1) Digestive Diseases Week Conference, Los Angeles - May 2006

- PRESENTATION ABSTRACT ID#S1397

- TITLE: Low-Dose Naltrexone as a Treatment For Active Crohn's
Disease
- AUTHORS: J. P. Smith; H. E. Stock; S. I. Bingaman; D. T. Mauger;
I. S. Zagon
- SESSION TITLE/SESSION TYPE: Clinical Intestinal Disorders:
Inflammat..., Poster Session
- PRESENTATION DATE/TIME: Sun, May 21, 8:00 AM
- location: West Hall A (LA Convention Center).

Low-Dose Naltrexone as a Treatment For Active Crohn's Disease

J. P. Smith (1); H. E. Stock (1); S. I. Bingaman (1); D. T. Mauger

(2); I. S. Zagon (3)

1. Medicine, The Pennsylvania State University College of Medicine,

Hershey, PA, USA.
2. Health Evaluation Sciences, The Pennsylvania State University
College of Medicine, Hershey, PA, USA.
3. Neural and Behavioral Sciences, The Pennsylvania State University
College of Medicine, Hershey, PA, USA.

Background and Aims:

Endogenous opioids and opioid antagonists have been shown to play a

role in healing and repair of tissues. In an open-labeled pilot
prospective trial, the safety and efficacy of low-dose naltrexone
(LDN), an opioid antagonist given at a dosage that exacerbates opioid-
opioid receptor interactions, was tested in humans as a treatment for
active Crohn's disease.

Methods:

Eligible subjects with histologically and endoscopically confirmed

active Crohn's disease with a Crohn's Activity Index (CDAI) score of
220-450 were enrolled in a study using 4.5 mg naltrexone/day.
Subjects were required to be off infliximab for at least 8-weeks, and
this medication was not allowed during the trial. Other drug therapy
for Crohn's disease utilized 4 or more weeks prior to enrollment was
continued at the same dosages.
Patients completed the Inflammatory Bowel Disease Questionnaire
(IBDQ) and the Short-form (SF-36) quality of life (QOL) surveys
before treatment, every four weeks on therapy, and 4-weeks after
completion of the study drug. Drug was administered orally each
evening for a 12-week period. Laboratory tests, erythrocyte
sedimentation rates, C-Reactive protein, and CDAI scores were
assessed monthly and 4 weeks after discontinuing the medication.

Results:

Seventeen patients with a mean initial CDAI score of 356 ± 27 were

enrolled in the study. CDAI scores decreased significantly (p<0.01)
with LDN, and remained statistically lower than baseline 4-weeks
after completing therapy (see Figure). Eighty-nine percent of
patients exhibited a response to therapy (>70-point decrease in CDAI,
p<0.001) and 67% achieved remission (CDAI score <150). QOL surveys
indicated marked improvement with LDN. No laboratory abnormalities
were noted. One subject undergoing routine endoscopic procedures
showed healing of the intestinal mucosa. In both subjects with open
fistulas, closure was noted with LDN. The most common side effect of
LDN was sleep disturbances (7 patients).

Conclusions:

LDN therapy offers an alternative safe, effective, and economic means

of treating subjects with active Crohn's disease.

http://ddw2006.abstractcentral.com/planner
2) Digestive Diseases Week Conference, Los Angeles - May 2006
PRESENTATION ABSTRACT ID# T1155 - TITLE: The Opioid Antagonist
Naltrexone Alleviates Chemically-Induced Colitis- AUTHORS: G. L.
Matters, J. F. Harms, L. R. Fitzpatrick, A. M. Parikh, N. J. Nilo, J.
P. Smith. SESSION TITLE/SESSION TYPE: Consequences of Intestinal
Inflammation, Poster Session - PRESENTATION DATE/TIME: Tue, May 23,
8:30 AM - location: West Hall A (LA Convention Center).

The Opioid Antagonist Naltrexone Alleviates Chemically-Induced Colitis

G. L. Matters (1); J. F. Harms (2); L. R. Fitzpatrick (3); A. M.

Parikh (2); N. J. Nilo(2); J. P. Smith (2)

1. Biochemistry and Molecular Biology, The Pennsylvania State

University
College of Medicine, Hershey, PA, USA.
2. Medicine, The Pennsylvania State University College of Medicine,
Hershey,
PA, USA.
3. Surgery, The Pennsylvania State University College of Medicine,
Hershey,
PA, USA.

Background and Aims: Endogenous opioids have been shown to influence

inflammatory responses through the modulation of cytokine production.
Additionally, opioid antagonists promote tissue growth and repair. It
was
hypothesized that the opioid antagonist naltrexone could reduce
inflammation
and promote repair of the bowel in a chemically-induced mouse model of
inflammatory bowel disease.

Methods: Forty-eight C57BL/6J mice were divided into two groups: one
received untreated drinking water and the other received 2% dextran
sodium
sulfate (DSS) for 5 days. On the third day after DSS was introduced, 8
animals in each group were injected subcutaneously with 0.1 ml saline
(control) or naltrexone (NTX, 0.1 or 10 mg/kg) daily for 5 days.
Disease
activity index (DAI) scores, based on weight loss and stool
hemoccult, were
calculated daily. Mice were necropsied on day 9 and inflammation of
the
distal colons was analyzed histologically. Colonic RNA was evaluated
by
microarray and real-time RT-PCR.

Results: By day 4, DSS-treated animals had significant weight loss (p

=
0.006) and a higher DAI score (p < 0.001) compared to water controls.
At
necropsy, DSS-treated mice that received NTX (10 mg/kg) had less
weight loss
(30.8%), lower DAI scores (24.6%), and less inflammation (25.0%)
compared to
DSS mice that received only saline. Real-time RT-PCR demonstrated an
increased expression of the cytokines IL-6 and IL-12 in DSS-treated
mice.
The increase in these pro-inflammatory cytokines was reversed by NTX
treatment to levels near or equal to the expression in mice without
colitis.
Furthermore, the expression of the transcription factors STAT3 and
STAT4,
downstream effectors of cytokine signaling, was upregulated in the
colons of
DSS-treated mice and similarly reversed by NTX.

Conclusions: NTX treatment reverses the disease manifestations and

histologic evidence of inflammation in DSS-induced colitis. The
mechanism by
which NTX acts to reverse colitis is related in part to the decreased
expression of pro-inflammatory cytokines (IL-6 and IL-12) and their
downstream mediators (STAT3 and STAT4).

http://ddw2006.abstractcentral.com/planner#
Dr. Mercola's Comments:

Some leading experts believe that low-dose naltrexone (LDN) holds great promise for the
treatment of millions of people suffering with autoimmune diseases, central nervous system
disorders, and even cancer and HIV/AIDS.

It’s extremely low-cost, and appears to be virtually free of detrimental side effects.

So why haven’t you heard about this before?

What is Naltrexone?

Naltrexone (generic name) is a pharmacologically active opioid antagonist, conventionally used

to treat drug- and alcohol addiction – normally at doses of 50mg to 300mg. As such, it’s been an
FDA approved drug for over two decades.

However, researchers have found that at very low dosages (3 to 4.5 mg), naltrexone has
immunomodulating properties that may be able to successfully treat cancer malignancies and a
wide range of autoimmune diseases like rheumatoid arthritis, multiple sclerosis (MS),
Parkinson’s, fibromyalgia, and Crohn’s disease, just to name a few.

At least one physician, Dr. Jacquelyn McCandless, has even found LDN to have a positive effect
on children with autism.

Recently I had the pleasure of interviewing Dr. Burton M. Berkson, MD, for my Inner
Circle,expert interview series, and he attested to achieving phenomenal results with low-dose
naltrexone (LDN) in both cancer patients and those with autoimmune diseases.

Unfortunately, very few physicians are aware of LDN, and none of the pharmaceutical giants
back it, meaning there are no friendly sales reps visiting your doctor talking about the potential
benefits of this drug in very low doses.

And why would they?

At an average price of $15 to $40 for a month’s supply, the income potential from LDN doesn’t
even come off in the rounding. It’s completely insignificant.

How Does Low-Dose Naltrexone (LDN) Work for Autoimmune Diseases and Cancer?

A growing body of research over the past 20 years indicates that your body’s secretion of
endorphins (your internal, natural opioids) play an important, if not central, role in the workings
of your immune system.

A review article entitled Opioid Therapy for Chronic Pain, published in a 2003 issue of the New
England Journal of Medicine, states:
"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.

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."

As explained on the informative website www.lowdosenaltrexone.org, when you take LDN at

bedtime -- which blocks your opioid receptors for a few hours in the middle of the night -- it is
believed to up-regulate vital elements of your immune system by increasing your body’s
production of metenkephalin and endorphins (your natural opioids), hence improving immune
function.

In addition to increased endorphin production, Dr. Bernard Bihari (who first discovered LDN as
a therapeutic agent for AIDS, in 1985), believes LDNs anti-cancer mechanism is likely due to an
increase in:

 the number and density of opiate receptors on the tumor cell membranes, making them more
responsive to the growth-inhibiting effects of the already present levels of endorphins, which in
turn induces apoptosis (cell death) in the cancer cells
 the absolute numbers of circulating cytotoxic T cells and natural killer cells, as well as killer cell
activity

Dr. Bihari has reportedly treated more than 450 cancer patients with LDN with promising results,
including cancers of the bladder, breast, liver, lung, lymph nodes, colon, and rectum.

According to Dr. Bihari, nearly a quarter of his patients had at least a 75 percent reduction in
tumor size, and nearly 60 percent of his patients demonstrated disease stability.

Recent Clinical Studies on Safety and Benefits of LDN for Autoimmune Diseases

Although the video above makes it seem as though there are virtually no scientific inquiries into
the safety and benefits of LDN, that’s not an entirely accurate assessment. Several studies have
been conducted, and more are in the pipeline.

For a more complete list of past and current research, please see the lowdosenaltrexone.org
website, but here are a couple of highlights.

LDN for Multiple Sclerosis – Dr. Maira Gironi, an Italian neurological researcher, treated 40
patients affected with Primary Progressive MS (PPMS) with LDN for six months, concluding
that LDN was not only safe and well-tolerated, but halted the progression of the disease in all but
one patient. The results from this pilot study were published in the journal Multiple Sclerosis in
September of last year.
LDN for Crohn’s Disease – The first clinical study of LDN published by a U.S. medical journal
was Dr. Jill Smith’s article, Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease,
published in the American Journal of Gastroenterology in 2007.

An impressive two-thirds of the patients in her pilot study went into remission, and 89 percent
responded to LDN treatment to some degree. She concluded that “LDN therapy appears effective
and safe in subjects with active Crohn’s disease.”

Other studies currently underway in various parts of the world, include:

 A Phase II placebo-controlled clinical trial on the efficacy of LDN for children and
adolescents with Crohn’s disease at Penn State.
 A clinical trial of LDN in HIV-infected citizens of Mali—the first scientific study of LDN for
HIV/AIDS in Africa—implemented in October 2007.
 A study of LDN in the treatment of MS at the University of California, San Francisco,
implemented in early 2007.
 A clinical trial of LDN in the treatment of fibromyalgia at Stanford Medical Center
implemented in October 2007.
 A study by the MindBrain Consortium in Akron, Ohio of, especially, the affective changes
in MS treated with LDN, begun late 2007.
 An animal research study at Penn State of naltrexone in a model of a disease that
mimics MS.
 Animal research on neurodegeneration at NIEHS, suggesting a protective role for
naltrexone.

Side Effects and Cautionary Warnings

So far, the only adverse events reported in clinical studies have been temporary insomnia and
vivid dreaming in some patients. However, there are a few cautionary warnings with this drug, as
with most others.

According to lowdosenaltrexone.org, if you fall in any of the categories below, you need to take
special precautions:

 If you use opioid agonists, i.e. narcotic medications such as Ultram (tramadol), morphine,
Percocet, Duragesic patch or codeine-containing medication, should not take LDN until such
medicine is completely out of your system.
 Patients taking thyroid hormone replacement for a diagnosis of Hashimoto’s thyroiditis with
hypothyroidism need to begin LDN at the very lowest range (1.5mg for an adult), as 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.
 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.

For more information about low-dose naltrexone, LDNers.org is another good resource.
And, if you or someone you love suffers from any of the autoimmune diseases listed in the
article links below, please review them for my personal recommendations on how to resolve the
underlying problems of your ailment.