Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions: A Systematic Review

JAMA Dermatol. 2019 Feb 1;155(2):229-236. doi: 10.1001/jamadermatol.2018.4093.


Importance: Dermatology 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 relevance: The 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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Chronic Disease
  • Dermatitis / drug therapy
  • Dermatitis / immunology
  • Dermatitis / physiopathology
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Naltrexone / administration & dosage*
  • Narcotic Antagonists / administration & dosage
  • Patient Satisfaction / statistics & numerical data
  • Severity of Illness Index
  • Treatment Outcome
  • United States


  • Narcotic Antagonists
  • Naltrexone