LDN - Low Dose Naltrexone

Information for physicians about LDN therapy (Update

Information below is based on information from Dr Bihari, Dr. Bob Lawrence, Stanford
University, Pennsylvania State University, and other sources. See sources for more information
and contact info. The active ingredient in LDN = Naltrexone, an opiate antagonist. Naltrexone
was first approved by the FDA (Food and Drug Administration, USA) and classified as a "C"
formulation.

Mechanisms
LDN blocks the opiate receptors (using left-facing part of Naltrexone molecule) in the brain for
3-4 hours during the period in which the body's endorphin production is greatest. This means that
the body is tricked into believing that there is a lack of endorphin and metenkephalin. The result
is an increased production, and thus increased levels of endorphin and metenkephalin. It is
important to note that in the elderly, and in patients with autoimmune disease, endorphin
deficiency is common (levels lower than the normal population). Endorphins play an essential
role in the regulation/modulation of the immune system; increased endorphins will therefore help
to stimulate production of T cells, and stabilize the immune system (restore the natural balance
between the different types of T cells). A properly balanced immune system is essential to
prevent the destructive inflammatory processes that occur with various autoimmune diseases. In
connection with the study on LDN and Fibromyalgia in 2010, Stanford University School of
Medicine found that Naltrexone (the right-facing part of Naltrexone molecule) has an anti-
inflammatory effect. This finding allows that LDN has two active mechanisms against
autoimmune diseases. The 2005 hypothesis of Dr. Yash Agrawal, MD, Ph.D., University of
Iowa, explains how LDN can prevent the death of myelin producing brain cells.

Should the dosage of LDN become too high, this will block endorphins for too long a period,
which will have the opposite effect upon the patient. LDN must be out of the system by 2 a.m.
nightly. Should a patient experience recurrence of disease, or new symptoms, suspect that the
dosage of LDN needs to be lowered slightly- usually by .50 - until the patient begins to improve.
Some patients with certain conditions cannot exceed 2.0 to 3.5 mg (one of these conditions is
MS).

www.LDNscience.org has posted a more thorough explanation of the mechanisms.

Studies
There are no completed large clinical trials on LDN. There are several smaller studies in MS,
Crohn's, Fibromyalgia, HIV/AIDS. The treatment must be considered experimental until large
clinical trials exist. Completed studies are very promising. In 2008 a small study on LDN and
MS in Italy documents that LDN is a safe and well-tolerated treatment for PPMS and can have a
positive effect on symptoms such as spasticity, pain, fatigue, depression and quality of life.
Furthermore, the study documents that LDN raises endorphins in the body. In May 2006 a small
study was published on LDN and Crohn's disease, which concludes with the following: LDN
provides an alternative, safe, effective and economical treatment of active Crohn's disease. This
was followed up by a newer and larger study confirming these findings. The anecdotal
"evidence" is overwhelming, however. A Google search on "low dose naltrexone" gives over
471,000 pages and this is just the English-language pages. There are thousands of MS patients
who have used the treatment and their experience is very good. Almost 900 MS patients have
reported their experiences in three different surveys.

Diagnoses
MS, Ulcerative colitis, Bechterew disease, Fibromyalgia, COPD, ME/CFS, Prommer (proximal
myopathy myoton), Arthritis, Parkinson, Sarcoidosis + many other diagnoses. There is extensive
clinical experience in the use of LDN especially against MS, having been prescribed for 26
years. There are thousands of patients who use this treatment every day.

Toxicity
Toxicity is well known and documented. In studies it has been found to be a mild risk of
reversible liver at a dose of 200-300 mg per day. This is almost 100 times the dose used in
LDN treatment. The treatment is therefore seen as quite unproblematic in terms of toxicity.

Dosage
The following indications are given as daily dose. The drug is usually taken once a day. LDN is
often used in a dose from 1.5 mg to 4.5 mg. 4.5 mg has been shown as the most effective dose
and if the patient can stand it, this is preferable. Commencement: Treatment should be stepped
up with a starting dose of 1.5 mg and increasing by 1.5 mg every 1-2 weeks up to 4.5 mg. If a
dose is well tolerated, the titration can be significantly shortened. In MS, the increase should be
slower, with dosage increases every 4 weeks to minimize adverse effects. If patients experience
discomfort and it is suspected that the dose may be too high, simply return to a smaller dose and
stand for a period before again trying to increase up to 4.5 mg. In some cases it has been found
that 4.5 mg is too much - settle it where the patient feels well. In individual cases, doses up to 9
mg proved appropriate. Too strong or weak a dose will not provide the desired effect.

Time of Intake
LDN is primarily consumed in the evening before 11 PM. This is connected with the body's
endorphin production cycle, which peaks between 2-4 AM. Consumption at the specified time
optimizes endorphin production. People who work at night should also take LDN at this time.
For anyone experiencing an adverse effect such as sleep problems, LDN can be taken in the
morning.

Side Effects
There is very little side effect reported with the use of LDN. The most common is difficulty
sleeping and "weird" dreams. These usually disappear after a period of use. In MS a daily dose of
4.5 mg may increase spasticity, particularly in men. Spasticity can be reduced by lowering the
dose to eg. 3 mg. In the first period after starting LDN, disease symptoms may increase slightly
in intensity, but will normally subside again within 1-2 weeks. In isolated instances, this period
persisted longer. The most common improvements in MS are: reduced spasms and fatigue,
improved cognition, better control of bladder, better heat tolerance, less numbness, improved
mobility and strength, better sleep, less pain, improved sexual function. For other diagnoses there
is likewise experienced a stop/decrease in disease progression and reduced symptoms.

Other Medication
LDN should not be given to people who use Morphine, Tramadol, Codeine or similar opioid
preparations.

Caution
Naltrexone can cause reversible liver damage at VERY high doses (200-300 mg). Although LDN
is taken at a dose of 1.5 - 4.5 mg and, therefore, is considered harmless, it is still be advisable to
check that the patient has normal liver and kidney function before starting treatment. In the
preliminary results from an Italian clinical trial of LDN in PPMS patients, reviewers [saw]
elevated liver values as one of the few side effects observed. It is important to note that these
were temporary. It can thus be expected that some patients will experience elevated liver
values, but that these return to normal after a period of time. Patients who are taking thyroid
hormone replacement for a diagnosis of Hashimoto's Thyroiditis with hypothyroidism should
begin LDN at the lowest range (1.5 mg for an adult). Note that LDN can cause a rapid reduction
in the autoimmune disease, which may then require a rapid reduction in the dose of thyroid
hormone replacement to avoid symptoms of hyperthyroidism. LDN has been used during
pregnancy with no short term reported side effects for mother or child. There is clinical
experience with LDN since 1985. There are no reports of any adverse long-term effects from
doctors who have used LDN for their patients for many years.