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Commentary: (Jan 2002) Low dose naltrexone is interesting, in theory, but it has not panned out as well as initially described in an article called "One Pill a Day Keeps Cancer at Bay." That article made it seem like everyone with NHL was benefiting. Dr. Bihari said the same to me at the time.. After a while the author, Christina White, called me to say that in her follow up she was disappointed that many who try it do not seem to benefit. I want to thank Christina publicly for her candor and good will.
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News ( 9/20/99) * Look here for up- to-the-minute progress of reporting patients * |
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Naltrexone's Mechanism in Cancer Treatment (from Bihari) |
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I'm interested in low dose Naltrexone for these reasons (9/20/99) |
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Anecdotal Reports: Successful Cases |
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How it Works |
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Where to Buy Naltexone |
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Medline Abstracts |
Links
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LowDoseNaltrexone.org - Information direct from Dr. Bihari. (NEW)
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Vera's Web site: Notes on Naltrexone
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Dr. Bihari says patients are reporting improvements and reductions in symptoms after 3 weeks on low dose naltrexone. (6/1/90) |
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Dr. Bihari says in his practice that best results have been for non-Hodgkin's lymphoma patients, compared to other cancers. (7/20/99) |
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Dr. Bihari has observed that it has taken 3 to 6 months for nhl patients to see regressions in node size, and that reductions have been gradual. (Communication 8/1/99, posted 8/6/99) |
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Joanne has been taking low-dose naltrexone for 5 months now. In that time, two nodes have increase in size from 3cm to 4cm. Her labs remain normal and she has no symptoms. We decided to start H2o2, so the reason for future results will not be clear cut. (9/18/99) |
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Christina White, the author of "One Pill a Day Keeps Some Cancers at Bay" may provide a link to more news about naltrexone. I look forward to posting the link, and wish to extend my appreciation for the information and hope her original article has provided. Note: Posting her original article withour waiting for her permission was wrong, and I apologize for doing it. |
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A member of nhl-other with CLL reports NO change in nodes after 5 months on naltrexone. He still needs prednesone therapy to reduce enlarged lymph nodes.(corrected 9/20/99) |
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I have been on Naltrexone for 4 months and have seen no changes. I have no physical symptoms of Waldenstroms macroglobulinemia(rare B cell lymphoma)at this point. But my blood test results have not improved-my IGM is slowly increasing. |
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11/99 Christina White (see above) called to report that she is not seeing much evidence of efficacy from patients she has contacted. She believes natlrexone may be most effective when used after achieving a remission from standard therapy as an aid to preventing recurrence. |
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12/12/99 |
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2/1/00 |
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2/14/00 |
Bernard Bihari, MD
June 1999
Cancer remains a leading cause of death in the world today. In the US alone, more than one million new cases are diagnosed each year and nearly 500,000 individuals lose their lives to the disease annually.
Naltrexone works by increasing endorphins, one of the body's major mechanisms for regulating the immune system - the primary defense system for preventing and controlling cancer. With the failure of chemotherapy to markedly improve cancer survival, the medical community desperately needs nontoxic, effective, new approaches to the treatment of this disease.
The Scientific Background
Dr. Bihari and Dr. Margaret Lewin, an oncologist at New York Hospital-Cornell Medical Center, have shown that low dose naltrexone, 3 mg. per day, at bedtime, holds promise in the treatment of certain kinds of cancer. A considerable amount of test tube and animal cancer research has indicated that endorphins regulate the growth of a number of cancers, in particular, those with receptors for endorphins in the cancer cell walls. These receptors are called opiate receptors. The malignancies in which Dr. Bihari and Dr. Lewin observed positive results all grow from tissues that are dense with opiate receptors. These include lymphoma, Hodgkin's Disease, lymphocytic leukemia, carcinoid, colorectal cancer, prostate cancer and cancer of the pancreas.
Naltrexone appears to work in cancer, as it does in HIV infection, by increasing the body's endorphin production. One major effect of naltrexone involves the direct action of the increased endorphins in shrinking such malignancies and inhibiting their growth, as endorphins do with several cancers in mice (see The Zagon Study discussed in the next section). In addition, the rise in endorphins increases the activity of the immune system's natural killer cells, which provide the surveillance system that protects the body against newly forming or metastasizing cancer cells of all types. This latter immune system effect of low dose naltrexone may play some role in the improved outcome in advanced cancer patients but could play an even greater role when cancer is diagnosed early by preventing future recurrences when primary tumors are surgically removed. Through this mechanism, it should reduce the rate of recurrence for patients with many types of cancer that lack opiate receptors. It should also reduce the risk of developing a variety of kinds of cancer in people in high-risk groups. In addition, low dose naltrexone therapy should help restore natural immune defenses that may have been injured through chemotherapy or radiation in patients treated for cancer.
The Zagon Study
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 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.1
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.2
Observational Studies and Discussion
In 1985, Dr. Bihari treated a patient who had recurrent non-Hodgkin's lymphoma, and who had refused chemotherapy for the relapse, with daily low dose naltrexone (the same dose used as an immune modulator in people with AIDS). The three biopsy-positive, golf-ball-sized lymph nodes in this patient's groin disappeared after twelve weeks. The patient stayed on the drug and remained tumor free until her death from a heart attack five years later.
After Dr. Bihari introduced Dr. Lewin to low dose naltrexone, she used it in her oncology practice for patients who had exhausted standard therapies, like chemotherapy and radiation, and were in a fatal decline. A sizable minority treated with the drug (using 3 mg. at bedtime) have had sustained remissions, all from the above-mentioned categories of cancer.
Low dose naltrexone might exert its effects on tumor growth through a mix of three possible mechanisms: (1) by inducing an increase in metenkephalin (an endorphin produced in large amounts in the adrenal medulla) and beta endorphin in the body; (2) by inducing an increase in the number and density of opiate receptors on the tumor cell membranes, thereby making them more responsive to the growth-inhibiting effects of the already-present levels of endorphins; and (3) by increasing the natural killer (NK) cell numbers and NK cell activity and cytotoxic CD8 numbers, which are quite responsive to increased levels of endorphins.3
It is of interest that the types of malignancies that in humans anecdotally appear to show a response to low dose naltrexone originate in tissues that have high densities of opiate receptors (e.g., lymphomas and cancer of the pancreas). If this is an important factor, one would also expect metastatic malignant melanoma, prostate cancer, cancer of the colon, neuroblastoma, and multiple myeloma to also be more likely to respond to low dose naltrexone than would other types of malignancies that have no opiate receptors (e.g., breast cancer, primary cancer of the lung, ovarian cancer, sarcomas of the bone and soft tissue, and gliomas in the brain).
If the results of the trials of low dose naltrexone in certain cancers are positive, the drug could eventually become an additional mainstay of cancer treatment, adjunctive with chemotherapy, radiation, and gene-based therapy, or even a replacement for current therapies, as primary treatment for those cancers that show little response to standard therapies.
Some types of cancer that are observed to respond to low dose naltrexone:
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Carcinoid |
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Colon Cancer |
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Rectal Cancer |
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Cancer of the Pancreas |
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Malignant Melanoma |
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Prostate Cancer |
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Lymphoma (Hodgkin's and Non-Hodgkin's) |
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Multiple Myeloma |
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Lymphocytic Leukemia |
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Cancer of the Small Intestine |
Zagon IS, McLaughlin PJ, Duration of opiate receptor blockade determines tumorigenic response in mice with neuroblastoma; a role for endogenous opioid systems in cancer, Life Sci 35, pp. 409-416, 1984.
Zagon IS, McLaughlin PJ, Opioid antagonist modulation of murine neuroblastoma: A profile of cell proliferation and opioid peptides and receptors, Brain Res 480, pp. 16-28, 1989.
Zagon IS, McLaughlin PJ., Opioid antagonist inhibit the growth of metastatic murine neuroblastoma, Cancer Letters 21, pp. 89-94, 1983.
Zagon IS, McLaughlin PJ, Naltrexone prolongs the survival time of mice treated with neuroblastoma, Life Sci 28, pp. 1095-1102, 1981.
2 Recant L, Voyles NR, Luciano M, Pert CB, Naltrexone reduces weight gain, alters "beta-endorphin", and reduces insulin output from pancreatic islets of the genetically obese mice, 1(4), pp. 309-313, 1980.
3 Matthew, PM, Froelich CJ, Sibbitt WL, Jr., Enhancement of natural cytotoxicity by beta-endorphin, J Immunol 130, pp. 1658-1662, 1983.
Update: Christina White's, the author who first reported the use of low dose naltrexone, recently shared the case of Cheryl C. from Texas who began Naltrexone in January of 1999 and has achieved significant regressions (almost a remission) after 5 months. She is in the process of forming a network of patients who have benefited from low dose naltrexone (LDN) who will be willing to take phone calls.
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There are numerous studies published on Medline about the anti-cancer effects of Naltrexone on tumors that have opiate receptors. |
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Two MDs have confirmed the effects of Naltrexone in their practices. Both are willing to discuss Naltrexone with oncologists who call them. See Dr. Bihari's CV. |
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Every professional who has looked at the use of low dose (3 mg.) Naltrexone agrees that it can do no harm. It's a drug that has been approved for use at 50 mg. At 3 mg. it has virtually no side effects. |
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It may be the perfect drug, in that it stays in your system a short while (while you sleep for 2 to 4 hours) and fools the brain into thinking it must produce endorphins, which the body continues to produce for 24 hours. |
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No one is profiting from promoting Naltrexone, as it's already approved, inexpensive, and the doctors who are discussing its benefits MAY have little self interest in promoting its use. CAUTIONARY NOTE: Dr. Bihari, however, does stand to gain from the belief that naltrexone can be effective in the treatment of cancer because he charges fees for phone consultations. I believe he is sincere, but I have not seen direct evidence, as yet, that it is working for any NHL patients that I know. It may still be too early for me to make judgments. |
IMPORTANT: I have not seen direct evidence of these findings reported by Dr. Bihari. To date, no NHL patients who have taken low dose naltrexone based on the information I've posted has reported improvements. It may take up to 6 months to see improvments, however, so Dr. Bihari's claims may yet prove correct.
After reading "One Pill a Day Keeps Some Cancers at Bay", I called Dr. Margaret Lewin, the oncologist at the Cornell Medical Center of New York's Hospital referenced in the article. She said this about Naltrexone: "The evidence is anecdotal, but highly suggestive." She said she feels comfortable using it in her practice because the 3 mg dose of Naltrexone at bed time is harmless. She then summarized a case in which her patient achieved a remission using it. Finally, she volunteered to discuss Naltrexone with Joanne's oncologist.
Dr. Bihari believes low dose Naltrexone works by stimulating the body into creating endorphins which then bind to tumors that have opiate receptors, causing the tumors to stop growing and then shrink. He said patients could look for gradual decreases in tumors after 2 or 3 months.
Christina White wrote this in One Pill a Day Keeps Some Cancer's at Bay:
John S. James wrote:
You will need a prescription to get Naltrexone. Have your doctor discuss Naltrexone with Dr. Bihari at 212-929-4196. If your doctor refuses, consider seeking a doctor who will be willing to let you try it. Naltrexone comes in 50 mg tablets, which must be recompounded by pharmacies into 3 mg capsules. Dr. Bihari does not recommend creating solutions of Naltrexone as it is not as stable.
There are numerous compounding pharmacies that are familiar with Naltrexone and have it on hand.
Apothecure Pharmacy 800-969-6601
Smith Pharmacy (NH) 603-539-2020
Bigelows Pharmacy (NYC) 212-533-2700
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Methionine enkephalin: a new cytokine-human studies. |
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Neuropeptides: conductors of the immune orchestra |
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Neuroimmunomodulation with enkephalins: in vitro enhancement of natural killer cell activity in peripheral blood lymphocytes from cancer patients. |
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Enkephalins: immunomodulators. |
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A molecular basis for interactions between the immune and neuroendocrine systems |
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Modulation of murine melanoma growth by naloxone |
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Inhibition of pulmonary metastases and enhancement of natural killer cell activity by methionine-enkephalin |
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Neuroimmunomodulation with enkephalins: in vitro enhancement of natural killer cell activity in peripheral blood lymphocytes from cancer patients. |
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Enhancement of host resistance to viral and tumor challenge by treatment with methionine-enkephalin |
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Inhibition of B16-BL6 melanoma growth in mice by methionine-enkephalin. |
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Effect of methionine-enkephalin plus ZnCl2 on active T cell rosettes. |
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Neuroimmunomodulation with enkephalins: effects on thymus and spleen weights in mice |
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Neuroimmunomodulation with enkephalins: enhancement of human natural killer (NK) cell activity in vitro |
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Enkephalins-enhancement of active T-cell rosettes from normal volunteers |
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Enkephalins-enhancement of active T-cell rosettes from lymphoma patients.(NHL-specific) |
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Enkephalin receptors and receptor-mediated signal transduction in cultured human lymphocytes. (NHL-specific) |
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Chronic intracerebroventricular administration of beta-endorphin augments natural killer cell cytotoxicity in rats |
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B-lymphoma cells are activated by peptide ligands of the antigen binding receptor or by anti-idiotypic antibody to induce extracellular acidification. |
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Effect of neuropeptides on macrophage mediated cytotoxicity in normal donors and cancer patients. |
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Antitumor activity of enkephalin analogues in inhibiting PYB6 tumor growth in mice and immunological effects of methionine enkephalinamide |
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Modulation of murine neuroblastoma in nude mice by opioid antagonists |
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Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor |
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Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor |
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Human neuroblastoma cell growth in tissue culture is regulated by opioid growth factor |
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Expression of the opioid growth factor, [Met5]-enkephalin, and the zeta opioid receptor in head and neck squamous cell carcinoma |
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Opioid growth factor ([Met5]enkephalin) prevents the incidence and retards the growth of human colon cancer |
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Inhibition of human colon cancer by intermittent opioid receptor blockade with naltrexone |
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Opioid antagonist modulation of murine neuroblastoma: a profile of cell proliferation and opioid peptides and receptors |
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Characterization of opioid binding sites in murine neuroblastoma |
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Endogenous opioids and the growth regulation of a neural tumor |
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Opioid receptors and endogenous opioids in diverse human and animal cancers |
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Modulation of human neuroblastoma transplanted into nude mice by endogenous opioid systems |
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Localization of enkephalin immunoreactivity in diverse tissues and cells of the developing and adult rat |
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Stereospecific modulation of tumorigenicity by opioid antagonists |
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Duration of opiate receptor blockade determines tumorigenic response in mice with neuroblastoma: a role for endogenous opioid systems in cancer |
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Opioid antagonists inhibit the growth of metastatic murine neuroblastoma |
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Naltrexone modulates tumor response in mice with neuroblastoma |
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Heroin prolongs survival time and retards tumor growth in mice with neuroblastoma |
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Enkephalin receptors and receptor-mediated signal transduction in cultured human lymphocytes. |
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Neurohormonal modulation of natural resistance to a murine lymphoma. |
