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.

Further evidence 

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

Treating cancer: preclinical evidence

  • Breast cancer: 
  • Gynecological cancers: 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: preclinical evidence

Inflammation
Immune function

Managing side effects and promoting wellness: preclinical evidence

Professional resources

Journal article

Li Z, You Y, Griffin N, Feng J, Shan F. Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy. International Immunopharmacology. 2018 Aug;61:178-184.

Keep reading about low-dose naltrexone

Authors

Nancy Hepp, MS

Lead Researcher and Program Manager
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Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher, program manager, and writer for CancerChoices. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS Lead Researcher and Program Manager

Reviewers

Laura Pole, RN, MSN, OCNS

Senior Clinical Consultant
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Laura Pole is senior clinical consultant for CancerChoices. Laura is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation, and education services for over 40 years. She is the co-creator and co-coordinator of the Integrative Oncology Navigation Training at Smith Center for Healing and the Arts in Washington, DC. Laura also manages the “Media Watch Cancer News That You Can Use” listserv for Smith Center/Commonweal. In her role as a palliative care educator and consultant, Laura has served as statewide Respecting Choices Faculty for the Virginia POST (Physician Orders for Scope of Treatment) Collaborative as well as provided statewide professional education on palliative and end-of-life care for the Virginia Association for Hospices and Palliative Care.

For CancerChoices, Laura curates content and research, networks with clinical and organizational partners, brings awareness and education of integrative oncology at professional and patient conferences and programs, and translates research into information relevant to the patient experience as well as clinical practice.

Laura sees her work with CancerChoices as a perfect alignment of all her passions, knowledge and skills in integrative oncology care. She is honored to serve you.

Laura Pole, RN, MSN, OCNS Senior Clinical Consultant

Dan Rubin, ND, FABNO

Naturopathic oncologist
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Dan Rubin, ND, FABNO, is a board certified naturopathic oncologist practicing in both Scottsdale and Flagstaff, Arizona. Dr. Rubin is the founding president of the Oncology Association of Naturopathic Physicians (OncANP) and has been a long-time member of the Arizona Naturopathic Physicians Medical Board. He is the co-founder of Naturopathic Specialists, LLC, with his wife, Debi Smolinski, ND. Dr. Rubin focuses on naturopathic and integrative approaches to people with cancer, treating both children and adults. He enjoys trail running in the Sonoran desert near his house.

Dan Rubin, ND, FABNO Naturopathic oncologist

Last update: May 20, 2022

CancerChoices provides information about integrative in cancer care, a patient-centered approach combining the best of conventional care, self care and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocial therapy, and acupuncture therapies and self-care lifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

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