ldn and cancer

LDN and Cancer
In Brief  Recent Developments  Noteworthy Cases  Background  LDN
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In Brief
Although prospective, controlled clinical trials on LDN in the
treatment of cancer are yet to be accomplished, as of March 2004
clinical "off-label" use of this medication by Dr. Bihari in some 450
patients with cancer — almost all of whom had failed to respond to
standard treatments — suggests that more than 60% of patients with
cancer may significantly benefit from LDN.

Of the 354 patients with whom Dr. Bihari had regular follow-up, 86
have shown objective signs of significant tumor shrinkage, at least a
75% reduction. 125 patients have stabilized and/or are moving toward
remission.

Dr. Bihari's results sharply contrast to prior usual cancer treatment
outcomes: either a cancer-induced death or a total cure. LDN therapy
presents a viable third alternative, the possible long-term
stabilization and/or gradual reduction of tumor mass volume.

Thus, with LDN, cancer can — in some cases — become a manageable
chronic disease. Patients have the possibility of living free of
symptoms, without, in many cases, the crippling side-effects of
chemotherapy and radiation treatment.

How It Works
Low dose naltrexone might exert its effects on tumor growth through a
mix of three possible mechanisms:

By inducing increases of metenkephalin (an endorphin produced in large
amounts in the adrenal medulla) and beta endorphin in the blood
stream;
By inducing an increase in the number and density of opiate receptors
on the tumor cell membranes, thereby making them more responsive to
the growth-inhibiting effects of the already-present levels of
endorphins, which induce apoptosis (cell death) in the cancer cells;
and
By increasing the natural killer (NK) cell numbers and NK cell
activity and lymphocyte activated CD8 numbers, which are quite
responsive to increased levels of endorphins.1 (abstract)
Cancers that are reported by Dr. Bihari to apparently respond to LDN:
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


What the Future Holds
If the results of trials of low dose naltrexone in certain cancers are
positive, the drug could eventually become an additional mainstay of
cancer treatment — adjunctive with chemotherapy, radiation, and other
cancer cell growth inhibitor receptor agonists — or even a replacement
for current therapies, as primary treatment for those cancers that
show little response to standard therapies.


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Recent Developments
As of March 2004
Since February 1999, Dr. Bihari has begun treatment of some 450 cancer
patients with LDN. Since many of these patients, particularly those
seen before October 2000, were seen only once in consultation with
medical follow-up by their oncologists, Dr. Bihari is missing up-to-
date follow-up data on 96 patients.

As of March 2004, of the remaining 354 patients, 84 have died, all but
4 of cancer-related causes. Most of these deaths have occurred in the
first 8 to 12 weeks on LDN. For the most part, these were patients who
were quite ill when first seen, and had exhausted all other treatment
possibilities. Of the remaining 270 patients, 220 have been on LDN for
six months or longer. Of these, 86 have shown significant movement
toward remission, identified for this purpose as a reduction of at
least 75% in tumor mass and tumor-related symptoms. Of the other 134
patients, 9 have continued to show tumor progression, whereas the
other 125 have stabilized and/or are moving toward remission but do
not yet meet the 75% reduction criterion.


Among those who have shown significant movement toward remission, most
had never received chemotherapy. The apparent remissions:

2 children with neuroblastoma
6 patients with non-Hodgkin's lymphoma
3 with Hodgkin's disease
5 with pancreatic cancer metastatic to the liver
5 with multiple myeloma
1 with carcinoid
4 with breast cancer metastatic to bone
4 with ovarian cancer
18 with non-small cell cancer of the lung
1 with small cell cancer of the lung
5 with prostate cancer (no prior hormone-blocking therapy)

(Although recently-diagnosed prostate cancer patients who have not
received other therapies appear to do well on LDN, patients with
prostate cancer who have already been treated with hormone-related
therapies, including testosterone-blocking drugs and PC-Spes, have not
responded to LDN.)
An overview of these results must assume the basic statistical
principle that the patients with no follow-up contact have not done as
well as those who have maintained continual medical contact with Dr.
Bihari. Measured in terms of disease stabilization and/or movement
toward remission, and assuming that patients in continual follow-up
are twice as likely to have had a good outcome thus far, it appears
that over one-half of all cancer patients whom Dr. Bihari has started
on LDN have done well.

Taking into account the relatively large number of patients who were
in advanced stages of disease when first seen by Dr. Bihari, and that
some patients in the "not followed up" and "LDN < 6 mos" groups will
likely have positive outcomes, it appears possible that more than 60%
of patients with cancer may significantly benefit from LDN. This is
underscored by Dr. Bihari's observation that better outcomes tend to
be seen when treatment with LDN is begun in earlier stages of the
disease. Of interest, there is a negligible rate of relapse in
patients who are started on LDN after or during successful initial
treatment with surgery (e.g., for breast cancer) or with chemotherapy
(e.g., for Hodgkin's disease or non-Hodgkin's lymphoma).

It will clearly require extensive study of LDN in prospective,
controlled clinical trials to determine which cancers respond best and
which other therapies are complementary to or synergistic with LDN.

Other Developments
LDN Alone in the Treatment of Cancer. Dr. Bihari now has 88 patients
with cancer in complete or partial remission whose improvement appears
to be clearly attributable to LDN alone. In contrast, the vast
majority of patients who consult with him for cancer tend to be on
other concurrent treatments as well, which obviously interferes with
drawing conclusions about LDN's role in their improvement. The
successful LDN-only group includes five breast cancer patients, one
patient who had widespread metastatic renal cell carcinoma, three with
Hodgkin's disease and six with non-Hodgkin's lymphoma. Other such
cases, some now on LDN for as long as four years, include a score of
patients with non-small cell lung cancer, as well as patients with
ovarian cancer, uterine cancer, pancreatic cancer (treated early),
untreated prostate cancer, colon cancer, malignant melanoma, throat
cancer, primary liver cancer, chronic lymphocytic leukemia, multiple
myeloma and some others.

NCI Examining LDN Cancer Cases. In June 2002 an oncologist and an
oncology physician's assistant from the National Cancer Institute
reviewed some 30 charts of cancer patients at Dr. Bihari's office.
About half were chosen as appearing to have responded to LDN without
question. With patients' permission, copies of these were sent to the
NCI for further data collection on its part for consideration for
NCI's Best Case Series.


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Noteworthy Cases
As of June 2004
Lung Cancer. C., a 61 year old woman, previously a heavy smoker, was
found to have a lesion in the right upper lobe of the lung in 1999 and
a supraclavicular node in April 2001. Biopsy showed that the node was
metastatic from the lung tumor. In August 2001 an MRI of the chest
showed supraclavicular clusters of nodes and stellate-shaped lesions
in the apex of the right upper lobe. She then started taking low dose
naltrexone. She began getting quarterly C-T scans of the chest, which
have shown no change over the following 40 months. The C-T scan
interval was changed to every 6 months. Her most recent C-T scan in
the spring of 2004 continues to show no change from the August 2001
films.

Malignant Melanoma. L. is a 53 year old woman with metastatic
malignant melanoma whom Dr. Bihari first saw in August 2000. Her
primary skin lesion had been removed from the lower back in late 1976.
A lump in the left groin was biopsy positive in December 1977. It
appeared to respond to treatment with BCG in a clinical trial in
January 1978. She was disease free for 20 years until a cancerous
lesion appeared near the site of the original primary. It was removed
surgically. She started a melanoma vaccine trial in April 1999 but
developed two new skin lesions on the low back over the next six
months. In February 2000 a bone scan showed a lesion in the left sixth
thoracic rib, with growth evident on a repeat bone scan in April 2000,
which also showed further lesions in the left sacrum and the L5
vertebra. She began taking low dose naltrexone in August 2000. She
showed no growth of these three bone lesions and no appearance of new
lesions over a forty month period since that time. She has remained on
naltrexone only.

Esophageal Cancer. Reverend X is a patient at John’s Hopkins Hospital
where he received most of his medical care. He first developed
problems with digestion and some pain in the mid-chest area with
swallowing in April 2002. An upper GI exam in May 2002 showed
narrowing and irregularity of the lower esophagus. In June 2002, a C-T
scan of the chest, abdomen and pelvis showed a 2cm thickening of the
lower esophagus extending into the upper stomach. Also seen were five
enlarged nodes in the chest and five in the abdomen. Rev X refused
chemotherapy and began low dose naltrexone in August 2002. In the
following months his difficulty in swallowing has significantly
decreased and his weight has stabilized. He notes an improved sense of
well being. He has had no therapy but low dose naltrexone.

Renal Cell Carcinoma. R., a 41-year-old man from Toronto with renal
cell carcinoma, with metastatic lesions in his liver and lungs,
contacted Dr. Bihari about 36 months ago. His oncologists told him
there was no effective therapy available, and he said he was anxious
to try treatment with LDN. There was no further contact with the
patient until early 2002 when his wife called to thank Dr. Bihari. She
said that he was doing quite well and that there had been complete
clearing of the metastatic lesions as demonstrated by chest and
abdominal CT scans.

Throat Cancer. D., a 54-year-old man who had cancer of the tonsillar
area in his throat along with two large metastatic lesions easily
visible in his neck, had refused the extensive head and neck surgery
proposed by his physicians. They held out little hope for him. Thirty
months ago, Dr. Bihari prescribed LDN. The patient's most recent
contact with Dr. Bihari was in May 2004 when he was examined. The
primary tumor had decreased by one-third in size and the two neck
masses had regressed by about 50%. The patient had received no
radiation or chemotherapy but had tried unproven alternative
treatments obtained in Mexico.

Non-Hodgkin's Lymphoma. B., a 75-year-old woman, was diagnosed with
non-Hodgkin's lymphoma in January 1999 by a biopsy of an enlarged
lymph node in the side of her neck. CT scans showed enlarged nodes in
her chest and abdomen, as well as an enlarged spleen. Bone marrow
biopsy showed "10% involvement". Her oncologist recommended a wait and
watch approach. She started LDN in July 1999. In January 2000, CT of
the chest showed an approximately 50% decrease in the size of all the
involved nodes. Repeat CT of the chest in November 2000 showed an 80%
decrease in total tumor mass.

Prostate Cancer. M. is a 59-year-old man with prostate cancer,
diagnosed with a biopsy and CT scan in September 1999. With no
treatment other than low dose naltrexone, after 4 months on LDN his
PSA dropped from 6.3 to 3.4. A special ultrasound, performed after 6
months on LDN, showed a 65% shrinkage of the tumor. His PSA remained
stable over the following 16 months when he became ill and died of
what may have been a cerebrovascular accident.

Pancreatic Cancer. D. was an 82-year-old woman with pancreatic cancer,
treated with surgical removal in April 1999. Scans showed that a tumor
mass had reappeared in the pancreatic area in August 1999, and two
metastatic lesions were noted in the liver at the same time. She
started low dose naltrexone in September 1999 and stopped taking
gemcytabine at that time after a short course of four weeks. Some four
months thereafter, an MRI demonstrated disappearance of the primary
tumor that had previously re-grown, and the liver metastases had
cleared entirely. Two months later, D. had a heart attack and died.

Carcinoid. C. is a 53-year-old woman with carcinoid, a malignancy that
generally arises in the appendix or small intestine and spreads to the
bones and throughout the abdominal cavity. She started LDN in June
1999. At that time, she had considerable abdominal swelling, diarrhea
two to three times a day, frequent episodes of flushing due to the
tumor, poor energy and appetite, and significant metastatic spread to
numerous bones. No other treatment for the cancer was administered;
none was available. By December 1999, much of the cancer-induced
swelling of the abdomen had receded, the diarrhea had completely
stopped, the flushing had stopped, and the pain in her right elbow,
due to a bony metastasis, had markedly decreased. Follow up in
February 2001 indicated that she still had some of the above symptoms
and, though clinically stable, was not showing further movement
towards remission. A telephone follow-up call in April 2004 indicated
that she was experiencing only minimal symptoms.

Multiple Myeloma. W. is a 72-year-old man with multiple myeloma,
diagnosed in the summer of 1998 when a medical workup for severe back
pain (that occurred while playing golf ) revealed fractures of three
vertebrae. Tumor was present in several other bones, blood counts were
low, and a bone marrow biopsy showed 20% replacement of normal marrow
with myeloma cells. His serum paraproteins were very high, as they
often are in people with myeloma, at 12.6 and with no response to high
dose chemotherapy. He started LDN in January 1999 and continued
intermittent chemotherapy until October 1999. Since then, he had no
chemotherapy but remained on LDN daily. There was a gradual
normalization of all of his blood counts, as well as a drop in his
abnormal serum proteins from 12.6 to a normal level of 1.4. Bone scans
showed continued slow healing of affected bones, and two bone marrow
biopsies showed no sign of myeloma. He had deferred plans for a high-
dose chemotherapy with stem cell transplant procedure which had been
earlier, and had decided to "watch and wait" while continuing nightly
LDN. He was back to playing golf and tennis regularly, but there has
been no contact since early 2003.

Hodgkin's Disease. H., a 36-year-old RN with Hodgkin's disease, was
diagnosed in October 1991 with fevers, multiple infections (including
toxoplasmosis of the brain), and a positive lymph node biopsy. She had
a brief remission of several months following treatment with
antibiotics and chemotherapy. She refused repeat chemotherapy when
tumor activity resumed, and she remained ill with fevers and many
gradually growing tumor masses (externally and internally) over the
next four years. She started LDN in June 1997. No other therapy was
provided. By October 1997, her fevers had cleared, all of her external
enlarged lymph nodes had shrunk to normal, and all of the enlarged
nodes seen in the spring of 1997 on CT scans were gone. She was
determined by her oncologist to be in remission. Since that time, she
has moved, gotten married, and not returned repeated phone calls. A
long term friend reported that she continues to do well except for
some persistent memory loss (due to brain lesions associated with her
toxoplasmosis). She has stayed on LDN since and, as of the last phone
contact in October 2003, had had no sign of relapse.

Non-Hodgkin's lymphoma. J., a 48-year-old man, had a CT scan in
January 1999 because of low back pain after an auto accident. In
addition to a bulging disc in his spine, the CT scan showed many
enlarged abdominal lymph nodes. Biopsies of nodes in two locations
were diagnostic of a non-Hodgkin's lymphoma. The patient refused
chemotherapy and treated himself with antioxidants and multiple
nutritional supplements. He added low dose naltrexone in October 1999.
A repeat CT scan in late January 2000 showed a significant reduction
in the size of the pathological nodes, each being reduced in size by
about one-third. A more recent CT scan in early August 2003 showed
further shrinkage of the enlarged nodes, which were reduced to less
than 50% of their original size. The reduction of tumor mass occurred
in the absence of chemotherapy or other standard treatments, with low
dose naltrexone his only pharmacologic therapeutic agent.

Breast Cancer. M. is a 41-year-old patient with breast cancer,
diagnosed and treated elsewhere in 1998, whose course was complicated
by a recurrence involving metastasis to the hip. Outpatient hospice
services were sought. Her walking was so badly impaired that she had
to be assisted by her friends on her first office visit to Dr. Bihari
in June 2000 — at which time she began LDN. She revisited his office
in mid-October and reported that she not only was able to return to
work but also was well enough to play tennis again. Repeat bone scan
in October 2000 showed a 40% reduction in metastatic tumor mass. She
then enrolled in an experimental chemotherapy trial at a major cancer
treatment center in New York in December of 2001 and died of liver
failure on the fourth day of the trial.

Non-small Cell Lung Cancer. M. is a patient in his late 50’s who first
visited Dr. Bihari in June 2000. A chronic cigarette smoker, he was
told in May 2000 that he had metastatic non-small cell lung cancer.
Many abnormal opaque areas had been seen on his chest x-ray, and a
biopsy performed on a sizable mass in his right neck had confirmed the
diagnosis. He had refused chemotherapy. On examination, he had a 3cm
x 4cm x 2cm mass in his right neck. He was started on LDN in mid-June
2000 and, at the beginning of November, revisited Dr.Bihari for the
first time. At that time, the patient reported that energy was better
and his appetite was good. He had regained 15 pounds, and had returned
to working full time. The volume of the neck mass appeared to have
decreased by 50%. An MRI exam in November 2000 showed 80% shrinkage of
the right neck mass and 20% shrinkage of the masses in both lungs. As
of April 2004, the mass in his right neck remained halved in size,
with no further growth of his pulmonary lesions.

Ovarian Carcinoma. V., a 49-year-old woman, first visited Dr. Bihari
in early September 2000. She had a five-year history of ovarian
carcinoma, with a persistently growing tumor despite repeated courses
of chemotherapy and multiple debulking surgery. There was recent
increased involvement of the descending colon with the disappearance
of formed stools, and she was now experiencing vomiting.
Hospitalization was under consideration. She had lost 15 pounds in the
two weeks prior to her visit. She was started on LDN at that time, in
addition to her existing low-dose Taxol therapy, and within ten days
the signs of large bowel obstruction had disappeared. In four weeks, a
repeat CA 125 revealed that this tumor marker had dropped from 1600 to
87. Within the first week of November 2000, it was reported down to
42, and her gynecologic oncologist told her that, on abdominal-pelvic
examination, he found no masses. She had regained some 25 pounds and
felt “wonderful”. A repeat MRI showed no visible masses. In March
2001, the CA 125 had risen to 52, then 70, with no return of symptoms
or of palpable masses on abdominal and pelvic exams. However, in
October 2001 the abdominal masses recurred despite LDN and she died of
metastatic cancer four months later.


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Background
Before it was first used to treat cancer, LDN had been in use in the
treatment of HIV/AIDS. A double-blinded placebo-controlled trial in
1986 showed significant immune system protection from HIV in a group
of patients given the active drug. The development of LDN was based on
several biological facts. One was the fact that naltrexone, which had
been licensed in 1984 as an adjunct in treating heroin addiction, has
the ability to induce increases in the endorphin levels in the body.
Another was the fact that endorphins are the primary supervisors or
(homeostatic) regulators of the immune system, representing 90% of
immune system hormonal control. Ninety percent of the day's endorphins
are produced by the pituitary and adrenal glands between 2a.m. and
4a.m.

Dr. Bihari and his colleagues then showed that endorphin blood levels
averaged less than 25% of normal in people with AIDS. These facts all
provided the background for the discovery of the value of LDN in HIV/
AIDS. The nocturnal production of endorphins allowed Dr. Bihari and
his colleagues to experiment with small doses of naltrexone taken at
bedtime in order to jump-start endorphin production. They found that
LDN increased endorphin production when taken at bedtime in doses of
1.5mg to 4.5mg. Doses lower than 1.5mg had no effect on endorphin
production. Doses higher than 4.5mg produced no more of an endorphin
boost, but did block endorphins for significantly longer, thereby
reducing the benefit of increased endorphin levels.

During the course of the placebo-controlled trial of LDN in people
with AIDS in 1986, a friend of Dr. Bihari's (M.B.) called him when she
discovered that she was experiencing an exacerbation of non-Hodgkin's
lymphoma which had gone into remission five years earlier after
treatment with chemotherapy. Because of her awareness of the decreased
likelihood of a long-term remission with a second round of
chemotherapy, she called to ask if his AIDS drug might help her
cancer. A recently published study of human lymphoma transplanted into
mice suggested that it might. In this study, all of the mice in an
untreated group died of lymphoma. A second group of mice was pre-
treated with a single injection of beta-endorphin before the lymphoma
transplant. Half of this second group did not get ill with lymphoma.
The other half of these mice did, but with a much more slowly growing
tumor and a much prolonged life span compared with that of the non-pre-
treated group.

Dr. Bihari agreed to treat M.B. with LDN, and used the three golf-ball-
sized tumors in her groin as markers of response. All three shrank and
disappeared over the next six months. M.B. stayed on LDN and had no
further exacerbations of her malignancy. She died six years later in
her mid-seventies from her third heart attack.

Several months later, Dr. Bihari, while in Paris to present the LDN
AIDS results at an International AIDS Conference, met a woman (C.P.)
in her early forties who was quite ill with metastatic malignant
melanoma. This had spread from a malignant mole on her arm to her
brain, which showed four metastases on C-T scan. Her speech was
slurred, her balance and handwriting impaired, and she suffered from
headache and recent memory impairment. Her oncologist in Paris said
the malignancy was untreatable, and believed that she had perhaps
three to six months of life remaining. On his return to New York, Dr.
Bihari shipped LDN to C.P.'s daughter, who started the patient on it.
Nine months later, with all neurological signs and symptoms having
cleared, C.P. had a repeat C-T scan that showed no residual tumor.

C.P. remained on LDN for the succeeding 12 years, stopping it without
her family's knowledge in late 1999. Until that time, she had remained
in complete remission, without any recurrence of her malignancy. Eight
or nine months after stopping LDN she developed nodules under her skin
and began to cough up blood. A C-T scan of the chest showed multiple
metastatic lesions. Biopsy of one of the subcutaneous nodules
confirmed recurrence of malignant melanoma. Dr. Bihari shipped LDN to
the patient's family and she resumed it in early 2000. Eight months
later, the nodules in the skin had cleared and a repeat C-T scan of
the chest showed no residual tumor. She appears to be, once again, in
remission.

Over the years encompassed by these two cases, 1986 to 1999, Dr.
Bihari focused his research energy on the study of LDN's effect on
immune function and on immunological approaches to the treatment of
HIV/AIDS. In 1999, however, conversations with three small
pharmaceutical companies revealed some interest in the development of
LDN, with a goal of getting FDA approval for immune-related diseases
including cancer. With this development possibility, Dr. Bihari
decided to revisit the potential value of treating cancer with LDN.

Dr. Bihari began an informal private-practice-based evaluation of the
effects of LDN with a variety of types of cancer in February 1999. He
had seen positive results with a small but growing number of patients
with cancer during the preceding 14 years, while developing the drug
as an immune modulator for HIV/AIDS. The drug was compounded by
pharmacists in 3mg capsules and taken once a day at bedtime. Most
patients have recently had their LDN dose increased to 4.5mg daily. It
is nontoxic and has no side effects. Its only interaction with other
drugs is with narcotics (such as morphine, Demerol and Percocet),
which it briefly blocks.

Mechanisms
The mechanisms involved in the apparent beneficial effect of LDN on
cancer have three main elements. The first is the effect of LDN, when
taken late at night, in inducing a sharp increase in pituitary and
adrenal production of beta-endorphin and metenkephalin, respectively,
in the pre-dawn hours, when 90% of the day's manufacture of these
hormones occurs. Most studies have shown that naltrexone induces a two
to three-fold increase in production of metenkephalin, the endorphin
that most specifically activates delta-opioid receptors, the primary
endorphin-related anti-growth factor on cancer cells. The low dose of
naltrexone, which in higher doses would block endorphin and enkephalin
action on the receptor, is gone from the body in about three or four
hours — whereas the elevated levels of endorphins and enkephalins
persist all day.

The second step involved in the anti-cancer effect of these hormones
results from direct activation of opioid receptors of cancer cells by
the increased endorphins. If this activation occurs while the cell is
dividing, it dies. In fact, relatively small concentrations of
metenkephalin, when added to human pancreatic cancer cells or human
colon cancer cells growing in the test tube, have been shown to kill
both. The apparent mechanism of cell killing is called apoptosis
(programmed cell death). This appears to be one of the mechanisms by
which endorphins and enkephalins combat cancer.

A third element, which may play a major role in controlling cancer,
involves the cells of the immune system, which is regulated/
orchestrated to a great extent by endorphins. In particular,
endorphins raise the circulating levels of natural killer cells and
lymphocyte-activated CD-8 cells, the two immunological cell types that
prevent cancer by killing cancer cells as they arise.

It should be emphasized that Dr. Bihari's patients were all treated in
a private practice setting without the scientific rigor of a
prospective clinical trial. This precludes any scientific claims about
the drug's efficacy in treating any of the above-mentioned types of
cancer. The results thus far do, however, raise the possibility that
the manipulation of opioid receptors on cancer cells as anti-growth
factors through the use of endorphins and endorphin-inducing opioid
antagonists may eventually prove to have considerable merit,
particularly in view of the many years of published, supportive
laboratory research findings.

Those cancer cells that have opioid receptors on their cell membranes,
and that may, therefore, respond to LDN, include all of those that
arise from the gastrointestinal tract. This includes the mouth,
esophagus,liver, pancreas, stomach, small intestine, colon and rectum.
Lymph glands and the spleen have large numbers of opioid receptors,
suggesting that Hodgkin's disease, non-Hodgkin's lymphoma, multiple
myeloma and lymphocytic leukemia should respond to LDN. Other
malignancies with sizable numbers of opioid receptors on their cell
membranes include breast cancer, neuroblastoma, prostate cancer,
malignant melanoma, renal cell carcinoma, glioblastoma, astrocytoma,
endometrial cancer and small cell and large cell cancers of the lung.

Research History
Ian Zagon, Ph.D., whose research group has done much of the basic
animal work in the area of cancer treatment and endorphins, showed in
1981 in a mouse neuroblastoma model that very small doses (0.1 mg./kg)
of naltrexone, given once a day, inhibit tumor growth, prolong
survival in those mice that develop tumors and protect some mice from
developing tumors altogether.2, 3 (abstract)

Zagon had hypothesized that the small daily doses of naltrexone work
to enhance the endorphin-related protective effect against cancer in
mice by increasing the number and density of opiate receptors on tumor
cells. He hypothesized as well that the increase in endorphins known
to be induced by naltrexone might play a part in the protective effect
of the small daily dose by working directly on the tumors' opiate
receptors.4 (abstract)

In 1996 and 1997, Zagon and his co-workers, reported on laboratory
research using specially-bred mice that had no immune system (so-
called "nude mice"). They transplanted, in separate experiments, human
colon cancer and human pancreatic cancer into the animals and compared
the growth of the cancer between those mice that received daily
injections of metenkephalin and a control group that received placebo.
In each experiment, metenkephalin acted as a negative regulator of
tumorigenesis and was significantly able to suppress tumor appearance
and growth in the treated group.5 (abstract)

Of especial importance, in 1996 the same group of researchers
demonstrated that by utilizing LDN to induce an intermittent blockade
of opioid receptors in similar laboratory animals (nude mice), the
growth of inoculated human colon cancer was markedly retarded. "At the
time (10 days) when all control mice had tumors, 80% of the mice in
the 0.1 mg/kg NTX group had no signs of neoplasia." When measurements
of metenkephalin plasma levels were made, the group that received LDN
had metenkephalin levels that were elevated 2.5-fold compared with the
control group. The researchers concluded that the results suggested
"that daily intermittent opioid receptor blockade with NTX [low dose
naltrexone] provokes the interaction of opioids and receptors in the
interval following drug availability, with opioids serving to inhibit
tumorigenicity of human colon cancer".6 (abstract)

New findings by Zagon and colleagues at The Pennsylvania State
University in Hershey were published in the December 1999 issue of the
journal Brain Research. They had identified the specific cell receptor
for one of the endorphins, metenkephalin (the levels of which are
increased by LDN). Zagon stated that the opioids act as growth
inhibitors, as well as neurotransmitters, and that this feature has
implications for cancer treatment. Metenkephalin is found in all
tissues, and appears to be associated with cells undergoing renewal or
proliferation. Zagon's group was described as having mounted Phase I
trials using metenkephalin in an attempt to control the growth of
pancreatic cancer in humans. Pancreatic tumors appear to have low
levels of the metenkephalin receptor. Low peptide [metenkephalin] or
[opioid] receptor levels may exist in cancer cells in general since
they want to stimulate their own growth, Zagon said.7 (abstract)


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Footnotes
Matthew, PM, Froelich CJ, Sibbitt WL, Jr., Bankhurst AD, Enhancement
of natural cytotoxicity by beta-endorphin, J Immunol 130, pp.
1658-1662, Apr 1983. Read the abstract.
Zagon IS, McLaughlin PJ, Naltrexone prolongs the survival time of mice
treated with neuroblastoma, Life Sci 28, pp. 1095-1102, 1981.
(Abstract unavailable.)
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