, although CBD attenuates epileptiform LFP amplitude and duration in the Mg2+-free model, the rate of signal spread across the preparation is not changed (see Discussion).

Fig. 2.

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Fig. 2.

CBD attenuates epileptiform activity induced by Mg2+-free aCSF. A, representative traces showing the effects of 100 μM CBD on Mg2+-free aCSF-induced LFP bursts in different regions of hippocampal slices. Dotted lines represent an individual LFP (as shown in B). B, effects of 1 and 100 μM CBD on a representative individual Mg2+-free aCSF-induced LFP burst. C, bar graphs showing the effects of acute treatment of increasing CBD concentrations on normalized burst amplitude (Ci), normalized burst duration (Cii), and normalized burst frequency in Mg2+-free aCSF (Ciii). Note that burst amplitudes have been adjusted for run-down and burst frequencies have been adjusted for run-up as described under Materials and Methods. Values are means ± S.E.M. for the last 10 LFP bursts in each condition. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001 (two-tailed Mann-Whitney U test).

Fig. 3.

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Fig. 3.

CBD attenuates epileptiform activity induced by Mg2+-free and 4-AP aCSF. Representative contour plots illustrating CBD effects upon spatiotemporal epileptiform burst features. A, in the continued presence of Mg2+-free aCSF: quiescent period between epileptiform burst events also showing hippocampal slice orientation (i), peak source in the absence of CBD (ii), and peak source in the presence of CBD (100 μM) (iii). B, in the continued presence of 100 μM 4-AP: quiescent period between epileptiform burst events also showing hippocampal slice orientation (i), peak source in the absence of CBD (ii), and peak source in the presence of CBD (100 μM) (iii).

Effects of CBD in the 4-AP Model of in Vitro Epileptiform Activity.

We next examined the effects of CBD on epileptiform bursting events in the 4-AP model of status epilepticus-like activity. 4-AP acts to block postsynaptic voltage-dependent K+ channels and inhibits neuronal repolarization to effectively increase excitability. In 100 μM 4-AP aCSF, CBD (100 μM) caused a significant decrease in LFP burst amplitude in CA1 only (Fig. 4, A, B, and Ci). In contrast, CBD (0.01–0.1 μM) caused an unexpected small, but significant, increase in LFP burst amplitude in the DG, which was not apparent at higher CBD concentrations in this or other hippocampal regions (Fig. 4Ci). CBD caused a decrease in burst duration in the DG (0.01–100 μM CBD) and CA3 (0.1–100 μM CBD) but was without an overall effect on CA1 (Fig. 4, A, B, and Cii). CBD (0.01–100 μM) also caused a significant decrease in burst frequency in all regions tested (Fig. 4Ciii). In the same manner as for the Mg2+-free model, contour plots of 4-AP-induced epileptiform LFP burst events (Fig. 3B) permitted spatiotemporal visualization of activity across the slice preparation (Supplemental Fig. 1). 4-AP aCSF-induced bursts typically were initiated in CA3 before spreading to CA1 with a propagation speed of 0.146 ± 0.033 m/s (n = 5). CBD (100 μM) caused a clear suppression of 4-AP-induced epileptiform LFP burst amplitude (Fig. 3B; Supplemental Fig. 1). Propagation speed across the brain slice in 4-AP aCSF was not affected by 100 μM CBD (0.176 ± 0.046 m/s, n = 6; P > 0.5).

Fig. 4.

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Fig. 4.

CBD attenuates epileptiform activity induced by 4-AP aCSF. A, representative traces showing effects of 100 μM CBD on 4-AP aCSF-induced LFP bursts in different regions of a hippocampal slice. Dotted lines represent an individual LFP (as shown in B). B, effects of 1 and 100 μM CBD on a representative individual 4-AP aCSF-induced LFP burst. C, bar graphs showing the effects of acute treatment of increasing CBD concentrations on normalized burst amplitude (Ci), normalized burst duration (Cii), and normalized burst frequency in the 4-AP aCSF (Ciii). Note that burst amplitudes have been adjusted for run-down and burst frequencies have been adjusted for run-up as described under Materials and Methods. Values are means ± S.E.M. for the last 10 LFP bursts in each condition. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001 (two-tailed Mann-Whitney U test).

Taken together, these data show that CBD displayed clear concentration-related, region-specific, anticonvulsant properties in two different in vitro models of epileptiform activity, attenuating LFP burst amplitude and duration, but with no effect on the rate of signal propagation in either model.

Effects of CBD in the PTZ Model of Generalized Seizures.

We next assessed the effects of CBD (1, 10, and 100 mg/kg i.p.) on PTZ-induced generalized seizures in adult male rats. PTZ acts as a GABAA receptor antagonist and this model is well defined and used as a standard for the identification of potential anticonvulsants to treat generalized clonic seizures (Löscher et al., 1991). Seizures were defined by a standard scoring scale (see Materials and Methods). CBD at any dose did not significantly alter the latency to the first sign of PTZ-induced seizures (Fig. 5A) or latency to development of clonic (Fig. 5B) seizures. Unexpectedly, CBD (1 mg/kg) reduced latency to tonic-clonic seizures (P < 0.01) (Fig. 5C). No other effects of CBD on latency to specific seizure states were observed. In contrast to the lack of definitive effects on seizure latency, CBD (100 mg/kg) demonstrated clear anticonvulsant effects via measures of seizure severity (Fig. 6, A and B) and mortality (Fig. 6C). When the severity of PTZ-induced seizures is considered, vehicle-treated animals reached a median score of 5 (tonic-clonic seizures with a loss of righting reflex), the most severe on the scoring scale (Fig. 6A). In contrast, animals treated with 100 mg/kg CBD exhibited a significantly reduced median score of 3.5 (forelimb clonus with a tonic component, but with the righting reflex preserved; n = 15 animals; P < 0.001) (Fig. 6A). This was associated with a marked decrease in the proportion of animals that developed the most severe tonic-clonic seizures, which was reduced from 53% in vehicle to 7% by 100 mg/kg CBD (n = 15 animals, P < 0.001) (Fig. 6B). Finally, percent mortality was significantly reduced from 47% in vehicle to 7% by 100 mg/kg CBD (n = 15 animals, P < 0.001) (Fig. 6C). Overall, these in vivo data confirm our in vitro results above and fully support an anticonvulsant action for CBD.

Fig. 5.

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Fig. 5.

CBD has no clear effects on seizure latency in vivo. Bar graphs showing lack of effects of CBD (1, 10, and 100 mg/kg) on latency to the first sign of a seizure (A), latency to clonic seizures (B), and latency to tonic-clonic seizures (C). Each data set n = 15 animals. Note that CBD (1 mg/kg) reduced latency to tonic-clonic seizures; this proconvulsant action was not observed at higher CBD doses. **, P ≤ 0.01 (one-way analysis of variance) with a post hoc Tukey test).

Fig. 6.

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Fig. 6.

CBD reduces seizure severity and mortality in vivo. Bar graphs showing effects of CBD (1, 10, and 100 mg/kg) on median seizure severity (A), percentage of animals reaching tonic-clonic seizures (B), and percent mortality (C). Each data set n = 15 animals. CBD (100 mg/kg) significantly reduced all of these parameters: ***, P ≤ 0.001 (nonparametric binomial test).

Effects of CBD in Receptor Binding Assays.

It is known that hippocampal CB1 receptor expression on glutamatergic terminals is selectively down-regulated under epileptic conditions (Ludányi et al., 2008); moreover, activation of CB1 receptors by eCBs is protective against seizures (Monory et al., 2006) and exogenous CB1 agonists decrease epileptiform activity in hippocampal neurons (Shen and Thayer, 1999; Blair et al., 2006). Therefore, we determined potential CBD actions at CB1 receptors. Competition binding assays were performed for CBD against the CB1 receptor antagonist [3H]SR141716A in isolated cortical membranes; CBD effects were compared with those of the standard synthetic CB receptor agonist WIN55,212-2 and the CB1 receptor antagonist AM251 (Fig. 7A). AM251 displacement of [3H]SR141716A binding occurred with high affinity (Ki = 190 ± 56 pM; n = 4) and was best fitted by a one-site competition model (Hill slope = −1.08 ± 0.13; n = 4). In contrast, WIN55,212-2 displacement was best fitted to a two-site model with a high-affinity site (Ki = 7.03 ± 4.1 nM; % Rh = 27.4 ± 5.0%; n = 4) and a low-affinity site (Ki = 904 ± 155 nM; n = 4); in these experiments, Hill slopes for either the low- or high-affinity site did not match unity. CBD displacement of [3H]SR141716A occurred with low affinity (Ki = 1.82 ± 0.38 μM; n = 4) and was best fitted by a one-site model (Hill slope = −1.15 ± 0.11; n = 4).

Fig. 7.

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Fig. 7.

CBD displaces [3H]SR141716A binding with low affinity and lacks agonist effects in [35S]GTPγS binding assays in cortical membranes. A, representative competition curves for the CB receptor agonist WIN55,212-2, the selective CB1 receptor antagonist AM251, and CBD against 1 nM [3H]SR141716A (a selective CB1 receptor antagonist) binding to cortical membranes. Points are means ± S.E.M. of triplicate points. B, agonist-binding curves for the CB receptor agonist WIN55,212-2, the selective CB1 receptor antagonist AM251, and CBD stimulation of [35S]GTPγS binding to cortical membranes. Points are means ± S.E.M. of triplicate points from three separate experiments.

Finally, we investigated potential functional effects of CBD using [35S]GTPγS binding assays in rat cortical membranes; CBD actions were compared with effects of WIN55,212-2 and AM251 (Fig. 7B). We first confirmed the presence of functional CB receptors. Accordingly, WIN55,212-2 caused an increase in percent stimulation of [35S]GTPγS binding with an EC50 of 95.1 ± 0.1 nM (n = 3); for 10 μM WIN55,212-2, Emax = 98.6 ± 3.5% (n = 3). AM251 had no stimulatory effect on [35S]GTPγS binding at tested concentrations of <1 μM; at micromolar concentrations AM251 caused a moderate depression of [35S]GTPγS binding (10 μM AM251: −20.3 ± 4.3%, n = 3). CBD had no effect at concentrations ≤1 μM; large decreases in [35S]GTPγS binding were seen at 10 μM CBD (−28.8 ± 10.3%, n = 3) and 100 μM CBD (−76.7 ± 15.9%, n = 3).

Thus, overall, CBD had clear antiepileptogenic and antiseizure effects but only low affinity and no clear agonist effects at cortical CB1 receptors.

Discussion

CBD Reduces Excitability in in Vitro Models of Epileptiform Activity.

In the present study, we use extracellular MEA recordings to demonstrate that CBD attenuates epileptiform activity in both the Mg2+-free and 4-AP in vitro models of status epilepticus in the mammalian hippocampus, a prominent epileptogenic region (Ben-Ari and Cossart, 2000). The major effects of CBD were to decrease LFP burst amplitude and duration in a hippocampal region-specific manner. In general, the CA1 region was most sensitive to CBD effects. Thus, LFP amplitude was significantly reduced at lower CBD concentrations in CA1 than in CA3 (with DG remaining unaffected) in Mg2+-free aCSF, and CA1 was the only region in which LFP amplitude was affected in 4-AP aCSF. This is of interest because the CA1 region represents the major output of the hippocampus, relaying information to cortical and subcortical sites and is intimately involved in propagation of epileptic activity (McCormick and Contreras, 2001). Contour plots constructed from data in the Mg2+-free and 4-AP models confirmed that LFP bursts typically originated in the CA3 region and propagated toward CA1 (Feng and Durand, 2005), strongly suggesting that CA1 is a major focus of epileptic activity in the two models used and illustrating that CBD exerts a significant antiepileptiform effect in this region.

Overall, CBD induced more prominent effects in Mg2+-free than in 4-AP aCSF. This result may reflect inherent differences between the two models, which affect NMDA glutamate receptors and K+ channels, respectively. CBD had contrasting actions on LFP burst frequency between models; frequency was increased in all regions by CBD in Mg2+-free aCSF but was decreased in all regions in 4-AP aCSF. It is interesting to note that 100 μM CBD was without effect on burst frequency in the Mg2+-free model, in contrast to data for all the lower concentrations of CBD tested. This finding was the only indication of any biphasic action of CBD, a common phenomenon associated with cannabinoids whereby increasing concentrations cause changes in the pharmacological “direction” of action (Pertwee, 2008).

In light of the region-specific effects of CBD, it will be of interest in the future to investigate the cellular mechanisms of action of CBD using intracellular recording from individual neurons in selected hippocampal regions. In both the Mg2+-free and 4-AP models, contour plots and subsequent analyses showed that CBD caused clear attenuation in LFP burst amplitude but had no overall effect on burst propagation speed. These findings suggest that CBD acts to reduce the magnitude of epileptiform activity while leaving speed of information transmission across the hippocampal slice intact. It is possible that this action may result in a more tolerable side effect profile for CBD in comparison with existing AEDs if used in a clinical setting.

CBD Has Anticonvulsant Properties in the PTZ Model of Generalized Seizures.

CBD had beneficial effects on seizure severity and lethality in response to PTZ administration without delaying the time taken for seizures to develop. CBD (100 mg/kg) demonstrated clear anticonvulsant effects in terms of significant reductions in median seizure severity, tonic-clonic seizures, and mortality. Particularly striking effects were that <10% of animals developed tonic-clonic seizures or died when treated with CBD in comparison to approximately 50% of vehicle-treated animals. The present data strongly substantiate a number of earlier in vivo studies suggesting that CBD has anticonvulsant potential (Lutz, 2004; Scuderi et al., 2009). CBD has been reported to have relatively potent anticonvulsant action in maximal electroshock (a model of partial seizure with secondary generalization) (Karler et al., 1974; Consroe and Wolkin, 1977). Moreover, CBD prevented tonic-clonic seizures in response to electroshock current (Consroe et al., 1982). There are limited clinical data on CBD effects on seizure frequency in humans (Gordon and Devinsky, 2001). However, in one small double-blind study of eight patients with uncontrolled secondary generalized epilepsy treated with 200 to 300 mg of CBD, four remained symptom-free and three had signs of improvement (Cunha et al., 1980). One potential concern was the high doses of CBD used by Cunha et al. (1980). Because all new therapies must be introduced initially in an adjunct capacity to existing medication, the present study suggests that one attractive possibility is a role for CBD as an adjunct in generalized seizures. In this regard, earlier animal studies indicate that CBD enhances the effects of phenytoin (although CBD reduced the potency of other AEDs) (Consroe and Wolkin, 1977). In the future, it will be of interest to extend studies to other animal seizure models and also to combination therapies with selective AEDs to determine the full clinical anticonvulsant potential of CBD against a range of epilepsy phenotypes.

Mechanism of Action.

Cannabinoid actions are mediated by CB1 and CB2 receptors, potentially by the GPR55 receptor, and also by cannabinoid receptor-independent mechanisms (Howlett et al., 2004; Ryberg et al., 2007). In regard to epilepsy, CB1 receptors are densely expressed in the hippocampal formation (Herkenham et al., 1990; Tsou et al., 1998) where their activation is widely reported to be antiepileptic in animal models (Shen and Thayer, 1999; Wallace et al., 2001; but see Clement et al., 2003). Here, we demonstrate that CBD displaced the selective CB1 receptor antagonist [3H]SR141716A in cortical membranes with relatively low affinity (Ki = 1.82 μM); these data are in line with values reported in whole brain membranes (reviewed in Pertwee, 2008) and our data in cerebellar membranes (Smith et al., 2009). CB receptor/G-protein coupling may differ among distinct brain regions (Breivogel et al., 1997; Dennis et al., 2008); therefore, we investigated CBD effects on [35S]GTPγS binding in isolated cortical membranes. We showed that CBD has no stimulatory agonist activity but that CBD at micromolar concentrations decreases G protein activity. These findings are also in agreement with studies in mouse whole brain membranes (Thomas et al., 2007), which showed that CBD has only low affinity at CB1 and CB2 receptors but acts efficaciously as an antagonist at both receptor types (Thomas et al., 2007; see Pertwee, 2008). There are a number of potential mechanisms by which ligands acting at CB receptors may mediate anticonvulsant effects. Receptor agonists may act at CB1 on excitatory presynaptic terminals to inhibit glutamate neurotransmitter release. Such a mechanism is unlikely here as CBD has no agonist effect in GTPγS binding assays (Thomas et al., 2007). An alternative is that antagonists act at CB1 receptors on inhibitory presynaptic terminals to increase GABA release. We have demonstrated such a mechanism for the phytocannabinoid Δ9-tetrahydrocannabivarin in the cerebellum (Ma et al., 2008), where displacement of eCB tone may lead to increased inhibition. It may also be speculated that the decreases in G protein activity seen in GTPγS binding assays represent an inverse agonist action at CB1 receptors; for example, if CBD were acting as an inverse agonist at CB1 receptors on inhibitory presynaptic terminals an increase in GABA release could lead to reduced excitability. However, mechanisms involving increases in GABA release are unlikely here as CBD was effective in reducing seizures in vivo in the presence of the GABAA receptor antagonist PTZ. Moreover, CBD-induced reductions in [35S]GTPγS binding to whole brain membranes were retained in CB1 knockout [cnr1(−/−)] mice, suggesting that CBD is not an inverse agonist at CB1 receptors (Thomas et al., 2007). Overall, the low affinity and lack of agonist activity at CB1 receptors suggests that the CBD anticonvulsant effects reported here are potentially mediated by CB1 receptor-independent mechanisms. In addition to the study of Thomas et al., showing that CBD actions were unaltered in cnr1(−/−) mice, CBD anticonvulsant effects in the maximal electroshock model were unaffected by the CB1 receptor antagonist SR141716A, whereas those of Δ9-THC and WIN55,212-2 were blocked (Wallace et al., 2001).

In addition to CB receptors, a number of alternative molecular targets may also contribute to CBD effects on neuronal excitability. CBD has been reported to be an antagonist at GPR55, a non-CB1/CB2 receptor (Ryberg et al., 2007); in contrast, a recent study demonstrated that CBD has no effect at GPR55 (Kapur et al., 2009). CBD may cause an increase in anticonvulsant eCBs via the reported inhibition of the catabolic enzyme fatty acid hydrolyase, which degrades anandamide, and/or the blockade of anandamide uptake (Watanabe et al., 1996; Rakhshan et al., 2000; Bisogno et al., 2001). CBD is reported to be a weak agonist at human TRPV1 receptors (Bisogno et al., 2001); a more recent study suggests an action for CBD at rat and human transient receptor potential vanilloid 2 but not rat transient receptor potential vanilloid 1 receptors (Qin et al., 2008). More relevant to potential effects on neuronal excitability in the CNS is the demonstration that CBD exerts a bidirectional action on [Ca2+]i levels in hippocampal neurons (Ryan et al., 2009). Under control conditions, CBD induces increases in [Ca2+]i; in contrast, in the presence of 4-AP (which induces seizure-like [Ca2+]i oscillations) or increased extracellular K+, CBD acts to reduce [Ca2+]i and thus epileptiform activity, via an action on mitochondria Ca2+ stores. A further recent report provides the first evidence that CBD can also block low-voltage-activated (T-type) Ca2+ channels (Ross et al., 2008), important modulators of neuronal excitability. Finally, CBD may also enhance the activity of inhibitory glycine receptors (Ahrens et al., 2009). Overall, the demonstration that CBD acts on multiple molecular targets that each play a key role in neuronal excitability reinforces the potential of CBD as an AED.

In conclusion, our data in separate in vitro models of epileptiform activity and, in particular, the beneficial reductions in seizure severity caused by CBD in an in vivo animal model of generalized seizures suggests that earlier, small-scale clinical trials for CBD in untreated epilepsy warrant urgent renewed investigation.

Acknowledgments

We thank Professor Philip Strange for useful discussion and Colin Stott (GW Pharmaceuticals) and Professor Gernot Riedel (University of Aberdeen) for pharmacokinetics data.

Footnotes

  • This work was supported by a GW Pharmaceuticals and Otsuka Pharmaceuticals award, by a University of Reading Research Endowment Trust Fund award; and The Wellcome Trust [Grant 070739].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.109.159145

  • Graphic The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    CNS
    central nervous system
    CB
    cannabinoid
    eCB
    endocannabinoid
    Δ9-THC
    Δ9-tetrahydrocannabinol
    CBD
    cannabidiol
    AED
    antiepileptic drug
    MEA
    multielectrode array
    aCSF
    artificial cerebrospinal fluid
    4-AP
    4-aminopyridine
    LFP
    local field potential
    NMDA
    N-methyl-d-aspartate
    BSA
    bovine serum albumin
    SR141716A
    N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
    AM251
    N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
    GTPγS
    guanosine 5′-O-(3-thio)triphosphate
    WIN55,212-2
    [2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone
    PTZ
    pentylenetetrazole.
    • Received July 22, 2009.
    • Accepted November 9, 2009.

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Cannabindiol

  • August 24, 2012 3:41 am

CBD (cannabidiol) – Cannabidiol is the cannabinoid obtaining most recent mainstream exposure for its multitude of benefits with non-psychoactive effects. Unites States Patent #6,630,507 – Hampson, et al. found cannabinoids (specifically CBD) effective as antioxidants & neuroprotectants without providing any psychoactive effects. Neuroprotective antioxidant more potent than ascorbate or topopherol with ability to pass the blood-brain barrier. Works as a CB1 antagonist in the presence of THC at low concentration (nM). Modulates THC adverse events including anxiety, tachycardia, hunger & sedation.  CBD increases endogenous cannabinoid levels by two mechanisms: as a weak uptake inhibitor of AEA and an inhibitor of its hydrolysis.  Acts as a TRPV1 agonist (similar to capsaicin, lacking noxious effects).

Cannabindiol Crosses the Blood Brain Barrier

  • August 24, 2012 3:27 am

11/08/08
Dr. Courtney speaks on the CANNABIS ISSUES PANEL of experts and authors at the 18th ANNUAL SOUTHERN HUMBOLDT HEMP FEST

Emcee: Jimmy Durchslag:

Next we have William Courtney, DR. BILL COURTNEY, Cannabis Medical Consultant. Many of you… I know he’s based in Mendocino, has an office in Willits, but he’s also here in our area, regularly. He’s my medical consultant. And I know if you’ve e’er seen him, you get a lot of information about cannabis–it’s health effects. So he’s going to talk to us about that. Dr. Bill. Welcome. (applause)

Dr. Bill:

Thank you. I just noticed today that this is the 18th Annual Hemp Fest. Interestingly, the International Cannabinoid Research Society has also had it’s 18th Annual.

And this is the manual that came out of the 18th Annual research [He shows the bound sheaf of papers.] And it’s free online. If you go to [sounds like "Icarus"] ICRS, and go to the symposium page, like you were going to sign up for the symposium, this is a PDF.

And for those who are not able to go online, there are a stack of cd’s over there. You can take this to Staples and for $20 print your own copy.

“Icarus” [ICRS], this year, was phenomenal! It was only overshadowed by my discovery of the United States Patent on CBD and cannabinoids.

But, since there is so much to talk about, I want to focus a little bit on Icarus, first, and then we’ll get into the U. S. Patent.

The thing that came out of this years’ ICRS that was quite amazing is there’s a whole series of acid molecules in the raw plant – the 21 carbon molecules. Those break down with the slightest amount of heat or aging. THC-A, which previously was thought of as a storage molecule, is in fact and active molecule, and when you heat it, you break that carboxy group off to create THC, which is psychoactive. So a lot of our activities over the last 40 years have been aimed at how to improve the thc potency, because we had assumed that the psychoactivity was tantamount to the medicinal aspects.

But as we look at it closer it turns out that there’s an awful lot about the green plant, before it’s been treated culturally, with heat, that has a lot of benefit. And this years’ Icarus introduced a lot of these: cannabidiol acid, cannabichromic acid, cannabigerol acid: all of those 21 carbon molecules have unique medical properties. In particular, CBD-A, or cannabidiol acid, is an antibiotic. As soon as you put it into a tea, you simmer it, you saute it, you bake it, you smoke it, you lose that antibiotic function, and it converts it into CBD; with additional heat it converts into thc; and so with prolonged heating you increase the amount of THC (but our plant currently has a lot of THC, so that really isn’t essential.

My current position, for those of you who I’ve met with clinically, I’m recommending that the greens be part of your diet.

If you look at the world around us you see that the deer eat it; they don’t really eat a lot, but they kind of munch at it. Iguanas eat it. Birds eat it. Rats. Dogs. Cats. Animals understand that.

A few of the leaves allows you access to, not only THC, but the THC-A, these other cannabinoids, all of which are fat molecules, that move into the adipose tissue of your body. And if you eat it regularly for two months, you eventually will become saturated, which is a desirable state in which these various chemicals can be found, and are plentiful, in the fat tissue of the body.

The benefit of them being fat molecules that store in the fat is that it acts like a depo, in the sense that if your body needs a particular supplement, it can draw down from the fat tissue that particular cannabinoid. And these cannabinoids, we now know, provide anti-epileptic, they provide antibiotic, antiviral, antifungal, anti-anxiolitic, anti-psychotic, a tremendous range of medicinal activities.

And there was an article out of last years’ Icarus that talked about the unique ability of body to draw down the specific cannabinoid as it’s needed. So, ideally, if it’s a part of your diet, the way that it is with the rest of the animals who are not enculturated, if you have a minor fungal infection, you’ll pull down an antifungal before it becomes clinical, and you’ll prevent the problem from becoming even noticeable. The same with an anti-psychotic, the same with an anti-anxiolitic (anti-anxiolitic is something that reduces anxiety, cuts anxiety. So, it’s such a wide range of conditions that this plant is capable of contributing to our body’s ability to modulate.

And I think that’s one of the take-home messages of this last Icarus, is that all this plant does is facilitate the body’s ability to take care of itself.

If each person here would take ten hours and review the immune system on the web, go to Wikepedia, look up all the links, learn about the immune system, how anti-inflammatory, auto-immune, how it detects self, not-self, precancerous changes. I mean, the immune system is absolutely amazing. And what cannabis does is facilitate the regulation of the immune system.

The body produces endogenous cannabinoids. You may have heard of endorphins: that’s endogenous morphine. Well, in a similar fashion, the body produces endogenous cannabinoid.

I’m currently submitting an article for publication which would contract that to “encannans”, and the reason that I selected that word is because it removes part of this tone of cannabis, which causes such panic in so many people, and, in order to reach out across the aisle to the Republicans. . . You know you want to not insult them too strongly from the get-go, that first impression is hard to redo. . .

But also part of that article is the history of these molecules. Lipins are the little fat messenger molecules. Those are found in archeia, which is a primitive single-celled organism that was in existence four billion years ago. These little fat molecules would attach to a protein receptor, which we now call a cannabinoid receptor, and the structure of those (they go back and forth through the membrane seven times) that specific structure is still found in the proteins in the membrane of your T cells and D cells (white blood systems in your immune system found in your lymph nodes, spleen, thiamus).

So the entire immunologic system in the human being communicates through the CB2 receptor, which is similar to the same receptor that was first evolved (if evolution is a part of your world view) billions and billions of years ago. So we had this incredibly conserved system (and conservation is when a design is so effective that it doesn’t change over time). Most biological designs evolve over maybe a couple million years, and they turn over and evolve, but this was so effective and so incredible that it has. . . 4 billion years later you can find it in the cells that are involved in fighting cancer, and that are fighting infection.

I may be getting a little bit detailed here, but all to say, if you want to look at this Icarus, and I highly, highly recommend that you do this, send me an email, and I can send you this as a pdf file that you can just look at electronically, or you can take it to Staples, print it out, and for those of us who like to look at a physical copy, you can make notes and go back and forth.

We’re hoping to bring the Second International CB2 Conference to Mendocino. I attended the First International, which was in Banff in May of ’06, and Ive been speaking with Keith Sharkey, who coordinated that. Researchers from all over the world, from Israel, Japan, Germany, United Kingdom, Canada, all convened for three days and we did nothing but exchange information about this 2nd cannabinoid binding receptorthat CB2 receptor we were just talking about–thats in the immune system.

Because medicine is nothing but about enhancing immunology, and immunology is nothing but about detecting self/non-self, thats foreign bodies, protection from cancers, and trying to make a peace in the world where your own cells can decide to defy.

A million times a day, cells begin to divide that shouldn’t be dividing and the immune system has to say, “Hey, you know, the shrubs are getting a little hairy there; we’ve got to trim them down. We’ve got enough renal cells or kidney cells. We’ve got enough bone cells, muscle cells.” So the immune system’s highly competent at dealing with that, but it can become more competent. And that is exactly what cannabinoids do, whether you’re talking about the body’s endogenous cannabinoids, or the plant, which can be phytocannabinoids (which just means cannabinoids from plants) or exogenous cannabinoids. Both of those terms refer to those 20 carbon molecules that are produced outside of the body, but bind to the protein receptors on the cells in our body and therefore help regulate it. So whether we’re talking about the body’s chemistry, or the plant chemistry, their role is to modulate the function of the immune system. And a modulator is a chemical substance that can either increase the activity of the immune system, or decrease it.

And it’s like, medicine always bothered me when I would study traditional pharmaceuticals, and they’d say, “Well, they can give diarrhea or constipation.” Well, that’s great, you know, huh!? Can you choose, or do you just kind of get stuck with what you get stuck with? Well, the same with. . . A modulator is a substance which provides feedback. Every cell in the body has a function: brain cells, nerve cells, blood cells, bone cells, muscle cells. There’s something that they’re supposed to be doing. And it could be overactive. And, if it’s overacting, the body would like to tone it down, slow it down. And the feedback it gets from the cannabinoids say, “Wow, this is too much, we need to slow it down, dial it in.” If the system is insufficiently active, then it wants to speed it up to normal.

So a cannabinoid is a modulator that restores optimal function. That’s what the body’s system is doing. That’s what the plant does. The plant facilitates the rapid restoration of the normal function.

And I focus a lot on the immune system because that’s so central to disease and illness, but it modulates the endocrine system. It modulates the neuromuscular system. It modulates bone remodeling – osteoporosis and osteomalacia. Those are conditions in which there are two cells, one of which burrows through the bone and chews up the old bone, then a new one, the osteoblast comes and lays down new bone, and so the bone is completely rebuilt every seven years. That’s the bone life-cycle, the longest in the body. And these two cells are involved in that constant remodeling. Well, they communicate by cannabinoids. It’s become the “duh!” [laughs] of modern physiology.

Everything uses these very simple fat molecules to provide feedback, and as we age with the loss of some of the female hormones, in particular, that communication falters, and the osteoclasts (that cell that burrows and dissolves the bone) just keeps tunneling away, and the osteoblast just kind of kicks back and gets out of sync and doesn’t lay down new bone, and we perforate, making the bone porous. And so the cannabinoids facilitate that one-to-one communication, restore, (Restore may be a leap. Lots of times I get overzealous in my hopes.) at least will facilitate the communication which will prevent further porosity changes. It will stop the condition from progressing and, if the design is consistent, I actually believe it will increase the density and restore normal density with that communication. Because, if you’re burrowing, and you cross a tunnel, you don’t have to burrow through that tunnel because it’s missing, but the new one will come through and lay down new bone.

So, I’m going to stick with my thing. I think it will actually improve the condition. So, bone-remodeling, cancers, inflammatory conditions, prostate cancer, growth regulation, metastasis, all that, can be found in this free book on the web. Consider this the most gracious gift of the web to people who have an interest in health. And, like I said, just send me your email, I’ll send you an electronic copy that you can peruse.

And, we hopefully will review this before the 2nd Cannabinoid Conference. I’ll try to do a one to two or three day review of the language, and we’ll go from the terms, the definitions; we’ll look at a little bit of chemistry, then we’ll look at a little bit of microbiology (which is a big love of mine) and how biochemistry is involved in the functions of the cell: all that to kind of prepare us for this group of visiting dignitaries which, you know, will tell us where the dream is today.

Something that is incredibly overwhelming is the discovery of Patent 6,630,507B1. The United States of America has been assigned the patent rights to cannabinoids as antioxidants and neuroprotectants.

Over on the table there is a face sheet, these are free hand-outs. You go home. You type in USPTO (which is US Patent and Trademark Office) and google, it will take you to their site. Search by patent number. Just type that patent number in. It’ll bring you up the electronic copy of this patent (for those of you can do that), for those who can’t, there are hard copies over there and if you want to make a donation for print and paper you can. But these are primarily for people who don’t have access to the web, and are not into electronic copies. This should be read probably a minimum of ten times, and then committed to memory. It really is absolutely phenomenal. It reminded me of more organic chemistry than I ever knew. Whenever you write a patent, you hire a very expensive attorney, who really is an English literature graduate doctoral person, and there are some patent attorneys who aren’t like that, but in general their skill is in being very articulate.

And this talks about the chemistry of, particularly, cannabidiol. On two separate occasions the government lists cannabidiol on separate line item claims. It spells out the conditions for which cbd is uniquely beneficial – the oxidated stress diseases–and that includes everything from diabetes, rheumatoid arthritis, the neo-plasias, coronary vascular disease.

In particular they isolate the neuro conditions.

CBD can cross the blood-brain barrier. So, it’s a fat molecule that can get into the brain, which is very hard to do, because the brain is very protective, but because this has 34 million years of research on its side it knows how to walk between the lines and the body has allowed it access to the brain. So, for Parkinsons, for Alzheimers, for strokes whether embowelic, hemmorhagic, or traumatic, or surgical, these are all conditions where CBD is uniquely beneficial.

For the first time ever in three years of looking, this has human dosage schedules. This is of phenomenal importance to you legally. It tells out what you are entitled to do, and then you just look at the plant, and the plant tells you how much plant material you need to generate that.

Speeding quickly forward through many other things, part of what I talk to all my patients about is the ability to fractionate for cbd, which means. . . There’s a piece of paper over there which tells you the technique. That’s another thing to read and memorize, because it’s the single most important thing for your health, and for your legal safety.

You take fine grind cannabis.

At my office there’s this $400 thermometer, which is supposed to be very accurate. You get a variable temperature heat gun, which allows you to provide a constant single temperature for hours at a time, so that it’s better than any of the vaporizers, because it’s very, very, very steady. So you come in here. You turn the heat on until it goes to 166 degrees Centigrade. Take the file; mark that place on your heat gun, so you can get back to that.

Take your cannabis. You grind the cannabis to a fine degree which increases the surface area so that you can get to the cannabinoids in the plant material.

Put the heat to it. The longer you heat it the more THC is boiled.

We’ve now gotten down to the physics of the cannabinoids. The vaporization temperature is a temperature at which a liquid goes through a phase change to a gas. Like with water, at a 100 degrees Centigrade water begins to boil. You’ll never get water at 101 degrees because it turns into a vapor before it can get that hot.

THC boils at 157 degrees, that’s Delta 9. Delta 8 boils at a 175. Cannabidiol at 188. So if you have a very specific temperature, you can heat the cannabis and vaporize the THC. If you want THC, you go ahead and use that, or do whatever you can do with that, but there’s so much of it there that for most people, we need to lower the THC content so you can get to the CBD.

So once you’ve heated it you’ve stripped the THC out of it. You now have cannabidiol plant material. That CBD plant material is nonpsychoactive, and it’ll allow you to begin to get to the dosage schedule that this patent recommends.

For the last year I’ve been recommending 5 milligrams per kilogram body weight. That is an amount of cannabidiol that it takes for this particular mouse strain to block the development of diabetes.

Now, I’ve been hanging my hat on that for a year, but I now have 5,000 pegs to hang my hat on, thanks to the United States government patent. Because. . . They talk about higher doses. They talk about 10 milligrams per kilogram body weight. They talk about 20 and 40. Huge. Hugely important!

But if you just stick with the 5 mg/kg, that still requires you to process a lot of plant material, because the amount of cbd is so low. There is a strain called “White Russian”, which is 100% more CBD, and there’s some new strains coming out of Mendocino which could have up to 700% more CBD. These strains will make it a lot easier to get access to the 500 mg a day, which is the schedule that I’ve been recommending to my patients.

That’s the same amount that you would use of vitamin C, and at that level, in this particular mouse strain, you block the development of diabetes 60% of the time. There’s a particular mouse strain that 86% of these mice develop diabetes. The pharmaceutical industry tests all oral and injectable medications on this mouse strain because it’s such a reliable model for diabetes, so, you know, does glucophage inhibit diabetes? Does insulin/hemulin? It’s an amazing animal model for diabetes.

If you give that animal model which 86% of the time will develop diabetes, if you give them 5 mg/kg body weight, 60% of them do not go on to develop diabetes. It completely blocks the. . .[audience applause]

Yeah, 14 million Americans go blind with diabetes a year! Kidney renal failure. I’ve got patients I see in their homes who are on dialysis, people who’s knees have been cut off, people who’s vision fails because of diabetic retinopathy.

And, we could prevent that with something that’s non psychoactive, and that’s just an amazing molecule, as is thoroughly detailed in this patent. Which is why every person here needs to just know this thing inside and out. And it will take you a while. I mean, I’m still studying it and every time I read it there’s more stuff there. It really is phenomenal.

I have a room upstairs at 4:20, and any specific questions on either fractionating for cannabinoids (and pick up that sheet and study that–key to your legal and central to your physical health). . . There’s one over there on green leaf.

Did we talk about green leaf yet?

So if you talk about those molecules that are present in the fresh green leaf, I try to use 8 leaves a day. I juice it with carrots. I started out with carrots – I do four in the morning, four in the afternoon, but after eating carrot juice for five or six months you begin to turn orange a little bit (I knew someone in college who actually did), and so I now put in beets and broccoli (just because Bush doesn’t like it, it figures it’s got to be good for you), anything laying around – kales. It makes a drink.

And it’s phenomenal because you get these cannabinoids in, they’re non-psychoactive, they saturate the body and they facilitate the body’s regulation. And so, I tell each of my patients: the single most important thing you put in your mouth after water, on a daily basis, is, approximately, eight green leaves a day.

That number is unknown, but I’ve had 90 year old people who have gotten out of their wheelchairs who’ve had arthritis that was so inflammatory and painful. . . By down-regulating the inflammatory system you decrease the swelling and inflammation, you increase mobility and articulate function. Its prevention of alzheimers, of coronary vascular disease. Prophylactic uses.

Prophylactic uses are the most pivotal in this document. I don’t know how they’ll stand up in court but I plan on using them very soon, like November 6th Im going to be in court presenting this information on this prophylactic use. That’s until they take my license away. But then I’ll keep doing it, so…

If you have any questions, talk to me later upstairs, and I’ll answer them if I’m able. [audience applause]

emcee Jimmy:

Dr. Courtney! Thank you, Bill. Obviously a wealth of information there. He has his very attractive banner up here. Is that drcourtney@mcn.org? yes, if you want a copy of the Icarus document which he has offered on line. His card is there. There’re a couple books here that he’s involved with, and he’ll be upstairs after this panel to answer questions and give more information.

The workshop room is up in that corner. 4:20, he said. I don’t know how that time got chosen, probably just randomly. So, thank you for that.

 

 

 

Source:http://www.civilliberties.org/courtney.html

Apricots – A Healthy Treat

  • August 23, 2012 7:24 pm

Apricots are an ideal treat for snacks and deserts. They are very tasty, easy to digest and are very high in fiber, low in calories, virtually fat free and are very nutritious. Just 3 fresh apricots or 10 dried halves provide more than 25% of your recommended nutrient intake of vitamin A in it’s plant beta carotene form. When consumed from foods beta carotene is an antioxidant, a substance that protects against cell damage when the body uses oxygen. This damage is thought to be instrumental in aging and the development of heart disease, cancer, and many other diseases.

Fresh apricots are high in vitamin C, another antioxidant that also helps your body absorb iron. A lot of this is lost when apricots are canned or dried. But no matter what form of apricots you choose they are still high in iron as well as potassium, essential for proper nerve and muscle function that helps maintain normal blood pressure and balance your body fluids.

All apricots contain a natural salicylate, a compound similar to the active ingredient in aspirin. People with allergies to aspirin may experience allergic reactions to eating apricots.

Ounce for ounce even dried apricots are more nutritious than most fresh or canned fruits. Dried apricots are only 32% water, while other fruits are 85% water. Apricots are a much more concentrated source of calories, 50 calories in 4 ounces of fresh apricots versus 260 calories in 4 ounces about 30 halves of the dried apricots. When eaten in moderation the dried apricots are a convenient, compact form of nutrition and a great snack.

Apricots are very often treated with sulfur dioxide before they are dried to preserve their color and certain nutrients. This sulfite treatment may trigger an asthma attack or an allergic reaction in certain people. Unless the dried apricots are labeled as sulfite-free if you have asthma avoid them.

Now; on to the laetrile issue when it comes to apricot pits. Laetrile or amygdalin is a very controversial substance derives from apricot pits. Legally it can not be sold as a medical treatment, but it is available as a nutritional supplement sometimes called vitamin B17 in health food stores. It is promoted in other literature or by word of mouth as an alternative treatment for cancer, heart disease, allergies, liver disorders and other diseases. Now numerous scientific studies have failed to find any benefit from laetrile. Laetrile from apricot pits and other sources can liberate cyanide. Consuming large amounts of laetrile has the risk of cyanide poisoning and doctors warn that apricot pits in any form should not be consumed.

For more information on nutrition and healthy foods, alternative natural cures supplements and more Jack’s site alternative-natural-cures.net is a good place to start!

Article Source: http://EzineArticles.com/?expert=Jack_Phillips

DCA and Cancer

  • August 23, 2012 5:29 am

According to the American Cancer Society, the odds you’ll develop cancer in your lifetime are one in two, if you’re a man, and one in three, if you’re a woman.1 But an experimental cancer drug shown to shrink tumors by correcting metabolic oddities in cancer cells shows promise in the fight against this deadly disease. The synthetic drug DCA (dichloroacetate) DOES indeed kill cancer cells, both in the lab and in human beings. However, whether it can reverse tumor growth without harming you in other ways remains to be seen.

The first clinical trial, although small, involving patients with brain cancer (glioblastoma) was encouraging, and the results were published in Science of Translational Medicine in 20102 . However, there is still a great deal more work to be done before DCA can be pronounced a safe and effective cancer treatment.

An interesting aspect of DCA is that it’s an inexpensive, non-patentable molecule, which makes it of minimal value to pharmaceutical companies that profit by patenting expensive new drugs. Therefore, clinical trials are slow to get going due to lack of funding by Big Pharma. Researchers must await sufficient money to trickle in from government sources and public donations before moving forward.

In the paragraphs below, my aim is to give you information from both sides of the story—the potential benefits as well as the possible risks.

Rats Fed DCA Showed Dramatic Tumor Regression

The impetus behind most of the DCA research has been cardiologist Evangelos Michelakis of the University of Alberta in Edmonton, Canada. In 2007, Michelakis and his colleagues sparked a firestorm of interest when they announced rats fed DCA showed rapid tumor regression without any apparent side effects. Michelakis has been the first to say these results are preliminary and cautions cancer patients to refrain from running out and buying the drug, prior to clinical trials.

Yet, many desperate cancer patients with few remaining options are doing just that, and side effects ARE being reported.

There are currently three clinical trials involving use of DCA to treat cancer that are currently recruiting participants3. Some of these studies plan to combine DCA with other chemotherapy drugs and radiation, all known to have damaging effects in your body.  However, if you have cancer and are tempted to participate, there are some things you should know in order to make an informed decision about the risk versus the benefits of this experimental treatment.

Cancer Cells and Healthy Cells Have Different Metabolic Processes

In order to understand how DCA kills cancer cells, it is necessary to understand a bit about how the cellular metabolism of cancer cells differs from that of your normal, healthy cells. Cancer cells have very different metabolic processes than normal cells, in terms of how they derive their energy.4 It’s a rather complicated distinction, so please bear with me as I try to explain it in the simplest terms possible.

There are two major pathways your cells use to covert sugar into energy: glucose oxidation and glycolysis:

  1. Glucose oxidationis the primary energy metabolism in normal cells and takes place in your mitochondria, which are the little “power plants” inside your cell; it requires the presence of oxygen, as its name suggests. This is why you breathe and your heart beats to circulate oxygen throughout your body. Glucose oxidation is sometimes referred to as cellular respiration.
  2. Glycolysis takes place in your cell’s cytoplasm. It can occur without the presence of oxygen. Glycolysis is less efficient for normal cells, but it is acancer cell’spreferredmeans of energy metabolism, and it depends on the availability of sugar.

So, when your cells are oxygen-starved they have a backup plan. They can extract energy from sugar without the presence of oxygen, by glycolysis.

Pyruvate is required for glucose oxidation. There is an enzyme (pyruvate dehydrogenase kinase, or PDK) that acts as gatekeeper to regulate the flow of pyruvate into the mitochondria. If PDK is active, it suppresses the transport of pyruvate into the mitochondria, and your cell is forced to rely on glycolysis, even if oxygen is available. If PDK is inactive, pyruvate is shuttled into the mitochondria, even if oxygen is low.

Unlike normal cells, cancer cells are masterful at deriving energy from glycolysis—they have very active PDK. The way to make a cancer cell unhappy is by suppressing PDK, forcing the cell to use glucose oxidation, instead of glycolysis. This is called the Warburg theory of cancer, or the Warburg hypothesis5. This is where DCA comes in.

DCA Instigates Mass Suicide among Cancer Cells

DCA suppresses PDK (the mitochondrial gatekeeper), and this fires up the cell’s mitochondria. Not only does this force the cancer cell to abandon its preferred metabolic process, but it flips the cell’s “suicide switch” as well. This happens because mitochondria are the primary regulators of apoptosis, or cellular suicide—they are loaded with sensors that react to abnormalities by pushing the cell’s self-destruct button.

When a cancer cell’s mitochondria realize it’s a cancer cell, it spontaneously kills itself. This is the reason chemotherapy and radiation result in such terrible side effects—your healthy cells actually die much more easily because of this self-destruct button.

The reason cancer is so fast growing is that the mitochondria have been deactivated, so the cells evade apoptosis, as well as being able to grow in the absence of oxygen (glycolysis)6. DCA reverses this.In effect, DCA directly causes cancer cell apoptosis and works synergistically other cancer therapies, such as radiation, gene therapy, and viral therapy. A number of scientific studies have been performed to date, and most are encouraging.

DCA–Cancer Research Review

Most of the studies thus far have been done on cell cultures in the lab (in vitro), as opposed to on cancer patients themselves (in vivo). Yet the results are impressively consistent across the board, suggesting DCA is effective against a wide variety of cancer types. The DCA Site7 has a good list of all clinical studies through 2011.

The study that sparked the DCA excitement appeared in Cancer Cell in January 20078 According to an article in the Edmonton Journal9 in the 2007 rat study, DCA killed lung, breast, and brain cancer cells but left healthy cells alone. The rats’ tumors decreased by up to 70 percent in three weeks of DCA treatment, without negative side effects.

This announcement led to a cyclone of excitement from cancer patients everywhere who scrambled to get their hands on the new “cancer cure,” in spite of warnings from Michelakis himself (and others) against prematurely self-medicating with the compound. Several more studies soon followed, including the first clinical trial2 involving brain cancer patients. In that trial, the research team selected five glioblastoma patients with a particularly aggressive form of brain cancer. They treated them with oral DCA for 15 months.

Tumor tissue was compared before and after DCA treatment in three of the five patients. In all three, there were signs that the tumor growth had slowed, and more cancer cells were undergoing programmed cell death after the treatment with DCA. Unfortunately, one of the five patients died. Another had “debulking” surgery before completing the full course of DCA treatment.Below are some of the other DCA cancer studies, all within the past five years. (Note that none of these involved human subjects.)

  • Endometrial Cancer: DCA causes apoptosis in endometrial cancer cells.10
  • Prostate Cancer: DCA produces significant cytotoxic effects in prostate cancer cells11
  • Breast Cancer: DCA has anti-proliferative properties against breast cancer cells and caused apoptosis of those cells12
  • Colorectal Cancer: DCA reduced colon cancer tumors by 20 to 40 percent13
  • Cervical Cancer: Researchers concluded DCA is a quick and effective cure for advanced cervical carcinoma14

For comprehensive information about DCA’s method of action, history, and related scientific research, refers to The DCA Site7, and to this 2011 article in the International Journal of Cancer15. It should be noted that caffeine may radically increases the effects of DCA16. In fact, this effect is so pronounced that some researchers are working on developing a “DCA-caffeine” cancer treatment protocol.

Now that you’re aware of DCA’s cancer-fighting effects, let’s take a look at the adverse effects identified thus far.

DCA’s Side Effects Can Be Daunting

DCA is not a natural agent—it’s a chemical produced in the water chlorination process. It’s a small molecule, which accounts for one of its major advantages: DCA is easily absorbed by your body and can reach areas other drugs can’t, such as your brain, which is why it’s of particular interest for treating brain cancers. This, however, can be a two-edged sword, because any compound that easily permeates your brain can exert all sorts of unexpected and worrisome neurological effects.

DCA is a byproduct of another chemical called trichloroethylene (TCE), a volatile organic compound believed to cause cancer. TCE is used mainly as a solvent to remove grease from metal parts, but is also used in adhesives, paint removers, and typewriter correction fluids. The Agency for Toxic Substances and Disease Registry reports TCE is “reasonably anticipated to be a human carcinogen” and may cause birth defects. They state TCE may also cause the following17:

  • Skin rashes
  • Nerve, kidney, and liver damage
  • Impaired heart and immune function
  • Unconsciousness
  • Death

When DCA is added to the drinking water of laboratory mice, it causes liver cancer. While DCA may offer hope and a novel approach to treating cancer, it is far from a “miracle cure.” Of course, chemotherapy drugs are quite toxic as well!

DCA has been used successfully in children with metabolic disorders, with no signs of toxic poisoning. But adults appear to suffer more adverse effects—especially peripheral neuropathy and encephalopathy, such as the case described in a letter to the editor of the Journal of Neurology18. According to a survey performed by The DCA Site19, there are a fair number of serious side effects reported by those taking DCA, many of them neurological. Research suggests the side effects are at least somewhat dose-dependent, but safe dosing guidelines have not yet been established.

In the online survey, the side effects reported by DCA users include:

Tingling and numbness in the fingers, toes and lips; peripheral neuropathy Leg weakness Hand tremors Ankle swelling Increased urination
Mild nausea Anxiety and depression Dizziness Sleepiness Breathing “heavier” than usual

 

In some studies, under some circumstances, DCA seems to actually make cancer cells stronger. For example, an in-vitro animal study20 published in May 2010 revealed that some types of colon cancer cells are actually protected by DCA when grown under anoxic conditions or as xenografts in mice (xenografts are tissues transplanted into one species from a dissimilar species). And when DCA is combined with frontline drugs, it sometimes interferes with their effectiveness. The neurological side effects are compounded when DCA is used with other anti-cancer drugs, which are also neurotoxic.

So, if you’re already using a cancer medication, DCA’s effects are going to be unpredictable and potentially dangerous. This underscores the importance of fully understanding the mechanisms of action of an agent before it enters clinical trials.

A Safer Alternative: FOODS that Cause Cancer Cells to Self-Destruct

What if there were natural agents that induced cancer cell suicide, without the side effects of DCA? As it turns out, these agents DO exist—and you may already have some in your kitchen pantry or supplement cabinet. Here are a few21:

  • Co-Q10/Ubiquinol
  • Curcumin (the active agent in the spice turmeric)
  • Capsaicin (the compound that makes hot peppers hot)
  • Se-methylselenocysteine aka methylselenocysteine (found in garlic and broccoli)
  • Ellagic acid (from pomegranates and other fruits)

There are many all-natural cancer-prevention strategies, and research shows they may cut your risk in half. Consequently, by implementing multiple strategies, you can radically lower your risk of cancer as well as other chronic diseases.

Lifestyle Factors that Influence Your Cancer Risk

A healthful lifestyle encourages proper gene expression, as the science of epigenetics has shown. We now know you are in control of your genes, instead of being controlled by them. You actually have tremendous power to shape and direct your health! Your thoughts, your environmental exposures, and your food choices all directly affect your gene expression.

The best “cancer cure” is to prevent it from taking hold in the first place. Cancer cells are circulating in everyone, all the time. The stronger your immune system is, the less likely your cellular function will run amok. Your diet is extremely important in keeping your immune system strong. One of the primary cancer-promoters is sugar. Cancer cells love sugar and use it to fuel their rapid proliferation (by glycolysis, as discussed earlier). This includes ALL forms of sugar, including fructose and grains. The higher your blood glucose level, the more prolific the cancer cells will be.

According to breast cancer expert, author, and board certified surgeon Dr. Christine Horner:

“To me, sugar has no redeeming value at all, because they found that the more we consume it, the more we’re fuelling every single chronic disease,” Dr. Horner says. “In fact, there was a study done about a year ago… and the conclusion was that sugar is a universal mechanism for chronic disease. It kicks up inflammation. It kicks up oxygen free radicals. Those are the two main processes we see that underlie any single chronic disorder, including cancers. It fuels the growth of breast cancers, because glucose is cancer’s favorite food. The more you consume, the faster it grows.”

Your diet is the one of the best ways to either feed or prevent cancer. Processed foods, soft drinks, red meat from CAFO-raised animals, trans fats, and any food containing or contaminated with xenoestrogens promote cancer growth. Plant foods, particularly cruciferous vegetables and flax seeds, as well as many herbs and spices are cancer-preventive. Beneficial fats of particular importance for cancer prevention are omega-3 and omega-9, which effectively slow down tumor growth in estrogen-sensitive cancers, such as those of the breast, prostate and colon.

Generally speaking, your diet should focus on fresh, whole, unprocessed foods (vegetables, meats, raw dairy, nuts, and so forth) that come from healthy, sustainable, local sources, such as small organic farms. For the highest nutrient content, you will want to make raw food a significant portion of your diet.

Personally, I aim to eat about 80 to 85 percent of my food raw, including raw eggs and humanely raised organic animal products that have not been raised on a CAFO (confined animal feeding operation).

For more information about which foods to eat and which to avoid, please consult my comprehensive nutrition plan.

Vitamin D May Cut Your Cancer Risk in Half

There’s overwhelming evidence pointing to the fact that vitamin D deficiency plays a roll in cancer development. If there were something close to a silver bullet for cancer, vitamin D would be it.

If you currently have cancer, evidence shows that higher blood levels of vitamin D—probably around 80-90 ng/ml—are beneficial. If natural sun exposure is not practical, then a safe tanning bed or oral supplement are the next best things. Just keep in mind that it’s BEST to get your vitamin D from natural sun exposure. It appears vitamin D may play an important role in sulfur metabolism, and taking it orally may not provide the same benefit as deriving it from the sun. To learn the details about how to optimize your vitamin D, including dosage and blood testing, please review our comprehensive vitamin D article.

Vitamin D has been found to offer protection from cancer by several mechanisms, including:

  • Regulating genetic expression
  • Increasing apoptosis of defective, mutant cells thereby reducing cancer cell replication
  • Causing cells to become differentiated (cancer cells often lack differentiation)
  • Choking off the growth of new blood vessels from pre-existing ones, which is a step in the transition of dormant tumors turning cancerous

Exercise Can Also Slash Your Cancer Risk

If you are like most people, when you think of reducing your risk of cancer, exercise doesn’t immediately come to mind. However, there is some fairly compelling evidence that exercise can slash your cancer risk. One of the primary ways exercise lowers your risk for cancer is by reducing elevated insulin levels, which creates a low sugar environment—and remember, cancer cells LOVE sugar! Additionally, exercise improves the circulation of immune cells in your blood. Consider integrating exercise with intermittent fasting to greatly catalyze your healing and rejuvenation.

Restore Your Sleep

Getting proper sleep is critical, both in terms of getting enough sleep and sleeping during the right hours. According to Ayurvedic medicine, the ideal sleeping hours are between 10 pm and 6 am. Modern research has confirmed the value of this recommendation as certain hormonal fluctuations occur throughout the day and night, and if you engage in the appropriate activities during those times, you’ll “ride the wave,” so to speak. Working against your biology by staying awake when you should be sleeping, or vice versa, interferes with these natural hormone rhythms.

Manage Your Stress

Research tells us that if you experience a traumatic or highly stressful event, such as a death in the family or loss of a job, your risk of breast cancer is 12 times higher in the five years that follows. It is imperative to your health and longevity that you address your emotional well-being. Stress has a direct impact on inflammation, and inflammation drives many of the chronic diseases that kill people prematurely every day.

Meditation, prayer, yoga, and EFT (an energy psychology tool) are all viable options that can help you maintain emotional/psychological equilibrium. I’m sure you can think of others—the bottom line is, find what works best to de-stress yourself and practice it daily.

Avoid as Many Chemicals, Toxins, and Pollutants as Possible

Just as stress is toxic to your emotional health, chemical overload is toxic to your physical health, and both can weaken your immune system. Get rid of as much toxic junk as you can. This includes harsh chemical household cleaners, soaps, personal hygiene products, air fresheners, bug sprays, lawn pesticides, insecticides and the rest. Replace them all with green, non-toxic alternatives.

  • An experimental cancer drug called DCA (dichloroacetate) shows promise in the fight against cancer by altering cancer cell metabolism and inducing apoptosis (cellular suicide); DCA appears to exert anti-tumor effects against several forms of cancer, including brain, endometrial, cervical, prostate, breast, and colorectal cancers
  • DCA forces cancer cells to shift from their preferred method of generating energy (glycolysis) to the method normal cells prefer (glucose oxidation) and “reawakens” cancer cells’ mitochondria
  • There are serious side effects reported by some adults self-administering DCA, including peripheral neuropathy and encephalopathy, so more research is needed before DCA can be considered safe
  • Optimizing your vitamin D level is one of the most important steps you can take to protect yourself from cancer
  • Certain foods mimic the actions of DCA without ANY side effects, such as broccoli and the spice turmeric