Low Dose Naltrexone (LDN)

LDN is an off label use of naltrexone, a medication that is FDA approved for opioid dependence or alcohol dependence, as it is a strong opioid antagonist.  For its approved FDA use, Naltrexone is dosed 50 to 300mg/day. Low dose naltrexone uses 0.5 to 4.5mg typically.
The use of LDN for such diseases as cancer was first proposed by Ian Zagon, PhD, and LDN’s broader clinical effects in humans were proposed by Bernard Bihari, MD in the 80’s while treating HIV patients.      
LDN’s clinical uses have been found to lessen inflammation and to modulate the immune system. To this end, LDN has been used for problems associated with HIV/AIDS, Lyme, MS, Hashimoto’s, fibromyalgia, rheumatic issues, inflammatory bowel diseases, cancer, as well as autism, fatigue, depression. There is a small but growing body of clinical research to support these claims.
Link to LDN Clinical trials, http://www.ldninfo.org/ldn_trials.htm  and http://www.ldnresearchtrust.org/Clinical-trials-studies
Proposed Mechanism of Action: It is not entirely clear how LDN works. It is suspected that by inhibiting opioid receptors it causes the body to increase production of endorphins and enkephalins in order to compensate for the blocked receptors. These increased levels of endogenous opioids persist after the naltrexone has been eliminated from the body. Dr. Bihar’s research showed an increase in T-lympocytes.
It may also act directly on these immune cells to stimulate or restore normal function. There is research currently underway, to prove the hypothesis that naltrexone improves or modulates the immune system by acting on a receptor called TLR4. Several published papers have shown that naltrexone binds to the TLR4 receptor, and has a clinically measurable effect. This is evident in Crohn’s disease and Ulcerative Colitis.
Dosing LDN:
Start with 0.5mg 1/2 to 2 hours before bed. Increase it by 0.5mg every one to two weeks until you reach 4.5mg, or to the point you notice solid improvement. Your ideal dose is likely between 1.5mg and 4.5mg.
Some patients start at 1.5mg and increase it by 0.5mg to1.0mg every week. The more fragile/sensitive the patient, the lower the dose and the slower they should advance the dose.
The Use of Low-dose Naltrexone, and the Occurrence of Side Effects:
 Many patients who start LDN do not experience any severe side effects.
Initially, your symptoms may become worse – in MS, this can be characterized by increased fatigue, or increased spasticity. In CFS/ME, this can be the onset of apparent ‘flu-like’ symptoms.
LDN can cause sleep disturbances if taken at nighttime – this is most likely because of the increase in endorphin release. These disturbances can take the form of vivid dreams, or insomnia. Some individuals feel like their sleep is better with LDN.  If after experimenting with different dosages and sleep is still disturbed, simply switch your dosing to the a.m.  Many patients who take LDN in the morning still get excellent benefits.
In less than ten percent of cases treated, increased introductory symptoms may be more severe or more prolonged than usual, lasting sometimes for several weeks. Rarely, symptoms may persist for two or three months before the appropriate beneficial response is achieved.
If side effects are troublesome, then reducing your dose by 0.5mg for 7 days, before increasing it again, is a good idea and common practice.
Some patients, very rarely, experience gastro-intestinal side effects such as nausea and or constipation/diarrhea. The reason for this is currently unknown, but may be due to the presence of large numbers of TLR4 receptors in intestines. Patients experiencing this side effect can request LDN Sublingual Drops, which transfer the LDN directly into the bloodstream – avoiding the stomach area.
Patients who do have these side effects should increase their dose by no more than 0.5mg per week – and should consult with their physician or pharmacist for appropriate treatment for the stomach upset, if necessary.  
If you have autoimmune hypothyroidism – Hashimoto’ s — 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. It is recommended that you monitor your thyroid labs when starting LDN.
Intrinsic Toxicity of the Drug:
Naltrexone, in full doses of 50-300mg, has been shown to transiently increase liver enzymes. Patients being prescribed Naltrexone for addictions must have liver function tests performed before initiating therapy. This is not necessary with LDN – as the dose is much smaller, however, patients with advanced liver failure should consult their clinician before considering treatment.
Patients with renal or liver failure should only start treatment after a consultation with their own clinician or specialist, and should be monitored during the treatment initiation period.
It is normal for people with poor renal or liver function to experience a transient elevation – but this usually resolves after a few weeks.
Contraindications and Special Precautions:
 LDN is compatible with most other therapies. It does not directly interact with steroids, however, can negate the effect of opiate based painkillers. Patients should give their doctor a full drug history before starting therapy. Patients who are taking multiple medications and/or herbal medicines – especially those with cancer or advanced disease, should take careful advice from a qualified doctor or pharmacist before initiating LDN.
If you have had an organ transplant and are taking immune-suppressing therapy, you cannot take LDN.
Taking LDN can potentially lead to organ rejection.
If you are taking long-acting or continuously-administered “opiate” pain medicine, you cannot take LDN.
Taking LDN will likely lead to an immediate opiate withdrawal reaction (pain, nausea, vomiting, diarrhea, sweating). Examples of opiates include codeine, oxycodone, morphine, fetanyl, methadone, hydromorphone, tramadol. (Many patients report that they can use/benefit from tramadol/ultram if it’s taken 5 hours away from the LDN dose.)
Use of immunosuppressant medications –such as steroids– for any length of time will act to counter LDN’s benefits, most of which are based on its ability to normalize the immune system. If you have MS You can take LDN with Copaxone but not with Avonex or Beta Seron.
The safety of the use of LDN in pregnancy and breast-feeding has not been established and is therefore not recommended.   
Recommended Pharmacies (be sure to use a pharmacy with extensive experience in compounding LDN):
Belmar Pharmacy, Lakewood, CO.  Tel: 800-525-9473. Fax 866-415-2923. https://www.belmarpharmacy.com/
Skip’s Pharmacy, Boca Raton, FL.  Tel: 561-218-0111 or 800-553-7429.  Fax 561-218-8873. http://www.skipspharmacy.com/
For non-USA patients, Dickson Chemist, Glasgow, Scotland.  Tel: +44-141-647-8032 or +44-800-027-0673. Phone: +44-141-647-8032. http://www.dicksonchemist.co.uk/new/