Naltrexone for AIDS/ARC

WITH BERNARD BIHARI, MD, OF THE DOWNSTATE MEDICAL CENTER IN BROOKLYN, NY. HOWEVER, SOME INFORMATION CAME FROM OTHER SOURCES, AND DR. BIHARI DID NOT SEE THE DRAFT BEFORE IT WENT TO PRESS. ANY ERRORS ARE THE SOLE RESPONSIBILITY OF THE WRITER. JSJ

Naltrexone is an experimental treatment which physicians can use now. It is inexpensive, and a gentle treatment which mobilizes the person's own healing power. It has no known side effects or dangers. About 20 physicians and several hundred persons with AIDS or ARC -- most of them in the New York City area -- are now using naltrexone.

How effective is it? We cannot report about results, because a technical paper is being prepared for a medical journal, and if the results get out in the press, the journal will not publish it. All we can say is that those using this treatment believe it clearly holds promise -- even though it is also clear that naltrexone alone does not help everyone.

As a treatment for AIDS/ARC, naltrexone is new. Although clinical trials started 14 months ago, we do not know any physician on the West Coast who is now using it. Until the results of trials are published, patients and physicians will have to hear about naltrexone by word of mouth, or through articles like this one, and then take initiative to find out
more.

The bottom line is that your physician can talk to the head researcher running clinical trials on naltrexone, at the phone number given below, and/or to a physician using the drug in private practice for AIDS and ARC, to find out what he or she needs to know about whether this treatment would be appropriate for you, and how to use it properly. Anyone with AIDS or ARC should consider this option. The most important point of this
article is that these doctors are happy to talk with other physicians.

Naltrexone's Standard Medical Use

Naltrexone has been approved by the FDA for about two years, for use as a "narcotic antagonist", to keep heroin or other opiate addicts off the drugs. Naltrexone works by blocking the "opiate receptors" -- sites on the cell membranes where opiates have their effect. If a person on naltrexone later takes heroin or another opiate, it will have no effect. But the person must
be completely off narcotics before starting naltrexone, or it will cause an immediate, extreme withdrawal reaction.

Naltrexone itself is not a narcotic, and not at all addicting. It is taken by mouth, not injected, in doses of 50 mg per day for preventing addiction. It has also been tried in very large doses, 200-300 mg per day, for treating obesity. At these doses, there are toxic side effects.

Naltrexone for AIDS or ARC

For treating AIDS or ARC, naltrexone must be used in very small doses -- only about one twentieth of the dose used by ex- addicts. Too large a dose would be ineffective, and might even have the opposite of the intended effect. Because the only tablets available in pharmacies contain the large dose for ex-addicts, the pharmacy must dissolve one pill (more than a two-
week supply) and give the patient instructions for measuring out an exact amount of the liquid.

No side effects have ever been found at the small doses used for treating AIDS or ARC.

Also, because of the small dose, the daily cost of the medicine alone is only about fifteen cents. Of course the actual cost will be more, because of the special preparation which the pharmacy must do.

Naltrexone is an immune enhancer. It may need to be combined with an antiviral or with other treatments, for some patients. One doctor at least is now testing naltrexone on patients who, on their own, are simultaneously taking ribavirin. (U.S. doctors cannot prescribe ribavirin, although it has been approved for medical use in over 30 countries, and is showing increasingly good results when used for AIDS or ARC.)

We caution the reader not to dismiss naltrexone as only a minor treatment, because of the small dose. Many of the patients using it have AIDS or severe ARC.

How Does It Work?

The theory behind the low-dose naltrexone treatment for persons with AIDS or ARC is very complex. But this theory has a special importance, because it may also explain the physiological mechanism by which physical exercise, and even positive mental attitudes, can help in healing AIDS.

We can only outline some of the elements of this theory, based on results of immunology research over the last several years. Dr. Bihari and his colleagues used these results to develop the low-dose naltrexone treatment, which might be valuable for other diseases, including cancer and autoimmune diseases, as well as for AIDS. They started a three-month
double-blind trial for AIDS and ARC in mid 1985. After the three months, they started treating all the patients with naltrexone. The original patients have now been using it for up to 14 months; others joined the study later.

The theory of naltrexone is based on endorphins. Endorphins, produced by the pituitary gland, could be described as the body's natural opiates. The endorphin system -- the endorphins themselves, and the opiate receptor sites in cells, which is where they act -- help the body respond to stress. Endorphins are responsible for the "runner's high", the good feeling people get after exercise.

In the last several years, immunologists have also discovered that endorphins are a major link in communication between the brain and the immune system. Every cell in the immune system -- T-cells, B-cells, platelets, etc. -- has opiate receptors, that respond to endorphins.

Unlike most other immune modulators, which only affect one or two parts of the immune system, endorphins seem to be a natural up-regulator of the whole system, and probably a normal means by which the system heals itself. For unknown reasons, AIDS seems to interfere with this process of healing, perhaps by causing a very high level of alpha interferon (see below).

Naltrexone temporarily blocks the opiate receptors which are part of the endorphin system. But at the same time, it increases the amount of endorphins, and also the number and sensitivity of receptors. Both these effects increase the overall activity of the endorphin system.

The blocking effect of the low naltrexone dose wears off within several hours, but the up-regulation of the endorphin system works even during the blocking period, and then lasts throughout the day. The naltrexone must be taken at night as the pituitary produces most endorphins in the early morning.

The key test of whether naltrexone is working is not T-cell counts, but rather a reduction in the abnormally high level of alpha interferon found in persons with AIDS. Unfortunately, the alpha interferon test is only available to researchers, not to physicians in private practice. But since low-dose naltrexone is not harmful in any case, physicians can use it even though they cannot do the key test of how well it is working. (At this
summer's Paris AIDS conference, Dr. Bihari reported that a majority of patients treated with naltrexone showed a drop in alpha interferon levels.)

Miscellaneous

* Physical exercise can increase the level of endorphins. Dr. Bihari suggests that aerobic exercises (not bodybuilding exercises) would be most effective.

* Endorphins may be part of the physical basis of the healing effect of positive thoughts and images, healthy attitudes, and good morale. There is no scientific proof at this time.

* No one has found any problem combining naltrexone with antivirals or with other immune modulators.

However, naltrexone must not be combined with any narcotic painkiller, including codeine, percodan, morphine, or demerol. The painkillers would prevent the therapeutic effect of naltrexone. However, the combination is not dangerous, and patients who must go on narcotics should continue taking the naltrexone.

* Patients should continue using naltrexone as long as there is any immune deficiency. It is a long-term treatment. Some patients will see results soon, others will take longer to obtain an effect, and some will not be helped at all (at least not by naltrexone alone).

* It is perfectly legal for physicians in private practice to prescribe naltrexone for AIDS or ARC, even though the drug was approved for other purposes. The physician must find a pharmacy willing to prepare it. Physicians in New York have not found it hard to have pharmacies dissolve the naltrexone tablets, once they explain how to do it. At least four pharmacies in New York
are now preparing naltrexone this way; we don't know of any on the West Coast. (Most San Francisco pharmacies do not usually stock naltrexone, although they can order it.)

Information for Physicians

Physicians may call Bernard Bihari, MD, Downstate Medical Center, Brooklyn, NY, (718) 270-1094. He developed the low-dose naltrexone therapy, and is running the clinical trials.

Physicians may also call Lawrence A. Higgins, MD, MPH, at (212) 598-9445. He is using naltrexone in private practice. Some of his patients have also been using ribavirin in combination with naltrexone, so he can answer questions about using these treatments in combination.

Very little published information is available at this time. All we know about is the abstract of Dr. Bihari's Paris poster session, and a three-page writeup about the ongoing trials in Experimental Drugs for AIDS and ARC: A Directory of Clinical Trials (September 1986 draft, published by the American Foundation for AIDS Research, New York, NY).

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I would like to thank Martin Delaney and David Winterhalter, of Project Inform, for calling my attention to the naltrexone research, and putting me in touch with Dr. Bihari.