Low-dose Naltrexone

• Improved survival at 1 year among people with high-grade malignant gliomas treated with radiotherapy plus naltrexone (100 mg every other day), compared with radiotherapy alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹Lissoni P, Meregalli S et al. Radioendocrine therapy of brain tumors with the long acting opioid antagonist naltrexone in association with radiotherapy. Tumori. 1993 Jun 33;79: 198-201. Note: The dose in this study is a standard dose, much higher than a typical low dose for most off-label uses of naltrexone (0.5-5mg per day). This dose is applicable here because glial cells are derived from macrophages and are stimulated by opioid peptides, which are blocked by naltrexone.  

Naltrexone and alpha-lipoic acid: weak evidence of tumor response and improved survival or reversal among people with lymphoma or pancreatic cancer treated with LDN and alpha-lipoic acid

• Reversal of confirmed follicular lymphoma and survival at 1 year in 1 person treated with LDN and initially with alpha-lipoic acid in a case report²Berkson 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.
• Greatly extended survival compared to expectations and 2 complete remissions among people with metastatic pancreatic cancer treated with a protocol of alpha-lipoic acid and low-dose naltrexone in case studiesa descriptive and exploratory analysis of a person, group, or event regarding changes observed over time; because changes due to treatment are not compared to similar changes over time without treatment, a case study is considered a weak study design³Berkson 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; Berkson BM, Rubin DM, Berkson AJ. 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.

Intravenous alpha-lipoic acid and vitamin C, low-dose naltrexone, hydroxycitrate, and a healthy lifestyle program: weak evidence of recovery from metastatic renal cell carcinoma with a combination of therapies including LDN

• Recovery from metastatic renal cell carcinoma (RCC) to stable disease with disappearance of the signs and symptoms of stage IV RCC and a return to work, continuing 9 years past first treatment in 1 person treated with intravenous alpha-lipoic acid and vitamin C, low-dose naltrexone, hydroxycitrate, and a healthy lifestyle program in a case study⁴Berkson BM, Calvo Riera F. The long-term survival of a patient with stage iv renal cell carcinoma following an integrative treatment approach including the intravenous α-lipoic acid/low-dose naltrexone protocol. Integrative Cancer Therapies. 2018 Sep;17(3):986-993.

Lipoic acid, hydroxycitrate, and low-dose naltrexone: weak evidence of tumor response during chemotherapy among people with chemoresistant advanced metastatic cancers treated with a combination therapy including LDN

• Tumor response during chemotherapy (1 person), or stable disease or very slow progression among 5 of 10 people with chemoresistant advanced metastatic cancers treated with a combination of intravenous lipoic acid at 600 mg (Thioctacid), hydroxycitrate at 500 mg t.i.d. (Solgar), and low-dose naltrexone at 5 mg (Revia) at bedtime in case studies⁵Schwartz L, Buhler L, Icard P, Lincet H, Steyaert JM. Metabolic treatment of cancer: intermediate results of a prospective case series. Anticancer Research. 2014 Feb;34(2):973-80.

• Fewer pro-inflammatory cytokines and symptoms among women with fibromyalgia treated with LDN compared to baseline in an uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁶Parkitny L, Younger J. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for fibromyalgia. Biomedicines. 2017 Apr 18;5(2):16.
• Clinical improvement among 74.5% and remission in 25.5% of people with inflammatory bowel disease not in remission and not responding to conventional therapy treated with LDN compared to baseline in a small uncontrolled trial⁷Lie MRKL, van der Giessen J et al. Low dose naltrexone for induction of remission in inflammatory bowel disease patients. Journal of Translational Medicine. 2018 Mar 9;16(1):55.

• Higher lymphocyte numbers during treatment with subcutaneous low-dose interleukin-2a biological response modifier used as immunotherapy to boost the immune system in cancer therapy; also called IL-2 among people with untreatable metastatic solid tumors receiving 20 mg oral melatonin per day in the evening with the addition of 100 mg naltrexone in the morning compared to interleukin-2 and melatonin alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects; the researchers intentionally used a high dose of naltrexone, and during the light hours of the day instead of at night as is typical for LDN, to block a pathway that inhibits anticancer immunity and therefore to increase anticancer white blood cells during the treatment cycle⁸Lissoni P, Malugani F et al. Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low-dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced antitumor immunity by blocking the opioid system. Neuro Endocrinology Letters. 2002 Aug;23(4):341-4.