Diarrhea, vomiting and sweating ≠ colitis for me at this stage of the game. So what is it?

For half of March, and most of April, I had been completely gut-normal (hurray!). I’d even eaten (gasp) a few pieces of bread without problems—until my wife started puking last Thursday. Now, a rotavirus, for a gut-normal person, is an inconvenience. It’s an awful time of gastric upset, and then life goes back to normal, but for someone with IBD a rotavirus can wreak havoc and cause a flare up. I’m trying to avoid that. Yesterday I slept for 16 hours. I’ve doubled my probiotics, and started wild oregano (transdermally, but rubbing it on my skin. My gut can’t handle it.). I’m eating only in my food safe zone, and making sure I manage the stress (and worry) of it well. I’ll keep you posted. Darn—I was doing so well…

Below, I’ve put together an informational post on LDN as it relates to Inflammatory Bowel Disease (IBD: Crohn’s and colitis), to conclude my journal series on my experience with it. I’ll continue to uptate you on my experience, but now after more than 6 months, it’s doing the most it can do, and I’m ready to move on to another topic. So, below is the “LDN Primer” I made for my doctor. It isn’t original writing. I’ve mostly created a mash-up from the sources listed at the end of this post.

What is low-dose naltrexone (LDN) and why is it important?

Naltrexone was approved by the FDA in 1984 in a 50mg dose for the purpose of helping heroin or opium addicts, by blocking the effect of such drugs. By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones that our brain and adrenal glands produce: beta-endorphin and metenkephalin. There are receptors for these endorphins and enkephalins in the immune system.

In 1985, Bernard Bihari, MD, a physician with a clinical practice in New York City, discovered the effects of a much smaller dose of naltrexone (approximately 3mg once a day before bed) on the body’s immune system. He found that this low dose, taken at bedtime, was able to enhance a patient’s response to infection by HIV, the virus that causes AIDS[1].

In the mid-1990’s, Dr. Bihari found that patients in his practice with cancer (such as lymphoma or pancreatic cancer) could benefit, in some cases dramatically, from LDN. In addition, people who had an autoimmune disease (such as lupus) often showed prompt control of disease activity while taking LDN. Since then, LDN has shown clinical improvements in a wide variety of illnesses; most notably, HIV/AIDS, Cancer, and autoimmune conditions.

How does LDN work?

LDN up-regulates beta-endorphin and metenkephalin thus, it boosts the immune system. The brief blockade of opioid receptors between 2 a.m. and 4 a.m. that is caused by taking LDN at bedtime each night is believed to produce a prolonged up-regulation of vital elements of the immune system by causing an increase in endorphin and enkephalin production. Normal volunteers who have taken LDN in this fashion have been found to have much higher levels of beta-endorphins circulating in their blood.

Increasingly, research is showing that endorphin secretions play a central role in the beneficial orchestration of the immune system. 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.

In general, in people with diseases that are partially or largely triggered by a deficiency of endorphins (including cancer and autoimmune diseases), or are accelerated by a deficiency of endorphins (such as HIV/AIDS), restoration of the body’s normal production of endorphins is the major therapeutic action of LD

Mechanism of LDN action

Clinical Trials of LDN and Autoimmune Conditions

  • A multi-institutional clinical trial of LDN for Primary Progressive MS in Italy, which includes endorphin measurements, published in September 2008.
  • Two Phase II placebo-controlled clinical trials of LDN for Crohn’s disease at Penn State.
  • A study of LDN in the treatment of MS at the University of California, San Francisco, published in February 2010.
  • A clinical trial of LDN in the treatment of fibromyalgia at Stanford Medical Center, published in May-June 2009.

LDN and IBD

Dr. Jill Smith’s paper, “Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease,” in the January issue of the American Journal of Gastroenterology (2007;102:1–9), officially presents LDN to the world of scientific medicine. Smith, Professor of Gastroenterology at Pennsylvania State University’s College of Medicine, found that two-thirds of the patients in her pilot study went into remission and fully 89% of the group responded to treatment to some degree. She concluded that “LDN therapy appears effective and safe in subjects with active Crohn’s disease.[i]

Shown is the rectum of a subject with active Crohn’s Disease before starting therapy with naltrexone 4.5 mg/day. The mucosa is ulcerated, edematous, and inflamed.

Shown is the rectum of a subject with active Crohn’s Disease before starting therapy with naltrexone 4.5 mg/day. The mucosa is ulcerated, edematous, and inflamed.

 

Shows the same area of the rectum in the same patient four weeks after naltrexone therapy. The lining is now healed, ulcers resolved, and the mucosa is healthy.

Shows the same area of the rectum in the same patient four weeks after naltrexone therapy. The lining is now healed, ulcers resolved, and the mucosa is healthy.

Dosage and Frequency

The usual adult dosage is 4.5mg taken once daily at night. Because of the rhythms of the body’s production of master hormones, LDN is best taken between 9pm and 3am. Most patients take it at bedtime. The therapeutic dosage range for LDN is from 1.5mg to 4.5mg once before bedtime.

For Inflammatory Bowel, LDN can be used either in pill form (1.5 mg) or in a transdermal cream. For those with active diarrhea and malabsorption issues, an LDN transdermal cream may be more efficacious.

Rarely, the naltrexone may need to be purchased as a solution — in distilled water — with 1mg per ml dispensed with a 5ml medicine dropper. If LDN is used in a liquid form, it is important to keep it refrigerated.

IMPORTANT: Do NOT give LDN in a slow-release form.

Reports have been received from patients that their pharmacies have been supplying a slow-release form of naltrexone. Pharmacies should be instructed NOT to provide LDN in an “SR” or slow-release or timed-release form. Unless the low dose of naltrexone is in an unaltered form, which permits it to reach a prompt “spike” in the blood stream, its therapeutic effects may be inhibited.

Fillers. Capsules of LDN necessarily contain a substantial percentage of neutral inactive filler. Experiments by the compounding pharmacist, Dr. Skip Lenz, have demonstrated that the use of calcium carbonate as a filler will interfere with absorption of the LDN capsule. Therefore, it is suggested that calcium carbonate filler not be employed in compounding LDN capsules. He recommends either Avicel, lactose (if lactose intolerance is not a problem), or sucrose fillers as useful fast-release fillers.

The FDA has found a significant error rate in compounded prescriptions produced at randomly selected pharmacies. Dr. Bihari has reported seeing adverse effects from this problem. Please see our report, Reliability Problem With Compounding Pharmacies. Please see the above list of recommended pharmacies for some suggested sources.

Side Effects and Precautions

Side effects

LDN has virtually no side effects. Occasionally, during the first week’s use of LDN, patients may complain of some difficulty sleeping. This rarely persists after the first week. Should it do so, dosage can be reduced from 4.5mg to 3mg nightly.

Precautions

  1. Because LDN blocks opioid receptors throughout the body for three or four hours, people using medicine that is an opioid agonist, i.e. narcotic medication — such as Ultram (tramadol), morphine, Percocet, Duragesic patch or codeine-containing medication — should not take LDN until such medicine is completely out of one’s system. Patients who have become dependant on daily use of narcotic-containing pain medication may require 10 days to 2 weeks of slowly weaning off of such drugs entirely (while first substituting full doses of non-narcotic pain medications) before being able to begin LDN safely.
  2. Those patients who are taking thyroid hormone replacement for a diagnosis of Hashimoto’s thyroiditis with hypothyroidism ought to begin LDN at the lowest range (1.5mg for an adult). 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.
  3. Full-dose naltrexone (50mg) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300mg daily. The 50mg dose does not appear to produce impairment of liver function, nor does the much smaller 3mg and 4.5mg doses.
  4. 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.

Sources:

http://www.lowdosenaltrexone.org/

http://www.ldnscience.org/

Chron’s Dad Blog: http://crohnsdad.wordpress.com/tag/ldn-for-crohns/


[1] The optimal adult dosage of LDN is now known to be 4.5mg/day.

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