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, but you can often use Sci-Hub to access them for free. However, the domain name of Sci-Hub changes frequently. At the time of the latest update of this page it was, but if that link doesn't work, you may have to do some Googling to locate the current incarnation.

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 studies and papers about LDN

de Saedeleer P. Low-Dose Naltrexone as a Treatment for Chronic Inflammation. Presentation. ILADS Europe 2018. Warsaw, Poland. 15th-16th June 2018.

Lie MRKL, van der Giessen J, Fuhler GM, et al. Low dose Naltrexone for induction of remission in inflammatory bowel disease patients. J Transl Med. 2018 Mar 9;16(1):55. PMID: 29523156

Raknes G, Simonsen P, Småbrekke L. The effect of Low Dose Naltrexone on Medication in Inflammatory Bowel Disease: A Quasi Experimental before-and-after Prescription Database Study. J Crohns Colitis. In press 2018. PMID: 29385430

Patten DK, Schultz BG, Berlau DJ. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders. Pharmacotherapy. In press 2018. PMID: 29377216

Weinstock LB, Brook JB, Myers TL, et al. Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment. BMJ Case Rep. 2018 Jan 11;2018. PMID: 29326369

Ludwig MD, Zagon IS, McLaughlin PJ. Featured Article: Modulation of the OGF-OGFr pathway alters cytokine profiles in experimental autoimmune encephalomyelitis and multiple sclerosis. Exp Biol Med (Maywood). 2018 Feb;243(4):361-369. PMID: 29307283

Berkson 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. Integr Cancer Ther. 2017 Dec 1:1534735417747984. PMID: 29258346

Banerjee AG, Cheatle M. 080 - Quench the Fire! A Case Report of Burning Mouth Syndrome Treated with Low Dose Naltrexone After Failure of Response to Extensive Pain Management Trials. Presentation. APM Annual Meeting. Palm Springs, CA, US. 8th-11th November 2017. link

Strazzulla LC, Avila L, Lo Sicco K, et al. Novel Treatment Using Low-Dose Naltrexone for Lichen Planopilaris. J Drugs Dermatol. 2017 Nov 1;16(11):1140-1142. PMID: 29141063

Raknes G, Småbrekke L. Low dose naltrexone in multiple sclerosis: Effects on medication use. A quasi-experimental study. PLoS One. 2017 Nov 3;12(11):e0187423. PMID: 29099849

Campbell V, McGrath C, Corry A. Low-dose naltrexone: a novel treatment for Hailey-Hailey disease. Br J Dermatol. In press 2017. PMID: 28991360

Amezcua L, Nelson F. Ethical Considerations of Patient-Funded Research for Multiple Sclerosis Therapeutics. Neurotherapeutics. 2017 Oct;14(4):945-951. PMID: 28779373

Ibrahim O, Hogan SR, Vij A, et al. Low-Dose Naltrexone Treatment of Familial Benign Pemphigus (Hailey-Hailey Disease). JAMA Dermatol. In press 2017. PMID: 28768313

Ipsen D. Low Dose Naltrexone Therapy. Presentation. WANP Annual Conference. Seattle, WA, US. 30th September-1st October 2017.

Weinstock LB, Myers TL, Steinhoff M, et al. Successful Treatment of Adult-Onset Dermatitis Herpetiformis with Low Dose Naltrexone. J Clin Med Case Stud. 2017 Sep;2(3):27-29. link

Kiselev B. Treatment of Cyclic Vomiting Syndrome / Abdominal Hypersensitivity with Low Dose Naltrexone and Acceptance Commitment Therapy. AMP Annual Meeting. Chicago, IL, US. 15th September 2017.

Weinstock LB. Restless Legs Syndrome - The role of SIBO and Inflammation. Integrative SIBO Conference. Lombard, IL, US. 25th-26th March 2017.

Ludwig MD, Zagon IS, McLaughlin PJ. Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone. Exp Biol Med (Maywood). 2017 Jan 1:1535370217724791. PMID: 28766982

Stockdale DP, Titunick MB, Biegler JM, et al. Selective opioid growth factor receptor antagonists based on a stilbene isostere. Bioorg Med Chem. 2017 Aug 15;25(16):4464-4474. PMID: 28693915

Ludwig MD, Turel AP, Zagon IS, et al. Long-term treatment with low dose naltrexone maintains stable health in patients with multiple sclerosis. Mult Scler J Exp Transl Clin. 2016 Sep 29;2:2055217316672242. PMID: 28607740

Battle P. Use of Low Dose Naltrexone and its Application to Inflammatory Bowel Disease, Cancer, and Autoimmune Disease. 22nd Clinical Applications for Age Management Medicine Conference. Orlando, FL, US. 27th-30th April 2016.

Parkitny L, Younger J. Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines. 2017 Apr 18;5(2). PMID: 28536359

Ringerike T, Pike E, Nevjar J, et al. The Use of Naltrexone in Low Doses Beyond the Approved Indication [Internet]. Oslo, Norway: Knowledge Centre for the Health Services at The Norwegian Institute of Public Health (NIPH); 2015 Apr. PMID: 28510411

Leonard JB, Nair V, Diaz CJ, et al. Potential drug interaction with opioid agonist in the setting of chronic low-dose opioid antagonist use. Am J Emerg Med. 2017 Aug;35(8):1209.e3-1209.e4. PMID: 28410920

Raknes G, Småbrekke L. Low-dose naltrexone and opioid consumption: a drug utilization cohort study based on data from the Norwegian prescription database. Pharmacoepidemiol Drug Saf. 2017 Jun;26(6):685-693. PMID: 28370746

Metyas SK, Yeter K, Solyman J, et al. Low Dose Naltrexone in the Treatment of Fibromyalgia. Curr Rheumatol Rev. In press 2017. PMID: 28325149

Mischoulon D, Hylek L, Yeung AS, et al. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. J Affect Disord. 2017 Jan 15;208:6-14. PMID: 27736689

Raknes G, Småbrekke L. A sudden and unprecedented increase in low dose naltrexone (LDN) prescribing in Norway. Patient and prescriber characteristics, and dispense patterns. A drug utilization cohort study. Pharmacoepidemiol Drug Saf. 2017 Feb;26(2):136-142. PMID: 27670755

Yi Z, Guo S, Hu X, et al. Functional modulation on macrophage by low dose naltrexone (LDN). Int Immunopharmacol. 2016 Oct;39:397-402. PMID: 27561742

Tawfik DI, Osman AS, Tolba HM, et al. Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats. Neuropeptides. 2016 Oct;59:39-45. PMID: 27392602

Liu WM, Scott KA, Dennis JL, et al. Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy. Int J Oncol. 2016 Aug;49(2):793-802. PMID: 27279602

Sushchyk SA, Xi ZX, Wang JB. Combination of levo-tetrahydropalmatine and low dose naltrexone: a promising treatment for the prevention of cocaine relapse. J Pharmacol Exp Ther. J Pharmacol Exp Ther. 2016 May;357(2):248-57. PMID: 26903543

Weinstock LB, Myers TL, Walters AS, et al. Identification and Treatment of New Inflammatory Triggers for Complex Regional Pain Syndrome: Small Intestinal Bacterial Overgrowth and Obstructive Sleep Apnea. A A Case Rep. 2016 May 1;6(9):272-6. PMID: 26867023

Shell L. Low Dose Naltrexone for Treatment of Patients with Pain. Presentation. IntNSA 40th Annual Education Conference. Las Vegas, NV, US. 5th-8th October 2016.

Noon K, Sturgeon M, Kao B, et al. (418) A novel glial cell inhibitor, low dose naltrexone, reduces pain and depression, and improves function in chronic pain: A CHOIR study. J Pain. 2016 Apr;17(4):S79. link

Mackey S. Naltrexone for Treatment of Fibromyalgia. Presentation. The American Academy of Pain Medicine 32and Annual Meeting. Palm Springs, CA, US. 18th-21st February 2016.

Hota D, Srinivasan A, Dutta P, et al. Off-Label, Low-Dose Naltrexone for Refractory Painful Diabetic Neuropathy. Pain Med. 2016 Apr;17(4):790-1. PMID: 26814245

Plesner KB, Vægter HB, Handberg G. [Low dose naltrexone for treatment of pain]. Ugeskr Laeger. 2015 Oct 9;177(43). PMID: 26509454

Roginsky G, Alexoff A, Ehrenpreis ED. Initial Findings of an Open-Label Trial of Low-Dose Naltrexone for Symptomatic Mesenteric Panniculitis. J Clin Gastroenterol. 2015 Oct;49(9):794-5. PMID: 26280708

Turel AP, Oh KH, Zagon IS, et al. Low Dose Naltrexone for Treatment of Multiple Sclerosis: A Retrospective Chart Review of Safety and Tolerability. J Clin Psychopharmacol. 2015 Oct;35(5):609-11. PMID: 26203498

McLaughlin PJ, Zagon IS. Duration of opioid receptor blockade determines biotherapeutic response. Biochem Pharmacol. 2015 Oct 1;97(3):236-46. PMID: 26119823

Ludwig M, Turel AP, Zagon IS, et al. Treatment of clinically isolated syndrome with low dose naltrexone. Clin Case Rep Rev 1. link

Hammer LA, Waldner H, Zagon IS, et al. Opioid growth factor and low-dose naltrexone impair central nervous system infiltration by CD4 + T lymphocytes in established experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Exp Biol Med (Maywood). 2016 Jan;241(1):71-8. PMID: 26202376

Raffaeli W, Indovina P. Low-dose naltrexone to prevent intolerable morphine adverse events: a forgotten remedy for a neglected, global clinical need. Pain Med. 2015 Jun;16(6):1239-42. PMID: 25643645

McLaughlin PJ, McHugh DP, Magister MJ, et al. Endogenous opioid inhibition of proliferation of T and B cell subpopulations in response to immunization for experimental autoimmune encephalomyelitis. BMC Immunol. 2015 Apr 24;16:24. PMID: 25906771

Nathoo S, Glover SC. Tu1365 Low Dose Naltrexone in the Treatment of Crohn's Disease: A Case Series. Gastroenterol. 2015 Apr;148(4):S870. link

Hammer LA, Zagon IS, McLaughlin PJ. Low dose naltrexone treatment of established relapsing-remitting experimental autoimmune encephalomyelitis. J Mult Scler 2:136. link

Pape W, Wöller W. [Low dose naltrexone in the treatment of dissociative symptoms.] Nervenarzt. 2015 Mar;86(3):346-51. PMID: 25421416

Johnson B, Ulberg S, Shivale S, et al. Fibromyalgia, autism, and opioid addiction as natural and induced disorders of the endogenous opioid hormonal system. Discov Med. 2014 Oct;18(99):209-20. PMID: 25336035

Khan A. Long-term remission of adenoid cystic tongue carcinoma with low dose naltrexone and vitamin D3--a case report. Oral Health Dent Manag. 2014 Sep;13(3):721-4. PMID: 25284545

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. 2015;20(6):694-701. PMID: 24785567

Cottel J. Remission of Clinically Isolated Syndrome with Low Dose Naltrexone. Poster. Science and Connection: A New Era of Integrative Health and Medicine. San Diego, CA, US. 26th-30th October 2014.

Weinstock LB. Naltrexone therapy for Crohn's disease and ulcerative colitis. J Clin Gastroenterol. 2014 Sep;48(8):742. PMID: 24583747

Zagon IS, McLaughlin PJ. Endogenous opioids and the treatment of multiple sclerosis. J Neurol Neurophysiol S12:011. link

Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. PMID: 24526250

Lie M, Fuhler G, de Lima C, et al. P418. Low dose naltrexone in therapy resistant IBD, a case series. Poster. 9th Congress of ECCO. Copenhagen, Denmark. 20th-22nd February 2014. link

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

Kais S. P-015 YI Low-Dose Naltrexone Therapy Improves Active Ulcerative Colitis. Infl Bowel Dis. 2013 Dec;19(S1):S29. link

Meng J, Meng Y, Plotnikoff NP, et al. Low dose naltrexone (LDN) enhances maturation of bone marrow dendritic cells (BMDCs). Int Immunopharmacol. 2013 Dec;17(4):1084-9. PMID: 24455776

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

de Haar C, van der Ent C, Peppelenbosch MP, et al. P388 Immunological changes in IBD patients responding to low-dose naltrexone treatment. J Crohns Colitis. 2012 Feb;6(S1):S164. 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

Ploesser J, Weinstock LB, Thomas E. Low Dose Naltrexone: Side Effects and Efficacy in Gastrointestinal Disorders. Int J Pharm Compd. 2010 March/April;14(2):171-173. PMID: 23965429

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

Gilhooly TC. Low dose naltrexone as a treatment for multiple sclerosis. Br J Neurosci Nurs. 2009 Nov 13;5(11):494.

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

Rahn KA, McLaughlin PJ, et al. Low-Dose Naltrexone (LDN) Prevents, or Delays Onset and Reduces Severity of EAE in Mice”, World Congress on Treatment and Research in Multiple Sclerosis. Montreal, Canada. 17th-20th September 2008.

Thomas GA, Rahn KA, McLaughlin PJ, et al. Low- Dose Naltrexone (LDN) Reduces Inflammatory Response and Demyelination, and Attenuates Behavioral Scores in MOG-Induced EAE. The 2nd World Congress on Controversies in Neurology (CONy). Athens, Greece. 23th-26th October 2008.

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

Matioli F, Ribeiro JC, Fukuhara PS, et al. Low dose naltrexone improves the muscular conditions in mdx mice. 2007. linkki

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, Canada. 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

Current and future studies on LDN

The pharmaceutical company Immune Therapeutics (formerly 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 studying LDN in the prevention of cervical cancer. They got LDN approved in the US as an orphan drug for Crohn's disease in children and it has been approved as a normal prescription medication in several third-world countries.

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. Apparently he is trying to set up an MS study, as well. He was starting a CFS/ME study as well, but it's currently paused. Stanford university is studying LDN in the pain syndrome CRPS. A new study is studying LDN in osteoarthritis, rheumatoid arthritis and psoriatic arthritis. A new fibromyalgia study is going on in Denmark. A study tried both LDN and another glial inhibitor dextromethorphan for Gulf War syndrome, the results are pending. A study of LDN for juvenile fibromyalgia was unfortunately cancelled, as was a trial supposed to evaluate LDN in both Crohn's disease and ulcerative colitis.

A clinical trial for glioma (a type of brain cancer) has been completed, but not yet published, though the results are available from the link. Another trial for metastatic melanoma, castrate resistant prostate cancer and renal cancer was unfortunately terminated. According to the partially published results, 2/7 of participants experienced some sort of response.

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


Wang DM, Jiao X, Plotnikoff NP, et al. Killing effect of methionine enkephalin on melanoma in vivo and in vitro. Oncol Rep. 2017 Oct;38(4):2132-2140. PMID:

Meng Y, Gao X, Chen, et al. Methionine enkephalin (MENK) mounts antitumor effect via regulating dendritic cells (DCs). Int Immunopharmacol. 2017 Mar;44:61-71. PMID: 28088065

Wang DM, Wang GC, Yang J, et al. Inhibition of the growth of human melanoma cells by methionine enkephalin. Mol Med Rep. 2016 Dec;14(6):5521-5527. PMID: 27878237

Kim JY, Ahn HJ, Kim JK, et al. Morphine Suppresses Lung Cancer Cell Proliferation Through the Interaction with Opioid Growth Factor Receptor: An In Vitro and Human Lung Tissue Study. Anesth Analg. 2016 Dec;123(6):1429-1436. PMID: 27167686

Xu X, Gao Y, Wen L, et al. Methionine enkephalin regulates microglia polarization and function. Int Immunopharmacol. 2016 Nov;40:90-97. PMID: 27584058

Zhao D, Plotnikoff N, Griffin N, et al. Methionine enkephalin, its role in immunoregulation and cancer therapy. Int Immunopharmacol. 2016 Aug;37:59-64. PMID: 26927200

Janku F, Johnson LK, Karp DD, et al. Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer. Ann Oncol. 2016 Nov;27(11):2032-2038. PMID: 27573565

Melander O, Orho-Melander M, Manjer J, et al. Stable Peptide of the Endogenous Opioid Enkephalin Precursor and Breast Cancer Risk. J Clin Oncol. 2015 Aug 20;33(24):2632-8. PMID: 26169618

Li X, Meng Y, Plotnikoff NP, et al. Methionine enkephalin (MENK) inhibits tumor growth through regulating CD4+Foxp3+ regulatory T cells (Tregs) in mice. Cancer Biol Ther. 2015;16(3):450-9. PMID: 25701137

Wang Q, Gao X, Yuan Z, et al. Methionine enkephalin (MENK) improves lymphocyte subpopulations in human peripheral blood of 50 cancer patients by inhibiting regulatory T cells (Tregs). Hum Vaccin Immunother. 2014;10(7):1836-40. PMID: 25424790

Li W, Chen W, Herberman RB, et al. Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine enkephalin (MENK). Cancer Lett. 2014 Mar 28;344(2):212-22. PMID: 24291668

Zagon IS, McLaughlin PJ. Opioid growth factor and the treatment of human pancreatic cancer: a review. World J Gastroenterol. 2014 Mar 7;20(9):2218-23. PMID: 24605021

Zagon IS, Porterfield NK, McLaughlin PJ. Opioid growth factor - opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer. Exp Biol Med (Maywood). 2013 Jun;238(6):589-99. PMID: 23918871

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

Liu J, Chen W, Meng J, et al. Induction on differentiation and modulation of bone marrow progenitor of dendritic cell by methionine enkephalin (MENK). Cancer Immunol Immunother. 2012 Oct;61(10):1699-711. PMID: 22392190

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

Donahue RN, McLaughlin PJ, Zagon IS. Under-expression of the opioid growth factor receptor promotes progression of human ovarian cancer. Exp Biol Med (Maywood). 2012 Feb;237(2):167-77. PMID: pubmed/22328595

Fanning J, Hossler CA, Kesterson J, et al. Expression of the opioid growth factor-opioid growth factor receptor axis in human ovarian cancer. Gynecol Oncol. 2012 Feb;124(2):319-24. PMID: 22037317

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

Shan F, Xia Y, Wang N, et al. Functional modulation of the pathway between dendritic cells (DCs) and CD4+T cells by the neuropeptide: methionine enkephalin (MENK). Peptides. 2011 May;32(5):929-37. PMID: 21335041

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

Lissoni P, Meregalli S, Fossati V, et al. Radioendocrine therapy of brain tumors with the long acting opioid antagonist naltrexone in association with radiotherapy. Tumori. 1993 Jun 30;79(3):198-201. PMID: 8236504

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

Satoh M, Nakamura M, Akatsu T, et al. Toll-like receptor 4 is expressed with enteroviral replication in myocardium from patients with dilated cardiomyopathy. PMID: 14688801

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

Ludwig MD, Zagon IS, McLaughlin PJ. Elevated serum [Met5]-enkephalin levels correlate with improved clinical and behavioral outcomes in experimental autoimmune encephalomyelitis. Brain Res Bull. 2017 Sep;134:1-9. PMID: 28647454

Hammer LA, Zagon IS, McLaughlin PJ. Improved clinical behavior of established relapsing-remitting experimental autoimmune encephalomyelitis following treatment with endogenous opioids: implications for the treatment of multiple sclerosis. Brain Res Bull. 2015 Mar;112:42-51. PMID:

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. 2014 Nov;96(5):895-905. PMID: 25015957

Hammer LA, Zagon IS, McLaughlin PJ. Treatment of a relapse-remitting model of multiple sclerosis with opioid growth factor. Brain Res Bull. 2013 Sep;98:122-31. PMID: 23973432

Campbell AM, Zagon IS, McLaughlin PJ. Astrocyte proliferation is regulated by the OGF-OGFr axis in vitro and in experimental autoimmune encephalomyelitis. Brain Res Bull. 2013 Jan;90:43-51. PMID: 22985690

Campbell AM, Zagon IS, McLaughlin PJ. Opioid growth factor arrests the progression of clinical disease and spinal cord pathology in established experimental autoimmune encephalomyelitis. Brain Res. 2012 Sep 7;1472:138-48. PMID: 22820301

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

Turel AP, Rahn K, McLaughlin PJ, et al. Methionine Enkephalin Prevents and Reverses Clinical Disease of EAE in Mice: Implications for a Biologic Approach to Treating Multiple Sclerosis, The 2nd World Congress on Controversies in Neurology (CONy). Athens, Greece. 23th-26th October 2008.

McLaughlin PJ, Rahn KA, Bonneau RH, et al. Complete Blockade of Opioid Receptors Exacerbates EAE in Mice. World Congress on Treatment and Research in Multiple Sclerosis. Montreal, Canada. 17th-20th September 2008.

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

Buchanan MM, Hutchinson M, Watkins LR, et al. Toll-like receptor 4 in CNS pathologies. J Neurochem. 2010 Jul;114(1):13-27. PMID: 20402965

Chakass D, Philippe D, Erdual E, et al. mu-Opioid receptor activation prevents acute hepatic inflammation and cell death. Gut. 2007 Jul;56(7):974-81. PMID: 17299060

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

Puente J, Maturana P, Miranda D, et al. Enhancement of human natural killer cell activity by opioid peptides: similar response to methionine-enkephalin and beta-endorphin. Brain Behav Immun. 1992 Mar;6(1):32-9. PMID: 1571602

Bhargava HN. Opioid peptides, receptors, and immune function. NIDA Res Monogr. 1990;96:220-33. PMID: 2172824

Lin J. [Effects of the enkephalins on natural killer cytotoxicity]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1990 Dec;12(6):457-60. PMID: 2151267

Maestroni GJ, Conti A. Beta-endorphin and dynorphin mimic the circadian immunoenhancing and anti-stress effects of melatonin. Int J Immunopharmacol. 1989;11(4):333-40. PMID: 2570759

Oleson DR, Johnson DR. Regulation of human natural cytotoxicity by enkephalins and selective opiate agonists. Brain Behav Immun. 1988 Sep;2(3):171-86. PMID: 2907409

Faith RE, Liang HJ, Plotnikoff NP, et al. Neuroimmunomodulation with enkephalins: in vitro enhancement of natural killer cell activity in peripheral blood lymphocytes from cancer patients. Nat Immun Cell Growth Regul. 1987;6(2):88-98. PMID: 3600678

Wybran J, Schandene L, Van Vooren JP, et al. Immunologic properties of methionine-enkephalin, and therapeutic implications in AIDS, ARC, and cancer. Ann N Y Acad Sci. 1987;496:108-14. PMID: 3496822

Faith RE, Murgo AJ, Clinkscales CW, et al. Enhancement of host resistance to viral and tumor challenge by treatment with methionine-enkephalin. Ann N Y Acad Sci. 1987;496:137-45. PMID: 3474965

Sharp BM, Tsukayama DT, Gekker G, et al. Beta-endorphin stimulates human polymorphonuclear leukocyte superoxide production via a stereoselective opiate receptor. J Pharmacol Exp Ther. 1987 Aug;242(2):579-82. PMID: 3039121

Brown SL, Van Epps DE. Opioid peptides modulate production of interferon gamma by human mononuclear cells. Cell Immunol. 1986 Nov;103(1):19-26. PMID: 3026654

Wybran J. Enkephalins and endorphins: activation molecules for the immune system and natural killer activity? Neuropeptides. 1985 Feb;5(4-6):371-4. PMID: 2987737

Plotnikoff NP, Murgo AJ, Miller GC. Enkephalins: immunomodulators. Fed Proc. 1985 Jan;44(1 Pt 1):118-22. PMID: 3967769

Wybran J. Enkephalins and endorphins as modifiers of the immune system: present and future. Fed Proc. 1985 Jan;44(1 Pt 1):92-4. PMID: 2981735

Faith RE, Liang HJ, Murgo AJ, et al. Neuroimmunomodulation with enkephalins: enhancement of human natural killer (NK) cell activity in vitro. Clin Immunol Immunopathol. 1984 Jun;31(3):412-8. PMID: 6713744

Wound healing

McLaughlin PJ, Pothering CA, Immonen JA, et al. Topical treatment with the opioid antagonist naltrexone facilitates closure of full-thickness wounds in diabetic rats. Exp Biol Med (Maywood). 2011 Oct 1;236(10):1122-32. PMID: 21917593

Bigliardi PL, Sumanovski LT, Buchner S, et al. Different expression of mu-opiate receptor in chronic and acute wounds and the effect of beta-endorphin on transforming growth factor beta type II receptor and cytokeratin 16 expression. J Invest Dermatol. 2003 Jan;120(1):145-52. PMID: 12535211

Zagon IS, Verderame MF, Allen SS. Cloning, sequencing, expression and function of a cDNA encoding a receptor for the opioid growth factor, [Met(5)]enkephalin. Brain Res. 1999 Dec 4;849(1-2):147-54. PMID: 10592296


Cai Z, Ratka A. Opioid system and Alzheimer's disease. Neuromolecular Med. 2012 Jun;14(2):91-111. PMID: 22527793

Sun YM, Hoang T, Neubauer JA, et al. Opioids protect against substantia nigra cell degeneration under conditions of iron deprivation: a mechanism of possible relevance to the Restless Legs Syndrome (RLS) and Parkinson's disease. J Neurol Sci. 2011 May 15;304(1-2):93-101. PMID: 21376342

Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007 Jan;8(1):57-69. PMID: 17180163

Zhang W, Hong JS, Kim HC, et al. Morphinan neuroprotection: new insight into the therapy of neurodegeneration. Crit Rev Neurobiol. 2004;16(4):271-302. PMID: 15862109

Lin X, Xue LY, Wang R, et al. Protective effects of endomorphins, endogenous opioid peptides in the brain, on human low density lipoprotein oxidation. FEBS J. 2006 Mar;273(6):1275-84. PMID: 16519691

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

Liu B, Jiang JW, Wilson BC, et al. Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther. 2000 Oct;295(1):125-32. PMID: 10991969

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

Hill MP, Hille CJ, Brotchie JM. Delta-opioid receptor agonists as a therapeutic approach in Parkinson's disease. Drug News Perspect. 2000 Jun;13(5):261-8. PMID: 12937640

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

Chang RC, Rota C, Glover RE, et al. A novel effect of an opioid receptor antagonist, naloxone, on the production of reactive oxygen species by microglia: a study by electron paramagnetic resonance spectroscopy. Brain Res. 2000 Jan 31;854(1-2):224-9. PMID: 10784126

Nappi G, Petraglia F, Martignoni E, et al. beta-Endorphin cerebrospinal fluid decrease in untreated parkinsonian patients. Neurology. 1985 Sep;35(9):1371-4. PMID: 2991818

Sandyk R, Gillman MA. Opioid hypofunction in Parkinson's disease. Med Hypotheses. 1985 Feb;16(2):179-82. PMID: 2581117


Zangen A, Nakash R, Roth-Deri I, et al. Impaired release of beta-endorphin in response to serotonin in a rat model of depression. Neuroscience. 2002;110(3):389-93. PMID: 11906780

Bernstein HG, Krell D, Emrich HM, et al. Fewer beta-endorphin expressing arcuate nucleus neurons and reduced beta-endorphinergic innervation of paraventricular neurons in schizophrenics and patients with depression. Cell Mol Biol (Noisy-le-grand). 2002;48 Online Pub:OL259-65. PMID: 12643442

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