Low-dose Naltrexone

This prescription drug is used off-label in low doses to treat people with cancer, with notable but very preliminary successes in cases where the cancers were difficult-to-treat or quite advanced.

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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Modes of action: opioid receptors

Opioid receptors are involved in tumor growth, angiogenesis, and immunosuppression ¹Carli M, Donnini S, Pellegrini C, Coppi E, Bocci G. Opioid receptors beyond pain control: The role in cancer pathology and the debated importance of their pharmacological modulation. Pharmacological Research. 2020 Sep;159:104938. Naltrexone has been found to prevent angiogenesis, although at modest magnitudes.²Zagon IS, McLaughlin PJ. Opioids and the apoptotic pathway in human cancer cells. Neuropeptides. 2003 Apr;37(2):79-88. 

Low-dose naltrexone upregulates the expression of opioid growth factor receptor (OGFr) and OGFr antagonist, suppressing colony formation, migration, and invasion in cervical cancer cells.³Liu N, Yan L et al. Low-dose naltrexone plays antineoplastic role in cervical cancer progression through suppressing PI3K/AKT/mTOR pathway. Translational Oncology. 2021 Apr;14(4):101028; Couto RD, Fernandes BJD. Low doses naltrexone: the potential benefit effects for its use in patients with cancer. Current Drug Research Reviews. 2021 Jan 26; Ma M, Wang X, Liu N, Shan F, Feng Y. Low-dose naltrexone inhibits colorectal cancer progression and promotes apoptosis by increasing M1-type macrophages and activating the Bax/Bcl-2/caspase-3/PARP pathway. International Immunopharmacology. 2020 Jun;83:106388. Naltrexone acts on all opioid receptors, blocking the interaction between OGF and OGFr.⁴Wang R, Zhang Y, Shan F. Interaction of opioid growth factor (OGF) and opioid antagonist and their significance in cancer therapy. International Immunopharmacology. 2019 Oct;75:105785.

Preclinical evidence 

Notable preclinical evidence is listed here; clinical evidence is in How can low-dose naltrexone help you? What the research says ›

Improving treatment outcomes

Breast cancer

• Better survival rates among dogs with mammary cancer with LDN and chemotherapy compared to chemotherapy alone in a preclinical trial⁵Machado MC, da Costa-Neto JM et al. The effect of naltrexone as a carboplatin chemotherapy-associated drug on the immune response, quality of life and survival of dogs with mammary carcinoma. PLoS One. 2018 Oct 4;13(10):e0204830. 
• Inhibited cancer cell growth of solid Ehrlich carcinoma in mice in a preclinical trial⁶Aboalsoud A, El-Ghaiesh SH, Abd Elmonem FF, Salem ML, Abdel Rahman MN. The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: the role of OGFr, BCL2, and immune response. International Immunopharmacology. 2020 Jan;78:106068.

Gynecological cancer

• Inhibited cervical cancer progression in nude mice in a preclinical trial⁷Liu N, Ma M et al. Low-dose naltrexone inhibits the epithelial-mesenchymal transition of cervical cancer cells in vitro and effects indirectly on tumor-associated macrophages in vivo. International Immunopharmacology. 2020 Sep;86:106718.

Head and neck cancer

• Slowed growth of squamous cell cancer of the head and neck in mice with LDN combined with exogenous opioid growth factor⁸McLaughlin 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.

Neuroblastoma

• Lower tumor incidence, longer delays until tumor appearance, and increased survival time among neuroblastoma-inoculated mice receiving 0.1 mg of naltrexone per kilogram per day, compared to 10 milligrams of naltrexone per kilogram per day in a preclinical trial⁹Zagon IS, McLaughlin PJ. Naltrexone modulates tumor response in mice with neuroblastoma. Science. 1983 Aug;221:671-673.

Ovarian cancer

• Repressed tumor progression in mice with established ovarian tumors with LDN in combination with cisplatin but not taxol in preclinical studies¹⁰Donahue 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.
• Reduced tumor nodule number and weight in mice with transplanted  human ovarian cancer with either opioid growth factor or LDN compared to placebo¹¹Donahue 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.

Optimizing your body terrain

Inflammation

• Reduced inflammatory response in preclinical trials¹²Trofimovitch D, Baumrucker SJ. Pharmacology update: low-dose naltrexone as a possible nonopioid modality for some chronic, nonmalignant pain syndromes. American Journal of Hospice and Palliative Medicine. 2019 Oct;36(10):907-912; Kučić N, Rački V et al. Immunometabolic modulatory role of naltrexone in BV-2 microglia cells. International Journal of Molecular Sciences. 2021 Aug 5;22(16):8429.

Immune function

• Modulated mTOR/S6K expression in BV-2 microglial cells in a lab trial¹³Kučić N, Rački V et al. Immunometabolic modulatory role of naltrexone in BV-2 microglia cells. International Journal of Molecular Sciences. 2021 Aug 5;22(16):8429. 
• Naltrexone blocked TLR4 (toll-like receptor 4) signaling in rats in a small lab study.¹⁴Hutchinson MR, Zhang Y et al. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). European Journal of Neuroscience. 2008;28(1):20-29. 
• Altered immune response with very low dosages (4.5 mg or less) in rats¹⁵Jankovic BD, Radulovic J. Enkephalins, brain and immunity: modulation of immune responses by methionine-enkephalin injected into the cerebral cavity. International Journal of Neuroscience. 1992;67(1-4): 241-270.
• Increased expression of macrophage markers and cytokines (tumor necrosis factor-α, TNF-α) in mice¹⁶Ma M, Wang X, Liu N, Shan F, Feng Y. Low-dose naltrexone inhibits colorectal cancer progression and promotes apoptosis by increasing M1-type macrophages and activating the Bax/Bcl-2/caspase-3/PARP pathway. International Immunopharmacology. 2020 Jun;83:106388.

Managing side effects and promoting wellness

Body composition

• Less weight loss associated with cisplatin in animals when LDN was added to treatment in a preclinical trial¹⁷Donahue 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.

Quality of life

• Better quality of life among dogs with mammary cancer with LDN and chemotherapy compared to chemotherapy alone in a preclinical trial¹⁸Machado MC, da Costa-Neto JM et al. The effect of naltrexone as a carboplatin chemotherapy-associated drug on the immune response, quality of life and survival of dogs with mammary carcinoma. PLoS One. 2018 Oct 4;13(10):e0204830. 

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