The low dose naltrexone (LDN) reference page

This is a list of research and other scientific references related to low dose naltrexone. I have collected it all myself and it originally appeared on my Finnish LDN site in June 2007 (though I've since updated it and added more studies). If you see this list anywhere else on the Internet but here and my Finnish site, you can rest assured I am the source. I don't think I can claim copyright or anything on a list of other people's studies, but I also don't want anyone to think I "ripped off" someone else.

You can access the abstract of most of these studies by clicking the "PMID" link, which goes to the study's page on the PubMed database. Many of the full papers require either payment or an institution subscription.

It is sometimes difficult to classify whether a study is about low dose naltrexone or just "related", as e.g. some autism studies have used fairly low doses of naltrexone (but still larger than "traditional" LDN) and e.g. IBS trials have used quite low doses of naltrexone, such as 0.5 mg. There is also a considerable amount of research about ultra low dose naltrexone, which means naltrexone used in doses of only micrograms, picograms or nanograms, but that falls outside of the scope of this page.

Clinical trials and other papers about LDN

Ghai B, Bansal D, Hota D, et al. Off-label, low-dose naltrexone for refractory chronic low back pain. Pain Med. 2014 May;15(5):883-4. PMID: 24967470

Dodou K, Armstrong A, Kelly I, et al. Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6β-naltrexol, using a novel LC Q-ToF MS assay. Pharm Dev Technol. In press 2014. PMID: 24785567

Segal D, Macdonald JK, Chande N. Low dose naltrexone for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2014 Feb 21;2:CD010410. PMID: 24558033

Rogosnitzky M, Finegold MJ, McLaughlin PJ et al. Opioid growth factor (OGF) for hepatoblastoma: a novel non-toxic treatment. Invest New Drugs. 2013 Aug;31(4):1066-70. PMID: 23275062

Chopra P, Cooper MS. Treatment of Complex Regional Pain Syndrome (CRPS) using low dose naltrexone (LDN). J Neuroimmune Pharmacol. 2013 Jun;8(3):470-6. PMID: 23546884

Bihari B. Bernard Bihari, MD: low-dose naltrexone for normalizing immune system function. Altern Ther Health Med. 2013 Mar-Apr;19(2):56-65. PMID: 23594453

Younger J, Noor N, McCue R et al. Low-dose naltrexone for the treatment of fibromyalgia: Findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013 Feb;65(2):529-38. PMID: 23359310

Smith JP, Field D, Bingaman SI et al. Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn's disease: a pilot study. J Clin Gastroenterol. J Clin Gastroenterol. 2013 Apr;47(4):339-45. PMID: 23188075

Ramanathan S, Panksepp J, Johnson B. Is fibromyalgia an endocrine/endorphin deficit disorder? Is low dose naltrexone a new treatment option? Psychosomatics. 2012 Nov-Dec;53(6):591-4. PMID: 22480625

Younger J et al. Low-dose naltrexone reduces the symptoms of fibromyalgia: A double-blind and placebo-controlled crossover study. AAPM 2012; Abstract 251. link

Traore AK, Thiero O, Dao S, et al. Single cohort study of the effect of low dose naltrexone on the evolution of immunological, virological and clinical state of HIV+ adults in Mali. J AIDS HIV Res. 2011 Oct;3(10):180-8. link

Traore AK, Thiero O, Dao S, et al. Impact of low dose naltrexone (LDN) on antiretroviral therapy (ART) treated HIV+ adults in Mali: A single blind randomized clinical trial. J AIDS HIV Res. 2011 Oct;3(10):189-98. link

[No authors listed]. Low-dose naltrexone: tricking the body to heal itself. Exp Biol Med (Maywood). 2011 Sep 1;236(9):vii-viii. PMID: 21991594 (link)

Frech T, Novak K, Revelo MP, et al. Low-dose naltrexone for pruritus in systemic sclerosis. Int J Rheumatol. 2011;2011:804296. PMID: 21918649

[No authors listed]. Low-dose naltrexone: harnessing the body's own chemistry to treat human ovarian cancer. Exp Biol Med (Maywood). 2011 Jul 1;236(7):viii. PMID: 21887861

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. Exp Biol Med (Maywood). 2011 Sep 1;236(9):1036-50. PMID: 21807817

Raknes G, Giverhaug T. [Low dosage naltrexone]. Tidsskr Nor Laegeforen. 2011 Aug 9;131(15):1415-6. PMID: 21844938

Holmoy T. [Research on low dosage naltrexone]. Tidsskr Nor Laegeforen. 2011 Jul 1;131(13-14):1277-8. PMID: 21725378

Raknes G, Giverhaug T. [Naltrexone--high expectations to low dosages]. Tidsskr Nor Laegeforen. 2011 May 6;131(8):844-6. PMID: 21556092

Donahue RN, McLaughlin PJ, Zagon IS. Low-dose naltrexone suppresses ovarian cancer and exhibits enhanced inhibition in combination with cisplatin. Exp Biol Med (Maywood). 2011 Jul 1;236(7):883-95. Epub 2011 Jun 17. PMID: 21685240

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. PMID: 21584896

Raknes G, Giverhaug T. [Low dosage naltrexone]. Tidsskr Nor Laegeforen. 2011 Aug 9;131(15):1415-6. PMID: 21844938

Donahue RN, McLaughlin PJ, Zagon IS. The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice. Gynecol Oncol. 2011 Aug;122(2):382-8. PMID: 21531450

Smith JP, Bingaman SI, Ruggiero F, et al. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial. Dig Dis Sci. 2011 Jul;56(7):2088-97. PMID: 21380937

Hesselink JM, Kopsky DJ. Enhancing acupuncture by low dose naltrexone. Acupunct Med. 2011 Jun;29(2):127-30. PMID: 21415049

Rahn KA, McLaughlin PJ, Zagon IS. Prevention and diminished expression of experimental autoimmune encephalomyelitis by low dose naltrexone (LDN) or opioid growth factor (OGF) for an extended period: Therapeutic implications for multiple sclerosis. Brain Res. 2011 Mar 24;1381:243-53. PMID: 21256121

ALSUntangled Group. ALSUntangled No. 8: Low dose naltrexone for ALS. Amyotroph Lateral Scler. 2011 Jan;12(1):76-8. PMID: 21174518

Sharafaddinzadeh N, Moghtaderi A, Kashipazha D, et al. The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial. Mult Scler. 2010 Aug;16(8):964-9. PMID: 20534644

Shannon A, Alkhouri N, Mayacy S, et al. Low-dose naltrexone for treatment of duodenal Crohn's disease in a pediatric patient. Inflamm Bowel Dis. 2010 Sep;16(9):1457. PMID: 20014017

Cree BA, Kornyeyeva E, Goodin DS. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol. 2010 Aug;68(2):145-50. PMID: 20695007

Guttuso T, Salins N, Lichter D. Abstract #13: Low-Dose Naltrexone's Tolerability and Effects in Fatigued Patients with Parkinson's Disease: An Open-Label Study. Neurotherapeutics. 2010 Jul;7(3):332. link

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. Integr Cancer Ther. 2009 Dec;8(4):416-22. PMID: 20042414

Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 2009 May-Jun;10(4):663-72. PMID: 19453963

Desjardins S, Doyen C, Contejean Y, et al. Treatment of a serious autistic disorder in a child with Naltrexone in an oral suspension form. Encephale. 2009 Apr;35(2):168-72. PMID: 19393386

Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Med Hypotheses. 2009 Mar;72(3):333-7. PMID: 19041189

Gironi M, Martinelli-Boneschi F, et al. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. Mult Scler. 2008 Sep;14(8):1076-83. PMID: 18728058

Patel PN. Low-dose naltrexone for treatment of multiple sclerosis: clinical trials are needed. Ann Pharmacother. 2007 Sep;41(9):1549-50. PMID: 17623758

Berkson BM, Rubin DM, Berkson AJ. Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone. Integr Cancer Ther. 2007 Sep;6(3):293-6. PMID: 17761642

Mannelli P, Patkar AA, Peindl K, et al. Effectiveness of Low-Dose Naltrexone in the Post-Detoxification Treatment of Opioid Dependence. J Clin Psychopharmacol. 2007 Oct;27(5):468-74. PMID: 17873678

Smith JP, Stock H, Bingaman S, et al. Low-dose naltrexone therapy improves active Crohn's disease. Am J Gastroenterol. 2007 Apr;102(4):820-8. PMID: 17222320

Good P. Low-dose naltrexone for multiple sclerosis and autism: does its benefit reveal a common cause? Med Hypotheses. 2006;67(3):671-2. PMID: 16759815

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. Integr Cancer Ther. 2006 Mar;5(1):83-9. PMID: 16484716

Agrawal YP. Low dose naltrexone therapy in multiple sclerosis. Med Hypotheses. 2005;64(4):721-4. PMID: 15694688

Bihari B. Efficacy of low dose naltrexone as an immune stabilizing agent for the treatment of HIV/AIDS [letter]. AIDS Patient Care. 1995 Feb;9(1):3. PMID: 11361353

Bouvard MP, Leboyer M, Launay JM, et al. Low-dose naltrexone effects on plasma chemistries and clinical symptoms in autism: a double-blind, placebo-controlled study. Psychiatry Res. 1995 Oct 16;58(3):191-201. PMID: 8570775

Bihari B, Drury F, Ragone V, et al. Low dose naltrexone in the treatment of AIDS: long term follow-up results. V International Conference on AIDS. Poster M. C.P. 62. Montreal, June 1989.

Bihari B, Drury F, Ragone V, et al. Low dose naltrexone in the treatment of AIDS. IV International Conference on AIDS. Poster 3056. Stockholm, June 1988. link

Other research and publications related to the subject (e.g. the mode of action of LDN)

Cancer

Sarkar DK, Zhang C. Beta-endorphin neuron regulates stress response and innate immunity to prevent breast cancer growth and progression. Vitam Horm. 2013;93:263-76. PMID: 23810011

Zagon IS, Donahue R, McLaughlin PJ. Targeting the opioid growth factor: opioid growth factor receptor axis for treatment of human ovarian cancer. Exp Biol Med (Maywood). 2013 May;238(5):579-87. PMID: 23856908

Chen W, Liu J, Meng J et al. Macrophage polarization induced by neuropeptide methionine enkephalin (MENK) promotes tumoricidal responses. Cancer Immunol Immunother. 2012 Oct;61(10):1755-68. PMID: 22419372

Sarkar DK, Zhang C, Murugan S, et al. Transplantation of {beta}-Endorphin Neurons into the Hypothalamus Promotes Immune Function and Restricts the Growth and Metastasis of Mammary Carcinoma. Cancer Res. 2011 Oct 1;71(19):6282-91. PMID: 21835894

Boehncke S, Hardt K, Schadendorf D, et al. Endogenous μ-opioid peptides modulate immune response towards malignant melanoma. Exp Dermatol. 2011 Jan;20(1):24-8. PMID: 20955200

Smith JP, Bingaman SI, Mauger DT, et al. Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer. Open Access J Clin Trials. 2010 Mar 1;2010(2):37-48. PMID: 20890374

Avella DM, Kimchi ET, Donahue RN, et al. The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer. Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R459-66. PMID: 19923357

McLaughlin PJ, Zagon IS, Park SS, et al. Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis. PMID: 19835629

Zagon IS, Donahue RN, McLaughlin PJ. Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers.Am J Physiol Regul Integr Comp Physiol. 2009 Oct;297(4):R1154-61. PMID: 19675283

Donahue RN, McLaughlin PJ, Zagon IS. Cell proliferation of human ovarian cancer is regulated by the opioid growth factor-opioid growth factor receptor axis. Am J Physiol Regul Integr Comp Physiol. 2009 Jun;296(6):R1716-25. PMID: 19297547

McLaughlin PJ, Kreiner S, Morgan CR, et al. Prevention and delay in progression of human squamous cell carcinoma of the head and neck in nude mice by stable overexpression of the opioid growth factor receptor. Int J Oncol. 2008 Oct;33(4):751-7. PMID: 18813788

Zagon IS, Kreiner S, Heslop JJ, et al. Prevention and delay in progression of human pancreatic cancer by stable overexpression of the opioid growth factor receptor. Int J Oncol. 2008 Aug;33(2):317-23. PMID: 18636152

Sarkar DK, Boyadjieva NI, Chen CP, et al. Cyclic adenosine monophosphate differentiated beta-endorphin neurons promote immune function and prevent prostate cancer growth. Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9105-10. PMID: 18562281

Zagon I, Donahue RN, Rogosnitzky M, et al. Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function. Exp Biol Med (Maywood). 2008 Aug;233(8):968-79. PMID: 18480416

Zagon IS, Rahn KA, McLaughlin PJ. Opioids and migration, chemotaxis, invasion, and adhesion of human cancer cells. Neuropeptides. 2007 Dec;41(6):441-52. PMID: 17910895

Zagon IS, Verderame MF, Hankins J, et al. Overexpression of the opioid growth factor receptor potentiates growth inhibition in human pancreatic cancer cells. Int J Oncol. 2007 Apr;30(4):775-83. PMID: 17332915

McLaughlin PJ, Verderame MF, Hankins JL, et al. Overexpression of the opioid growth factor receptor downregulates cell proliferation of human squamous carcinoma cells of the head and neck. Int J Mol Med. 2007 Mar;19(3):421-8. PMID: 17273790

McLaughlin PJ, Zagon IS. Progression of squamous cell carcinoma of the head and neck is associated with down-regulation of the opioid growth factor receptor. Int J Oncol. 2006 Jun;28(6):1577-83. PMID: 16685459

Zagon IS, Jaglowski JR, Verderame MF, et al. Combination chemotherapy with gemcitabine and biotherapy with opioid growth factor (OGF) enhances the growth inhibition of pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2005 Nov;56(5):510-20. PMID: 15947928

Zagon IS, McLaughlin PJ. Opioids and differentiation in human cancer cells. Neuropeptides. 2005 Oct;39(5):495-505. PMID: 16169076

Jaglowski JR, Zagon IS, Stack BC, et al. Opioid growth factor enhances tumor growth inhibition and increases the survival of paclitaxel-treated mice with squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol. 2005 Jul;56(1):97-104. PMID: 15791460

McLaughlin PJ, Jaglowski JR, Verderame MF, et al. Enhanced growth inhibition of squamous cell carcinoma of the head and neck by combination therapy of paclitaxel and opioid growth factor. Int J Oncol. 2005 Mar;26(3):809-16. PMID: 15703840

Zagon IS, McLaughlin PJ. Opioid growth factor (OGF) inhibits anchorage-independent growth in human cancer cells. Int J Oncol. 2004 Jun;24(6):1443-8. PMID: 15138586

Smith JP, Conter RL, Bingaman SI, et al. Treatment of advanced pancreatic cancer with opioid growth factor: phase I. Anticancer Drugs. 2004 Mar;15(3):203-9. PMID: 15014352

McLaughlin PJ, Levin RJ, Zagon IS. Opioid growth factor (OGF) inhibits the progression of human squamous cell carcinoma of the head and neck transplanted into nude mice. Cancer Lett. 2003 Sep 25;199(2):209-17. PMID: 12969794

McLaughlin PJ, Stack BC, Levin RJ, et al. Defects in the opioid growth factor receptor in human squamous cell carcinoma of the head and neck. Cancer. 2003 Apr 1;97(7):1701-10. PMID: 12655527

Blebea J, Mazo JE, Kihara TK, et al. Opioid growth factor modulates angiogenesis. J Vasc Surg. 2000 Aug;32(2):364-73. PMID: 10917997

McLaughlin PJ, Levin RJ, Zagon IS. The opioid growth factor receptor in human head and neck squamous cell carcinoma. Int J Mol Med. 2000 Feb;5(2):191-6. PMID: 10639600

Bisignani GJ, McLaughlin PJ, Ordille SD, et al. Human renal cell cancer proliferation in tissue culture is tonically inhibited by opioid growth factor. J Urol. 1999 Dec;162(6):2186-91. PMID: 10569617

McLaughlin PJ, Levin RJ, Zagon IS. Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor. Int J Oncol. 1999 May;14(5):991-8. PMID: 10200353

Zagon IS, Smith JP, McLaughlin PJ. Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor. Int J Oncol. 1999 Mar;14(3):577-84. PMID: 10024694

McLaughlin PJ, Zagon IS, Skitzki J. Human neuroblastoma cell growth in tissue culture is regulated by opioid growth factor. Int J Oncol. 1999 Feb;14(2):373-80. PMID: 917516

Levin RJ, Wu Y, McLaughlin PJ, et al. Expression of the opioid growth factor, [Met5]-enkephalin, and the zeta opioid receptor in head and neck squamous cell carcinoma. Laryngoscope. 1997 Mar;107(3):335-9. PMID: 9121309

Zagon IS, Hytrek SD, Smith JP, et al. Opioid growth factor (OGF) inhibits human pancreatic cancer transplanted into nude mice. Cancer Lett. 1997 Jan 30;112(2):167-75. PMID: 9066724

Zagon IS, Hytrek SD, McLaughlin PJ. Opioid growth factor tonically inhibits human colon cancer cell proliferation in tissue culture. Am J Physiol. 1996 Sep;271(3 Pt 2):R511-8. PMID: 8853370

Zagon IS, Hytrek SD, Lang CM, et al. Opioid growth factor ([Met5]enkephalin) prevents the incidence and retards the growth of human colon cancer. Am J Physiol. 1996 Sep;271(3 Pt 2):R780-6. PMID: 885340

Hytrek SD, McLaughlin PJ, Lang CM, et al. Inhibition of human colon cancer by intermittent opioid receptor blockade with naltrexone. Cancer Lett. 1996 Mar 29;101(2):159-64. PMID: 8620464

Murgo AJ. Modulation of murine melanoma growth by naloxone. Cancer Lett. 1989 Feb;44(2):137-42. PMID: 2920373

Zagon IS, McLaughlin PJ. Opioid antagonist modulation of murine neuroblastoma: a profile of cell proliferation and opioid peptides and receptors. Brain Res. 1989 Feb 20;480(1-2):16-28. PMID: 2540873

Zagon IS, McLaughlin P. Endogenous opioids and the growth regulation of a neural tumor. Life Sci. 1988;43(16):1313-8. PMID: 2845218

Faith RE, Murgo AJ. Inhibition of pulmonary metastases and enhancement of natural killer cell activity by methionine-enkephalin. Brain Behav Immun. 1988 Jun;2(2):114-22. PMID: 3233355

Zagon IS, McLaughlin PJ, Goodman SR, et al. Opioid receptors and endogenous opioids in diverse human and animal cancers. J Natl Cancer Inst. 1987 Nov;79(5):1059-65. PMID: 2824913

McLaughlin PJ, Zagon IS. Modulation of human neuroblastoma transplanted into nude mice by endogenous opioid systems. Life Sci. 1987 Sep 21;41(12):1465-72. PMID: 3041143

Murgo AJ. Inhibition of B16-BL6 melanoma growth in mice by methionine-enkephalin. J Natl Cancer Inst. 1985 Aug;75(2):341-4. PMID: 3860686

Zagon IS, McLaughlin PJ. Duration of opiate receptor blockade determines tumorigenic response in mice with neuroblastoma: a role for endogenous opioid systems in cancer. Life Sci. 1984 Jul 23;35(4):409-16. PMID: 6087062

Froelich CJ, Bankhurst AD. The effect of beta-endorphin on natural cytotoxicity and antibody dependent cellular cytotoxicity. Life Sci. 1984 Jul 16;35(3):261-5. PMID: 6087056

Zagon IS, McLaughlin PJ. Opioid antagonists inhibit the growth of metastatic murine neuroblastoma. Cancer Lett. 1983 Nov;21(1):89-94. PMID: 6640516

Zagon IS, McLaughlin PJ. Naltrexone modulates tumor response in mice with neuroblastoma. Science. 1983 Aug 12;221(4611):671-3. PMID: 6867737

Mathews PM, Froelich CJ, Sibbitt WL Jr., et al. Enhancement of natural cytotoxicity by beta-endorphin. J Immunol. 1983 Apr;130(4):1658-62. PMID: 6300232

HIV and other infections

Steele AD, Henderson EE, Rogers TJ. Mu-opioid modulation of HIV-1 coreceptor expression and HIV-1 replication. Virology. 2003 Apr 25;309(1):99-107. PMID: 12726730

Gekker G, Lokensgard JR, Peterson PK. Naltrexone potentiates anti-HIV-1 activity of antiretroviral drugs in CD4+ lymphocyte cultures. Drug Alcohol Depend. 2001 Nov 1;64(3):257-63. PMID: 11672940

Sharp BM, Gekker G, Li MD, et al. Delta-opioid suppression of human immunodeficiency virus-1 expression in T cells (Jurkat). Biochem Pharmacol. 1998 Aug 1;56(3):289-92. PMID: 9744564

Risdahl JM, Khanna KV, Peterson PK, et al. Opiates and infection. J Neuroimmunol. 1998 Mar 15;83(1-2):4-18. PMID: 9610668

Arnalich F, Martinez P, Hernanz A, et al. Altered concentrations of appetite regulators may contribute to the development and maintenance of HIV-associated wasting. AIDS. 1997 Jul 15;11(9):1129-34. PMID: 9233460

Chao CC, Gekker G, Hu S, et al. kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):8051-6. PMID: 8755601

Spinazzola F, Barletta C, Demartino G, et al. Beta-endorphins ACTH and cortisol in CSF and plasma of HIV infected patients. Riv Eur Sci Med Farmacol. 1995 Sep-Oct;17(5):161-5. PMID: 8766783

Bruno RL, Sapolsky R, Zimmerman JR, et al. Pathophysiology of a central cause of post-polio fatigue. Ann N Y Acad Sci. 1995 May 25;753:257-75. PMID: 7611635

Zagon IS, McLaughlin PJ. An opioid growth factor regulates the replication of microorganisms. Life Sci. 1992;50(16):1179-87. PMID: 1313136

Plotnikoff N, Wybran J. Methionine-enkephalin shows promise in reducing HIV in blood. Am Fam Physician. 1989 Sep;40(3):234. PMID: 2773759

Autoimmune diseases

Cao AT, Yao S, Stefka AT, et al. TLR4 regulates IFN-γ and IL-17 production by both thymic and induced Foxp3+ Tregs during intestinal inflammation. J Leukoc Biol. In press 2014. PMID: 25015957

Reynolds JM, Martinez GJ, Chung Y, et al. Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation. Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):13064-9. PMID: 22826216

Zagon IS, McLaughlin PJ. Targeting opioid signaling in Crohn's disease: new therapeutic pathways. Expert Rev Gastroenterol Hepatol. 2011 Oct;5(5):555-8. PMID: 21910569

Siddique I, Khan I. Mechanism of regulation of Na-H exchanger in inflammatory bowel disease: role of TLR-4 signaling mechanism. Dig Dis Sci. 2011 Jun;56(6):1656-62. PMID: 21221801

Zagon IS, Donahue RN, Bonneau RH, et al. T lymphocyte proliferation is suppressed by the opioid growth factor ([Met(5)]-enkephalin)-opioid growth factor receptor axis: implication for the treatment of autoimmune diseases. Immunobiology. 2011 May;216(5):579-90. PMID: 20965606

Zagon IS, Donahue RN, Bonneau RH, et al. B lymphocyte proliferation is suppressed by the opioid growth factor-opioid growth factor receptor axis: Implication for the treatment of autoimmune diseases. Immunobiology. 2011 Jan-Feb;216(1-2):173-83. PMID: 20598772

McNearney TA, Sluka KA, Ahn C, et al. Plasma endogenous enkephalin levels in early systemic sclerosis: clinical and laboratory associations. Clin Exp Rheumatol. 2010 Mar-Apr;28(2 Suppl 58):S7-11. PMID: 20576209

Zagon IS, Rahn KA, Bonneau RH, et al. Opioid growth factor suppresses expression of experimental autoimmune encephalomyelitis. Brain Res. 2010 Jan 15;1310:154-61. PMID: 19931226

Kishimoto C, Okabe TA, Hattori M, et al. Naloxone, an opiate receptor antagonist, ameliorates acute experimental autoimmune myocarditis by reducing cytotoxic activities. J Cardiovasc Pharmacol. 2008 Nov;52(5):445-51. PMID: 19033824

Matters GL, Harms JF, McGovern C et al. The opioid antagonist naltrexone improves murine inflammatory bowel disease. J Immunotoxicol. 2008 Apr;5(2):179-87. PMID: 18569389

Marks DJ, Harbord MW, MacAllister R, et al. Defective acute inflammation in Crohn's disease: a clinical investigation. Lancet. 2006 Feb 25;367(9511):668-78. PMID: 165034?5

Philippe D, Dubuquoy L, Groux H. Anti-inflammatory properties of the mu opioid receptor support its use in the treatment of colon inflammation. J Clin Invest. 2003 May;111(9):1329-38. PMID: 12727924

Gironi M, Furlan R, Rovaris M, et al. Beta endorphin concentrations in PBMC of patients with different clinical phenotypes of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2003 Apr;74(4):495-7. PMID: 12640071

Sacerdote P, Lechner O, Sidman C. Hypothalamic beta-endorphin concentrations are decreased in animals models of autoimmune disease. J Neuroimmunol. 1999 Jun 1;97(1-2):129-33. PMID: 10408966

Wiedermann CJ, Sacerdote P, Propst A, et al. Decreased beta-endorphin content in peripheral blood mononuclear leukocytes from patients with Crohn's disease. Brain Behav Immun. 1994 Sep;8(3):261-9. PMID: 7865897

Jankovic BD. Enkephalins and immune inflammatory reactions. Acta Neurol (Napoli). 1991 Oct;13(5):433-41. PMID: 1663693

CFS/ME etc

Pall ML. Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO- cycle. Med Hypotheses. 2007 Apr 18. PMID: 17448611

Conti F, Pittoni V, Sacerdote P. Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with chronic fatigue syndrome. Clin Exp Rheumatol. 1998 Nov-Dec;16(6):729-32. PMID: 9844768

Whiteside TL, Friberg D. Natural killer cells and natural killer cell activity in chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):27S-34S. PMID: 9790479

Immune system in general

Lucas K, Maes M. Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013 Aug;48(1):190-204. PMID: 23436141

Hua H, Lu C, Li W, et al. Comparison of stimulating effect on subpopulations of lymphocytes in human peripheral blood by methionine enkephalin with IL-2 and IFN-γ. Hum Vaccin Immunother. 2012 Aug;8(8):1082-9. PMID: 22854663

Davis RL, Buck DJ, Saffarian N, et al. The opioid antagonist, beta-funaltrexamine, inhibits chemokine expression in human astroglial cells. J Neuroimmunol. 2007 May;186(1-2):141-9. PMID: 17475341

Buckley RH. Primary immunodeficiency diseases due to defects in lymphocytes. N Engl J Med. 2000 Nov 2;343(18):1313-24. PMID: 11058677

Kowalski J. Effect of enkephalins and endorphins on cytotoxic activity of natural killer cells and macrophages/monocytes in mice. PMID: 9196278

Roy S, Loh HH. Effects of opioids on the immune system. Neurochem Res. 1996 Nov;21(11):1375-86. PMID: 8947928

Hsueh CM, Chen SF, Ghanta VK, et al. Expression of the conditioned NK cell activity is beta-endorphin dependent. Brain Res. 1995 Apr 24;678(1-2):76-82. PMID: 7620901

Makman MH. Morphine receptors in immunocytes and neurons. Adv Neuroimmunol. 1994;4(2):69-82. PMID: 7952830

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Wound healing

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Neuroprotection

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Liu B, Hong JS. Neuroprotective effect of naloxone in inflammation-mediated dopaminergic neurodegeneration. Dissociation from the involvement of opioid receptors. Methods Mol Med. 2003;79:43-54. PMID: 12506689

Liu B, Hong JS. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther. 2003 Jan;304(1):1-7. PMID: 12490568

Liu Y, Qin L, Wilson BC, et al. Inhibition by naloxone stereoisomers of beta-amyloid peptide (1-42)-induced superoxide production in microglia and degeneration of cortical and mesencephalic neurons. J Pharmacol Exp Ther. 2002 Sep;302(3):1212-9. PMID: 12183682

Lu X, Bing G, Hagg T. Naloxone prevents microglia-induced degeneration of dopaminergic substantia nigra neurons in adult rats. Neuroscience. 2000;97(2):285-91. PMID: 10799760

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Liu B, Du L, Kong LY, et al. Reduction by naloxone of lipopolysaccharide-induced neurotoxicity in mouse cortical neuron-glia co-cultures. Neuroscience. 2000;97(4):749-56. PMID: 10842020

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Liu B, Du L, Hong JS. Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther. 2000 May;293(2):607-17. PMID: 10773035

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Psychiatric

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Pain

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Leone M, Sacerdote P, D'Amico D, et al. Beta-endorphin concentrations in the peripheral blood mononuclear cells of migraine and tension-type headache patients. Cephalalgia. 1992 Jun;12(3):154-7. PMID: 1298216

Other

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Unfinished and future studies on LDN

Jarred Younger, the researcher behind the previous studies of LDN for fibromyalgia, is trying to get funding for a phase III study, which could be a big step towards the FDA approval of LDN for this indication. In even better news, the pharmaceutical company TNI Biotech has acquired all of Bernard Bihari's patents of LDN. They are also planning phase III studies of LDN (for HIV and cancer?) and are opening a new hospital for cancer and infectious diseases in Malawi, which will be treating patients with LDN. They are trying to get LDN approved as an orphan drug in children's Crohn's disease.

A new study is evaluating LDN in both Crohn's disease and ulcerative colitis. An interesting new trial will try LDN for depression, though for some reason the dose is just 2 x 1 mg a day. There are also clinical trials undergoing for glioma (a type of brain cancer) and another trial for metastatic melanoma, castrate resistant prostate cancer and renal cancer. A study of LDN for juvenile fibromyalgia was unfortunately cancelled.