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A Therapeutic Level of Vitamin C Supplementation

  • January 8, 2013 4:30 am

Dosage Table: Vit. C

Home

A Therapeutic Level of Vitamin
C Supplementation as Employed by F .R. Klenner, M.D.
(from “The Significance of High Daily Intake
of Ascorbic Acid in Preventive Medicine,” p. 51-59, Physician’s
Handbook on Orthomolecular Medicine
, Third Edition, Roger Williams, PhD,
ed.)

A Working Summation of Dr. Klenner’s
Formula:

350 mg Vitamin C per kg body weight per day
(350 mg./kg./day)

 mg. of Vitamin “C”

 Body Weight

 Number of Doses

 Amt. per dose

35,000 mg.

220 lbs.

17-18

2,000 mg

18,000 mg

110 lbs.

18

1,000 mg.

9,000 mg.

55 lbs.

18

500 mg.

4,500 mg.

28 lbs.

9

500 mg.

2,300 mg.

14-15 lbs.

9

250 mg.

1,200 mg.

7-8 lbs.

9

130 – 135 mg.

These quantities may seem high; Klenner
actually used as much as four times as much
, typically by
injection.  These are moderate oral doses. You may also give twice as
many doses, with half as much “C” per dose.  Injections of C
may be arranged with your physician.

Vitamin C may be given as liquid, powder,
tablet or chewable tablet.  Infants often prefer finely powdered,
naturally sweetened chewable tablets, which may be crushed between two
spoons. You may make your own liquid vitamin C by daily dissolving C powder
in a small (1 ounce) dropper bottle and adding a sweetener if
necessary.  Dr. Klenner of course recommended daily preventive doses,
which might be about 1/6 of the above therapeutic amount, divided 3 times
daily.

Persons with sensitivity to citrus fruits,
tomatoes or cranberries may feel more comfortable taking vitamin C as
ascorbate, a non-acidic vitamin C. Calcium ascorbate is most frequently
chosen and sodium ascorbate the least, except for injection. Transition down
to a maintenance level (about 60 mg/kg/day) should be made gradually, over a
period of a week or two. A kilogram is 2.2 pounds.

YOU CAN READ DR. KLENNER’S CLINICAL GUIDE FOR FREE

Dr. Klenner’s Clinical Guide to the Use of Vitamin C is now posted
in its entirety
at http://www.seanet.com/~alexs/ascorbate/198x/smith-lh-clinical_guide_1988.htm




Copyright C 2005 and
previous years by Andrew W. Saul.



Cancer & Fungus

  • September 9, 2012 2:08 am

Cancer is a fungus, can be caused by a fungus, or is accompanied by
late-stage fungal infections, and now the Mayo Clinic confirms this. They
are not the first to say so though. Many, even from the official world of
orthodox oncology, recognize the similarities of cancer and fungal
infections, the decay that ties these two together in a dance that all too
often ends in miserable death.

The Mayo Clinic[1] is saying that a fungal infection of the
gastrointestinal tract mimics cancer and inflammatory bowel disease. The
invasive fungus, Basidiobolus ranarum, is typically found in the soil,
decaying organic matter and the gastrointestinal tracts of fish, reptiles,
amphibians, and bats.

Patients with this fungal infection had non-specific symptoms such as
abdominal pain or a mass that could be felt on examination. Before a
conclusive diagnosis of the fungal infection was made, most patients were
thought to have abdominal cancer, inflammatory bowel disease or
diverticulitis. Surgical resection of the area of involvement and
prolonged antifungal therapy successfully treated most patients.

Interestingly, a few years ago researchers at Johns Hopkins were surprised
that the drug itraconazole, commonly used to treat toenail fungus, can
also block angiogenesis, the growth of new blood vessels commonly seen in
cancers. Tumor angiogenesis is the proliferation of a network of blood
vessels that penetrates into cancerous growths, supplying nutrients and
oxygen and removing waste products.[2] Cancer researchers studying the
conditions necessary for cancer metastasis have discovered that
angiogenesis is one of the critical events required for metasteses to
occur.[3]In mice induced to have excess blood vessel growth, treatment
with itraconazole reduced blood vessel growth by 67% compared to placebo.
“We were surprised, to say the least, that itraconazole popped up as a
potential blocker of angiogenesis,” says Dr. Jun O. Liu, professor of
pharmacology. “We couldn’t have predicted that an antifungal drug would
have such a role.” Itraconazole was found to reduce the numbers of
circulating cancer cells, prevent the worsening of prostate cancers, and
delay the need for chemotherapy. However, it has serious side effects when
given in the necessary high dosages that include hypertension, low
potassium levels and fluid retention. These side effects require treatment
with other medications. Effects of high doses of itraconazole could lead
to heart failure.[4]

For two decades John Hopkins has recognized the increasing frequency of
severe fungal infections in patients with neoplastic diseases. Most fungal
infections are caused by the commonly recognized opportunistic fungi
Candida spp and Aspergillus spp, and the pathogenic fungi Cryptococcus
neoformans, Histoplasma capsulatum, Coccidiodes immitis, and less often by
Blastomyces dermatidis. However, recently newer pathogens such as
Pheohyphomycetes, Hyalohyphomycetes, Zygomycetes and other fungi of
emerging importance such as Torulopsis glabrata, Trichosporon beigelii,
Malassezia spp, Saccharomyces spp, Hansenula spp, Rhodotorula spp, and
Geotrichum candidum have appeared as significant causes of infection in
this patient population.

Dr. Tullio Simoncini does not say that cancer is caused by yeast; what he
is telling the world is that the cancer is a yeast overgrowth. What causes
the cancer (or a yeast-filled tumor) is another thing. Simoncini has
always insisted that tumors are white because they are fungi. Some have
made fun of him, but looking around at the extremely sparse information
about the subject, I ran into one person saying:

If someone had asked me a year ago what color the inside of a tumor was, I
would have guessed red and gray. When they did the biopsy, I asked to see
the tissue specimens: five quarter-inch to half-inch strings of vermicelli
(Italian for little worms) with little streakings of blood. They didn’t
look evil to me, just strings of fat. The entire mass was white inside as
the pathology report stated.

Specialists in throat and mouth cancer say that cancers can be red or
white patches: any patch that appears randomly and is red or white in
color could be a mouth cancer symptom. The white patches in the mouth are
called leukoplakia and the red patches are called erythroplakia, which
are pre-cancerous conditions. Though these red or white patches are not
always cancerous, it could be the result of a fungal infection caused by
Candida called thrush.[5] Thrush will lead to a red patch that often
bleeds after the white patch disappears. A small amount of this fungus
lives in your mouth most of the time. It is usually kept in check by your
immune system and other types of germs that also normally live in your
mouth. However, when your immune system is weak, the fungus can grow.

Fungal Mycotoxins

It just so happens that a toxin produced by mold on nuts and grains can
cause liver cancer, according to University of California Irvine
Researchers. And a French case-control study of 1,010 breast cancer cases
and 1,950 controls with nonmalignant diseases found that breast cancer was
associated with increased frequency of mold-fermented cheese
consumption.[6] Fungi produce mycotoxins, which can kill us or cause
cancer.

Dr. Wang and Groopman from the Environmental Health Sciences Department at
Johns Hopkins published on the effects of mold toxins on DNA in Mutation
Research, a leading cancer journal.[7] They said mycotoxins with
carcinogenic potency include aflatoxins, sterigmatocystin, ochratoxin,
fumonisins, zearalenone, and some Penicillium toxins. Most of these
carcinogenic mycotoxins are genotoxic agents. Aflatoxin is a potent
genotoxic agent, is mutagenic in many model systems and produces
chromosomal aberrations, micronuclei, sister chromatid exchange,
unscheduled DNA synthesis, and chromosomal strand breaks. Most strikingly,
the relationship between aflatoxin exposure and development of human
hepatocellular carcinoma (liver cancer) is demonstrated by studies.

Harrison et al. (1993) examined human breast cancer tissue for evidence of
the presence of aflatoxin. The researchers examined human DNA from a
variety of tissues and organs to identify and quantify aflatoxin
DNA-adducts. Such adducts are considered to be proof of the mycotoxin’s
presence in a particular tissue. Aflatoxins may in fact be a risk factor
for cancer induction in a variety of organs in man, in the same manner as
that of cigarette smoking. [8]

DNA from normal and tumorous tissue obtained from patients with cancer of
the breast was examined. Tumor tissues had higher aflatoxin-adduct levels
than did normal tissue from the same individual. The result of this study
verifies the presence of carcinogenic aflatoxin within the cancer tissue
and thus implicates aflatoxin as a cause of breast cancer. That is the
same as saying cancer is a fungus or is caused by a fungus and this is
what Dr. Simoncini has been saying all along.

Intensive Care Units are particularly on alert with immunocompromised and
oncology patients for fungal infections. “Patients with brain tumors used
to have a life expectancy of 3-12 months, but better treatment has allowed
them to live a bit longer,” said Brenda Shelton, clinical nurse specialist
at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins
University, Baltimore. “The last two brain tumor ICU patients we treated
died of infection, not of their disease. One patient had a rare fungus,
and the other had candidemia. Years ago, you would not see most of these
fungal infections in patients with brain tumors because they would not
live long enough.”

“The biggest misconception is the belief that fungal infections are rare,”
Shelton said. “Another misconception is fungal infections are like every
other severe infection. They are harder to manage, harder to eradicate and
more frequent than people realize.” One of the most common complications
involved in treating patients with hematologic cancer is fungal
infections.

Aspergillus niger fungal infection in human lungs produces large amounts
of oxalic acid, which is extremely toxic to the blood vessels and which
may cause fatal pulmonary hemorrhages. Consequently, oxalic acid (calcium
oxalate crystals) in the sputum or lung specimens of patients is also an
indication of an Aspergillus infection of the lung. These calcium oxalate
crystals are the same as the calcium oxalate found in breast cancers. The
presence of oxalates in the breast is indicative of the presence of fungi
interwoven within the stages of breast cancer development. Since humans do
not make oxalic acid themselves, this is an appropriate conclusion.[9]

Dr. Robert Young states, “Bacteria, yeast/fungi, and mold are not the
cause of a cancerous condition but are the result and the evidence of
cells and tissues biologically transforming from a healthy state and to an
unhealthy state.” Dr. Young astutely observed that, “over-acidification of
the body leads to the development of chronic yeast and fungal infections
and ultimately a cancerous condition of the cells and tissues.”

If one has cancer, chances are pretty good that one
also has a fungal infection to one degree or another.

According to The Home Medical Encyclopedia, in 1963 about one-half of all
Americans suffered from an “unrecognized” systemic fungal condition. Far
more Americans suffer from fungal infections today as antibiotics, hormone
replacement therapies, and birth control pills continue to be consumed
like candy. Thus more and more children are becoming infected with
candidal meningitis or viral meningitis, which means their systems are
suffering under the weight of fungi who put out an assortment of
poisons—or mycotoxins.

Sodium Bicarbonate is an Antifungal Agent

The current controversy over sodium bicarbonate and its use in oncology
might be relatively new but baking soda has a long history of helping
people get through the worst medical conditions. The Eloquent Peasant, an
Egyptian literary work dated around 2000 B.C., refers to a peddler selling
natron, a natural blend of sodium bicarbonate, chloride and sodium
carbonate used in mummification, just one of hundreds of uses this
compound has been put to. Baking soda’s first widespread use was probably
as a leavening agent for bread and other baked goods. It has been used
commercially since 1775, although the now-famous Arm & Hammer brand wasn’t
introduced until 1867.[10]

Sodium bicarbonate (Na2HCO3) is recognized by most as ordinary baking
soda, which is found in deposits around the globe. Its backbone
characteristic is to maintain balance of carbon dioxide, bicarbonate and
pH. Sodium bicarbonate is available and sold in every supermarket and
pharmacy in the world and is widely used in emergency rooms and intensive
care wards in injectable forms but is sold as a common household substance
that is used for hundreds of different things.

Read my book, Sodium Bicarbonate, and see that something as inexpensive as
baking soda will outperform the most expensive pharmaceuticals. Across a
wide range of disorders, including cancer and diabetes, we find conclusive
evidence and plenty of theoretical backing to suggest that sodium
bicarbonate is a frontline universal medicine that should be employed by
all practitioners of the healing and medical arts for a broad range of
disorders that are afflicting contemporary man.

Dr. Mark Allan Sircus, Ac., OMD, DM (P)
Director International Medical Veritas Association
Doctor of Oriental and Pastoral Medicine
http://publications.imva.info
http://blog.imva.info

Cancer is a fungus, can be caused by a fungus, or is accompanied by
late-stage fungal infections, and now the Mayo Clinic confirms this. They
are not the first to say so though. Many, even from the official world of
orthodox oncology, recognize the similarities of cancer and fungal
infections, the decay that ties these two together in a dance that all too
often ends in miserable death.

The Mayo Clinic[1] is saying that a fungal infection of the
gastrointestinal tract mimics cancer and inflammatory bowel disease. The
invasive fungus, Basidiobolus ranarum, is typically found in the soil,
decaying organic matter and the gastrointestinal tracts of fish, reptiles,
amphibians, and bats.

Patients with this fungal infection had non-specific symptoms such as
abdominal pain or a mass that could be felt on examination. Before a
conclusive diagnosis of the fungal infection was made, most patients were
thought to have abdominal cancer, inflammatory bowel disease or
diverticulitis. Surgical resection of the area of involvement and
prolonged antifungal therapy successfully treated most patients.

Interestingly, a few years ago researchers at Johns Hopkins were surprised
that the drug itraconazole, commonly used to treat toenail fungus, can
also block angiogenesis, the growth of new blood vessels commonly seen in
cancers. Tumor angiogenesis is the proliferation of a network of blood
vessels that penetrates into cancerous growths, supplying nutrients and
oxygen and removing waste products.[2] Cancer researchers studying the
conditions necessary for cancer metastasis have discovered that
angiogenesis is one of the critical events required for metasteses to
occur.[3]In mice induced to have excess blood vessel growth, treatment
with itraconazole reduced blood vessel growth by 67% compared to placebo.
“We were surprised, to say the least, that itraconazole popped up as a
potential blocker of angiogenesis,” says Dr. Jun O. Liu, professor of
pharmacology. “We couldn’t have predicted that an antifungal drug would
have such a role.” Itraconazole was found to reduce the numbers of
circulating cancer cells, prevent the worsening of prostate cancers, and
delay the need for chemotherapy. However, it has serious side effects when
given in the necessary high dosages that include hypertension, low
potassium levels and fluid retention. These side effects require treatment
with other medications. Effects of high doses of itraconazole could lead
to heart failure.[4]

For two decades John Hopkins has recognized the increasing frequency of
severe fungal infections in patients with neoplastic diseases. Most fungal
infections are caused by the commonly recognized opportunistic fungi
Candida spp and Aspergillus spp, and the pathogenic fungi Cryptococcus
neoformans, Histoplasma capsulatum, Coccidiodes immitis, and less often by
Blastomyces dermatidis. However, recently newer pathogens such as
Pheohyphomycetes, Hyalohyphomycetes, Zygomycetes and other fungi of
emerging importance such as Torulopsis glabrata, Trichosporon beigelii,
Malassezia spp, Saccharomyces spp, Hansenula spp, Rhodotorula spp, and
Geotrichum candidum have appeared as significant causes of infection in
this patient population.

Dr. Tullio Simoncini does not say that cancer is caused by yeast; what he
is telling the world is that the cancer is a yeast overgrowth. What causes
the cancer (or a yeast-filled tumor) is another thing. Simoncini has
always insisted that tumors are white because they are fungi. Some have
made fun of him, but looking around at the extremely sparse information
about the subject, I ran into one person saying:

If someone had asked me a year ago what color the inside of a tumor was, I
would have guessed red and gray. When they did the biopsy, I asked to see
the tissue specimens: five quarter-inch to half-inch strings of vermicelli
(Italian for little worms) with little streakings of blood. They didn’t
look evil to me, just strings of fat. The entire mass was white inside as
the pathology report stated.

Specialists in throat and mouth cancer say that cancers can be red or
white patches: any patch that appears randomly and is red or white in
color could be a mouth cancer symptom. The white patches in the mouth are
called leukoplakia and the red patches are called erythroplakia, which
are pre-cancerous conditions. Though these red or white patches are not
always cancerous, it could be the result of a fungal infection caused by
Candida called thrush.[5] Thrush will lead to a red patch that often
bleeds after the white patch disappears. A small amount of this fungus
lives in your mouth most of the time. It is usually kept in check by your
immune system and other types of germs that also normally live in your
mouth. However, when your immune system is weak, the fungus can grow.

Fungal Mycotoxins

It just so happens that a toxin produced by mold on nuts and grains can
cause liver cancer, according to University of California Irvine
Researchers. And a French case-control study of 1,010 breast cancer cases
and 1,950 controls with nonmalignant diseases found that breast cancer was
associated with increased frequency of mold-fermented cheese
consumption.[6] Fungi produce mycotoxins, which can kill us or cause
cancer.

Dr. Wang and Groopman from the Environmental Health Sciences Department at
Johns Hopkins published on the effects of mold toxins on DNA in Mutation
Research, a leading cancer journal.[7] They said mycotoxins with
carcinogenic potency include aflatoxins, sterigmatocystin, ochratoxin,
fumonisins, zearalenone, and some Penicillium toxins. Most of these
carcinogenic mycotoxins are genotoxic agents. Aflatoxin is a potent
genotoxic agent, is mutagenic in many model systems and produces
chromosomal aberrations, micronuclei, sister chromatid exchange,
unscheduled DNA synthesis, and chromosomal strand breaks. Most strikingly,
the relationship between aflatoxin exposure and development of human
hepatocellular carcinoma (liver cancer) is demonstrated by studies.

Harrison et al. (1993) examined human breast cancer tissue for evidence of
the presence of aflatoxin. The researchers examined human DNA from a
variety of tissues and organs to identify and quantify aflatoxin
DNA-adducts. Such adducts are considered to be proof of the mycotoxin’s
presence in a particular tissue. Aflatoxins may in fact be a risk factor
for cancer induction in a variety of organs in man, in the same manner as
that of cigarette smoking. [8]

DNA from normal and tumorous tissue obtained from patients with cancer of
the breast was examined. Tumor tissues had higher aflatoxin-adduct levels
than did normal tissue from the same individual. The result of this study
verifies the presence of carcinogenic aflatoxin within the cancer tissue
and thus implicates aflatoxin as a cause of breast cancer. That is the
same as saying cancer is a fungus or is caused by a fungus and this is
what Dr. Simoncini has been saying all along.

Intensive Care Units are particularly on alert with immunocompromised and
oncology patients for fungal infections. “Patients with brain tumors used
to have a life expectancy of 3-12 months, but better treatment has allowed
them to live a bit longer,” said Brenda Shelton, clinical nurse specialist
at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins
University, Baltimore. “The last two brain tumor ICU patients we treated
died of infection, not of their disease. One patient had a rare fungus,
and the other had candidemia. Years ago, you would not see most of these
fungal infections in patients with brain tumors because they would not
live long enough.”

“The biggest misconception is the belief that fungal infections are rare,”
Shelton said. “Another misconception is fungal infections are like every
other severe infection. They are harder to manage, harder to eradicate and
more frequent than people realize.” One of the most common complications
involved in treating patients with hematologic cancer is fungal
infections.

Aspergillus niger fungal infection in human lungs produces large amounts
of oxalic acid, which is extremely toxic to the blood vessels and which
may cause fatal pulmonary hemorrhages. Consequently, oxalic acid (calcium
oxalate crystals) in the sputum or lung specimens of patients is also an
indication of an Aspergillus infection of the lung. These calcium oxalate
crystals are the same as the calcium oxalate found in breast cancers. The
presence of oxalates in the breast is indicative of the presence of fungi
interwoven within the stages of breast cancer development. Since humans do
not make oxalic acid themselves, this is an appropriate conclusion.[9]

Dr. Robert Young states, “Bacteria, yeast/fungi, and mold are not the
cause of a cancerous condition but are the result and the evidence of
cells and tissues biologically transforming from a healthy state and to an
unhealthy state.” Dr. Young astutely observed that, “over-acidification of
the body leads to the development of chronic yeast and fungal infections
and ultimately a cancerous condition of the cells and tissues.”

If one has cancer, chances are pretty good that one
also has a fungal infection to one degree or another.

According to The Home Medical Encyclopedia, in 1963 about one-half of all
Americans suffered from an “unrecognized” systemic fungal condition. Far
more Americans suffer from fungal infections today as antibiotics, hormone
replacement therapies, and birth control pills continue to be consumed
like candy. Thus more and more children are becoming infected with
candidal meningitis or viral meningitis, which means their systems are
suffering under the weight of fungi who put out an assortment of
poisons—or mycotoxins.

Sodium Bicarbonate is an Antifungal Agent

The current controversy over sodium bicarbonate and its use in oncology
might be relatively new but baking soda has a long history of helping
people get through the worst medical conditions. The Eloquent Peasant, an
Egyptian literary work dated around 2000 B.C., refers to a peddler selling
natron, a natural blend of sodium bicarbonate, chloride and sodium
carbonate used in mummification, just one of hundreds of uses this
compound has been put to. Baking soda’s first widespread use was probably
as a leavening agent for bread and other baked goods. It has been used
commercially since 1775, although the now-famous Arm & Hammer brand wasn’t
introduced until 1867.[10]

Sodium bicarbonate (Na2HCO3) is recognized by most as ordinary baking
soda, which is found in deposits around the globe. Its backbone
characteristic is to maintain balance of carbon dioxide, bicarbonate and
pH. Sodium bicarbonate is available and sold in every supermarket and
pharmacy in the world and is widely used in emergency rooms and intensive
care wards in injectable forms but is sold as a common household substance
that is used for hundreds of different things.

Read my book, Sodium Bicarbonate, and see that something as inexpensive as
baking soda will outperform the most expensive pharmaceuticals. Across a
wide range of disorders, including cancer and diabetes, we find conclusive
evidence and plenty of theoretical backing to suggest that sodium
bicarbonate is a frontline universal medicine that should be employed by
all practitioners of the healing and medical arts for a broad range of
disorders that are afflicting contemporary man.

Dr. Mark Allan Sircus, Ac., OMD, DM (P)
Director International Medical Veritas Association
Doctor of Oriental and Pastoral Medicine
http://publications.imva.info
http://blog.imva.info

Chemo: Proteins

  • September 1, 2012 1:39 am

A team of researchers looking into why cancer cells are so resilient accidentally stumbled upon a far more important discovery. While conducting their research, the team discovered that chemotherapy actually heavily damages healthy cells and subsequently triggers them to release a protein that sustains and fuels tumor growth. Beyond that, it even makes the tumor highly resistant to future treatment.

Reporting their findings in the journal Nature Medicine, the scientists report that the findings were ‘completely unexpected’. Finding evidence of significant DNA damage when examining the effects of chemotherapy on tissue derived from men with prostate cancer, the writings are a big slap in the face to mainstream medical organizations who have been pushing chemotherapy as the only option to cancer patients for years.

The news comes after it was previously ousted by similarly-breaking research that expensive cancer drugs not only fail to treat tumors, but actually make them far worse. The cancer drugs were found to make tumors ‘metasize’ and grow massively in size after consumption. As a result, the drugs killed the patients more quickly.

Known as WNT16B, scientists who performed the research say that this protein created from chemo treatment boosts cancer cell survival and is the reason that chemotherapy actually ends lives more quickly. Co-author Peter Nelson of the Fred Hutchinson Cancer Research Center in Seattle explains:

“WNT16B, when secreted, would interact with nearby tumour cells and cause them to grow, invade, and importantly, resist subsequent therapy.”

The team then complimented the statement with a word of their own:

“Our results indicate that damage responses in benign cells… may directly contribute to enhanced tumour growth kinetics.”

Sodium Bicarbonate

  • August 29, 2012 7:31 am

Most of us are going to be surprised to find out that there is an oncologist in Rome Italy , Dr. Tullio Simoncini, destroying cancer tumors with sodium bicarbonate. Sodium bicarbonate is safe, extremely inexpensive and unstoppably effective when it comes to cancer tissues. It’s an irresistible chemical, cyanide to cancer cells for it hits the cancer cells with a shock wave of alkalinity, which allows much more oxygen into the cancer cells than they can tolerate. Cancer cells cannot survive in the presence of high levels of oxygen. Sodium bicarbonate is, for all intent and purposes, an instant killer of tumors. Full treatment takes only days, as does another cancer treatment that heats the cancer cells with laser generated heat. (At bottom see combining ph shift with heat.)

The extracellular (interstitial) pH (pHe) of solid tumours is significantly more acidic compared to normal tissues.

Case one: A patient diagnosed with pulmonary neoplasm of the lung, underwent treatment with sodium bicarbonate, before submitting to surgery to remove part of the lung. Treatment consisted of sodium bicarbonate administered orally, by aerosol, and IV. After first treatment reduction of nodules and absorption was evident, and after 8 months was no longer visible at all. Treatments also reduced size of the liver and results were confirmed by both X-ray and CAT scan. Studies have shown how manipulation of tumour pH with sodium bicarbonate enhances some forms of chemotherapy. Proteins can be modified both in vivo and in vitro by increases in acidity. In fact pH is the regulatory authority that controls most cellular processes. The pH balance of the human bloodstream is recognized by medical physiology texts as one of the most important biochemical balances in all of human body chemistry. pH is the acronym for “Potential Hydrogen”. In definition, it is the degree of concentration of hydrogen ions in a substance or solution. It is measured on a logarithmic scale from 0 to 14. Higher numbers mean a substance is more alkaline in nature and there is a greater potential for absorbing more hydrogen ions. Lower numbers indicate more acidity with less potential for absorbing hydrogen ions. Our body pH is very important because pH controls the speed of our body’s biochemical reactions. It does this by controlling the speed of enzyme activity as well as the speed that electricity moves through our body. The higher (more alkaline) the pH of a substance or solution, the more electrical resistance that substance or solution holds. Therefore, electricity travels slower with higher pH. If we say something has an acid pH, we are saying it is hot and fast. Alkaline pH on the other hand, biochemically speaking, is slow and cool.

Cancer tissues have a much higher concentration of toxic chemicals, pesticides, etc then do healthy tissues.

In 1973, a study conducted by the Department of Occupational Health at Hebrew University-Hadassah Medical School in Jerusalem found that when cancerous breast tissue is compared with non-cancerous tissue from elsewhere in the same woman’s body, the concentration of toxic chemicals such as DDT and PCBs was “much increased in the malignant tissue compared to the normal breast and adjacent adipose tissue.” This should say something to the oncologists of the world about chemical etiologies that are going undiagnosed and untreated.

Part of any successful cancer treatment includes chelation and detoxification of heavy metals and a host of toxic chemicals, which are all invading our bodies’ everyday. It is literally raining mercury, uranium contamination is increasing, lead we are discovering is even more toxic than anyone ever believed and is even in the bread that we eat, arsenic is in our chicken, the government still wants you to get your yearly mercury flu shot, dentists of course are still using hundreds of tons of mercury exposing patients to internalized toxic waste dumps (mercury vapors from hell), fluoride is still put in the water and chlorine is breathed in most showers. This just covers a small slice of the toxic disaster that is the hallmark of life in the 21st century. But oncologists have just not been able to understand that cancer patients are suffering from poisoning on a massive scale with all the chemicals scientists have already established cause cancer.

The IMVA recommends alkaline foods and sodium bicarbonate so that the pH of the blood remains high, which in turn means that the blood is capable of carrying more oxygen. This in turn keeps every cell in the body at peak efficiency and helps the cell eliminate waste products. Detoxification and chelation will proceed more easily and safely under slightly alkaline conditions. Increased urinary pH reduces oxidative injury in the kidney so it behooves us to work clinically with bicarbonate.

Patients receiving sodium bicarbonate achieved urine pHs of 6.5 as opposed to 5.6 with those receiving sodium chloride. This alkalinization is theorized to have a protective effect against the formation of free-radicals that may cause nephropathy. Dr. Michael Metro.

Body ph level changes are intense in the profundity of their biological effects. Even genes directly experience external pH. pH differentially regulates a large number of proteins. Increased oxidative stress, which correlates almost exponentially with ph changes into the acidic, is especially dangerous to the mitochondria, which suffer the greatest under oxidative duress. Epigenetics, which may now have begun eclipsing traditional genetics, commonly describes how factors such as diet and smoking, rather than inheritance influence how genes behave.

The great advantage of knowing the prime cause of a disease is that it can then be attacked logically and over a broad front. Dr. Otto Warburg.

Dr. Otto Warburg, two times Nobel Prize winner, stated in his book, The Metabolism of Tumors that the primary cause of cancer was the replacement of oxygen in the respiratory cell chemistry by the fermentation of sugar. The growth of cancer cells is initiated by a fermentation process, which can be triggered only in the absence of oxygen at the cell level. What Warburg was describing was a classic picture of acidic conditions. Just like overworked muscle cells manufacture lactic acid by-products as waste, cancerous cells spill lactic acid and other acidic compounds causing acid pH. After we just saw how important sulfur is in human health and how useful a basic chemical like sodium thiosulfate can be, we now get a crash course in the power of sodium bicarbonate and the act of instantly turning cancer cells alkaline. Might as well shoot a guided cruise missile at them – so effective, safe, quick and precise is sodium bicarbonate, inexpensive as well. Just a few pennies a day of it will keep cancer further away, keeping it at arms length from ourselves, patients and loved ones. It is something we can use to treat our water with as well, excellent to put in distilled or reverse osmosis water or any water for that matter. A true understanding of cancer is impossible without understanding why some tissues in the body are deficient in oxygen and therefore prone to cancer. Cancerous tissues are acidic, whereas healthy tissues are alkaline. Water (H2O) decomposes into H+ and OH- . When a solution contains more H+ than OH- then it is said to be acid. When it contains more OH- than H+ then it is said to be alkaline. When oxygen enters an acid solution it can combine with H+ ions to form water. Oxygen helps to neutralize the acid, while at the same time the acid prevents oxygen from reaching the tissues that need it. Acidic tissues are devoid of free oxygen. An alkaline solution is just the reverse. Two hydroxyl ions ( OH- ) can combine to produce one water molecule and one oxygen atom. In other words, an alkaline solution can provide oxygen to the tissues.

The pH scale goes from 0 to 14, with 7 being neutral. Below 7 is acid and above 7 is alkaline. The blood, lymph and cerebral spinal fluid in the human body are designed to be slightly alkaline at a pH of 7.4.

At a pH slightly above 7.4 cancer cells become dormant and at pH 8.5 cancer cells will die while healthy cells will live. This has given rise to a variety of treatments based on increasing the alkalinity of the tissues such as vegetarian diet, the drinking of fresh fruit and vegetable juices, and dietary supplementation with alkaline minerals such as calcium, potassium, magnesium, cesium and rubidium. But nothing can compare to the instant alkalinizing power of sodium bicarbonate for safe and effective treatment of cancer. Like magnesium chloride or sulfates are excellent emergency medicines, basic chemicals, nutritional in nature, sodium bicarbonate is a nutritional medicine meaning it cannot and will not end up controlled by CODEX. To control bicarbonate they would have to demand mothers stop making cake with it. We might thus identify sodium bicarbonate as an emergency medicine for cancer with the above supporting approaches working on broader levels to help overall physiology change to a degree where body chemistry is unfavorable for new cancer growth. Cancer seems to grow slowly in a highly acid environment (because the acids cause it to partially destroy itself) and may actually grow more quickly as your body becomes more alkaline prior to reaching the healthy pH slightly above 7.4 where the cancer becomes dormant. Therefore it is important to get pH above 7.4 quickly. Once one has achieved a pH above 7.4, it is useful to monitor saliva pH regularly to ensure that the body remains sufficiently alkaline.

Earlier and more frequent use of sodium bicarbonate was associated with higher early resuscitability rates and with better long-term neurological outcome. Sodium bicarbonate is beneficial during CPR.

“The therapeutic treatment of bicarbonate salts can be administered orally, through aerosol, intravenously and through catheter for direct targeting of tumors.” All of Dr. Tullio Simoncini’s treatments with sodium bicarbonate are directed as specifically as possible to the organs involved, for example, vaginally as well as abdominally into the peritoneal space for cervical cancer, through the hepatic artery for liver cancer in order to get the solution as close to the affected area as possible. Sodium bicarbonate administered orally, via aerosol or intravenously can achieve positive results in most tumors, including the brain, while others, such as the serious ones of the bones can remain unaffected. Dr. Simoncini, with the help of interventionist radiologists was able to reach those areas of the body that had previously been inaccessible. This was achieved through positioning appropriate catheters either in cavities for peritoneum and pleura, or in arteries to reach other organs.

The most effective measure to treat RT-induced mucositis in patients with head and neck cancer is frequent oral rinsing with a sodium bicarbonate rinse, to reduce the amount of oral microbial flora.

Case two: A nine-year-old child is hospitalized and diagnosed with Ewing ‘s Sarcoma on the right humerus. Despite several chemotherapy cycles surgery removed the humeral bone. Growth of three tumor masses continued despite continued efforts to stop progression. Sodium bicarbonate salts treatment were then started administered by catheter into the right sub-clavian artery in order to administer the salts (phleboclysis of 500 cc at five per cent) directly on the tumoral masses. Of the 3 masses shown by the scographic scan of May 7, 2001, whose size is respectively:

a. 6,5 cm
b. 4,4 cm
c. 2,4 cm

After the sodium bicarbonate salts treatment only one tumor was left, with a size of only 1.5 cm , which is most likely residual scarring, as shown by the echography of September 10, 2001.

Sodium bicarbonate injection is also indicated in the treatment of metabolic acidosis which may occur in severe renal disease, uncontrolled diabetes, and circulatory insufficiency due to shock or severe dehydration, extracorporeal circulation of blood, cardiac arrest and severe primary lactic acidosis. Sodium bicarbonate is further indicated in the treatment of drug intoxications, including barbiturates. Sodium carbonate has been found effective in treating poisoning or overdose from many chemicals and pharmaceutical drugs by negating the cardiotoxic and neurotoxic effects.

Sodium bicarbonate is useful in treating neurological disorders in children.

Knowledge of sodium bicarbonate is important for parents because the rate of childhood cancer is growing exponentially. But parents who resist the radiation burning, cutting and the lethal chemicals are regularly hauled before the courts only to have their children taken away from them. Oncologists are increasingly resorting to the justice system to have children made wards of the courts who then turn them over to medically irresponsible practitioners. It is inexcusable separating a child from his mother and father in the middle of a medical crisis. Adding to the stress by tormenting patients’ hearts and souls has nothing to do with safe or effective medicine. The naked truth is doctors and medical institutions have not earned the necessary trust for this level of intervention in people’s lives. With patient safety slipping year by year, children are not safe in hospitals, much less so if forced at gunpoint from their parents embrace.

An extremely simple therapy used by physicians who treat autism is to supply a mild antidote that neutralizes the excess acids. The most convenient product is a nonprescription drug called AlkaSeltzer Gold™. Do not use any other kind of AlkaSeltzer™. AlkaSeltzer Gold™ is simply a very safe product (sodium and potassium bicarbonate) that helps to neutralize excess acids of any kind. Dr. William Shaw – Biological Treatments for Autism and PDD.

One mother wrote, “It worked so well for both of my children that the die-off was an uneventful experience, even though they both had very high levels of yeast.” The restoring of acid/alkaline balance also relieves many allergies. “These children also had grave disturbances in electrolyte chemistry, and tended to be acidotic (low CO). The data that unfolded was fascinating and clearly earmarked the acidosis and hypoxic state (low serum bicarbonate = low O2 levels). Potassium bicarbonate, sodium bicarbonate, magnesium carbonate and the like were used. Now we began to understand why so many children responded to Buffered C (potassium bicarbonate, calcium carbonate, magnesium carbonate), and others needed a more specific buffer (in some children for example niacin was grossly depleted and they required niacin bicarbonate),” wrote Patricia Kane.

The acid/alkaline balance is one of the most overlooked aspects of health, though many have written much about it. In general, the American public is heavily acid, excepting vegetarians.

Case three: A 62-year-old patient undergoes surgery in December 1998 for endometrial adenocarcinoma, followed by successive cycles of radiotherapy and anti-hormone therapy. Following the thickening of the peritoneum and the growth of several lymph nodes due to carcinosis; from the clinical point of view, the patient’s condition decayed with the presence of exhaustion, general swelling, intestinal meteorism, irregularity of evacuation, steady feeling of heaviness and blood pressure instability. Treatment with a 5% sodium bicarbonate solution administered alternately thru an endoperitoneal catheter and via IV showed rapid improvement to a normal condition of health. A final CAT scan confirms the regression of the peritoneal carcinosis and a stabilization of the size of the lymph nodes when compared to the preceding year.

The kidneys are usually the first organs to show chemical damage upon uranium exposure, military manuals suggest doses or infusions of sodium bicarbonate to help alkalinize the urine if this happens. This makes the uranyl ion less kidney-toxic and promotes excretion of the nontoxic uranium-carbonate complex. The oral administration of sodium bicarbonate diminishes the severity of the changes produced by uranium in the kidneys.

Case four: A 40-year-old patient underwent surgical intervention (left radical mastectomy) for mammarian carcinoma seven months earlier. After three months of chemotherapy, the patient is affected by: “diffused pulmonary and hepatic metastasis; bone metastasis particularly to the fifth and sixth lumbar vertebrae, with invasion and compression of the medullar channel, which is causing extreme pain which makes the patient unresponsive to any treatment.” All pain suppressant drugs – morphine included – are totally ineffective and the patient is totally prostrate even unable to sleep. Believing that fungal colonies amassed in the medullar channel will respond to administration of sodium bicarbonate salts, lumbar injections are begun.

Dr Tullio Simoncini recounts: “As I administer it by slowly injecting 50 cc of sodium bicarbonate solution at 8.4 %, the patient tosses and with a thread of a voice confesses to me that she has slept only two hours in the last week. Exhausted, she whispers to me: “If only I could sleep half an hour tonight.” But the day after, she calls me on the phone and says: “I have slept all night”. After two more lumbar injections of the bicarbonate salts in the next month, the pain disappeared completely. Magnetic Resonance imaging reports performed before and after treatment were defined by hospital head of the radiology department as “shocking.”

Sodium bicarbonate is the chemical compound with the formula NaHCO3. Sodium bicarbonate (baking soda) is commonly used as an antacid for short-term relief of stomach upset, to correct acidosis in kidney disorders, to make the urine alkaline during bladder infections and to minimize uric acid crystallization during gout treatment. Prescription sodium bicarbonate products are given by injection to treat metabolic acidosis and some drug intoxications. Sodium bicarbonate is available as a nonprescription medical as well as a general house hold item. It is also used with other non-prescription drugs for short-term treatment of various conditions to treat anything from fever to moderate pain. Sodium bicarbonate possesses the property of absorbing heavy metals, dioxins and furans. Comparison of cancer tissue with healthy tissue from the same person shows that the cancer tissue has a much higher concentration of toxic chemicals, pesticides, etc.

Sodium bicarbonate neutralizes acids present in gases (in particular hydrochloric acid, suphur dioxide, hydrofluoric acid) to form sodium salts (sodium chloride, sodium sulphate, sodium fluoride, sodium carbonate), which are all known as Residual Sodium Chemicals. Sodium bicarbonate can be made into a paste salve with vinegar, it relieves burning from bug stings (particularly bee stings), poison ivy, nettles, and sunburn. It is used as an antacid to treat acid indigestion and heartburn. Mixed with water in a 10% solution can soften earwax for removal.

Substituting a sodium bicarbonate solution for saline infusion prior to administration of radiocontrast material seems to reduce the incidence of nephropathy. Dr. Thomas P. Kennedy American Medical Association Because sodium bicarbonate has long been known and is widely used, it has many other names including sodium hydrogen carbonate, sodium bicarb, baking soda, bread soda, cooking soda, bicarb soda, saleratus or bicarbonate of soda. It is soluble in water. This white solid is crystalline but often appears as a fine powder. It has a slight alkaline taste resembling that of sodium carbonate. It is a component of the mineral natron and is found dissolved in many mineral springs. It is also produced artificially. World wide production is on the scale of 100,000 ton/year. Sodium bicarbonate is primarily used in cooking (baking) where it reacts with other components to release carbon dioxide, that helps dough “rise.”

It is commonly used to increase the pH and total alkalinity of the water for pools and spas. Sodium bicarbonate can be added as a simple solution for restoring the pH balance of water that has a high level of chlorine. It is sometimes used in septic tanks to control pH and bacteria.

Sodium bicarbonate-rich mineral water in conjunction with a low-salt diet may have a beneficial effect on calcium homeostasis.

Distilled water is not safe, it lacks bicarbonates and minerals and yes, it is acid forming to the body. Yet it is an excellent aid in detoxification and chelation for its purity pulls on toxicities in the body. Part of the reason why our body is acid is that it lacks enough bicarbonate necessary to neutralize the acid. Whenever the water lacks the proper bicarbonates to neutralize the water in distilled water your body basically becomes a little more acid. But we can easily treat distilled or reverse osmosis water by adding bicarbonate and magnesium and perhaps even some sodium thiosulfate. (The art and science of water treatment will be covered in The Waters of Life, another IMVA publication due out later this year. The conscious use of water favorably increases medical outcomes, often it even determines the prognosis. You cannot separate out hydration from pH. Dehydration would certainly push the body toward acidity.)

pH of the blood is the most important factor to determine the state of the microorganisms in the blood.

The native chemical and physical properties of sodium bicarbonate account for its wide range of applications, including cleaning, deodorizing, buffering, and fire extinguishing. Sodium bicarbonate neutralizes odors chemically, rather than masking or absorbing them. Consequently, it is used in bath salts and deodorant body powders. Sodium bicarbonate tends to maintain a pH of 8.1 (7 is neutral) even when acids, which lower pH, or bases, which raise pH, are added to the solution. Its ability to tabletize makes it a good effervescent ingredient in antacids and denture cleaning products. Sodium bicarbonate is also found in some anti-plaque mouthwash products and toothpaste. Sodium bicarbonate also is indicated in severe diarrhea which is often accompanied by a significant loss of bicarbonate. Vigorous bicarbonate therapy is required in any form of metabolic acidosis where a rapid increase in plasma total CO2 content is crucial e.g. cardiac arrest, circulatory insufficiency due to shock or severe dehydration , and in severe primary lactic acidosis or severe diabetic acidosis.

Sodium Bicarbonate Injection, USP is administered by the intravenous route. In cardiac arrest, a rapid intravenous dose of one to two 50 mL vials (44.6 to 100 mEq) may be given initially and continued at a rate of 50 mL (44.6 to 50 mEq) every 5 to 10 minutes if necessary (as indicated by arterial pH and blood gas monitoring) to reverse the acidosis. Caution should be observed in emergencies where very rapid infusion of large quantities of bicarbonate is indicated. Bicarbonate solutions are hypertonic and may produce an undesirable rise in plasma sodium concentration in the process. of correcting the metabolic acidosis. In cardiac arrest, however, the risks from acidosis exceed those of hypernatremia.

In the current system, if a promising compound can’t be patented, it is highly unlikely ever to make it to market — no matter how well it performs in the laboratory or in emergency room situations. The hormone melatonin, sold as an inexpensive food supplement in the United States , has repeatedly been shown to slow the growth of various cancers when used in conjunction with conventional treatments. Dr. Paolo Lissoni, another Italian oncologist has written many articles about this hormone and conducted clinical trials. But he has despaired over the pharmaceutical industry’s total lack of interest in his treatment approach.

We need a new approach to fight cancer, one that will work safely and effectively since the majority of us are now destined to have to suffer through cancer at one point or another in our lives. The situation in the field of oncology is horrendous and in the area of childhood oncology they have earned their place in the book The Terror of Pediatric Medicine, (which one can download as a free e-book.)

Most people today cringe at the idea of finding a cancer then slashing, burning and poisoning it to smithereens. Most would agree that the mainstream cancer approach offers only marginal benefits at best, and providers push screening and aggressive treatment in part because they have nothing else to give, and also because it’s very profitable.

If the body’s cellular metabolism and pH is balanced it is susceptible to little illness or disease.

Since 1971, when President Nixon declared war on cancer, the budget of the National Cancer Institute has increased to $4.8 billion from half a billion and cancer rates are still going up. For most of the past half-century, medical treatment of invasive tumors like those of the breast and colon has relied mainly on drugs, radiation or both, in effect carpet-bombing the DNA of cancer cells. These highly toxic treatments do not address the root causes of cancer and are extremely dangerous, medical approaches involving the highest risks.

The great variety of cancers must reflect a fundamental mechanism by which the disease arises, one that has not been so clearly apparent until now.

Though allopathic medicine already uses sodium bicarbonate it will not any day soon turn to its own arsenal of already available safe and inexpensive medications like sodium bicarbonate or magnesium chloride. The medical industrial complex seems unwilling to change its views on cancer so patients will need to quietly ask their doctors for intravenous bicarbonate without specifying it as a substance they want to use to cure their cancer. It will be easier to find someone if one approaches with a need to treat acidic conditions than the actual cancer. Few doctors are willing to risk their licenses so it is better not to put them in an uncomfortable situation that they cannot control.

The closer the pH is to 7.35 – 7.45, the higher our level of health and well being and our ability to resist states of disease.

Sadly this does not address the need for the use of catheters which target tumors more directly thus pushing us toward a more complete protocol that will target cancer in a more general and comprehensive way. This needs to be done anyway because killing the tumor with a rush of alkalinity that provokes an oxygen rush into the cells will not prevent the condition from reoccurring. Though we can think that acidity is a basic cause of cancer a more basic cause is addressed when we look at what leads to the acidic conditions that are so prevalent in our bodies today.

Sodium bicarbonate is an anti-fungin substance that is very diffusible and thus very effective.

Dr Tullio Simoncini says, “It is useful to consider the extreme sensitivity of fungi to saline and electrolytic solutions. These solutions, because of their extreme capacity for diffusion, are able to reach all the myceliar biological expressions, including the most infinitesimal ones. Salts and bicarbonates, by making the “terrain” completely inorganic, eliminates the slightest organic fonts that fungi could use for nourishment. In this context, sodium bicarbonate, which is currently used in children’s oral candidoses, appears to be a simple and handy weapon capable of uprooting, inhibiting, or attenuating any neoplastic formation wherever it is possible to easily apply it.”

Cancer is actually a four-letter word — ACID, especially lactic acid as a waste product due to the low oxygen level and waste products of yeast and fungus.

For centuries, medicated baths have been one of the first lines of treatment for psoriasis. Even today, with sophisticated immunosuppressive treatments available, Dead Sea salts and spa waters are recognized to be beneficial in the management of psoriatic patients. To assess statistically the efficacy of sodium bicarbonate baths in psoriasis patients, thirty-one patients with mild-moderate psoriasis were studied. Almost all patients who used NaHCO3- reported a statistically valuable improvement. NaHCO3- baths reduced itchiness and irritation; in general, the patients themselves recognized a beneficial impact on their psoriasis, so much so that they have continued to bathe in NaHCO3- even after the end of the study.

“Sodium bicarbonate therapy is harmless, fast and effective because it is extremely diffusible. A therapy with bicarbonate for cancer should be set up with strong dosage, continuously, and with pauseless cycles in a destruction work which should proceed from the beginning to the end without interruption for at least 7-8 days. In general a mass of 2-3- 4 centimetres will begin to consistently regress from the third to the fourth day, and collapses from the fourth to the fifth. Generally speaking, the maximum limit of the dosage that can be administered in a session gravitates around 500 cc of sodium bicarbonate at five per cent solution, with the possibility of increasing or decreasing the dosage by 20 per cent in function of the body mass of the individual to be treated and in the presence of multiple localisations upon which to apportion a greater quantity of salts,” instructs Dr Simoncini.

In the early stages of acidic pH in the body’s tissues, the warning symptoms are mild. These include such things as skin eruptions, headaches, allergies, colds, flu and sinus problems. These symptoms are frequently treated (manipulated) with antibiotic drugs and suppressive medications. The longer and the deeper we become acidic the more our illness takes hold so it’s best to fight acidic conditions early on and in every presenting clinical situation. Certainly a highly toxic drug like anti viral Tamiflu won’t do a fraction of the job sodium bicarbonate will do especially if it’s combined with magnesium chloride and iodine as well as high levels of vitamin C.

In late stages of acidic pH we need to turn to the most alkaline minerals to increase our throw weight of alkalinity into cancer cells. Mass spectrographic and isotope studies have shown that potassium, rubidium, and especially cesium are most efficiently taken up by cancer cells. This uptake was enhanced by Vitamins A and C as well as salts of zinc and selenium. The quantity of cesium taken up was sufficient to raise the cell to the 8 pH range.

There seems little grace left in medicine and it is a disgrace that allopathic medicine does not even use its own emergency medicines, proven heavies like magnesium sulfate and chloride, sodium bicarbonate and iodine to anywhere near a thousandth of a percent of their real medical potentials.

Combining pH shift with Heat

” Give me a chance to create fever and I will cure any disease.” – Parmenides 2,000 years ago

Fever is one of the body’s own defensive and healing forces, created and sustained for the deliberate purpose of restoring health. The high temperature speeds up metabolism, inhibits the growth of the invading virus or bacteria, and literally burns the enemy with heat. Fever is an effective protective and healing measure not only against colds and simple infections, but against such serious diseases as polio and cancer.

The idea of destroying cancer with heat is certainly not new and has been widely accepted for a very long time, but has had very limited applications because it was finally concluded that, in order to ensure destruction of the cancerous growth, it is necessary to reach a temperature deadly to healthy cells as well. Many attempts have been made to bypass this problem and some methodologies have been developed like: localized hyperthermia, laserthermia, radio-fractionated hyperthermia and TTT. But they all have limitations and cannot complete the job, because they cannot achieve total necrosis and, unless the entire mass of neoplastic tissue is destroyed, the cancer will continue to grow. But:

Hyperthermia gives cancer a hard time:
1. removing accumulations of stored toxic chemicals that cause cancer.
2. improving circulation so that tissues are both nourished with oxygen and flushed of acidic metabolic wastes.
3. weakening or even killing cancer cells that have a lower tolerance for heat than healthy cells.

Thus we should easily conclude that far-infrared sauna treatments are going to help a cancer sufferer no matter which way we slice the treatment protocol. But for a more targeted heat to kill cancer tumors we have Dr. Antonella Carpenter who has perfected the treatment of cancer cells with heat through her use of lasers. She generates the death of the cells by suffocation via heat. Dr Carpenter, a physicist with a clinic in Little Rock , says, “As long as the entire neoplastic mass is exposed to the laser light, for the correct amount of time, the success is complete and the results, as well as the healing stages, are always the same.” Her cancer treatment is called Light Induced Enhanced Selective Hyperthermia, which in itself pretty much summarizes all the characteristics of this new therapy. With this form of treatment cancer cells reach a deadly temperature level quickly and are subject to irreversible damage and therefore die, either immediately or within 48 hours. In a separate chapter we will be talking about hyperthermia in another context, that of the hot bathtub which we will learn to fill with healing substances like sodium bicarbonate. We will be creating our own hot springs , healing pools that will do wonders for our health. Medical treatments of the first order can be had right inside your very own bathtub.

Mark Sircus Ac., OMD
Director International Medical Veritas Association

http://www.imva.info

http://www.magnesiumforlife.com

director@imva.info
International Medical Veritas Association Copyright 2007 All rights reserved.

IMPORTANT DISCLAIMER: The communication in this email is intended for informational purposes only. Nothing in this email is intended to be a substitute for professional medical advice.

Dr Simoncini’s Website

LDN – Low Dose Naltrexone

  • August 29, 2012 7:29 am


FDA-approved naltrexone, in a low dose, can boost the immune system — helping those with HIV/AIDS, cancer, autoimmune diseases, and central nervous system disorders.


 

Welcome to the Low Dose Naltrexone (LDN) Home Page

Updated: Jul 1, 2011

The authors of this website do not profit from the sale of low-dose naltrexone or from website traffic, and are in no way associated with any pharmaceutical manufacturer or pharmacy.

[Your user agent does not support frames or is currently configured not to display frames. Instead, <A href="nav.htm">click here</A> for buttons to help navigate this website.]

 

For announcements and discussion about Low Dose Naltrexone,
subscribe to the LDN Yahoo Group:

The LDN Yahoo Group is an announcement and discussion group for those interested in LDN, and who wish to be notified about updates to this website. We expect that official announcements to the group will be fairly infrequent, typically not more than one per month. Group members not wishing to receive general discussion e-mail from other members may set their message delivery option to “Special Notices” when joining, or by logging on to the LDN Yahoo Group site and clicking on “Edit My Membership.”

 


 

An Important Chance for LDN

Letter from the Editor:

A unique opportunity has arisen to reach the goal of genuine medical acceptance for LDN. A physician named Tomasz Sablinski, with a very strong background in the pharmaceutical industry, has committed himself to breaking through the barriers that block important but ignored discoveries such as LDN.

He has joined with Daniel Reda, founder of the online site CureTogether, to form a plan for LDN, with the help of the Internet and the members of the LDN-Yahoo Group.

Please read their proposal, which can be found here.

David Gluck, MD
Editor, www.ldninfo.org

[N.B. – The editor has no formal affiliation with and no financial interest in either TLS or CureTogether.]

 

 


 

“Low Dose Naltrexone (LDN) may well be the most important therapeutic breakthrough in over fifty years. It provides a new, safe and inexpensive method of medical treatment by mobilizing the natural defenses of one’s own immune system.

LDN substantially reduces health care costs and improves treatment of a wide array of diseases. Unfortunately, because naltrexone has been without patent protection for many years, no pharmaceutical company will bear the expense of the large clinical trials necessary for FDA approval of LDN’s new special uses. It is now up to public institutions to seize the opportunity that LDN offers.”

  — David Gluck, MD


 

Latest Results from Clinical Trials of LDN
March 2010

Around the globe, there has been a quantum leap forward in the number of ongoing research studies on LDN.

Latest developments include:

Click this box for details on all clinical trials of LDN.

 


 

 


LDN Website Contents

> On this page you can find answers to these questions:

> You can go to more detailed information on these linked pages:

 


 

 


What is low-dose naltrexone and why is it important?

> Low-dose naltrexone holds great promise for the millions of people worldwide with autoimmune diseases or central nervous system disorders or who face a deadly cancer.

> In the developing world, LDN could provide the first low-cost, easy to administer, and side-effect-free therapy for HIV/AIDS.

Naltrexone itself was approved by the FDA in 1984 in a 50mg dose for the purpose of helping heroin or opium addicts, by blocking the effect of such drugs. By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones that our brain and adrenal glands produce: beta-endorphin and metenkephalin. Many body tissues have receptors for these endorphins and enkephalins, including virtually every cell of the body’s immune system.

In 1985, Bernard Bihari, MD, a physician with a clinical practice in New York City, discovered the effects of a much smaller dose of naltrexone (approximately 3mg once a day) on the body’s immune system. He found that this low dose, taken at bedtime, was able to enhance a patient’s response to infection by HIV, the virus that causes AIDS. [Note: Subsequently, the optimal adult dosage of LDN has been found to be 4.5mg.]

In the mid-1990′s, Dr. Bihari found that patients in his practice with cancer (such as lymphoma or pancreatic cancer) could benefit, in some cases dramatically, from LDN. In addition, people who had an autoimmune disease (such as lupus) often showed prompt control of disease activity while taking LDN.


 

First Study of LDN Published
in US Medical Journal

Dr. Jill Smith’s original article, “Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease,” in the January issue of the American Journal of Gastroenterology (2007;102:1–9), officially presents LDN to the world of scientific medicine. Smith, Professor of Gastroenterology at Pennsylvania State University’s College of Medicine, found that two-thirds of the patients in her pilot study went into remission and fully 89% of the group responded to treatment to some degree. She concluded that “LDN therapy appears effective and safe in subjects with active Crohn’s disease.” (For further information on Smith’s study, please see the linked Clinical Trials page.)

Endoscopic Improvement in Crohn’s Colitis with Naltrexone
Figure A: Shown is the rectum of a subject with active Crohn’s Disease before starting therapy with naltrexone 4.5 mg/day. The mucosa is ulcerated, edematous, and inflamed.
Figure B: Shows the same area of the rectum in the same patient four weeks after naltrexone therapy. The lining is now healed, ulcers resolved, and the mucosa is healthy.
Copyrights: do not reproduce the above images and captions without written permission from Jill P. Smith, MD, Professor of Medicine, H-045 GI Division, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033

 


How does LDN work?

> LDN boosts the immune system, activating the body’s own natural defenses.

Up to the present time, the question of “What controls the immune system?” has not been present in the curricula of medical colleges and the issue has not formed a part of the received wisdom of practicing physicians. Nonetheless, a body of research over the past two decades has pointed repeatedly to one’s own endorphin secretions (our internal opioids) as playing the central role in the beneficial orchestration of the immune system, and recognition of the facts is growing.

Witness these statements from a review article of medical progress in the November 13, 2003 issue of the prestigious New England Journal of Medicine: “Opioid-Induced Immune Modulation: …. Preclinical evidence indicates overwhelmingly that opioids alter the development, differentiation, and function of immune cells, and that both innate and adaptive systems are affected.1,2 Bone marrow progenitor cells, macrophages, natural killer cells, immature thymocytes and T cells, and B cells are all involved. The relatively recent identification of opioid-related receptors on immune cells makes it even more likely that opioids have direct effects on the immune system.3

The brief blockade of opioid receptors between 2 a.m. and 4 a.m. that is caused by taking LDN at bedtime each night is believed to produce a prolonged up-regulation of vital elements of the immune system by causing an increase in endorphin and enkephalin production. Normal volunteers who have taken LDN in this fashion have been found to have much higher levels of beta-endorphins circulating in their blood in the following days. Animal research by I. Zagon, PhD, and his colleagues has shown a marked increase in metenkephalin levels as well. [Note: Additional information for Dr. Zagon can be found at the end of this page.]

Bihari says that his patients with HIV/AIDS who regularly took LDN before the availability of HAART were generally spared any deterioration of their important helper T cells (CD4+).

In human cancer, research by Zagon over many years has demonstrated inhibition of a number of different human tumors in laboratory studies by using endorphins and low dose naltrexone. It is suggested that the increased endorphin and enkephalin levels, induced by LDN, work directly on the tumors’ opioid receptors — and, perhaps, induce cancer cell death (apoptosis). In addition, it is believed that they act to increase natural killer cells and other healthy immune defenses against cancer.

In general, in people with diseases that are partially or largely triggered by a deficiency of endorphins (including cancer and autoimmune diseases), or are accelerated by a deficiency of endorphins (such as HIV/AIDS), restoration of the body’s normal production of endorphins is the major therapeutic action of LDN.


 

CBS News Reports:
“Wonder drug” LDN Could Help Treat Cancer, Multiple Sclerosis

 

JACKSONVILLE, FLA (CBS) — February, 2008 — This report features an interview with Lori Miles, an MS sufferer who can now walk again, thanks to LDN. Also quoted in the piece is Dr. Daniel Kantor, neurologist and director of the Comprehensive Multiple Sclerosis Program at the Shands Jacksonville Neuroscience Institute: “I would like all of us to write to our congressmen, ask the FDA and NIH—National Institutes of Health—to fund more research about LDN.”

 


What diseases has it been useful for and how effective is it?

> Bernard Bihari, MD, as well as other physicians and researchers, have described beneficial effects of LDN on a variety of diseases:

Cancers
  • Bladder Cancer
  • Breast Cancer
  • Carcinoid
  • Colon & Rectal Cancer
  • Glioblastoma
  • Liver Cancer
  • Lung Cancer (Non-Small Cell)
  • Lymphocytic Leukemia (chronic)
  • Lymphoma (Hodgkin’s and Non-Hodgkin’s)
  • Malignant Melanoma
  • Multiple Myeloma
  • Neuroblastoma
  • Ovarian Cancer
  • Pancreatic Cancer
  • Prostate Cancer (untreated)
  • Renal Cell Carcinoma
  • Throat Cancer
  • Uterine Cancer
Other Diseases
  • Common Colds (URI’s)
  • Emphysema (COPD)
  • HIV/AIDS
AutoimmuneNeurodegenerative:

  • ALS (Lou Gehrig’s Disease)
  • Alzheimer’s Disease
  • Autism Spectrum Disorders
  • Multiple Sclerosis (MS)
  • Parkinson’s Disease
  • Primary Lateral Sclerosis (PLS)
  • Transverse Myelitis

Other Autoimmune Diseases:

  • Ankylosing Spondylitis
  • Behcet’s Disease
  • Celiac Disease
  • Chronic Fatigue Syndrome
  • CREST syndrome
  • Crohn’s Disease
  • Dermatomyositis
  • Endometriosis
  • Fibromyalgia
  • Hashimoto’s Thyroiditis
  • Irritable Bowel Syndrome (IBS)
  • Myasthenia Gravis (MG)
  • Pemphigoid
  • Psoriasis
  • Rheumatoid Arthritis
  • Sarcoidosis
  • Scleroderma
  • Sjogren’s Syndrome
  • Stiff Person Syndrome (SPS)
  • Systemic Lupus (SLE)
  • Ulcerative Colitis
  • Wegener’s Granulomatosis

> LDN has demonstrated efficacy in thousands of cases.

Cancer. As of mid-2004, Dr. Bihari reported having treated over 300 patients who had a cancer that had failed to respond to standard treatments. Of that group, some 50%, after four to six months treatment with LDN, began to demonstrate a halt in cancer growth and, of those, over one-third have shown objective signs of tumor shrinkage.

Autoimmune diseases. Within the group of patients who presented with an autoimmune disease (see above list), none have failed to respond to LDN; all have experienced a halt in progression of their illness. In many patients there was a marked remission in signs and symptoms of the disease. The greatest number of patients within the autoimmune group are people with multiple sclerosis, of whom there were some 400 in Dr. Bihari’s practice. Less than 1% of these patients has ever experienced a fresh attack of MS while they maintained their regular LDN nightly therapy.

HIV/AIDS. As of September 2003, Dr. Bihari had been treating 350 AIDS patients using LDN in conjunction with accepted AIDS therapies. Over the prior 7 years over 85% of these patients showed no detectable levels of the HIV virus — a much higher success rate than most current AIDS treatments, and with no significant side effects. It is also worth noting that many HIV/AIDS patients have been living symptom-free for years taking only LDN with no other medications.

Central Nervous System disorders. Anecdotal reports continue to be received concerning beneficial effects of LDN on the course of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS—Lou Gehrig’s disease), and primary lateral sclerosis. Dr. Jaquelyn McCandless has found a very positive effect of LDN, in appropriately reduced dosage and applied as a transdermal cream, in children with autism.

> How is it possible that one medication can impact such a wide range of disorders?

The disorders listed above all share a particular feature: in all of them, the immune system plays a central role. Low blood levels of endorphins are generally present, contributing to the disease-associated immune deficiencies.

Research by others — on neuropeptide receptors expressed by various human tumors — has found opioid receptors in many types of cancer:

  • Brain tumors (both astrocytoma and glioblastoma)
  • Breast cancer
  • Endometrial cancer
  • Head and neck squamous cell carcinoma
  • Myeloid leukemia
  • Lung cancer (both small cell and non-small cell)
  • Neuroblastoma and others…

These findings suggest the possibility for a beneficial LDN effect in a wide variety of common cancers.


How can I obtain LDN and what will it cost?

> LDN can be prescribed by your doctor, and should be prepared by a reliable compounding pharmacy.

Naltrexone is a prescription drug, so your physician would have to give you a prescription after deciding that LDN appears appropriate for you.

Naltrexone in the large 50mg size, originally manufactured by DuPont under the brand name ReVia, is now sold by Mallinckrodt as Depade and by Barr Laboratories under the generic name naltrexone.

LDN prescriptions are now being filled by hundreds of local pharmacies, as well as by some mail-order pharmacies, around the US. Some pharmacists have been grinding up the 50mg tablets of naltrexone to prepare the 4.5mg capsules of LDN; others use naltrexone, purchased as a pure powder, from a primary manufacturer.

> LDN is not expensive.

One of the first pharmacies to compound LDN was Irmat Pharmacy in Manhattan. Their recent price for a one-month’s supply of 4.5mg LDN (30 capsules) was $38. Irmat does monthly quality control testing on its LDN, accepts prescriptions from any licensed physician, checks for insurance coverage, and includes shipment anywhere in the US or to other countries. In contrast, Gideon’s Drugs charges only $15 for a one month’s supply of 4.5mg LDN but it does not accept insurance and it will charge for shipment.

> Pharmacies that are known to be reliable compounders of LDN:

Pharmacy Phone Fax
Irmat Pharmacy, New York, NY (212) 685-0500
(800) 975-2809
(212) 532-6596
Gideon’s Drugs, New York, NY (212) 575-6868 (212) 575-6334
The Compounder Pharmacy, Aurora, IL (630) 859-0333
(800) 679-4667
(630) 859-0114
The Pharmacy Shop and
Compounding Center, Canandaigua, NY
(585) 396-9970
(800) 396-9970
(585) 396-7264
McGuff Compounding Pharmacy,
Santa Ana, CA
(714) 438-0536
(877) 444-1133
(877) 444-1155
Skip’s Pharmacy, Boca Raton, FL (561) 218-0111
(800) 553-7429
(561) 218-8873
Smith’s Pharmacy, Toronto, Canada (416) 488-2600
(800) 361-6624
(416) 484-8855
Dickson Chemist, Glasgow, Scotland +44-141-647-8032
+44-800-027-0673
+44-141-647-8032

IMPORTANT: Make sure to specify that you do NOT want LDN in a slow-release form.

Reports have been received from patients that their pharmacies have been supplying a slow-release form of naltrexone. Pharmacies should be instructed NOT to provide LDN in an “SR” or slow-release or timed-release form. Unless the low dose of naltrexone is in an unaltered form, which permits it to reach a prompt “spike” in the blood stream, its therapeutic effects may be inhibited.

Fillers. Capsules of LDN necessarily contain a substantial percentage of neutral inactive filler. Experiments by the compounding pharmacist, Dr. Skip Lenz, have demonstrated that the use of calcium carbonate as a filler will interfere with absorption of the LDN capsule. Therefore, it is suggested that calcium carbonate filler not be employed in compounding LDN capsules. He recommends either Avicel, lactose (if lactose intolerance is not a problem), or sucrose fillers as useful fast-release fillers.

> IMPORTANT: Make sure to fill your Rx at a compounding pharmacy that has a reputation for consistent reliability in the quality of the LDN it delivers.

The FDA has found a significant error rate in compounded prescriptions produced at randomly selected pharmacies. Dr. Bihari has reported seeing adverse effects from this problem. Please see our report, Reliability Problem With Compounding Pharmacies. Please see the above list of recommended pharmacies for some suggested sources.


What dosage and frequency should my physician prescribe?

The usual adult dosage is 4.5mg taken once daily at night. Because of the rhythms of the body’s production of master hormones, LDN is best taken between 9pm and 3am. Most patients take it at bedtime.

Notable exceptions:

  • People who have multiple sclerosis that has led to muscle spasms are advised to use only 3mg daily and to maintain that dosage.
  • For intial dosage of LDN in those patients who have Hashimoto’s thyroiditis with hypothyroidism and who are taking thyroid hormone replacement medication, please read Cautionary Warnings, below.

Rarely, the naltrexone may need to be purchased as a solution — in distilled water — with 1mg per ml dispensed with a 5ml medicine dropper. If LDN is used in a liquid form, it is important to keep it refrigerated.

The therapeutic dosage range for LDN is from 1.5mg to 4.5mg every night. Dosages below this range are likely to have no effect at all, and dosages above this range are likely to block endorphins for too long a period of time and interfere with its effectiveness.

> IMPORTANT: Make sure to specify that you do NOT want LDN in a slow-release form (see above).


Are there any side effects or cautionary warnings?

> Side effects:

LDN has virtually no side effects. Occasionally, during the first week’s use of LDN, patients may complain of some difficulty sleeping. This rarely persists after the first week. Should it do so, dosage can be reduced from 4.5mg to 3mg nightly.

> Cautionary warnings:

  1. Because LDN blocks opioid receptors throughout the body for three or four hours, people using medicine that is an opioid agonist, i.e. narcotic medication — such as Ultram (tramadol), morphine, Percocet, Duragesic patch or codeine-containing medication — should not take LDN until such medicine is completely out of one’s system. Patients who have become dependant on daily use of narcotic-containing pain medication may require 10 days to 2 weeks of slowly weaning off of such drugs entirely (while first substituting full doses of non-narcotic pain medications) before being able to begin LDN safely.
  2. Those patients who are taking thyroid hormone replacement for a diagnosis of Hashimoto’s thyroiditis with hypothyroidism ought to begin LDN at the lowest range (1.5mg for an adult). Be aware that LDN may lead to a prompt decrease in the autoimmune disorder, which then may require a rapid reduction in the dose of thyroid hormone replacement in order to avoid symptoms of hyperthyroidism.
  3. Full-dose naltrexone (50mg) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300mg daily. The 50mg dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3mg and 4.5mg doses.
  4. People who have received organ transplants and who therefore are taking immunosuppressive medication on a permanent basis are cautioned against the use of LDN because it may act to counter the effect of those medications.

When will the low-dose use of naltrexone become FDA approved?

> Although naltrexone itself is an FDA-approved drug, the varied uses of LDN still await application to the FDA after related scientific clinical trials.

The FDA approved naltrexone at the 50mg dosage in 1984. LDN (in the 3mg or 4.5mg dosage) has not yet been submitted for approval because the prospective clinical trials that are required for FDA approval need to be funded at the cost of many millions of dollars.

The successful results of the first US medical center research on LDN, an open-label trial that tested the use of LDN in Crohn’s disease (details here), was presented in May 2006 by Professor Jill Smith of the Pennsylvania State University College of Medicine. The National Institutes of Health has granted $500,000 for Dr. Smith’s group to continue the study as a larger placebo-controlled scientific trial of LDN in Crohn’s disease.

All physicians understand that appropriate off-label use of an already FDA-approved medication such as naltrexone is perfectly ethical and legal. Because naltrexone itself has already passed animal toxicity studies, one could expect that once testing is able to begin, LDN could complete its clinical trials in humans and receive FDA approval for one or more uses within two to four years.


What You Can Do

> Talk to your doctor.

If you are suffering from HIV/AIDS, cancer, or an autoimmune disease, LDN could help. In AIDS and cancer therapy, LDN is often used in conjunction with other medications.

Cancer. Anyone with cancer or a pre-cancerous condition should consider LDN. Many use LDN as a preventive treatment. Post-treatment, others have been using LDN to prevent a recurrence of their cancer. LDN has been shown in many cases to work with virtually incurable cancers such as neuroblastoma, multiple myeloma, and pancreatic cancer.

HIV/AIDS. As an AIDS drug, LDN leads to far fewer side effects than the standard “AIDS cocktail.” When used in conjunction with HAART therapies, LDN can boost T-cell populations, prevent disfiguring lipodystrophy, and lower rates of treatment failure.

Do not be afraid to approach your doctors — physicians today are increasingly open to learning about new therapies in development. Tell your doctors about this website, or print out and hand them the information, and let them weigh the evidence.

> Tell others.

If someone you know has HIV/AIDS, cancer, an autoimmune disease, or one of the aforementioned central nervous system disorders, LDN could save them from a great deal of suffering. If they use e-mail, send them the address of this website (www.lowdosenaltrexone.org). Or, print out the site and mail them the information.

> Help spread the word to the media, the medical community, and to developing countries.

Low-dose naltrexone has the potential to reduce the terrible human loss now taking place throughout the globe. It is a drug that could prevent millions of children from becoming AIDS orphans. It is a drug that could be a powerful ally in the war against cancer.

If you or someone you know has connections in the media, the medical community, or to those in developing countries involved in AIDS policy or treatment, please let them know about LDN.


About This Website

> This is a not-for-profit website.

This website is sponsored by Advocates For Therapeutic Immunology. The purpose of this website is to provide information to patients and physicians about important therapeutic breakthroughs in advanced medical immunology. The authors of this site do not profit from the sale of low-dose naltrexone or from website traffic, and are in no way associated with any pharmaceutical manufacturer or pharmacy.

> Consult your doctor.

This website is not intended as a substitute for professional medical help or advice. A physician should always be consulted for any medical condition.

> Contact us.

For information on how to contact us with questions or comments, click here.

Please note that no response can be given to individual questions concerning medical symptoms or treatment.


Additional Information

  • Bernard Bihari, MD, was the discoverer of the major clinical effects of low dose naltrexone. A private practitioner in Manhattan, Dr. Bihari was a Board-certified specialist in Psychiatry and Neurology. Dr. Bihari’s curriculum vitae.
  • David Gluck, MD (NY Lic. #083512), is the editor of this website, ldninfo.org. He is a Board-certified specialist in both Internal Medicine and Preventive Medicine. Dr. Gluck has served as medical director for JCPenney and MetLife, and is now semi-retired, living and working in New York City. [Ed. Note: Please do not confuse David Gluck, MD with an unrelated doctor of similar name in New York, David A. Gluck, who is a specialist in Obstetrics and Gynecology.]
  • Ian S. Zagon, PhD, has spent over two decades in doing basic research concerning endorphins. He is Professor of Neural and Behavioral Sciences, Pennsylvania State University, Dept. of Neural and Behavioral Sciences, H-109, Hershey Medical Center, Hershey, PA 17033; office phone: (717) 531-6409; email: isz1@psu.edu; website.

Footnotes

  1. Roy S, Loh HH. Effects of opioids on the immune system. Neurochem Res 1996;21:1375-1386
  2. Risdahl JM, Khanna KV, Peterson PK, Molitor TW. Opiates and infection. J Neuroimmunol 1998;83:4-18
  3. Makman MH. Morphine receptors in immunocytes and neurons. Adv Neuroimmunol 1994;4:69-82

The Endocannabinoid System

  • August 29, 2012 2:41 am

Saturating the endocannabinoid system with cannabinoids is the best maintenance of life. The ECS puts your biological systems in a normal range by up and down regulating all 210 types of cells. Raw cannabis has anti-proliferative properties as well as THC, but it is non-psychoactive, so a cancer patient could use as much as they need to be healed, beyond the ‘high’ that relieves pain. Seedlings form medicinal trichomes when they are a week old to protect themselves from predation, radiation and dessication. Hemp seed oil has 45 micrograms/6 tablespoons of THC according to calculations based on testpledge.com results.
CBD is patented by the Fda as a preventative for all oxidative diseases.All cannabis flowers contain cannabinoids, including hemp, males and hermaphrodites. Some may produce less trichomes by weight than others. For example, an Indica may be more visibly trichome-covered than industrial strains.

The body has the highest concentration of cannabinoids in breast milk; cannabinoids are essential nutrients. Our body breaks down Essential Fatty acids to make endogenous cannabinoids. Cannabinoids build up in the lipid tissue; once the body is saturated it reaches an optimum level of regeneration
THC is only found in trace amounts in raw cannabis. In 16-17% THCA strains, heat increases THC from 90 micrograms/ml to 10,060 micrograms/ml. This usually leaves 150 micrograms/ml of THCA and reduces the anti-oxidant tolerable dose to 1/50th.
Cannabis clinicians recommend 1-6 grams of cannabinoid acids such as THCA and 10 mg of THC a day.
For serious medical conditions, juice hemp flowers and leaves using a wheatgrass or masticating juicer. Mix 1 part cannabis to 10 parts carrot juice. Plants sprayed with inorganic pesticide shouldn’t be juiced; on the other hand most pests are edible. ”The money spent on diseases hemp could prevent equals the military budget” Dr. William Courtney

http://www.cannabis-med.org/index.php?tpl=page&id=69&lng=en

http://www.hemping.com/hemp-seed-whole-1-kg

http://www.hippiebutter.com/products/Hippie-Butter-Hemp-Seed-Oil.html

Brazillian Court Demands Nestle Label GMO Ingredients

  • August 29, 2012 12:36 am

 

Photo courtesy of NaturalSociety.com

It appears another victory has been declared in the battle against Monsanto and GMO ingredients. According to a major Brazilian business publication and GMWatch, a Brazilian court has demanded that multi-billion dollar food giant Nestle label all of their products as genetically modified that have over 1% GMO content. The ruling reportedly coincides with Brazilian law which demands all food manufacturers alert consumers to the presence of GMOs within their products.

Perhaps even more shocking is the fact that the court exposed a deep relationship between the Brazilian government and a major food industry lobby group that was forged in an effort to stop the court from issuing the ruling. This of course is predictable when considering that not only does Monsanto have a massive amount of political power with a figurehead in multiple branches of government, but when considering the previous WikiLeaks report that detailed how those who opposed Monsanto and biotechnology would be subject to ‘military style trade wars.’

The WikiLeaks documents revealed just how closely Monsanto has been working with the United States government, and just how serious the U.S. is about ensuring that the corporation’s GMO crops are widely accepted across the globe.

Amazingly, the Brazilian court took a stand against this corruption. Instead of groveling to Brazilian officials and mega biotechnology groups, the Brazilian business wire reports that the court determined the Brazilian government to be illegally working with the food industry entity known as ABIA. Furthermore, the court stated that consumers have the basic right to know what they are putting into their mouths — especially when it comes to GMO ingredients.

Nestle World Headquarters in Vevey, Switzerland – Panoramio.com

The court issued a fine of $2,478 per product that was found to violate the ruling after finding the presence of GMO ingredients in Nestle’s strawberry “Bono” cookies.

Other nations have taken similar actions against Monsanto and GMOs as a whole, with Poland banning Monsanto’s GM maize and Peru passing a monumental 10 year ban on GMOs as a whole. In the United States, the government continues to ignore and deny the concerns surrounding genetically modified crops and ingredients, instead streamlining the approval process for Monsanto’s new modified creations.

Source:  http://naturalsociety.com/brazilian-court-demands-nestle-label-gmo-ingredients

Peru Passes Monumental Ten-Year Ban on Genetically Modified Foods

  • August 29, 2012 12:31 am

 

gmoapples 210x131 Peru Passes Monumental Ten Year Ban on Genetically Modified FoodsIn an act of defiance against bloated biotech companies like Monsanto, Peru has officially passed a law banning genetically modified ingredients within the nation for a period of 10 years. Peru’s Plenary Session of the Congress made the decision despite previous governmental pushes for GM legalization. Anibal Huerta, President of Peru’s Agrarian Commission, said the ban was needed to prevent the ”danger that can arise from the use of biotechnology.”

While the ban will stop the flow of GM foods within the nation’s borders, a recent test conducted by the Peruvian Association of Consumers and Users (ASPEC) found that 77 percent of supermarket products tested contained GM contaminants. Genetically modified ingredients are so widespread among nations that it will be extremely difficult for Peru and other countries to eliminate products containing GMOs completely.

“There is an increasing consensus among consumers that they want safe, local, organic fresh food and that they want the environment and wildlife to be protected,” wrote Walter Pengue from the University of Buenos Aires in Argentina, in a recent statement concerning GMOs in South America. “South American countries must proceed with a broader evaluation of their original agricultural policies and practices using the precautionary principle.”

Not surprisingly, GMO crops have been and continue to be banned around the world. Hungary has gained international recognition for their bold stand against biotech giant Monsanto, destroying all Monsanto corn fields littered with GMO crops. France also took a stand by banning Monsanto’s GMO Maize, and despite the ban ending, the nation continued to take a stand against GMOs.

On a smaller scale, colorado’s Boulder County was the latest health freedom hotspot to stand up against Monsanto and genetically modified produce, with Boulder County advisory committees announcing plans to phase out GMO crops on open space in pursuit of sustainable and ethical farming practices.

Additional Sources:

Translated Spanish Press Released

ASPEC Study

 

Source:NaturalSociety.com

How to Make Turmeric Honey For Inflammation

  • August 26, 2012 7:12 am

Karen Vaughan, L.Ac., Registered Herbalist (AHG) posted this in Alternative Health on November 6th, 2010

Turmeric root. Photo taken in Kent, Ohio with …
Image via Wikipedia

Turmeric honey is one of my favorite ways to give turmeric. Turmeric is an adaptogen, a nontoxic herb that regulates the immune and endocrine systems. It also is antiseptic, is hepatoprotective, invigorates the blood, and helps prevent or treat infection. Regarded as a panacea in Ayurveda, turmeric is widely used in food, medicine and skin care. Indian curries, Persian dishes like masak lemak, Thai and Indonesian dishes like rendang use curry to color and impart flavor. In skin care, its golden color and medicinal properties enhance dark skin. (I have had people react in alarm when a turmeric foot soak turned my pale legs yellow!) It is used ceremonially throughout South Asia, including Bengali weddings where it adorns the married couple or Pujas where the powder is moistened and formed into an image of Ganesha. Rich in pigments it is used for dyes and to color food. It is one of my favorite herbs.

Turmeric contains up to 5% essential oils and up to 5% curcumin, a polyphenol considered the most active constituient of turmeric, although I think it works best when mixed with its other natural antioxidants including curcuminoids, flavanoids and carotinoids. Volatile oils include tumerone, atlantone, and zingiberone which is also found in the related plant, ginger. Other constituents include Vitamins C and E, sugars, proteins, and resins. It is used in Chinese and Ayurvedic medicine for the treatment of inflammation, flatulence, jaundice, menstrual difficulties, hematuria, hemorrhage, and colic. Turmeric can also be applied topically in poultices to relieve pain and inflammation but will color the skin for a few days after removal.
Bengali Bride

Image by SoulSoup via Flickr

Turmeric is better absorbed when mixed with other constituents and when used as a whole herb since flavanoids are best served with their synergistic compounds. Pharmacokinetic studies in animals demonstrate that 40-85 percent of an oral dose of the isolate curcumin passes through the gastrointestinal tract unchanged, with most of the absorbed flavanoid being metabolized in the intestinal mucosa and liver. But that refers to the isolates. One manufacturer of curcumin BCM-95®, mixes it back with the original compounds and increases absorbtion 7.8 times more than curcumin alone. (It might be easier to stay with the original herb!) Adding 5% black pepper or long pepper increases availability by 2000%. And most compounds are increased in bioavailability when taken with honey or a fat source like ghee.

Turmeric: The Yellow Root
Image by Carlos Lorenzo via Flickr

I have been making turmeric honey for some time now. Although curry powder typically contains both turmeric and pepper, the concentration of turmeric is rather low so I prefer to work with turmeric. I take:

9 parts dried turmeric powder
1/2 part freshly ground black pepper (grind it finely)
1/2 part dried ginger powder

Mix thoroughly. Start adding a liquid honey into the powder. It helps to warm the honey which allows it to absorb better. I usually use a local honey, but a eucalyptus or manuka honey would add additional benefit. Just make sure the honey is not whipped or crystallized because you need it to be runny. Stir, slowly adding the honey until all the powder is dissolved and you have a thick paste. The amount will vary depending on the moisture content of the honey, but a pound of turmeric in honey usually fills a 20 oz jar. The exact proportions are not critical as this is a food grade herb.

Turmeric plant
Image via Wikipedia

What is it good for? All kinds of things. If you suffer from arthritis, back pain or any kind of joint pain, this helps reduce the inflammation. I suggest it to most clients who suffer from autoimmune disease as it reduces flares when taken consistently at a teaspoonful per day. I had one client who suffered from large lipomas in her arms- after 6 months they had shrunk from softball size to golf ball size. If your C-reactive protein levels are high, indicating inflammation, this can frequently lower them. It is useful for reducing symptoms of crohn’s disease, lupus, RA, fatty liver, hepatitis and to prevent gallstones. Turmeric helps detoxify so is useful after exposure to industrial or household toxins. It can be mixed with warm milk or nutmilks for children coming down with an infection. You can mix it with other herbs or use the turmeric honey alone.

Turmeric honey can be use topically on sores and ulcerations, although I would thin with honey or water. In India, turmeric powder is frequently applied to cuts, and honey also is used in this manner. You can use it as a soak for skin conditions, at least if you don’t mind the color.

When I discussed this with David Winston, he suggested that ghee might be substituted for honey for diabetic clients (who typically suffer from high levels of inflammation.) You can melt ghee over a low flame and mix with the powders. It will have a more bitter taste, and intuitively I think that the honey helps with assimilation. If you want to reduce the honey, try one part melted ghee to two parts honey and stir well- adding a spoonful of lecithin will help mix the two liquids before you add the turmeric mixture. Just don’t use the same proportion of honey and ghee as this is considered unhealthy in Ayurveda. And you can also thin honey with up to a third hot water to reduce it.

And a totally irrelevant thing to try as long as you have the turmeric out:

Curcumin is used to indicate pH, with a yellow color in the presence of acids and a red color in the presence of bases. The whole herb works too. Take a little turmeric in a clear drinking glass and mix a half glass of water into it. Now add a little lye drain cleaner or a lot of baking soda, and watch it turn a pleasing shade of red. ( I couldn’t make the turmeric turn any yellower than it was with citric acid, so either it has the same color from acid to neutral, or my water is slightly acid.)

Comparison of Cannabidiol, Antioxidants and Diuretics in Reversing Binge Ethanol-Induced Neurotoxicity

  • August 25, 2012 5:32 pm

Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health (C.H., A.H., L.E.E.); Section of Neurochemistry and Neuroendocrinology, Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism (R.L.E.); and Radiology and Biology Branch, National Cancer Institute (D.A.W.), National Institutes of Health, Bethesda, Maryland

  1. Address correspondence to:
    Dr. Robert Eskay, Bldg. 49, Room 5A-35, 9000 Rockville Pike, Bethesda, MD 20892. E-mail: bobsk@mail.nih.gov

Abstract

Binge alcohol consumption in the rat induces substantial neurodegeneration in the hippocampus and entorhinal cortex. Oxidative stress and cytotoxic edema have both been shown to be involved in such neurotoxicity, whereas N-methyl-d-aspartate (NMDA) receptor activity has been implicated in alcohol withdrawal and excitoxic injury. Because the nonpsychoactive cannabinoid cannabidiol (CBD) was previously shown in vitro to prevent glutamate toxicity through its ability to reduce oxidative stress, we evaluated CBD as a neuroprotectant in a rat binge ethanol model. When administered concurrently with binge ethanol exposure, CBD protected against hippocampal and entorhinal cortical neurodegeneration in a dose-dependent manner. Similarly, the common antioxidants butylated hydroxytoluene and α-tocopherol also afforded significant protection. In contrast, the NMDA receptor antagonists dizocilpine (MK-801) and memantine did not prevent cell death. Of the diuretics tested, furosemide was protective, whereas the other two anion exchanger inhibitors, L-644,711 [(R)-(+)-(5,6-dichloro2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy acetic acid] and bumetanide, were ineffective. In vitro comparison of these diuretics indicated that furosemide is also a potent antioxidant, whereas the nonprotective diuretics are not. The lack of efficacy of L-644,711 and bumetanide suggests that the antioxidant rather than the diuretic properties of furosemide contribute most critically to its efficacy in reversing ethanol-induced neurotoxicity in vitro, in our model. This study provides the first demonstration of CBD as an in vivo neuroprotectant and shows the efficacy of lipophilic antioxidants in preventing binge ethanol-induced brain injury.

Alcohol is the world’s most widely used psychoactive drug, but chronic, excessive alcohol consumption leads to permanent organ damage or death. Alcohol-induced brain damage produces some of the most insidious effects of alcoholism, including cognitive deficits such as learning and memory impairment (Pfefferbaum et al., 1998; White, 2003). The pattern of alcohol consumption is an important predictor of brain damage with episodic or binge drinkers (defined as those who consume four to five or more drinks in a row) being the most vulnerable group (Hunt, 1993). In the United States, about 40% of college students and a high percentage of older adult alcoholics fit this definition of binge drinking (Wechsler et al., 2002).

The rat model of alcohol consumption used in the current study is designed to mimic a single cycle of binge drinking in human alcoholics. Binge ethanol consumption patterns in the rodent have been demonstrated to negatively impact on the ability of the rat to learn new information, not unlike memory difficulties seen in human alcoholics. This is consistent with the observation that binge ethanol consumption causes observable neuronal cell loss, measured by agyrophilic profiles, which is especially prominent in entorhinal cortex and hippocampus, two regions known to be involved in memory and cognition (Collins et al., 1996; Obernier et al., 2002a). The mechanism behind ethanol-induced selective neuronal damage is not well understood, but several explanations have been proposed. These include excitotoxicity associated with excessive neurotransmitter release, oxidative stress leading to free radical damage (Eskay et al., 1995; Crews et al., 2004), and edema caused by alterations in cellular control of ion transport (Collins et al., 1998).

Chronic ethanol consumption leads to increases in the density of NMDA receptor expression and subsequently the size of evoked calcium responses (Hu and Ticku, 1995). The non-competitive NMDA receptor antagonist dizocilpine (MK-801) has been shown to prevent alcohol withdrawal seizures (Grant et al., 1992) and has been previously examined as a treatment for alcohol-induced brain injury. Unfortunately, MK-801 treatment failed to ameliorate ethanol-induced neuronal damage (Collins et al., 1998; Corso et al., 1998), but this was possibly due to neurotoxic effects of MK-801 itself (Thomas et al., 2002). More recently, it has been proposed that low-affinity, activity-dependent NMDA receptor antagonists such as memantine may be able to protect against excitotoxicity, without also blocking the basal glutamatergic neurotransmission required for normal brain functioning (Lipton and Chen, 2004).

Ethanol may also injure the brain by increasing oxidative stress. Although the mechanisms behind oxidative stress are again not well understood, numerous studies have demonstrated that chronic ethanol consumption is accompanied by both oxidative damage to cellular proteins, lipids, and DNA (Mansouri et al., 2001; McDonough, 2003) and reduced levels of the endogenous antioxidants glutathione and superoxide dismutase (Reddy et al., 1999; Thirunavukkarasu et al., 2003). The role of oxidants in alcoholic tissue damage was well demonstrated by Mansouri et al. (2001) when they showed that acute ethanol administration in the mouse causes a loss of mitochondrial DNA in the brain and other tissues. Mansouri et al. (2001) also demonstrated that this damage can be prevented by either antioxidant administration or inhibiting ethanol metabolism, which suggests the involvement of mitochondrial dysfunction in alcohol-induced oxidative stress. Furthermore, Herrera et al. (2003) showed that chronic ethanol treatment in the rat results in a decline in hippocampal neurogenesis and that the antioxidant ebselen can prevent such decrease.

Brain edema has also been a demonstrated result of repeated intoxication and withdrawal cycles, which are the hallmark of binge alcohol consumption (Collins et al., 1998). Such alcoholics show brain edema during alcohol withdrawal, possibly due to over secretion of vasopressin (Lambie, 1985). During cytotoxic brain edema, astrocytes and neuronal dendrites swell, which is believed to trigger a compensatory release of chloride ions and excitatory amino acids during the process of regulatory volume decrease (Aschner et al., 1999). The role for brain edema in alcohol-induced neuronal loss is supported by the efficacy of the diuretic furosemide, which has been shown to prevent such neurotoxicity (Collins et al., 1998).

In the current study, we use a rat model of binge alcohol consumption to determine the potential of cannabidiol (CBD) as a neuroprotectant against ethanol-induced neurotoxicity. We also compare the in vivo neuroprotectant effects of CBD to that provided by two categories of NMDA receptor antagonists, two other lipophilic antioxidants, and three diuretics, to determine the mechanism by which CBD protects against binge alcohol-induced damage.

Materials and Methods

Materials. Cannabidiol and reagents other than those specifically listed below were purchased from Sigma Chemical Co. (St. Louis, MO). Alkamuls EL-620 was a gift from Rhodia (Cranberry, NJ). Dihydrorhodamine was obtained from Molecular Probes (Eugene, OR). Hydrogen peroxide, tetraethylammonium chloride, ferric citrate, and sodium dithionite were all purchased from Aldrich Chemical Co. (Milwaukee, WI). L-644,711 was a gift from Merck (Somerset, NJ).

Solution Preparation for in Vivo Studies. Cannabidiol, butylated hydroxytoluene (BHT), and α-tocopherol (TOC) were administered in vivo using a saline vehicle containing 30% ethoxylated castor oil (Alkamuls EL-620) and 3% ethanol. Cannabidiol and BHT were first solubilized in ethanol and then mixed with Alkamuls EL-620. Since TOC (Sigma Chemical Co.) was supplied as a concentrate in corn oil, ethanol and Alkamuls were added to the TOC to achieve a similar preparation as described for CBD and BHT. Each preparation was diluted [1:1 (v/v)] with saline immediately before administration as a 2-ml i.p. bolus, which supplied either 20 or 40 mg/kg CBD, 40 mg/kg BHT, or 80 mg/kg TOC/day.

Furosemide was prepared by dissolving in 0.1 N NaOH, and the pH was adjusted to 7.3 with 0.1 N HCl. Then, 800 μl/kg of this 4.2 mg/ml solution was injected (s.c.) into rats every 8 h to achieve a dose of 10 mg/kg/day. Bumetanide was dissolved in ethanol and then diluted with PBS (0.2% ethanol in PBS) to a concentration of 0.9 mg/ml and given 400 μl/kg (s.c.) every 8 h to a total of 1 mg/kg/rat each day. L-644,711 was dissolved in PBS at 8.4 mg/ml and was injected 800 μl/kg (s.c.) every 8 h to give 20 mg/kg/day.

MK-801, nimodipine, and memantine were suspended in physiological saline and given s.c. every 4 h in a volume of 100 μl. MK-801 was given at 0.02 and 0.6 mg/kg/day, nimodipine at 6 mg/kg/day, and memantine 30 mg/kg/day.

Cyclic Voltammetry. Cyclic voltammetry was performed with a potentiostat/galvanostat (model 273/PAR 270 software; EG&G Princeton Applied Research, Princeton, NJ). The working electrode was a glassy carbon disk with a platinum counter electrode and silver/silver chloride reference. Tetraethylammonium chloride in 0.1 M acetonitrile was used as an electrolyte. Cyclic voltammetry scans were done from 0 to +1.8 V at a scan rate of 100 mV/s. All oxidation potentials are reported versus Ag/AgCl.

Iron-Catalyzed Dihydrorhodamine Oxidation (Fenton Reaction). Antioxidant activities of test compounds were evaluated by their ability to prevent oxidation of dihydrorhodamine to the fluorescent compound rhodamine. Test compounds in a 50:50 water/acetonitrile (v/v) solution were incubated with 50 μM dihydrorhodamine for 5 min in the presence of 1 mM hydrogen peroxide and an iron catalyst (10 μM dithionite-reduced ferrous citrate). After this time, dihydrorhodamine protection was assessed by spectrofluorometry (excitation, 500 nm; emission, 570 nm).

Animals. Male Sprague-Dawley rats (Taconic Farms, Rockville, MD), weighing approximately 250 g, were maintained under a 12-h light/dark cycle (lights on 6:00 AM and off at 6:00 PM) with “Zeigler” (Gardners, PA) rat chow and water available ad libitum. For 7 days before surgery, all animals were group housed, but they were individually housed after implantation of chronic indwelling gastric cannula. All surgical procedures were performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Rats were anesthetized with ketamine hydrochloride/xylazine (80:10 mg/kg i.p.). Hair along the abdomen and nape of the neck was clipped, and the skin was swabbed with Betadine. A 3-cm incision was made through the skin adjacent to the stomach, and a 1-cm incision was made through the gastric musculature. A flared 10-cm piece of medical grade silicone tubing (0.095 o.d.; New Age Industries, Southampton, PA) was inserted into the gastric fundus, and the gastric musculature was sutured closed around it. The silicone tubing was inserted under the skin to the nape of the neck and connected to an L-shaped 5-cm hypodermic stainless steel tube (15 gauge; Small Parts, Miami lakes, FL) woven into a 2-cm square of Dacron mesh pad. The Dacron pad was sutured to the musculature and skin at the neck and the incision closed with 3.0 silk suture (Ethicon, Piscataway, NJ). The gastric cannula was flushed with 0.9% saline and capped. A single subcutaneous injection of buprenorphine (100 μg/kg) was given for postsurgical analgesia, along with i.p. antibiotics gentamicin (8.5 mg/kg) and ampicillin (70 mg/kg). Animals were placed on a heating pad until they became ambulatory, at which time they were returned to their cages and fed ad libitum.

Alcohol Administration Procedure. Seven days after cannula implantation, all rats were given ad libitum access to alcohol-free liquid diet for 3 days formulated to provide 16.9% of calories as protein, 59.2% carbohydrate, and 23.9% fat (Research Diets Inc., Allentown, NJ). The morning of the next day, alcohol administration was begun (day 1 of the 4-day binge). Beginning at lights on, all rats were given 12 ml of liquid diet via gastric cannula every 8 h (6:00 AM, 2:00 PM, and 10:00 PM). In the ethanol-treated animals, the 12 ml of liquid diet was modified to contain 10 to 12% less calories from carbohydrate, which was replaced with an equal caloric quantity of ethanol. Rats were rated for level of intoxication at the time of each ethanol feeding and given the appropriate ethanol dose, as per the Majchrowicz procedure (Majchrowicz, 1975) for 4 days. Diuretics were administered s.c. three times daily, and glutamatergic blockers were administered s.c. six times daily for the 4-day ethanol treatment protocol. Cannabidiol and other antioxidants were administered i.p. twice a day (10:00 AM and 10:00 PM) on alcohol treatment days 2–4, since neurodegeneration has not been seen before 3 or 4 days of binge alcohol administration. All potential neuroprotectants tested were administered in a double-blinded manner. On the morning of the fifth day animals were deeply anesthetized with an i.p. injection of ketamine hydrochloride and xylazine (80:10 mg/kg) and transcardially perfused via gravity flow. Blood was cleared from the animal’s vasculature with 200 ml of wash solution (0.8% sodium chloride, 0.4% dextrose, 0.8% sucrose, 0.5% sodium nitrite, 0.023% calcium chloride, and 0.034% sodium cacodylate) followed by 250 ml of fixative solution (4% sucrose, 4% paraformaldehyde, and 1.43% cacodylic acid).

Biochemical Procedures. Blood alcohol levels (BALs) were monitored each day by a tail bleed, taken 2 h after initial daily ethanol administration (8:00 AM), and BALs were determined using a standard alcohol dehydrogenase-based diagnostic kit (Sigma Chemical Co.).

Brain Preparation. Neurodegeneration was assessed using the amino-cupric-silver technique of De Olmos as performed by Switzer’s Neuroscience Associates group (de Olmos et al., 1994; Switzer, 2000). In short, brains were removed from the skulls 24 h after perfusion and immersed in a solution containing 20% glycerol and 2% dimethyl sulfoxide to prevent freeze artifacts and then embedded in a gelatin matrix in groups of 16. The brain matrices were then sliced in the coronal plane by sliding microtome (40 μm in thickness). Every eighth section was then stained.

Staining Procedure. Briefly, sections were rinsed three times in deionized water and then placed for 4 days in an aqueous mixture of silver and copper nitrate, pyridine, and ethanol. Sections were then transferred through acetone, a diammine-silver solution, reduced in a weak formaldehyde solution, and bleached in a preparation of potassium ferricyanide and sodium borate (to remove unreduced silver). Sections were then mounted, dried, and counter stained with neutral red.

Quantification. Coronal sections from the ventral hippocampus, both left and right side (2 each side), were analyzed for degeneration counts at 6.00 and 6.32 mm posterior to bregma (Paxinos and Watson, 1986). Degenerating cells were defined as dark, argyrophilic neurons with dendrites clearly visible. Dark objects not clearly identified as neurons were not counted. The number of counts was determined from two consecutive circular microscope fields at 20× magnification for each tissue section. Data for hippocampal degeneration are presented as counts per square millimeter by dividing total number of degenerating cells counted in eight microscope fields by the calculated area of the fields counted (1-mm-diameter counting field). Two sections from both the left and right side of the entorhinal cortex were also counted at 7.00 and 7.32 mm posterior to bregma, in one microscope field at 20× magnification.

Data Analysis. Data are reported as mean values ± standard error. Degeneration data were examined for significance (at p < 0.05) using the nonparametric Kruskal-Wallis test with Mann-Whitney U tests for pairwise comparisons.

Results

Analysis of rats fed 10 to 12% ethanol (9–12 g/kg/day) in a liquid diet confirmed that blood alcohol levels were maintained between 2.0 and 4.0 g/l on days 2 to 4 (Table 1). At the end of the experiment, silver staining of coronal brain slices prepared from ethanol-treated animals revealed a significant loss of neurons throughout the hippocampal cortical circuits of the brain (Fig. 1). The most affected regions included the olfactory bulb and dentate gyrus granular cell layer, as well as perirhinal, piriform, and entorhinal cortices. Silver-stained cells were quantified in the hippocampus and entorhinal cortex. When 40 mg/kg CBD was coadministered with ethanol on days 2 to 4 of the protocol, alcohol-induced cell death was reduced by approximately 60% (p < 0.05) in both hippocampal granular cells and the entorhinal cortical pyramidal cells (Fig. 1).

View this table:

TABLE 1

Blood alcohol levels Rats were tail bled 2 h after the first ethanol feeding of the day, and blood alcohol levels were quantified using a standard alcohol dehydrogenase-based diagnostic kit.

Since excitotoxicity has also been proposed as a potential mechanism underlying ethanol-induced neurodegeneration, the effects of two NMDA receptor antagonists and an L-type calcium channel blocker were examined. The NMDA receptor antagonists MK-801 (0.6 mg/kg/day) and memantine (30 mg/kg/day) were administered in six divided doses to both control rats and animals subjected to a binge ethanol paradigm (described above). Similarly, two other groups of animals were given nimodipine (6 mg/kg/day), an L-type calcium channel blocker, both with and without ethanol. Three-day average BALs measured 2 h after administration in ethanol-, ethanol plus MK-801-, ethanol plus memantine-, and ethanol plus nimodipine-treated rats were 2.66 ± 0.38, 2.24 ± 0.28, 2.68 ± 0.22, and 2.42 ± 0.36 g/l, respectively, and they did not differ across groups. Figures 2 and 3 demonstrate that argyrophilic staining in both the hippocampus and entorhinal cortex of ethanol-treated animals was actually increased by the presence of 0.6 mg/kg/day MK-801. Furthermore, staining of piriform cortical (not shown) and hippocampal granule cells was evident with MK-801 treatment even in the absence of alcohol (Fig. 2A). Due to the apparent toxicity of this dose of MK-801, a second experiment was performed using a 30-fold lower dose of MK-801 (0.02 mg/kg/day) in conjunction with the ethanol treatment. This dose of MK-801 was found to be without neurotoxic consequences when given in the absence of ethanol, but it was again found to exacerbate the alcohol-induced damage in the entorhinal cortex (Fig. 3C). At 0.02 mg/kg/day dizocilpine had neither a protective nor toxic effect on the hippocampal dentate gyrus (Fig. 2C). Similarly, the low-affinity antagonist memantine and the L-type calcium channel blocker nimodipine neither exacerbated nor ameliorated damage in either the dentate gyrus or the entorhinal cortex.

  Fig. 1.

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Fig. 1.

Effect of CBD on ethanol-induced neurotoxicity in rats. Gastric-cannulated rats were randomly divided into six groups: pair-fed controls (Con; n = 5), ethanol (ET; n = 9), cannabidiol 20 mg/kg (CBD20; n = 6), cannabidiol 20 mg/kg + ET (CBD-ET 20; n = 8), CBD 40 mg/kg (CBD40; n = 6), and CBD 40 mg/kg + ET (CBD-ET 40; n = 8) and given ET three times daily in a binge ethanol model as described under Materials and Methods. CBD was given i.p. twice daily on days 2 to 4. A, photomicrographs of damage in hippocampus (left) and entorhinal cortex (right) after 4 days of binge ethanol administration with either concurrent vehicle (top) or CBD 40 mg/kg/day (bottom) treatment. Cells were stained by de Olmos silver staining method as described under Materials and Methods. B, enlarged photomicrographs of degeneration in dentate gyrus (left) and entorhinal cortex (right) of ethanol-treated rats depicting greater detail in the silver staining. Graphical representation of argyrophilic cell quantification in dentate gyrus (C) and entorhinal cortex (D). Silver staining was counted as described under Materials and Methods. Data represent mean values ± S.E.M. *, significant difference from Con, p < 0.05; #, significant difference from ET, p < 0.05, Mann-Whitney U pairwise comparisons. Data not shown for CBD-treated controls; no degeneration was found. Scale bar, 100 μm.

  Fig. 2.

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Fig. 2.

Effect of NMDA receptor blockade on ethanol-induced neurotoxicity in rat hippocampus. Gastric-cannulated rats were randomly divided into eight groups: pair-fed controls (Con; n = 5), ethanol (ET; n = 6), MK-801 (MK; n = 6), MK + ET (MK-ET; n = 8), nimodipine (Nim; n = 6), Nim + ET (Nim-ET; n = 8), memantine (Mem; n = 8), and Mem + ET (Mem-ET; n = 11) and given ET three times daily in a binge ethanol model as described under Materials and Methods. Potential neuroprotectants were given s.c. in six divided doses with daily totals for MK-801 (MK and MK-ET) at 0.6 mg/kg/day, nimodipine (Nim and Nim-ET) at 6 mg/kg/day, and memantine (Mem and Mem-ET) at 30 mg/kg/day just before ET administration and 4 h thereafter. A, photomicrographs of hippocampus granule cell layer after 4 days of binge ethanol administration (ET, left) compared with control diet (Con, right) treated with either vehicle (top) or MK-801 0.6 mg/kg/day (bottom). Cells were stained by De Olmos silver staining method as described under Materials and Methods. B, graphical representation of argyrophilic cell counting. Data represent mean values ± S.E.M. *, significant difference from Con, p < 0.05; #, significant difference from ET, p < 0.05, Mann-Whitney U pairwise comparisons. C, a second experiment was run as in B. Rats were divided into four groups: Con (n = 6), ET (n = 8), Lo MK (n = 8), and Lo MK-ET (n = 11) and given ET and MK-801 as described above using 0.02 mg/kg/day MK-801 in six divided doses. *, significant difference from Con, p < 0.05; Mann-Whitney U pairwise comparisons. Scale bar, 100 μm.

To further explore the mechanism underlying CBD neuroprotection against ethanol neurotoxicity, its efficacy was compared with that of antioxidants BHT and TOC both in vitro and in vivo. The antioxidant properties of CBD were compared in vitro with BHT and TOC, by cyclic voltammetry, which measures the oxidation or reduction potential (x-axis) of a compound. The y-axis, or current, is a measure of the number of electrons per unit time, reflecting primarily diffusion of the electrochemical species to and from the electrode surface. Cannabidiol, like BHT, exhibited an irreversible oxidation potential of 1.4 V (Fig. 4A), whereas TOC had a higher, but reversible potential of 1.5 V. By this criterion, CBD, BHT, and tocopherol are comparable antioxidants.

  Fig. 3.

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Fig. 3.

Effect of NMDA receptor blockade on ethanol-induced neurotoxicity in rat entorhinal cortex. Experimental conditions as described in Fig. 2. A, photomicrographs of entorhinal cortex after 4 days of binge ethanol administration (ET, left) compared with control diet (Con, right) treated with either vehicle (top) or MK-801 0.6 mg/kg/day (bottom). Cells were stained by De Olmos silver staining method as described under Materials and Methods. B, graphical representation of argyrophilic cell counting. Con (n = 5), ET (n = 6), MK-801 (MK; n = 6), MK + ET (MK-ET; n = 8), nimodipine (Nim; n = 6), Nim + ET (Nim-ET; n = 8), memantine (Mem; n = 8), and Mem + ET (Mem-ET; n = 11). Data represent mean values ± S.E.M. *, significant difference from Con, p < 0.05; #, significant difference from ET, p < 0.05, Mann-Whitney U pairwise comparisons. C, a second experiment was run as in Fig. 2B, using 0.02 mg/kg/day MK-801 in addition to, or apart from, ethanol treatment. Con (n = 6), ET (n = 8), Lo MK (n = 8), and Lo MK-ET (n = 11). Data represent mean values ± S.E.M. *, significant difference from Con, p < 0.05; #, significant difference from ET, p < 0.05, Mann-Whitney U pairwise comparisons. Scale bar, 200 μm.

To examine whether the antioxidant property of CBD might account for the protection it provided in the binge drinking model, the effects of BHT and TOC were also examined using the same 4-day binge-alcohol administration model. Three-day average BALs for ethanol-, ethanol plus BHT-, and ethanol plus TOC-treated rats were 3.03 ± 0.18, 2.63 ± 0.27, and 2.65 ± 0.25 g/l, respectively, and they were not statistically different. Both compounds (BHT at 40 mg/kg and TOC at 80 mg/kg) significantly reduced neuronal loss in the hippocampus and entorhinal cortex to a similar degree to that seen with CBD (Fig. 4B), a result consistent with the hypothesis that CBD protects due to its antioxidant properties.

  Fig. 4.

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Fig. 4.

Comparison of the antioxidative capacities of CBD, BHT, and α-tocopherol and their neuroprotective effects. A, oxidation profiles of 1 mM CBD, BHT, and α-tocopherol when subjected to cyclic voltammetry. Data represent mean values ± S.D. from six replicates. Quantification of degeneration in rat hippocampus (B) and entorhinal cortex (C) after 4-day binge ethanol administration as described in Fig. 1. Rats were divided into six groups: Con (n = 6), ET (n = 8), BHT (n = 6), BHT + ET (BHT-ET; n = 10), tocopherol (TOC; n = 6), and TOC + ET (TOC-ET; n = 7). BHT and TOC were given i.p. twice daily on days 2 to 4. BHT was used at a dose of 40 mg/kg, whereas TOC was administered at 80 mg/kg. Data represent mean values ± S.E.M. *, significant difference from Con, p < 0.05; #, significant difference from ET, p < 0.05, Mann-Whitney U pairwise comparisons. Data from BHT and TOC without ET treatment not shown; no degeneration seen.

A previous binge alcohol administration study indicated that the diuretic furosemide, which acts by inhibiting both Cl-/HCO-3 anion exchange and Na+/K+/2Cl- cotransport, also protects against alcohol-induced neurotoxicity (Collins et al., 1998). Although the mechanism by which furosemide protected was not confirmed, it was suggested that diuretics might protect by reducing alcohol-induced brain edema. To examine this hypothesis, furosemide and two other diuretics were compared in vivo. As with furosemide, bumetanide is a loop diuretic that inhibits Na+/K+/2Cl- cotransport, whereas L-644,711 is a modified loop diuretic that inhibits Cl-/HCO-3 anion exchange. Three day average BALs for ethanol-, ethanol plus furosemide-, ethanol plus bumetanide-, and ethanol plus L-644,711-treated rats were 3.17 ± 0.33, 2.68 ± 0.33, 3.41 ± 0.17, and 3.17 ± 0.29 g/l, respectively, and they did not differ statistically. As shown by Collins, 10 mg/kg furosemide significantly reduced cell loss in the entorhinal cortical neurons to a degree similar to that observed with CBD or other antioxidant treatments (Fig. 5, A and B). In contrast, neither 1 mg/kg bumetanide nor 20 mg/kg L-644,711 provided any significant protection against alcohol-induced neurotoxicity (Fig. 5, A and B).

The inconsistent protection observed with the three diuretics suggested that some other feature of furosemide might explain its protective properties against alcohol-induced injury. Since antioxidants provided significant protection in this model, the oxidation potentials of the three tested diuretics were examined by cyclic voltammetry. The results revealed that the oxidation potential of furosemide and bumetanide were similar to that of the antioxidants described above (compare Figs. 4A and 5C). In contrast, L-644,711 showed no appreciable ability to be oxidized and therefore would not have antioxidant properties. Since bumetanide had similar oxidation potential to the other protective compounds and yet failed to protect against alcohol-induced neurotoxicity, a second, antioxidant assay was performed. In the Fenton reaction assay, varying concentrations of a test compound are examined for their ability to prevent dihydrorhodamine oxidation by oxygen free radicals (generated by ferrous catalysis of hydrogen peroxide). This assay helps predict which of those compounds with antioxidant activity are likely to be effective antioxidants in a biological context, e.g., when antioxidant activity requires free-radical scavenging capability. Furosemide, as well as the antioxidants CBD and BHT, inhibited dihydrorhodamine oxidation with a similar relative EC50 of approximately 1 mM (the exact EC50 value is dependent on the amount of oxidant present). Despite the oxidation potential of bumetanide, as measured by cyclic voltammetry, it did not prevent oxidation of dihydrorhodamine (Fig. 5D). These in vitro antioxidant assays strongly suggest that furosemide is a biological antioxidant, unlike bumetanide or L-644,711. Together, the data presented in this study demonstrate that antioxidants, exhibiting both antioxidant potential by cyclic voltammetry and capable of inhibiting the oxidation of dihydrorhodamine in the Fenton reaction, protect against alcohol-induced brain injury, whereas the inconsistent protection observed with diuretics suggests that furosemide protection is at least partly a function of its antioxidative properties.

Discussion

Rats exposed to a 4-day binge ethanol treatment had significant cellular damage in the olfactory bulb, perirhinal, piriform, and entorhinal cortices, and the dentate gyrus granular cell layer, in agreement with previous reports (Collins et al., 1996; Obernier et al., 2002a). Since alcohol circulates freely through the whole brain, rather than selectively to these regions, it seemed most likely that damage to hippocampus and entorhinal cortex by ethanol reflects differential susceptibility of these neuronal populations to ethanol-induced damage, similar to ischemia-induced neuronal cell loss (Back et al., 2004).

Quantitative measurements of selected putative neuroprotectants were examined in the hippocampus and entorhinal cortex, areas with intense silver staining. It has previously been demonstrated that this silver staining technique identifies cells irreversibly committed to the cell death pathway (Switzer, 2000). Damage to these brain areas is particularly important because of their involvement in memory formation and recall. The selective vulnerability of the hippocampus and entorhinal cortex may therefore lead to significant behavioral sequela in binge drinkers impacting cognitive function and independence in performing activities of daily life. Rats demonstrate significant impairment in learning ability (Morris water maze test) 5 days after binge ethanol consumption (Obernier et al., 2002b) spending more time than controls in a previously trained quadrant during reversal training, demonstrating perseveration of an incorrect response not unlike that reported in human alcoholics (Lyvers and Maltzman, 1991).

We demonstrate here that CBD, a nonpyschoactive component of marijuana, substantially limits neuronal damage to hippocampal and entorhinal cortical brain regions when administered concurrently with alcohol in the rat binge alcohol model. CBD has been shown to prevent damage associated with glutamate toxicity in cortical neuron cultures and to have antioxidant properties (Hampson et al., 1998). We therefore examined both excitotoxic and antioxidant pathways for their neuroprotective ability. We attempted to inhibit excitotoxic damage in vivo through NMDA receptor blockade using both high- and low-affinity compounds. The high-affinity antagonist MK-801 protects organotypic slice cultures exposed to NMDA (Pringle et al., 2000) and eliminates alcohol withdrawal seizures (Grant et al., 1992) and accompanying deficits in reversal learning (Thomas et al., 2002). Previous work, however (Collins et al., 1998; Corso et al., 1998), failed to show neuroprotection against binge ethanol-induced neurodegeneration in rats given 1 or 2 mg/kg/day MK-801. We tested MK-801 at a dose (0.6 mg/kg/day) reported to be protective against the teratogenic affects of ethanol withdrawal (Thomas et al., 2002). In accord with results of Collins et al. (1998), rats treated with 0.6 mg/kg/day MK-801 demonstrated dramatic enhancement of, rather than protection from, ethanol-induced cellular damage in hippocampal and entorhinal cortical regions. In fact, MK-801 was toxic to hippocampal granule cells even in the absence of ethanol. Corso et al. (1998) reported no damage with 1 mg/kg/day MK-801 in the absence of ethanol with a single daily injection. The difference in these two reports may be the MK-801 administration frequency (half-life in rats 90 min; Schwartz and Wasterlain, 1991). An indwelling minipump (2 mg/kg/day) resulted in extensive damage, but a single injection (1 mg/kg/day) caused no damage. In our experiment, 0.6 mg/kg/day resulted in damage (six divided doses), suggesting that frequency and dosage contribute to the in vivo neurotoxicity of MK-801.

Administration of substantially less MK-801 (0.02 mg/kg/day) was without neurotoxic effects itself, whereas significantly exacerbating ethanol neurotoxicity in the entorhinal cortex. Thus, high-affinity NMDA receptor antagonists, although predictive of decreased glutamate-induced toxicity in cell culture, seem to have no therapeutic value in the binge ethanol model.

A new class of low-affinity antagonists have been developed with rapid on/off receptor-binding kinetics (Lipton and Chen, 2004). Memantine inhibits the development of alcohol dependence, evidenced by abrogation of audiogenic seizures (Kotlinska, 2001), and prevents ethanol-induced cognitive impairment in the rat (Lukoyanov and Paula-Barbosa, 2001). Memantine, however, did not affect the extent of neuronal damage in these studies. Blockade of L-type calcium channels also had no beneficial effects on alcohol-induced cell damage. Thus, it seems unlikely that the neuroprotection afforded by CBD occurs through inhibition of the excitotoxic cascade initiated by glutamate release. Rather, the present experiments confirm our previous cell culture findings, demonstrating that CBD neuroprotection against glutamate-induced neurotoxicity likely involves redox events downstream of NMDA receptor occupancy, engagement, and subsequent calcium influx (Hampson et al., 1998).

  Fig. 5.

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Fig. 5.

Comparison of furosemide and other compounds with similar pharmacological properties. A, in vivo comparison of diuretics as neuroprotectants in the hippocampus during binge ethanol consumption. Rats were divided into eight groups: Con (n = 6), ET (n = 8), furosemide (F, n = 6), F + ET (F-ET; n = 5), bumetanide (B; n = 6), B + ET (B-ET; n = 7), L-644,711 (L; n = 6), and L + ET (L-ET; n = 9) and were given intragastric ethanol for 4 days as in Fig. 1. Furosemide was given 10 mg/kg, bumetanide 1 mg/kg, and L-644,711 1 mg/kg. Data represent mean values ± S.E.M. *, significant difference from Con, p < 0.05; Mann-Whitney U pairwise comparisons. Data from F, B, and L without ET treatment not shown; no degeneration seen. B, quantification of degeneration in entorhinal cortex. Experimental conditions same as in A. Data represent mean values ± S.E.M. *, significant difference from Con, p < 0.05; #, significant difference from ET, p < 0.05, Mann-Whitney U pairwise comparisons. Data from F, B, and L without ET treatment not shown; no degeneration seen. C, oxidation profile of 1 mM furosemide, bumetanide, and L-644,711 subjected to cyclic voltammetry. Data represent mean values ± S.D. from six replicates. D, antioxidative properties of furosemide were compared with two other blood-brain barrier-permeable anion exchange inhibitors and the antioxidants CBD and BHT using a Fenton reaction system based on the oxidation of dihydrorhodamine by 1 mM hydrogen peroxide (with a 10 μM ferrous citrate catalyst). See Materials and Methods for experimental details. Data represent mean values ± S.D. from six replicates.

We compared the neuroprotective effects of CBD with two other common antioxidants, TOC and BHT. All three compounds reduced more than 50% of the argyrophilia after binge ethanol treatment in brain regions examined. Acute and chronic ethanol administration has demonstrated increases in reactive oxygen species such as malondialdehyde and reductions in superoxide dismutase and glutathione reductase antioxidant enzyme activity (Reddy et al., 1999; Thirunavukkarasu et al., 2003). Administration of the endogenous antioxidant melatonin, or quercetin, a flavonoid antioxidant, reverses brain lipid peroxidation and ameliorates memory retention deficits in chronically ethanol-treated mice (Raghavendra and Kulkarni, 2001; Singh et al., 2003). Because the brain contains a high concentration of polyunsaturated fatty acids and low levels of antioxidants (Sun and Sun, 2001), it may be particularly vulnerable to ethanol-induced oxidative stress. We show here that antioxidants prevent the cell death associated with binge ethanol consumption.

The 4-day binge ethanol model has been used to demonstrate not only neurodegeneration but also decreased proliferation and survival of nascent neural progenitors (Nixon and Crews, 2002). Ebselen, an antioxidant, completely reversed the decline in neuron generation in the granule cell layer after chronic ethanol treatment (Herrera et al., 2003). Thus, antioxidants seem to enhance neuronal replacement as well as prevent neuronal death after ethanol insult.

Previously, the compound furosemide was found neuroprotective in a similar binge model of alcohol-induced brain damage (Collins et al., 1998). It was hypothesized that the protective ability of furosemide derived from its diuretic properties, preventing compression-related trauma associated with fluid imbalance and cellular swelling due to high ethanol concentrations. We demonstrate here that compounds with similar abilities to inhibit anion exchange (bumetanide and L-644,711), one of which is neuroprotective in a mechanical trauma model (Kimelberg et al., 1989), did not prevent the alcohol-associated damage in the hippocampus and entorhinal cortex. Examination of furosemide and bumetanide revealed oxidation potentials similar to those of BHT and TOC. Only furosemide, however, effectively prevented oxidation in a Fenton reaction, revealing superior potential as a biological antioxidant.

The mechanisms by which alcohol induces neuronal oxidative damage are not known and could potentially include acetaldehyde-derived alkaloidal metabolite generation or inflammatory mechanisms. TNFα, a potent cytokine inducer of neutrophil infiltration and generator of oxidative species in microglia and macrophages, has a prominent role in alcohol-induced liver disease, but its role in alcohol-induced neurotoxicity is unknown. CBD has been shown to decrease TNFα release in a murine collagen-induced arthritis model (Malfait et al., 2000), and BHT can block TNFα activation of nuclear factor-κB (Zou and Crews, 2005), demonstrating that antioxidants can decrease inflammation. Oxidative stress and inflammation are likely linked and may be difficult to tease apart. Our findings here suggest that antioxidant properties rather than diuresis alone contribute most critically to protection against alcohol-induced neurotoxicity and that although individual measures of antioxidant activity may predict antioxidant potential, predictive assessment of antioxidant activity in vivo may be complex.

It is perhaps unsurprising that biological antioxidant activity in vivo may not be predictable based solely on electrochemical potential (or indeed any single in vitro parameter of redox activity). The biological compartment into which the compound partitions, the reactive species with which it interacts, and the oxidized species generated all likely effect biological antioxidant efficacy. In addition, the biochemical profile of oxidative stress is likely to differ depending on the pathophysiological stress, including the presence of infiltrating inflammatory cells, compromised vascular perfusion, and altered glial and microglial cell function. Imparting antioxidant potential may therefore require optimization of electrochemical properties, rather than maximization, in a drug series, depending on initial lipophilicity, tissue distribution, cellular compartmentalization, and interaction with multiple cellular and extracellular oxidants and pathogenic oxidative pathways.

Although neuroprotection is potentially afforded by mechanisms in addition to antioxidation, the robust effects observed here for CBD, TOC, BHT, and furosemide suggest that designing general antioxidant properties into drugs with other primary mechanisms of action, or even the use of combination therapy may be beneficial in decreasing drug toxicity and enhancing drug efficacy. Assuming antioxidant properties as a primary mechanism of action opens the possibility for use of chemical methods as predictors of therapeutic outcome. Cyclic voltammetry is indicative of a substrate’s capacity to yield electrons through an outer sphere electron transfer mechanism, whereas the Fenton reaction accounts for other mechanisms important in preventing oxidative tissue injury such as scavenging properties or interaction with metal catalysts. We submit that cyclic voltammetry is an “initial screen” for possible consideration as a biological antioxidant, whereas activity in the Fenton assay can “screen out” compounds before testing in vivo. The ability to couple convenient in vitro assays for antioxidant activity with an in vivo measurement of neuroprotection may be useful in iterative screening for neuroprotective compounds in a variety of disease states in which neurodegeneration occurs.

Footnotes

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

  • doi:10.1124/jpet.105.085779.

  • ABBREVIATIONS: NMDA, N-methyl d-aspartate; MK-801, dizocilpine; CBD, cannabidiol; L-644,711, (R)-(+)-(5,6-dichloro2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy acetic acid; Alkamuls EL-620, polyoxyethylene 30 castor oil; BHT, butylated hydroxytoluene; TOC, α-tocopherol; PBS, phosphate-buffered saline; BAL, blood alcohol level; TNF, tumor necrosis factor.

  • 1 These authors contributed equally to this work.

    • Received March 4, 2005.
    • Accepted May 3, 2005.

References

  1. Aschner M, Allen JW, Kimelberg HK, LoPachin RM, and Streit WJ (1999) Glial cells in neurotoxicity development. Annu Rev Pharmacol Toxicol 39: 151-173.
  2. Back T, Hemmen T, and Schuler OG (2004) Lesion evolution in cerebral ischemia. J Neurol 251: 388-397.
  3. Collins MA, Corso TD, and Neafsey EJ (1996) Neuronal degeneration in rat cerebrocortical and olfactory regions during subchronic “binge” intoxication with ethanol: possible explanation for olfactory deficits in alcoholics. Alcohol Clin Exp Res 20: 284-292.
  4. Collins MA, Zou JY, and Neafsey EJ (1998) Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema-based mechanism. FASEB J 12: 221-230.
  5. Corso TD, Mostafa HM, Collins MA, and Neafsey EJ (1998) Brain neuronal degeneration caused by episodic alcohol intoxication in rats: effects of nimodipine, 6,7-dinitro-quinoxaline-2,3-dione and MK-801. Alcohol Clin Exp Res 22: 217-224.
  6. Crews FT, Collins MA, Dlugos C, Littleton J, Wilkins L, Neafsey EJ, Pentney R, Snell LD, Tabakoff B, Zou J, and Noronha A (2004) Alcohol-induced neurodegeneration: when, where and why? Alcohol Clin Exp Res 28: 350-364.
  7. de Olmos JS, Beltramino CA, and de Olmos de Lorenzo S (1994) Use of an aminocupric-silver technique for the detection of early and semiacute neuronal degeneration caused by neurotoxicants, hypoxia and physical trauma. Neurotoxicol Teratol 16: 545-561.
  8. Eskay RL, Chautard T, Torda T, Daoud RI, and Hamelink C (1995) Alcohol, corticosteroids, energy utilization and hippocampal endangerment. Ann NY Acad Sci 771: 105-114.
  9. Grant KA, Snell LD, Rogawski MA, Thurkauf A, and Tabakoff B (1992) Comparison of the effects of the uncompetitive N-methyl-d-aspartate antagonist (+-)-5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (ADCI) with its structural analogs dizocilpine (MK-801) and carbamazepine on ethanol withdrawal seizures. J Pharmacol Exp Ther 260: 1017-1022.
  10. Hampson AJ, Grimaldi M, Axelrod J, and Wink D (1998) Cannabidiol and (-)delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA 95: 8268-8273.
  11. Herrera DG, Yague AG, Johnsen-Soriano S, Bosch-Morell F, Collado-Morente L, Muriach M, Romero FJ, and Garcia-Verdugo JM (2003) Selective impairment of hippocampal neurogenesis by chronic alcoholism: protective effects of an antioxidant. Proc Natl Acad Sci USA 100: 7919-7924.
  12. Hu XJ and Ticku MK (1995) Chronic ethanol treatment upregulates the NMDA receptor function and binding in mammalian cortical neurons. Brain Res Mol Brain Res 30: 347-356.
  13. Hunt WA (1993) Are binge drinkers more at risk of developing brain damage? Alcohol 10: 559-561.
  14. Kimelberg HK, Rose JW, Barron KD, Waniewski RA, and Cragoe EJ (1989) Astrocytic swelling in traumatic-hypoxic brain injury. Beneficial effects of an inhibitor of anion exchange transport and glutamate uptake in glial cells. Mol Chem Neuropathol 11: 1-31.
  15. Kotlinska J (2001) NMDA antagonists inhibit the development of ethanol dependence in rats. Pol J Pharmacol 53: 47-50.
  16. Lambie DG (1985) Alcoholic brain damage and neurological symptoms of alcohol withdrawal–manifestations of overhydration. Med Hypotheses 16: 377-388.
  17. Lipton SA and Chen HS (2004) Paradigm shift in neuroprotective drug development: clinically tolerated NMDA receptor inhibition by memantine. Cell Death Diff 11: 18-20.
  18. Lukoyanov NV and Paula-Barbosa MM (2001) Memantine, but not dizocilpine, ameliorates cognitive deficits in adult rats withdrawn from chronic ingestion of alcohol. Neurosci Lett 309: 45-48.
  19. Lyvers MF and Maltzman I (1991) Selective effects of alcohol on Wisconsin Card Sorting Test performance. Br J Addict 86: 399-407.
  20. Majchrowicz E (1975) Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia 43: 245-254.
  21. Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R, and Feldmann M (2000) The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA 97: 9561-9566.
  22. Mansouri A, Demeilliers C, Amsellem S, Pessayre D, and Fromenty B (2001) Acute ethanol administration oxidatively damages and depletes mitochondrial DNA in mouse liver, brain, heart and skeletal muscles: protective effects of antioxidants. J Pharmacol Exp Ther 298: 737-743.
  23. McDonough KH (2003) Antioxidant nutrients and alcohol. Toxicology 189: 89-97.
  24. Nixon K and Crews FT (2002) Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. J Neurochem 83: 1087-1093.
  25. Obernier JA, Bouldin TW, and Crews FT (2002a) Binge ethanol exposure in adult rats causes necrotic cell death. Alcohol Clin Exp Res 26: 547-557.
  26. Obernier JA, White AM, Swartzwelder HS, and Crews FT (2002b) Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats. Pharmacol Biochem Behav 72: 521-532.
  27. Paxinos G and Watson C (1986) The Rat Brain in Stereotaxic Coordinates, Academic Press, San Diego.
  28. Pfefferbaum A, Sullivan EV, Rosenbloom MJ, Mathalon DH, and Lim KO (1998) A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval. Arch Gen Psychiatry 55: 905-912.
  29. Pringle AK, Self J, and Iannotti F (2000) Reducing conditions produce a loss of neuroprotective efficacy of competitive but not non-competitive antagonists in a model of NMDA-mediated excitotoxicity in organotypic hippocampal slice cultures. Acta Neurochir Suppl 76: 79-80.
  30. Raghavendra V and Kulkarni SK (2001) Possible antioxidant mechanism in melatonin reversal of aging and chronic ethanol-induced amnesia in plus-maze and passive avoidance memory tasks. Free Radic Biol Med 30: 595-602.
  31. Reddy SK, Husain K, Schlorff EC, Scott RB, and Somani SM (1999) Dose response of ethanol ingestion on antioxidant defense system in rat brain subcellular fractions. Neurotoxicology 20: 977-987.
  32. Schwartz PH and Wasterlain CG (1991) Cardiac arrest and resuscitation alters the pharmacokinetics of MK-801 in the rat. Res Commun Chem Pathol Pharmacol 73: 181-195.
  33. Singh A, Naidu PS, and Kulkarni SK (2003) Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid. Free Radic Res 37: 1245-1252.
  34. Sun AY and Sun GY (2001) Ethanol and oxidative mechanisms in the brain. J Biomed Sci 8: 37-43.
  35. Switzer RC 3rd (2000) Application of silver degeneration stains for neurotoxicity testing. Toxicol Pathol 28: 70-83.
  36. Thirunavukkarasu V, Anuradha CV, and Viswanathan P (2003) Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity. Phytother Res 17: 737-743.
  37. Thomas JD, Fleming SL, and Riley EP (2002) Administration of low doses of MK-801 during ethanol withdrawal in the developing rat pup attenuates alcohol’s teratogenic effects. Alcohol Clin Exp Res 26: 1307-1313.
  38. Wechsler H, Lee JE, Kuo M, Seibring M, Nelson TF, and Lee H (2002) Trends in college binge drinking during a period of increased prevention efforts. Findings from 4 Harvard School of Public Health College Alcohol Study surveys: 1993–2001. J Am Coll Health 50: 203-217.
  39. White AM (2003) What happened? Alcohol, memory blackouts and the brain. Alcohol Res Health 27: 186-196.
  40. Zou JY and Crews FT (2005) TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition. Brain Res 1034: 11-24.

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