Functional modulation on macrophage by low dose naltrexone (LDN)

Zhou, Yi; Guo, Shengnan; Hu, Xu; Wang, Xiaonan; Zhang, Xiaoqing; Griffin, Noreen; Shan, Fengping

doi:10.1016/j.intimp.2016.08.015

Cited by 23 publications

(15 citation statements)

References 19 publications

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“…2 The primary effect of low-dose naltrexone results from a rebound increase in endogenous opioids and the downstream processes that those endorphins stimulate. 2,5,[12][13][14] In addition, high-dose naltrexone reduces immune cell function and chemotaxis by dampening immune cell ability to sensitize T cells and macrophages to other proinflammatory stimuli, such as interleukin 12, tumor necrosis factor, and nitrous oxide. 1 Naltrexone is not approved for the treatment of any primary skin disorder; however, research on animal models provides evidence that the medication may have several benefits on various aspects of skin disease.…”

Section: Naltrexone Mechanisms Of Actionmentioning

confidence: 99%

Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions

et al. 2019

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IMPORTANCEDermatology is encountering increasing rates of autoimmune disease manifesting in primary skin conditions that are difficult to treat without a risk of immunosuppression. Naltrexone is an orally active opioid antagonist that influences a variety of systemic pathways, including the immune system, in low doses of 1.5 to 4.0 mg/d. This phenomenon has piqued the interest of researchers and practitioners in regard to low-dose naltrexone's potential in the treatment of several autoimmune conditions. OBJECTIVE To review the existing literature on naltrexone treatment for dermatologic conditions.EVIDENCE REVIEW A primary literature search was conducted using PubMed in April 2018 for all articles published from 1971 to April 2018. Search terms consisted of naltrexone or low dose naltrexone or low-dose naltrexone and dermatology or skin or hair or nails. Reviews, animal studies, and nondermatologic and pharmacologic studies were excluded.FINDINGS From 1037 articles, 22 were deemed to be appropriate for inclusion in this review for a qualitative synthesis. The 22 articles included randomized clinical trials, case reports, and series. There were 7 articles on low-dose naltexone, 1 on topical naltrexone, and 14 on high-dose naltrexone use in dermatology. In high, low, and topical doses, naltrexone was effective in treating pruritus attributable to atopic dermatitis, prurigo nodularis, cholestatsis, burn injury, systemic sclerosis, Hailey-Hailey disease, and lichen planopilaris. High-dose naltrexone was ineffective in treating flushing and uremic pruritus most likely because of the lack of opioid involvement in the pathophysiologic mechanisms of these conditions. CONCLUSIONS AND RELEVANCEThe findings suggest that low-dose naltrexone is safe and effective in the treatment of Hailey-Hailey disease and lichen planopilaris and both low-and high-dose naltrexone successfully treat pruritus attributable to various pathologic conditions; however, more adverse effects occurred in those taking high doses. Low-dose naltrexone has the potential for the treatment of chronic inflammatory skin conditions; however, additional evidence is needed for dosing and long-term treatment guidelines.

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Section: Naltrexone Mechanisms Of Actionmentioning

confidence: 99%

Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions

et al. 2019

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“…Following experimental findings that low doses of naltrexone result in tumour growth suppression [14] and immune modulation [15], it is increasingly used at doses of around 4.5 mg. This is known as low dose naltrexone (LDN).…”

Section: Introductionmentioning

confidence: 99%

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis

Bolton

Hodkinson²,

Boda

et al. 2019

BMC Med

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BackgroundNaltrexone is an opioid antagonist used in many different conditions, both licensed and unlicensed. It is used at widely varying doses from 3 to 250 mg. The aim of this review was to extensively evaluate the safety of oral naltrexone by examining the risk of serious adverse events and adverse events in randomised controlled trials of naltrexone compared to placebo.MethodsA systematic search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, other databases and clinical trials registries was undertaken up to May 2018. Parallel placebo-controlled randomised controlled trials longer than 4 weeks published after 1 January 2001 of oral naltrexone at any dose were selected. Any condition or age group was included, excluding only studies in opioid or ex-opioid users owing to possible opioid/opioid antagonist interactions. The systematic review used the guidance of the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-analyses harms checklist throughout. Numerical data were independently extracted by two people and cross-checked. Risk of bias was assessed with the Cochrane risk-of-bias tool. Meta-analyses were performed in R using random effects models throughout.ResultsEighty-nine randomised controlled trials with 11,194 participants were found, studying alcohol use disorders (n = 38), various psychiatric disorders (n = 13), impulse control disorders (n = 9), other addictions including smoking (n = 18), obesity or eating disorders (n = 6), Crohn’s disease (n = 2), fibromyalgia (n = 1) and cancers (n = 2). Twenty-six studies (4,960 participants) recorded serious adverse events occurring by arm of study. There was no evidence of increased risk of serious adverse events for naltrexone compared to placebo (risk ratio 0.84, 95% confidence interval 0.66–1.06). Sensitivity analyses pooling risk differences supported this conclusion (risk difference −0.01, 95% confidence interval −0.02–0.00) and subgroup analyses showed that results were consistent across different doses and disease groups. Secondary analysis revealed only six marginally significant adverse events for naltrexone compared to placebo, which were of mild severity.ConclusionsNaltrexone does not appear to increase the risk of serious adverse events over placebo. These findings confirm the safety of oral naltrexone when used in licensed indications and encourage investments to undertake efficacy studies in unlicensed indications.Trial registrationPROSPERO 2017 CRD42017054421.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1242-0) contains supplementary material, which is available to authorized users.

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“…Naltrexone hydrochloride is an opioid antagonist that inhibits MOR and DOR [35,36]. Yi et al [37] demonstrated that low-dose naltrexone (LDN) increases the expression of opioid receptors. LDN can significantly increase CD64 expression and decrease CD206 expression.…”

Section: Opioids and Immune Systemmentioning

confidence: 99%

“…LDN can significantly increase CD64 expression and decrease CD206 expression. As a result of activation, macrophages release higher amounts of IL-12, TNF-α, IL-6 and IL-1β and reduced IL-10 levels, leading to inflammation or cell death [37].…”

Section: Opioids and Immune Systemmentioning

confidence: 99%

Opioids in Cancer Development, Progression and Metastasis: Focus on Colorectal Cancer

Szczepaniak

Fichna

Zielińska

2020

Curr. Treat. Options in Oncol.

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Colorectal cancer I Endogenous opioid system I Opioid receptors I Opioids I Opium Abbreviations COX-2 cyclooxygenase-2. _ CRC colorectal cancer. _ DCs dendritic cells. _ DEN diethylnitrosamine. _ GPCR Gprotein-coupled receptors. _ IBD inflammatory bowel disease. _ IL-1β interleukin 1β. _ IL-6 interleukin 6. _ MMT methadone maintenance treatment. _ MOR mu opioid receptor. _ n-Cdh n-cadherin. _ NK natural killer cell. _ Nx propofol with epidural anesthesia. _ PGE2 prostaglandin E2. _ TJ tight junction. _ TLR toll-like receptor. _ TNFα tumor necrosis factor α. _ TPA 2-o-tetradecanoyl-phorbol-13-acetate. _ uPA urokinase plasminogen activator. _ ZO zonulaoccludens. Opinion statement So far, opioids have been successfully used to reduce cancer pain in patients in order to improve their quality of life. However, the use of opioids leads to numerous side effects such as constipation, drowsiness, nausea, itching, increased sweating and hormonal changes. In this review, we described the action of opioids in several molecular pathways significant for maintenance of the intestinal homeostasis including the impact on the intestinal epithelium integrity, changes in microbiome composition, modulation of the immune system or induction of apoptosis and inhibition of angiogenesis. We summed up the role of individual opioids in the processes involved in the growth and development of cancer and elucidated if targeting opioid receptors may constitute novel therapeutic option in colon cancer.

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Functional modulation on macrophage by low dose naltrexone (LDN)

Cited by 23 publications

References 19 publications

Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions

Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis

Opioids in Cancer Development, Progression and Metastasis: Focus on Colorectal Cancer

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