Naltrexone is an old medicine, approved in the 1980s at a dose of 50 mg to block the effects of opioids and alcohol. At a much lower dose, typically a few milligrams taken at bedtime, it is called low-dose naltrexone, or LDN, and it is one of the most widely discussed repurposed drugs in integrative oncology. This article explains the biology behind LDN in cancer, what the human evidence shows, what trials are under way, and the drug interaction everyone taking it must know.
The Opioid Growth Factor Pathway
The body makes its own opioid-like molecules. One of them, met-enkephalin, also acts as a growth brake. Researchers at Penn State, led by Ian Zagon and Patricia McLaughlin, named it the opioid growth factor (OGF) and showed that it binds a receptor on many types of cancer cells, the OGF receptor, slowing their division.
The low dose is the key. A full dose of naltrexone blocks opioid receptors around the clock. A low dose blocks them only for a few hours. The body responds to that brief blockade by producing more OGF and more OGF receptors, and once the naltrexone wears off, the stronger OGF signal slows cell growth. The same group demonstrated this sequence in laboratory studies of human cancer cells.1
Effects on Inflammation and the Immune System
LDN also acts on immune cells, particularly the microglia of the brain and spinal cord, through a receptor called TLR4, which reduces the production of inflammatory signals. This anti-inflammatory action is the basis for its use in chronic pain and autoimmune conditions.2 Since chronic inflammation fuels cancer growth and can wake dormant cancer cells, this action is relevant to cancer as well. Our article on why cancer comes back explains that connection.
How Far LDN Has Been Studied in People
Case reports. The best-known human reports come from the physician Burton Berkson, who described patients with advanced pancreatic cancer who lived for years on a combination of intravenous alpha-lipoic acid and LDN.3 Case reports show what is possible in individual patients, not what to expect.
The one randomized trial. A 2026 review of the evidence identified only one randomized controlled trial of LDN in people with cancer. In 110 patients with high-grade glioma receiving radiation and temozolomide, LDN for 16 weeks did not improve fatigue or quality of life compared with placebo, and side effects were similar in both groups. That trial was designed to measure symptoms, not survival.4
Trials under way. A phase 2 trial at the University of Arkansas, starting in 2026, is testing LDN for fatigue in men with metastatic prostate cancer on hormone therapy.5 A phase 1 trial is combining naltrexone with the blood pressure drug propranolol and checkpoint immunotherapy in advanced melanoma, on the idea that blocking the body’s stress signals may strengthen the immune attack on tumors.6
In short, LDN has a coherent biological rationale, a long safety record at low doses, and encouraging individual reports, but its effect on cancer survival has not yet been tested in a clinical trial.
Side Effects and the Critical Drug Interaction
Opioid pain medicines. Naltrexone blocks opioid receptors, even at low doses. It must not be combined with opioid pain medicines such as morphine, oxycodone, hydrocodone, fentanyl or tramadol: it can block their pain relief and trigger withdrawal. Many people with cancer need opioids for pain at some point, so this is the most important fact about LDN.
Common side effects. Vivid dreams, trouble sleeping and headache are the most common, usually in the first weeks. Taking it in the morning instead of at bedtime often resolves sleep problems.
Thyroid medicine. People with autoimmune thyroid disease taking thyroid hormone have sometimes needed their dose adjusted after starting LDN, so thyroid levels are worth checking.
Where LDN Fits
LDN is inexpensive, generally well tolerated and acts on growth and inflammation pathways that other repurposed drugs do not. It is usually used as one part of a broader plan rather than on its own. Our book, The New Reality of Cancer, organizes repurposed drugs, including LDN, metformin and mebendazole, by the cancer pathways they act on.
Frequently Asked Questions
What is low-dose naltrexone?
Naltrexone taken at a small fraction of its standard 50 mg dose, typically a few milligrams a day. At this dose it blocks opioid receptors only briefly, which increases the body’s own growth-regulating opioid signals.
Does LDN work for cancer?
It has a strong laboratory rationale and individual case reports, but no clinical trial has yet tested whether it improves cancer survival.
Can LDN be taken with opioid pain medicine?
No. Naltrexone blocks opioid pain medicines and can cause withdrawal. The two should not be combined.
What are the side effects of LDN?
Vivid dreams, sleep disturbance and headache are the most common, usually in the first weeks.
About the author. Dr. Silver, MD, graduated from Temple University School of Medicine, trained as an interventional cardiologist, and has practiced medicine for nearly fifty years. A lymphoma survivor of about twenty-five years, he is co-author, with Dr. Lindmeier, DHSc, of The New Reality of Cancer: The Science of Recovery. Read more about Dr. Silver, MD.
Research by Dr. Lindmeier, DHSc, cancer educator and co-author of The New Reality of Cancer.
More articles on repurposed drugs for cancer and all articles.
References
- Donahue RN, McLaughlin PJ, Zagon IS. Low-dose naltrexone targets the opioid growth factor–opioid growth factor receptor pathway to inhibit cell proliferation: mechanistic evidence from a tissue culture model. Experimental Biology and Medicine. 2011;236(9):1036–1050.
- Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology. 2014;33(4):451–459.
- 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;8(4):416–422.
- Low-dose naltrexone: what is the evidence? A narrative review. Advances in Therapy. 2026. doi:10.1007/s12325-026-03612-5
- ClinicalTrials.gov. Low dose naltrexone for management of fatigue in prostate cancer patients on androgen deprivation therapy. NCT07224009. University of Arkansas.
- ClinicalTrials.gov. Naltrexone and propranolol combined with immunotherapy in advanced melanoma. NCT05968690.
This article is for education only. It is not medical advice and does not diagnose or treat any condition. Cancer Expert MD has no financial relationship with any laboratory, drug maker, supplement company, clinic or hospital.