Naltrexone itself 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. Many body tissues have receptors for these endorphins and enkephalins, including virtually every cell of the body's 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) 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. [Note: Subsequently, the optimal adult dosage of LDN has been found to be 4.5mg.]

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.

Dr. Jill Smith’s original article, "Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease," in the January issue of the American Journal of Gastroenterology (2007;102(4):820-8), 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.” (For further information on Smith's study, please see the linked Clinical Trials page.)

Endoscopic Improvement in Crohn’s Colitis with Naltrexone
Figure A: 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.
Figure B: 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.
Copyrights: do not reproduce the above images and captions without written permission from Jill P. Smith, MD, Professor of Medicine, H-045 GI Division, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033

Up to the present time, the question of "What controls the immune system?" has not been present in the curricula of medical colleges and the issue has not formed a part of the received wisdom of practicing physicians. Nonetheless, a body of research over the past two decades has pointed repeatedly to one's own endorphin secretions (our internal opioids) as playing the central role in the beneficial orchestration of the immune system, and recognition of the facts is growing.

Witness these statements from a review article of medical progress in the November 13, 2003 issue of the prestigious New England Journal of Medicine: "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.^1,2 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.³"

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 in the following days. Animal research by I. Zagon, PhD, and his colleagues has shown a marked increase in metenkephalin levels as well. [Note: Additional information for Dr. Zagon can be found at the end of this page.]

Bihari says that his patients with HIV/AIDS who regularly took LDN before the availability of HAART were generally spared any deterioration of their important helper T cells (CD4+).

In human cancer, research by Zagon over many years has demonstrated inhibition of a number of different human tumors in laboratory studies by using endorphins and low dose naltrexone. It is suggested that the increased endorphin and enkephalin levels, induced by LDN, work directly on the tumors' opioid receptors and, perhaps, induce cancer cell death (apoptosis). In addition, it is believed that they act to increase natural killer cells and other healthy immune defenses against cancer.

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 LDN.

By Ali Gorman

Hershey, Pa. - May 21, 2008 (WPVI) -- It's a drug already helping thousands of people battle addiction, but many people believe it also has the potential to help tens-of-thousands of patients with diseases like Crohn's, multiple sclerosis, Lupus, Parkinson's and even HIV.

It's called low dose naltrexone or LDN. Many patients who've tried it said it works and doesn't have bad side effects. But getting it to a pharmacy near you could be difficult. [Please click to read more. Video no longer available.]
What diseases has it been useful for and how effective is it? Bernard Bihari, MD, as well as other physicians and researchers, have described beneficial effects of LDN on a variety of diseases: