How LDN works and was discovered – Interview with Dr. Bihari
Dr. Kamau B. Kokayi Interviews Dr. Bihari
September 23, 2003
WBAI in New York City
“Global Medicine Review”
Dr. Kokayi: …the story about Low Dose Naltrexone is really fascinating. How did you
get the idea?
Dr. Bihari: Well, we were treating heroin addicts, and in 1984 a new drug for the
treatment of addiction came out. It was called Naltrexone, and it was designed to
block the heroin “high”and it was a flop. I used it for a lot of patients, as did most
addiction doctors across the country. At 50 milligrams a day, it made people feel
terrible. Not that it blocked the heroin so much as it blocked their own endorphins,
which is a source of our sense of well-being, so that people couldn’t sleep.
Dr. Kokayi: Your own opium, basically.
Dr. Bihari: Right. Your own equivalent. That’s what heroin is. And I knew from
work that had been done by the National Institute on Drug Abuse in developing the
drug that it had the ability to trigger the body into making more endorphins, but at the
high 50 milligram dosage, the dose was too high. It blocks those endorphins.
About six months later our addicts began dying in large numbers of AIDS. I ran HIV
tests on about a hundred addicts, and fifty percent were already HIV positive. This
was in 1985; currently it’s eighty eighty-five percent around the country. And we
began looking for some way to approach this new disease, with a view to the idea that
this disease was likely to turn into a worldwide epidemic.
Dr. Kokayi: That was about the time where people were just being blasted with AZT
with horrific results.
Dr. Bihari: Right. There was nothing else available. When I discovered that people
with HIV had less than twenty percent of the normal levels of endorphins, that meant
that the virus not only kills the immune system cells, it also weakens the whole
immune system, so that it’s not as able to fight the virus.
We began looking for ways to use this drug to raise endorphins without blocking
them. We hired a laboratory scientist to measure endorphin levels. We’d measure in
the afternoon, then we’d give the first dose at bedtime that night. Then we’d measure
again at the same time the next day; then again at one week, and again at one month.
We found that doses in the range of 1.75 to 4.5 milligrams (which is just a fraction of
the recommended dosage to addicts) would trigger or jumpstart endorphin production
during the night.
Except with exercise, endorphins are made only between two and four in the
morning. The brain sends a message out to the adrenal and pituitary glands and tells
them to make endorphins. Giving a dose three, four, five hours before that, at
bedtime, is enough to make that message from the brain much stronger.
Dr. Kokayi: Were you able to document that the levels of endorphins were then
Dr. Bihari: The level of endorphins went up by two hundred to three hundred
percent. We then started a little foundation and did a placebo-controlled trial in which
half the patients got the drug and half got sugar pills. A year later when we broke the
code, we discovered that people with HIV who took the drug had only an eight percent
death rate in the year, while people who were on the placebo had a thirty-three percent
death rate. And of course they had many more infections and their immune system
declined. That was a startling discovery.
Dr. Kokayi: Now let me jump ahead, because I’m always curious about why this
therapy hasn’t gotten the kind of publicity specifically for this disease.
Dr. Bihari: Well, at that time there was very little treatment. AZT came out about ’
87, and as you mentioned, it was not only a flop but made some people sicker. At the
time we did the study, there was nothing available.
So I met with doctors in New York and in San Francisco (where the largest number
of HIV doctors were at that time) and described this drug and how it worked, and
about forty to fifty doctors on the east and west coast began using it. Unfortunately,
they measured effectiveness by whether or not the numbers of the immune system
cells that are crucial in AIDS — the CD4 cells — were rising. On this drug, CD4 cells
don’t rise in people with AIDS. As I knew from the study, and have known since,
they simply stop dropping. That means you can freeze the disease wherever it is. And
if somebody is only mildly immune-suppressed, they stay that way.
Dr. Kokayi: That’s so important…
Dr. Bihari: It stops progression. It stops the count from growing. I have patients
going back as much as seventeen years who haven’t lost an immune system cell in that
time. They’re very healthy.
Dr. Kokayi: Wow, that needs to be on the evening news.
Dr. Bihari: The trouble was, we wrote a paper, but couldn’t get it published. Nobody
understood the concept.
Dr. Kokayi: You’re using the dose homeopathically. You’re using it not for the effect
that the medicine has on the person, but for the body’s reaction to the medicine.
Dr. Bihari: It strengthens the body’s own defenses. Rather than directly attacking,
the way antibiotics attack bacteria, or the way chemotherapy tries to attack cancer
cells, or the way anti-viral drugs attack viruses, the purpose of this is to take a weak
defense (which people with AIDS or cancer have), and strengthen it so that the body
can fight the disease more effectively.
Dr. Kokayi: I’ve often made the point that therapies like acupuncture, therapies that
are foreign to the cultural mindset of doctors and the American public, these therapies
can be effective, but they won’t be included or in mainstream medicine because the
concept is so foreign.
Dr. Bihari: It’s a different model of understanding the body — how it works and how
disease works. I think eventually there will be changes in the paradigm of the way we
think about diseases, and it’s going to be a struggle. But I think oncologists in
particular are getting more and more frustrated with the failure of chemotherapy.
Dr. Kokayi: Well, about time.
Dr. Bihari: The people I talk to at the National Cancer Institute, and the Food and
Drug Administration, are very negative. All they get from drug companies are
proposals to test new, more toxic chemotherapies, and they’re really looking very hard
for non-toxic ways of modifying the behavior of the cancer cells so that they stop the
cancer from growing.
Dr. Kokayi: Over the years have you had to modify what you were actually doing
with Naltrexone? Or is the initial model impetus pretty much on point?
Dr. Bihari: The initial model was pretty much on point. A small dose at bedtime
increases endorphin production during the night. In somebody who has a disease
which is related to low endorphins, the endorphins go back up to normal by the next
… [station break] ….
Dr. Kokayi: … can you tell us about some of the work with Naltrexone and cancer?
Dr. Bihari: During that year, when we were doing our first AIDS trial, an old friend
of mine called. Five years earlier, she’d had Non-Hodgkin’s Lymphoma. It had
initially responded to chemotherapy, but it had grown back after her husband died.
Her oncologist refused to treat her, saying it would be resistant to chemo the second
She knew what I’d been doing, and she called me and said, “Bernie, do you think your
AIDS drug would help my cancer?”
So I dug around and I found a large body of literature showing that when you give
endorphins, metenkephalins, beta endorphins and even low dose Naltrexone to mice
that had human cancer transplanted, that there is about an 80 percent recovery rate. I
gave her the drug in the same dose we were using in the AIDS trial. She had large
masses in her groin, her neck, her chest, and her abdomen, and they all slowly shrank
and disappeared over a (inaudible) period. (Inaudible) taking the drug every night.
Dr. Kokayi: Wow! You know, even if that’s just an anecdote….
Dr. Bihari: Yes.
Dr. Kokay: I mean, everyone who has that disease deserves a chance to see if they’re
going to be an anecdote as well.
Dr. Bihari: It was actually her idea. She stayed on the drug, and died about eight
years later, in her late seventies, of her third heart attack, which was unrelated.
Then I was in Paris the following summer, presenting a paper at an AIDS conference,
and I met a woman who had a cancer called malignant melanoma. It starts in the skin,
and in her case it had spread to the brain. She had four large brain tumors. The
oncologist told her family that she had perhaps three months to live. When I got back
to New York, I shipped her the drug from a pharmacy that was making it for our
study. She started on it, and her neurological symptoms from the tumors in her brain
slowly disappeared. Seven or eight months later she went back to the oncologist, had
a cat scan of the brain done, and the tumors were gone.
Dr. Kokayi: Fantastic.
Dr. Bihari: That was eighteen years ago, and she stayed on it.
Dr. Kokayi: This is such a non-toxic, simple [inaudible].
Dr. Bihari: There are absolutely no side effects. I continued doing a lot of the AIDS
work, but the last four or five years I’ve gotten much more interested in other uses.
We stumbled on the fact, also by chance, that the drug works very well for almost all,
if not all, of the autoimmune diseases like multiple sclerosis, rheumatoid arthritis,
lupus, sarcoidosis, and —
Dr. Kokayi: When you say “it works”, what actually happens? What’s been your
Dr. Bihari: Well, what happens is that the disease activity stops, as long as people
stay on it. If they have damage to the brain and spinal cord with multiple sclerosis,
that doesn’t disappear, because that’s due to scarring, but they stop getting new
I’ve had people on Low Dose Naltrexone for years. The longest is a friend of my
daughter, who’s been on it for eighteen years and has not had an attack as long as she
stayed on it.
Dr. Kokayi: So it’s almost as if it’s up-regulating the endorphin production but
somehow the endorphins actually block or inhibit the effect of the antibodies from
attacking the tissue.
Dr. Bihari: Not directly. It’s more that the autoimmune diseases are beginning to
look more and more like they’re diseases of endorphin deficiency. [Inaudible] models
of all the diseases I mention that can be bred in mice, the endorphin levels are always
fifteen to twenty percent of normal compared with normal mice.
[Female Voice] How can you naturally increase endorphin levels?
Dr. Bihari: There’s only three or four ways that I know. First, Naltrexone increases
them substantially, two to three hundred percent in people with low levels. Second,
aerobic exercise increases them, but not as much. If you do an hour of exercise four
or five times a week it will last three, four hours, and that’s one of the reasons that
exercise helps prevent cancer. A third way, oddly, is acupuncture. Acupuncture,
especially when used in treating addicts, increases endorphin levels in the blood and the
spinal fluid. And chocolate increases it.
Dr. Kokayi: [Inaudible] will be glad to hear that.
Female Voice: [inaudible] It actually works out, because you’re going to eat your
chocolate and then run to the gym.
Dr. Bihari: Chocolate has a substance in it called Phenylalanine, which slows
endorphins from being broken down in the body.
Dr. Kokayi: And that’s basically an amino acid that we find….
Dr. Bihari: Yes, that’s the food that has it in the largest amount. And only people with
a rare disease called [inaudible] can’t eat chocolate.
Dr. Kokayi: So some people will run to the health food store and get Phenylalanine.
Dr. Bihari: Well, Phenylalanine is helpful if you’re raising your endorphins by other
means. Then it keeps them from decaying. They last much longer. But the crucial
thing still seems to me to be the Naltrexone. Over the last five or six years, I’ve
treated about 420 patients who have various kinds of cancer with low dose
Naltrexone. Occasionally, for people who come to me with very advanced cancer, I
add intravenous metenkephalin, which is an endorphin… intravenously, three times a
week. It improved immune function substantially, and had no side effects, but that’s
generally not needed.
Among the people I’ve treated with Naltrexone for various kinds of cancer, on the
average the cancer stops growing in about two-thirds. For half of that group, it
eventually — after six, seven, eight months — goes on to slowly shrink and disappear.
Dr. Kokayi: And that’s about forty percent.
Dr. Bihari: Higher.
Dr. Kokayi: Well, it’s about forty percent of the total number.
Dr. Bihari: Sixty-five percent actually benefit and don’t go on to
develop [inaudible]. Thirty percent go into remission.
Dr. Kokayi: That’s phenomenal. I don’t think there’s any chemo or radiating
oncologist with numbers like that.
Dr. Bihari: There’s no downside. One of the reasons that the war on cancer failed is
that the oncologists doing the research failed to take into account that chemotherapy
really wipes out the immune system, which the body needs to fight cancer cells. So
they are giving drugs that kill cancer cells, but at the same time weakening the body’s
defense against cancer. Naltrexone strengthens the body’s defense, and the increased
endorphins kill cancer cells directly. Also, the immune system when it’s strengthened
kills cancer cells through its natural killer cells.
Dr. Kokayi: What you’re saying is, that a boost in endorphin levels also activates
other components of the immune system.
Dr. Bihari: The endorphins are the hormones centrally involved in regulating the
immune system. About 95% of the regulation or orchestration comes from
endorphins. People with cancer — especially adults – have very low natural killer
cells. They have a weakened immune system. I’ve discovered, after seeing such a
large number of people, that the vast majority of them have experienced major life
stresses lasting weeks, months to years – anywhere from two to six years before they
get the cancer.
Dr. Kokayi: That was one of my other questions. What really can keep those
endorphin levels down in the body?
Dr. Bihari: If a child gets sick — children are supposed to outlive us — so if a child
gets sick and dies, or if you have a very bad marital break-up, or if you discover a
business partner is embezzling money and it takes a couple of years to straighten
out… If you wake up every morning under stress — really serious stress, not
everyday stress — really serious stress, this can lower your endorphin production, and
it never returns to normal. So the person then walks around with low endorphins.
The body makes cancer cells all the time, but usually the immune system kills them as
they are forming. But if your endorphin levels are low, then your immune system is
weak, the cancers grow and you become much more vulnerable. The same thing
with exposure to really toxic substances.
Dr. Kokayi: Right. I’m wondering, I’m sure the listening audience would like to get
an idea. If you could just run down a list of some of the cancers that you have
successfully treated, types of cancers that have seemed to respond where the opiate
levels play a prominent role.
Dr. Bihari: Well, first one of the things we discovered was that almost all cancers
have a lot of receptors for endorphins on the cell surface, and that seems to be
necessary for it to work. Some of the cancers that respond most dramatically are
Multiple Myeloma, Lymphoma, Hodgkin’s disease, breast cancer, all the cancers of the
gastrointestinal tract, like pancreatic cancer, non small-cell cancer of the lung, the kind
associated with smoking. I’ve got several patients with tumors that have stopped
growing; they have no symptoms, and then after a year, year and a half, in about half
of that group, the tumors start shrinking and disappear.
Dr. Kokayi: This is lung cancer?
Dr. Bihari: These are lung cancers due to smoking.
Dr. Kokayi: Because there’s really —
Dr. Bihari: Very common.
Dr. Kokayi: It’s very common, but therapeutic effectiveness —
Dr. Bihari: There’s nothing —
Dr. Kokayi: There’s nothing, right —
Dr. Bihari: My own attitude about chemotherapy in patients I see with cancer, is if
they have one of those rare cancers that’s very sensitive to chemotherapy, like cancer
of the testicle, I encourage them to do that, to take it, and take Naltrexone afterwards
to prevent recurrence. These drugs are licensed to treat cancer. Naltrexone is not yet
licensed to treat cancer, although it’s a licensed drug. It’s been on the market for
nineteen years. It’s use in these low doses is called an “off-label” use. Any doctor
can prescribe it. And growing numbers of oncologists and neurologists in the country
are prescribing it.
Dr. Kokayi: I think it would be interesting you know just to talk a little bit about the
process … a lot of physicians don’t really know about it and it’s not talked about. This
is a big deal.
Dr. Bihari: Well, I think it could turn out to be a big deal when it’s picked up, if it’s
picked up. We set up a web site, www.ldninfo.org, which brings up about thirty
pages of written material describing all the diseases, and how they respond, and how
many cases we have of them. There’s some small trials going on, there’s two trials in
people with Crohn’s Disease, which is an autoimmune disease of the small intestine,
one in Jerusalem, and one in New York. There’s a trial in Israel for multiple
sclerosis. The national cancer institute has copies of twenty charts of my patients
who have agreed to share their charts. These are people who have done well on
Naltrexone when nothing else could explain how well they’ve done. They intend to
present them to a committee for recommendations as to whether to invest and test it in
the network of cancer research.
Dr. Kokayi: You know, when I think about Africa and AIDS, this is exactly the kind
of medicine there needs to be there….
Dr. Bihari: This is perfect. In fact, we’ve been working with the largest
pharmaceutical company in the developing world called (inaudible) in India to get a trial
going, probably in Africa, in the Republic of South Africa, in which half the HIV
patients get the drug, half get a placebo, and they should be able to show in about nine
months, using two to three hundred patients, that this drug stops progression.
Once it does, it will be manufacturable at less than ten dollars per year per person.
That’s been the big problem — the anti-HIV drugs are so expensive. The average
income in Africa is about eighty dollars per year.
Dr. Kokayi: I can only imagine just the financial stress that you’ve had to go through
just to keep this whole project alive. It’s one thing to prescribe things as an individual
doctor, but to get recognition within the scientific community is a bit difficult.
Dr. Bihari: It really bothers me when doctors say, “Oh, I can’t prescribe that,
because he hasn’t done a placebo-controlled trial.” That’s a full-time job, for two,
three years involving eight or nine centers around the country. I’m working with a
number of diseases in my office, and a lot of money goes out paying for the website,
for patents to cover low dose naltexone, and (inaudible) things like that. It’s very
veryexpensive. But I can’t stop doing it. My wife and I would love to do some
traveling — I think we’ve earned it — but I really can’t stop until the drug is out there.
It’s as much of a burden as it does a pleasure.
Dr. Kokayi: I really hope that at least your sharing with our listening audience today
helps to make people more aware. People should be clamoring for it. We’re running
out of time, but I wanted to go back to the treatment of autoimmune diseases. I
always pictured them as the body is attacking its own tissues. I pictured these
antibodies actually honing in there. But you’re saying that, in large measure it’s an
actual endorphin deficiency.
Dr. Bihari: It’s an endorphin deficiency which weakens the immune system, so that
certain cells in the body forget to distinguish between the body tissues and bacteria or
viruses, so when these cells are activated by an infection they attack the bacteria and
they attack you. Restoring the immune function to normal stops that. So far, the drug
works dramatically in all the diseases that are labeled autoimmune diseases.
Dr. Kokayi: And you’ve treated lupus with this.
Dr. Bihari: I’ve treated — I have two dozen cases of lupus. I have about the same
number of people with rheumatoid arthritis. I have about twenty people with Crohn’s
Disease. A number of rheumatologists who specialize in these diseases in New York
are now beginning to use it, because we have cases in common, and they see.
Dr. Kokayi: Right
Dr. Bihari: Because they’re using cancer drugs
Female Voice: Dr. Bihari, is this being used with children with ADD?
Dr. Bihari: I doubt that it would work, knowing the nature of ADD. I doubt that it
would work. It doesn’t do everything for everybody. I don’t think it would.
Dr. Kokayi: Again, going back to the idea of giving a medicine that at a
higher dose actually blocks the chemical system, but a lower dose actually augments
Dr. Bihari: And enhances the body’s defenses — that’s essential.
Dr. Koyayi: This idea gives the pharmaceutical industry something to do, rather than
giving people high doses of medication.
Dr. Bihari: It certainly would. It will take this drug to be licensed, picked up by a
pharmaceutical company and tested, licensed, and once it’s widely used, then this
approach to medicine — every medical researcher will start thinking about it. It’s an
entirely different approach to the body and illness.
Dr. Kokayi: What is the next step? Is there anything that the listening audience can
do that might be helpful for to make this more — not even make it more available,
because it’s just a prescription any doctor can write. I guess it’s the information —
Dr. Bihari: The information, getting it from the website, getting doctors to prescribe
it. I’m always happy to take calls from doctors and spend as much time as I need,
because the more doctors prescribe it, the more widely used it will be. Currently, as
far as we can calculate it, over eighty thousand people in the U.S. and western Europe
are on the drug, and the numbers are increasing rapidly.
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