Low-Dose Naltrexone
Also known by these names
- LDN
- Revia
- Depade
- Vivitrol
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Key Points
- Before using this therapy, consult your oncology team about interactions with other treatments and therapies. Also make sure this therapy is safe for use with any other medical conditions you may have.
- LDN must be prescribed by a physician.
- LDN is used “off-label” for a number of diseases, including cancer.
- LDN must be compounded by a pharmacist. Experienced clinicians urge that best results come from compounding which is exact and of the highest possible quality and consistency.
- Numerous studies in animals and humans show an immunomodulation effect.
- BCCT’s interest in LDN derives from human cancer case studies showing increased disease-free survival and quality of life.
- No published human clinical trials in cancer have been completed to date.
- No major safety issues have been reported, although cautions and contraindications are noted.
- LDN is inexpensive.
- Resources are available for finding compounding pharmacists and licensed prescribers.
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 Authors
Laura Pole, RN, MSN, OCNS, BCCT Senior Researcher
Read more Ms. Pole is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation and education services for more than 30 years. View profile.  Nancy Hepp, MS, BCCT Project Manager
Read more Ms. Hepp is a science researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. View profile. Last updated April 5, 2021.
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Summary
LDN (low-dose naltrexone) is a drug that shows promise in integrative cancer care. Clinical observation, hundreds of case studies, and lab, animal and human studies suggest that LDN may have significant potential to increase disease-free survival and quality of life in people with certain cancers.
LDN seems to exert its effect, in part, by modulating the immune system, particularly helpful to people with conditions of immune system dysfunction and cancer. Studies suggest that when taken at night, LDN increases endorphin production, which then orchestrates the activity of various cells in the body—including stem cells and certain immune cells like natural killer cells—benefiting wellness and health.
Although no clinical trials of LDN in cancer have been conducted to date, lab studies, as well as human studies in other diseases such as Crohn's, have helped to define its action as well as its safety profile.
LDN is inexpensive. It must be compounded, preferably by a pharmacist skilled in compounding this drug. LDN is generally well tolerated.
Description
Highlighted Video
BCCT advisor Brian Bouch, MD, delineates the history and use of low-dose naltrexone for cancer care.
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Naltrexone is an opioid antagonist used in conventional medicine to treat opioid and alcohol addiction, using doses of 50 mg or higher. When used in very low dosages (4.5 mg or less), naltrexone seems to modulate (control or influence) the immune system.
LDN is used off-label to treat a number of diseases and disorders. Off-label use is a drug’s application for a disease or condition that has not yet received FDA approval. Every US state allows for drugs to be used off-label as long as enough evidence supports its use. According to Dr. Linda Elsegood, enough small studies and case-study evidence supports off-label use of LDN.
Treating the Cancer
Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action
Modes of Action
According to Tom Gilhooly, MD, the exact modes of LDN’s effects are not yet known in cancer treatment, and even the mode of action of the drug itself is not entirely established. Dr. Gilhooly says some evidence suggests LDN works to reduce inflammation by influencing the immune response, and this may well be one of the ways LDN modifies the course of cancer.
Read more LDN dosed at night seems to affect cancer by several means:
- By causing an increase in endorphins.
- By simultaneously causing an increase in the number and density of opiate receptors on the membranes of cancer cells, making the cells more responsive to the endorphins’ effect inhibiting cell growth. This in turn induces cell death (apoptosis).
- By increasing the numbers of cell-killing T cell and natural killer cells circulating in the blood, and to also increase the activity of natural killer cells.
Additional studies suggest that methylnaltrexone, which is a molecular cousin of naltrexone, can prevent angiogenesis (creation of a blood supply by the tumor). Dr. Burt Berkson, an integrative medicine physician who has published case studies of LDN in cancer, suggests that this could be another important way that LDN hampers tumor growth.
In Life Over Cancer, integrative oncologist and BCCT advisor Keith Block, MD, suggests LDN as an off-label drug that could be particularly valuable during the growth-control phase of cancer “by activating Th1 cancer-fighting immune cells and apoptosis of cancer cells while binding opiate receptors that can stimulate cell replication." |
While no published prospective, controlled clinical trials on LDN in cancer treatment have been published, clinical observation, case studies, and lab and animal studies have shown LDN’s significant potential to increase disease-free status as well as overall survival and quality of life in people with certain cancers.
Clinical Evidence
Case studies and anecdotal evidence are promising but far from conclusive.
Tumor Shrinkage or Remission
Expand list
- Bernard Bihari, MD, used doses of 3.0 to 4.5 mg per dose of naltrexone to treat people with AIDS. Promising results from this work led Dr. Bihari to use LDN in the treatment of cancer. As of March 2014, Dr. Bihari reported using LDN in some 450 patients with cancer—almost all of whom had failed to respond to standard treatments. Of the 354 patients with whom he had regular follow-up, he reported these outcomes:
- 86 (24 percent) showed objective signs of significant tumor shrinkage—at least a 75 percent reduction.
- 125 patients (35 percent) stabilized and/or were moving toward remission.
- Dr. Bihari reported promising results for people with a number of different cancers including (but not limited to) these primary cancers:
- Anecdotal reports to Dr. Bihari indicate LDN was associated with remission in several cancers:
- In an anecdotal report, LDN was associated with lowered PSA and tumor shrinkage in prostate cancer patients who had not been treated at all, or those who had had chemo or radiation therapies, but not in those who had been treated with hormonal therapy.
- Dr. Burt Berkson has been able to show that a regimen of LDN plus intravenous infusions of alpha-lipoic acid reduced the size of lesions in four patients with pancreatic cancer. Dr. Berkson prescribed LDN in another patient with B-cell lymphoma and noted dramatic achievement of clinical and radiological remission.
Improved Survival
Expand list
- Improved survival at one year among people with high-grade malignant gliomas treated with radiotherapy, compared with radiotherapy alone in a small study
- Improved long-term survival and slowed progression of pancreatic cancer in case study reports when combined with alpha-lipoic acid; in two cases resulted in no evidence of disease at four and five months of treatment, respectively
- Improved survival in six of 10 people with advanced cancer, all of whom had failed standard chemotherapy and were given life expectancy between two and six months; treated with lipoic acid, hydroxycitrate and low-dose naltrexone, their disease was either stable or very slowly progressive several months later
Lab and Animal Evidence
Expand list
- Slowed growth of neuroblastoma cells in mice
- Inhibited cancer cell growth in mice while also depressing DNA synthesis and angiogenesis (development of new blood vessels) when combined with cisplatin
- Enhanced the anticancer action of the treatment with taxol or cisplatin, reducing DNA synthesis and angiogenesis with brief exposure to LDN
- Slowed growth of squamous cell cancer of the head and neck in mice when combined with opioid growth factor
- Reduced tumor volume and weight and decreased tumor DNA synthesis when combined with opioid growth factor and the medication imiquimod
- Reduced tumor progression of humanovarian cancer in mice by inhibiting cancer cell growth and angiogenesis when combined with opioid growth factor
- Repressed tumor progression by reducing DNA synthesis and angiogenesis (formation of blood vessels to supply tumors), and also enhanced the effects of cisplatin in mice and ovarian cancer cell cultures
Optimizing Your Terrain
Creating an environment within your body that does not support cancer development, growth or spread; see Body Terrain and the Tumor Microenvironment
- Immune system support: promotes health supporting immune-modulation which may reduce various oncogenic and inflammatory autoimmune processes
Managing Side Effects and Promoting Wellness
Managing or relieving side effects or symptoms, reducing treatment toxicity, supporting quality of life or promoting general well-being
Clinical Evidence
Read more
- Potential to enhance quality of life.
- May promote positive emotional states by the effect of endorphins improving mood and energy; LDN’s effect on increasing endogenous opioids (pain-relieving chemicals naturally produced by neurons) may relieve depression by increasing a person's ability to experience pleasure
- May enhance the reward system for exercise, palatable tastes, laughter, sex, social bonding, and even the placebo effect of positive expectations
- Alleviated the weight loss associated with cisplatin in animals
Access
Compounding Pharmacies
For listings of reputable compounding pharmacies in the US and abroad who prepare LDN, see the following sources:
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LDN requires a physician prescription but is not overly expensive. For example in 2017, a one-month supply from “The Compounder” was $36 US dollars (60 capsules for $64; 90 for $97), plus a $10 shipping fee. Multiple orders can sometimes be shipped in the same package, reducing costs further.
Naltrexone is not manufactured in low-dose form, needing to be specially compounded by a pharmacy. Preparation by a reliable compounding pharmacy yields the best quality and results. Beware that naltrexone is often created illegally and manufactured to substandard quality and sold via the Internet. No reputable pharmacy will sell LDN without a prescription.
Read more
The Low-Dose Naltrexone site gives the following cautions regarding compounding LDN:
- Patients must be sure to specify that you do NOT want LDN in a slow-release form. Some patients have reported 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.
- 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, calcium carbonate filler should 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.
- Make sure to fill your prescription at a compounding pharmacy with a reputation for consistent reliability in the quality of the LDN it delivers. 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 the low dose naltrexone report: Reliability Problem With Compounding Pharmacies. Please see that site’s list of recommended pharmacies for some suggested sources.
Cautions
In the animal and human studies and case reports in cancer and other diseases, LDN is generally well tolerated and without significant side effects. Dr. Berkson and others also note that patients are easily able to comply with treatment.
Adverse Events / Side Effects
Most side effects reported by patients can often be prevented by starting at a low dosage and increasing by 1 mg per week until reaching 4.5 mg.
Read more
Typical side effects (this list is not exhaustive, and readers should reference the summary of product characteristics for naltrexone for a full list of possible side effects):
- Occasionally, during the first week of use, some may complain of difficulty sleeping, nightmares and vivid dreams.
- Stomach cramps and diarrhea (transitory)
- Headache (during initial phase only)
- Hyperthyroidism (can come quickly if patient also has Hashimoto’s disease)
- Agitation or dizziness, extrapyramidal symptoms (infrequent)
- Constipation and/or diarrhea: Infrequent, and more common with IBS, IBD and Crohn’s disease
- Elevated liver enzymes (very infrequent and usually when a patient has late-stage liver failure)
- Reductions in renal function: (extremely rare)
Contraindications / Do Not Use If
These situations may cause clinicians to decide against LDN use:
Expand list
- Pregnancy: safety in pregnancy has not been established. However, Dr. Phil Boyle, in Ireland, reported to Elsegood that he has used LDN as an adjunct in his fertility practice for over ten years with no issues.
- Opioid medication use: because LDN blocks opioid receptors throughout the body for three or four hours, people using opioid agonists, such as narcotic medications Ultram (tramadol), morphine, Percocet, Duragesic patch or codeine-containing medication — should not take LDN until such medicine has completely cleared one's system. Patients who have become dependent on daily use of narcotic-containing pain medication may require 10 days to two 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.
- Thyroid hormone replacement use: patients 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). LDN may lead to a prompt decrease in the autoimmune disorder status, which then may require a rapid reduction in the dose of thyroid hormone replacement in order to avoid symptoms of hyperthyroidism.
- Liver disease: 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 300 mg daily. The 50mg dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3mg and 4.5mg doses.
Interactions
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.
Dosing
Guidelines are available from these sources:
The LDN Research Trust website lists physicians in the US and abroad who prescribe LDN, as well as compounding pharmacies.
Integrative Programs, Protocols and Medical Systems
- Programs and protocols
- Bastyr University Integrative Oncology Research Center protocol for stage IV breast cancer
- Block program
- Control growth when other treatment isn't working
- Elsegood LDN guidelines
- Dosing guidelines for LDN alone and for combined protocols for cancer:
- McKinney protocols
- Schachter LDN protocol
Non-cancer Uses of LDN
Originally, LDN was used in treating AIDS. In addition to cancer, LDN is also used in treating these diseases and conditions:
- Multiple sclerosis
- Lupus
- Inflammatory bowel disease
- Chronic fatigue syndrome and fibromyalgia
- Thyroid disorders
- Testless legs syndrome
- Depression
- Autism spectrum disorders
For a complete listing of diseases and disorders LDN may be useful in treating, see the Low Dose Naltrexone website.
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- Elsegood L. Ed. The LDN Book. Vermont: Chelsea Green Publishing. 2016.
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- Berkson BM, Rubin DM, Berkson AJ. Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone. Integrative Cancer Therapies. 2007 Sep;6(3):293-6.
- Block KI. Life over Cancer: The Block Center Program for Integrative Cancer Treatment. New York: Bantam Dell. 2009.
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- Berkson BM Rubin DM, Berkson AJ. Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone. Integrative Cancer Therapies. 2007 Sep;6(3):293-6.
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- Berkson BM et al. The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low-dose naltrexone protocol. Integrative Cancer Therapies. 2006 Mar;5(1):83-9; Berkson BM, Rubin DM, Berkson AJ. Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases. Integrative Cancer Therapies. 2009 Dec;8(4):416-22.
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- Donahue RN, McLaughlin PJ, Zagon IS. Low-dose naltrexone suppresses ovarian cancer and exhibits enhanced inhibition in combination with cisplatin. Experimental Biology and Medicine (Maywood). 2011 Jul;236(7):883-95.
- Donahue RN, McLaughlin PJ, Zagon IS. Low-dose naltrexone suppresses ovarian cancer and exhibits enhanced inhibition in combination with cisplatin. Experimental Biology and Medicine (Maywood). 2011 Jul;236(7):883-95.
- McLaughlin PJ, Stucki JK, Zagon IS. Modulation of the opioid growth factor ([Met(5)]-enkephalin)-opioid growth factor receptor axis: novel therapies for squamous cell carcinoma of the head and neck. Head & Neck. 2012 Apr;34(4):513-9.
- McLaughlin PJ, Stucki JK, Zagon IS. Modulation of the opioid growth factor ([Met(5)]-enkephalin)-opioid growth factor receptor axis: novel therapies for squamous cell carcinoma of the head and neck. Head & Neck. 2012 Apr;34(4):513-9.
- Donahue RN, McLaughlin PJ, Zagon IS. The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice. Gynecologic Oncology. 2011 Aug;122(2):382-8.
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- Berkson BM Rubin DM, Berkson AJ. Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone. Integrative Cancer Therapies. 2007 Sep;6(3):293-6.
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View All References
More Information
Integrative Cancer Resources on LDN
Read more
- National Cancer Institute Office of Cancer Complementary and Alternative Medicine: Alpha-Lipoic Acid Plus Low-Dose Naltrexone Reviewed for Cancer Treatment
- Moss Reports (purchase required): Select from the list of cancers down the left side of the page for a report describing uses of conventional, complementary, alternative and integrative therapies related to that cancer. Ralph Moss is among the most knowledgeable and balanced researchers of integrative cancer therapies. The cost of his Moss Reports is not negligible, but many patients find them of considerable value. Moss is also available for consultations.
- Podcast: Use of Low-Dose Naltrexone and Cancer: Dr. Lise Alschuler of Five to Thrive Live Radio interviews Akbar Khan, MD about the unique mechanisms of action and health-promoting effects of low-dose naltrexone, particularly in cancer. Dr. Khan is a graduate of the University of Toronto, Faculty of Medicine (1992). He completed his certification in Family Medicine in 1994. Dr. Khan co-founded Medicor Cancer Centres with his wife in 2006. Medicor is the first integrated private cancer clinic of its kind in Canada. The goal of opening this clinic was to provide better therapies for cancer patients, without the limitations of the government-funded Canadian health system. Since 2007, Dr. Khan has gained international recognition for his work with non-toxic off-label drugs, and has published groundbreaking cancer papers in various peer-reviewed medical journals. He is regularly invited to present lectures on complementary cancer therapy.
Sites Promoting LDN
Read more
- Low Dose Naltrexone website: The site is kept current, listing the most recent studies, with links to the following information:
- General information about LDN: What it is, how it works, diseases for which it is effective, including a link to information about LDN and Cancer
- How to obtain it and cost
- How to find a compounding pharmacy to prepare it
- Prescribing information
- Cautionary Warnings Existing research
- Editor’s Blog
- LDN Conferences
- FAQ’s
- The LDN Research Trust as well as LDN Radio: The LDN Research Trust was founded by a group of patients with multiple sclerosis, for whom LDN worked very well after all other treatments had failed. The primary aim of the Trust is to initiate clinical trials of low dose naltrexone. The site provides information on how LDN works, its use in treating pain and medical conditions and types of LDN. The LDN Radio Station provides presentations by LDN prescribers, researchers and pharmacists. It also lists pharmacists and medical subscribers by country and state/province. It is a sponsored publication of The LDN Book, which is a comprehensive resource for patients and clinicians on LDN.
- The LDN Book: Edited by Linda Elsegood, this book explains the drug’s origins, its primary mechanism, and the latest research (as of 2016) from practicing physicians and pharmacists as compiled by Linda Elsegood of The LDN Research Trust, the world’s largest LDN charity organization. The book features ten chapters contributed by medical professionals on LDN’s efficacy and two patient-friendly appendices. There are helpful tables on dosing, usage, side effects, combination protocols. It includes guidance to patients who wish to converse with their physicians about using LDN for their conditions.
More from Our Resources Database
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Cheryl J Petrovich:
Apr 14, 2020 at 12:30 AM
I want to try this for breast cancer. Wish me luck! Cheryl
Laura Pole:
Aug 05, 2019 at 10:37 AM
Lokesh, in addition to Nancy's suggestion, I would also point out a section of one of the LDN resources that tells you how you might obtain LDN.: http://www.lowdosenaltrexone.org/. On the home page, scroll down to the section called " How can I obtain LDN and what will it cost?" When you talk with your son's doctor about LDN, you can give him/her the information in this section. Wishing you clarity in exploring the best care for your son.
Nancy Hepp:
Aug 04, 2019 at 01:38 PM
Lokesh, we are not able to give specific medical advice. We recommend you ask your oncologist about using LDN or to refer you and your son to someone who has expertise in using LDN with conditions comparable to your son's. If you're not able to get information that way, try looking at sources listed on our Centers, Clinics and Clinicians page, https://bcct.ngo/integrative-cancer-care/centers-clinics-and-clinicians. You may want to print relevant parts of this page or refer to the books in the Integrative Programs, Protocols and Medical Systems section on this page for guidance to share with your oncology team.
We wish you and your son peace and healing as you continue your investigations.
Lokesh:
Aug 03, 2019 at 11:36 PM
My son suffering from ewing sarcoma mettasised to his bones and brain and at present he his under steroids and other medication can i start him LDN along with alopic acid, waiting for ur kind reply.