Low Dose Naltrexone (LDN)

Greetings Inspire Members - I am a Stage IV NSCLC patient with widespread bone mets. All other organs including brain are unremarkable, especially my brain some might say. I am currently on my third line of defense, and in fact have just now returned from my weekly infusion of Taxotere. I also got Avastin today. I am doing fairly well after a diagnosis of about 12 months ago. As most people in my condition do, I have done a lot of research trying to find anything that will increase my chances of whipping this demon or extending my life, with quality, as far as I can. I am certainly not against resorting to complimentary and/or alternative treatments as well. Until my DX, I was a pretty healthy guy for most of my 48 years, but this thing really took my legs out from underneath me.

I have seen a lot of discussion on this site about various drugs that each of you or a loved one has used, some with success and others with not so much. During my research, I stumbled onto a drug that is beginning to be utilized by some doctors to treat various cancers and it piqued my interest. Most of the evidence of its efficacy is anecdotal, but even the National Cancer Institute has taken an interest in it as you will see below in my posting.

I must first set the record straight, and I have read the guidelines for posting on this site. What I am about to share is not promotion of one treatment over another. I merely want you to have access to information so that YOU AND YOUR DOCOTR(S) can decide if it has merit, much like you do when you ask a question of the members here about Tarceva or Carboplatin or any other “standard conventional” drug. Case in point, my Onco wanted to start me on Erbitux, even though it has not yet been approved by the FDA for NSCLC. She thought that I might respond well to it and would have prescribed it “off label”. My insurance company has very reluctantly approved her request, and we may start in the near future. Again, my doctor wants to use a drug not approved for NSCLC because she believes that I may benefit. This is legal and ethical.

I also need to add that I have no financial interest in this drug. It has been on the market for over 20 years, and its patent and high cost have long run out. Naltrexone was originally designed and approved by the FDA for treating heroin addicts. Later it was discovered that it could be used for treating alcoholics and was prescribed off label for that use too.

First some history, parts of which are taken from a website set up by physicians specifically for information dissemination about LDN, I offer the following. An addiction doctor in NYC by the name of Dr. Bernard Bihari in the mid 1980's started to notice that his patients (sharing needles) were showing up with a previously unknown disease - it eventually became known as HIV/AIDS. He noticed that when they took lower doses of Naltrexone, their AIDS symptoms went away. He did this through his own double-blind placebo controlled trial in 1986. They still had AIDS, but they did not get sick any longer. It seemed that the lower doses somehow halted disease progression. What he did determine was the fact that Naltrexone in low doses increased endorphin production in the body, and he also discovered that endorphins are the primary regulators of the immune system. Thus he surmised that the enhanced immune system somehow kept the disease in check.
A friend of his who was re-diagnosed with non-Hodgkin’s lymphoma asked him, after a 5 year remission, if he thought that his new AIDS drug would help her. He found some recent studies that suggested it might based on lymphoma that had been transplanted into mice and treated with endorphins. The mice treated with endorphins fared considerably better than the control group. He agreed to prescribe the Low Dose Naltrexone (LDN) for his friend, and within 6 months, her 3 golf ball sized tumors shrank and disappeared. She stayed on LDN and had no further exacerbations of her malignancy. She died six years later in her mid-seventies from her third heart attack.
Several months later, Dr. Bihari, while in Paris to present the LDN AIDS results at an International AIDS Conference, met a woman (C.P.) in her early forties who was quite ill with metastatic malignant melanoma. This had spread from a malignant mole on her arm to her brain, which showed four metastases on C-T scan. Her speech was slurred, her balance and handwriting impaired, and she suffered from headache and recent memory impairment. Her oncologist in Paris said the malignancy was untreatable, and believed that she had perhaps three to six months of life remaining. On his return to New York, Dr. Bihari shipped LDN to C.P.'s daughter, who started the patient on it. Nine months later, with all neurological signs and symptoms having cleared, C.P. had a repeat C-T scan that showed no residual tumor.
C.P. remained on LDN for the succeeding 12 years, stopping it without her family's knowledge in late 1999. Until that time, she had remained in complete remission, without any recurrence of her malignancy. Eight or nine months after stopping LDN she developed nodules under her skin and began to cough up blood. A C-T scan of the chest showed multiple metastatic lesions. Biopsy of one of the subcutaneous nodules confirmed recurrence of malignant melanoma. Dr. Bihari shipped LDN to the patient's family and she resumed it in early 2000. Eight months later, the nodules in the skin had cleared and a repeat C-T scan of the chest showed no residual tumor. She appears to be, once again, in remission.
Over the years encompassed by these two cases, 1986 to 1999, Dr. Bihari focused his research energy on the study of LDN's effect on immune function and on immunological approaches to the treatment of HIV/AIDS. In 1999, however, conversations with three small pharmaceutical companies revealed some interest in the development of LDN, with a goal of getting FDA approval for immune-related diseases including cancer. With this development possibility, Dr. Bihari decided to revisit the potential value of treating cancer with LDN.
Dr. Bihari began an informal private-practice-based evaluation of the effects of LDN with a variety of types of cancer in February 1999. He had seen positive results with a small but growing number of patients with cancer during the preceding 14 years, while developing the drug as an immune modulator for HIV/AIDS. The drug was compounded by pharmacists in 3mg capsules and taken once a day at bedtime. Most patients have recently had their LDN dose increased to 4.5mg daily. It is nontoxic and has no side effects. Its only interaction with other drugs is with opioid based narcotics (such as morphine, Demerol and Percocet), which it briefly blocks.
The mechanisms involved in the apparent beneficial effect of LDN on cancer have three main elements. The first is the effect of LDN, when taken late at night, in inducing a sharp increase in pituitary and adrenal production of beta-endorphin and metenkephalin, respectively, in the pre-dawn hours, when 90% of the day's manufacture of these hormones occurs. Most studies have shown that naltrexone induces a two to three-fold increase in production of metenkephalin, the endorphin that most specifically activates delta-opioid receptors, the primary endorphin-related anti-growth factor on cancer cells. The low dose of naltrexone, which in higher doses would block endorphin and enkephalin action on the receptor, is gone from the body in about three or four hours, whereas the elevated levels of endorphins and enkephalins persist all day.
The second step involved in the anti-cancer effect of these hormones results from direct activation of opioid receptors of cancer cells by the increased endorphins. If this activation occurs while the cell is dividing, it dies. In fact, relatively small concentrations of metenkephalin, when added to human pancreatic cancer cells or human colon cancer cells growing in the test tube, have been shown to kill both. The apparent mechanism of cell killing is called apoptosis (programmed cell death). This appears to be one of the mechanisms by which endorphins and enkephalins combat cancer.
A third element, which may play a major role in controlling cancer, involves the cells of the immune system, which is regulated/orchestrated to a great extent by endorphins. In particular, endorphins raise the circulating levels of natural killer cells and lymphocyte-activated CD-8 cells, the two immunological cell types that prevent cancer by killing cancer cells as they arise.
It should be emphasized that Dr. Bihari's patients were all treated in a private practice setting without the scientific rigor of a prospective clinical trial. This precludes any scientific claims about the drug's efficacy in treating any of the above-mentioned types of cancer. The results thus far do, however, raise the possibility that the manipulation of opioid receptors on cancer cells as anti-growth factors through the use of endorphins and endorphin-inducing opioid antagonists may eventually prove to have considerable merit, particularly in view of the many years of published, supportive laboratory research findings.
Those cancer cells that have opioid receptors on their cell membranes, and that may, therefore, respond to LDN, include all of those that arise from the gastrointestinal tract. This includes the mouth, esophagus, liver, pancreas, stomach, small intestine, colon and rectum. Lymph glands and the spleen have large numbers of opioid receptors, suggesting that Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma and lymphocytic leukemia should respond to LDN. Other malignancies with sizable numbers of opioid receptors on their cell membranes include breast cancer, neuroblastoma, prostate cancer, malignant melanoma, renal cell carcinoma, glioblastoma, astrocytoma, endometrial cancer and small cell and large cell cancers of the lung.
LDN Alone in the Treatment of Cancer. Dr. Bihari now has 88 patients with cancer in complete or partial remission whose improvement appears to be clearly attributable to LDN alone. In contrast, the vast majority of patients who consult with him for cancer tend to be on other concurrent treatments as well, which obviously interferes with drawing conclusions about LDN's role in their improvement. The successful LDN-only group includes five breast cancer patients, one patient who had widespread metastatic renal cell carcinoma, three with Hodgkin's disease and six with non-Hodgkin's lymphoma. Other such cases, some now on LDN for as long as four years, include a score of patients with non-small cell lung cancer, as well as patients with ovarian cancer, uterine cancer, pancreatic cancer (treated early), untreated prostate cancer, colon cancer, malignant melanoma, throat cancer, primary liver cancer, chronic lymphocytic leukemia, multiple myeloma and some others.
NCI Examining LDN Cancer Cases. In June 2002 an oncologist and an oncology physician's assistant from the National Cancer Institute reviewed some 30 charts of cancer patients at Dr. Bihari's office. About half were chosen as appearing to have responded to LDN without question. With patients' permission, copies of these were sent to the NCI for further data collection on its part for consideration for NCI's Best Case Series.
Ian Zagon, Ph.D., whose research group has done much of the basic animal work in the area of cancer treatment and endorphins, showed in 1981 in a mouse neuroblastoma model that very small doses (0.1 mg./kg) of naltrexone, given once a day, inhibit tumor growth, prolong survival in those mice that develop tumors and protect some mice from developing tumors altogether.
Zagon had hypothesized that the small daily doses of naltrexone work to enhance the endorphin-related protective effect against cancer in mice by increasing the number and density of opiate receptors on tumor cells. He hypothesized as well that the increase in endorphins known to be induced by naltrexone might play a part in the protective effect of the small daily dose by working directly on the tumors' opiate receptors.
In 1996 and 1997, Zagon and his co-workers, reported on laboratory research using specially-bred mice that had no immune system (so-called "nude mice"). They transplanted, in separate experiments, human colon cancer and human pancreatic cancer into the animals and compared the growth of the cancer between those mice that received daily injections of metenkephalin and a control group that received placebo. In each experiment, metenkephalin acted as a negative regulator of tumorigenesis and was significantly able to suppress tumor appearance and growth in the treated group.
Of especial importance, in 1996 the same group of researchers demonstrated that by utilizing LDN to induce an intermittent blockade of opioid receptors in similar laboratory animals (nude mice), the growth of inoculated human colon cancer was markedly retarded. "At the time (10 days) when all control mice had tumors, 80% of the mice in the 0.1 mg/kg NTX group had no signs of neoplasia." When measurements of metenkephalin plasma levels were made, the group that received LDN had metenkephalin levels that were elevated 2.5-fold compared with the control group. The researchers concluded that the results suggested "that daily intermittent opioid receptor blockade with NTX [low dose naltrexone] provokes the interaction of opioids and receptors in the interval following drug availability, with opioids serving to inhibit tumorigenicity of human colon cancer".
New findings by Zagon and colleagues at The Pennsylvania State University in Hershey were published in the December 1999 issue of the journal Brain Research. They had identified the specific cell receptor for one of the endorphins, metenkephalin (the levels of which are increased by LDN). Zagon stated that the opioids act as growth inhibitors, as well as neurotransmitters, and that this feature has implications for cancer treatment. Metenkephalin is found in all tissues, and appears to be associated with cells undergoing renewal or proliferation. Zagon's group was described as having mounted Phase I trials using metenkephalin in an attempt to control the growth of pancreatic cancer in humans. Pancreatic tumors appear to have low levels of the metenkephalin receptor. Low peptide [metenkephalin] or [opioid] receptor levels may exist in cancer cells in general since they want to stimulate their own growth, Zagon said.
Doctors that prescribe LDN for cancer treatments are doing so "off label". This is perfectly legal and ethical. In fact, a recent study that I read showed that of the top 160 prescription drugs written in the US, about 20% are prescribed off label. Off label means that the Doctor can, and the FDA allows this, write a prescription for a drug for another use other than what it was originally designed for.

In any event, I wanted to share the above with you to show that there are doctors that are using LDN in the treatment of cancers, and that Dr. Bihari himself had success with lung cancers. Dr. Bihari is now retired and is in his mid 80’s. An unfortunate accident that severely fractured his pelvis forced him out of practice. You can GOOGLE Low Dose Naltrexone and find ample information. Again, I don’t want to break with the guidelines set up for us, so I cannot tell you what sites to visit. LDN is very widely being prescribed for auto-immune diseases, and has shown particularly great results in halting the progression of MS. Clinical trials are going on across the US, with one in Italy and one in Mali, Africa, but these are for auto-immune diseases and AIDS. No clinical trials are on-going for the use in cancer treatment.

I am using LDN at 4.5 mg at bedtime. There are no side effects other than some sleeplessness that generally diminishes with time. I have been taking it for about 5 weeks now, and it costs me about $0.50 per day if I get a 90 day supply. That’s right, 50 cents per day. A compounding pharmacy near me takes my Onco’s prescription and reformulates the 50 mg pills that the manufacturer provides into 4.5 mg pills for me specifically.

At least 5 conferences have been held in the U.S in recent years at institutions such as USC, Vanderbilt, the National Cancer Institute, the National Library of Medicine, and the New York Academy of Sciences. These are not locations that you would expect to see doctors selling snake oil nor sharing their experiences, including successes and failures, with the public. If there was no truth to what they were presenting, their licenses would truly be at risk. And if these institutions did not see some validity in the claims, they would not allow the conferences to be held there. The next conference will be held in Glasgow, Scotland next summer.

So, I am sorry about the very long posting, but there is much to share here. Again, I am not trying to influence anyone on their treatment regimen, but after doing my own research, I decided that there was no reason not to try this out, and I wanted to share it with you. My Onco is fairly open minded about complimentary and some alternative routes to treating cancer, and she somewhat reluctantly agreed. She also knew, because I am very much my own advocate, that if she refused, I would find someone who would prescribe for me. There are several doctors here in Colorado prescribing LDN for cancer. Her partners were less than excited about her decision, but she bowed to my request. Is it working for me? Don’t know. Will it work for me? Don’t know. It takes time for it to do its job. My cancer did not arise overnight, and it likely will not resolve overnight. For some very lucky individuals, the success comes quickly. But Dr. Bihari’s research with over 450 patients revealed that it generally takes at least 6 months for a halt in disease progression for those that respond – and not all do. Do your own research and decide for yourself. You will quickly learn that this is not some sales job by some slick pill peddler(s). You can only get this drug through your doctor and then you must have a compounding pharmacy make the pills for you. YOU CANNOT BUY THIS DRUG ON THE INTERNET OR ANYWHERE ELSE FOR THAT MATTER.

It should be noted that this IS NOT A CURE. What Dr. Bihari discovered is that when a patient had their cancer symptoms disappear, and perhaps not even show any tumors anymore on subsequent scans, if they stopped taking the LDN, the cancer generally reappeared rather quickly. If I can get my symptoms to disappear, and treat my disease as a chronic manageable disease, then that will suffice for me. Perhaps someday the cure will come along, and if I am here to use it, then that is wonderful indeed.

Again, I am not using Inspire to promote a product or myself. I have no interest in LDN whatsoever, other than I have found ample evidence that it may be something that can be of help to you or a loved one. You will have to decide for yourself. In saying this, I do not believe that I have stepped out of bounds on the Guidelines that are set for all members of Inspire. I am merely pointing you in a direction for help.

Blessings and divine health to all.
Steven