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Published Studies

Low-Dose Naltrexone (LDN): Human Clinical Research Overview

More than 60 published human studies have evaluated low-dose naltrexone (LDN) across a wide range of immune-mediated, inflammatory, pain, dermatologic, neurologic, and systemic conditions.
This directory summarizes key areas of investigation and links to the original research.

This page is based primarily on a 2025 scoping review that identified 68 human studies published over the past 15 years, the majority of which reported at least some clinical benefit in at least a subset of patients

 

Chronic Pain & Central Sensitization

Conditions studied

  • Chronic pain syndromes
  • Neuropathic pain
  • Centralized pain
  • Opioid-refractory pain

Representative findings

  • Multiple observational studies and retrospective analyses report meaningful pain reduction in a majority of patients.
  • Neuropathic pain conditions appear more responsive than purely nociceptive pain.

Example studies

  • Efficacy of Low-Dose Naltrexone in Chronic Pain (Irwin et al.)
  • Therapeutic Value of Naltrexone as a Glial Modulator (Vrooman et al.)

Fibromyalgia

Study volume: 8 human studies

What the literature shows

  • Mixed results in randomized trials
  • Subsets of patients demonstrate clinically meaningful reductions in pain, fatigue, and brain fog
  • Dose-response and titration strategies appear important

Example studies

  • Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone (Younger et al.)
  • Dose-Response Relationships of LDN in Fibromyalgia (Bruun-Plesner et al.)

Autoimmune & Inflammatory Bowel Disease

Conditions studied

  • Crohn’s disease
  • Ulcerative colitis
  • Inflammatory bowel disease (IBD)

Key findings

  • Several trials and case series report reduced disease activity, improved symptoms, and decreased reliance on other medications
  • Pediatric and adult populations studied

Example studies

  • Low-Dose Naltrexone for Induction of Remission in IBD (Lie et al.)
  • Safety and Tolerability of LDN in Pediatric Crohn’s Disease (Smith et al.)

Neurologic & Neuroimmune Conditions

Conditions studied

  • Multiple sclerosis
  • Complex regional pain syndrome (CRPS)
  • Painful diabetic neuropathy
  • Stiff-person syndrome
  • Neuropathic corneal pain

What stands out

  • Improvements in quality of life and symptom burden in select populations
  • Favorable safety profile compared with conventional therapies

Example studies

  • Pilot Trial of LDN in Multiple Sclerosis (Cree et al.)
  • LDN vs Amitriptyline in Painful Diabetic Neuropathy (Srinivasan et al.)

Dermatologic Conditions

Conditions studied

  • Hailey-Hailey disease
  • Psoriasis
  • Darier disease
  • Lichen planopilaris
  • Prurigo and excoriation disorders

Notable findings

  • Some of the strongest and most consistent case-level responses in the literature
  • Reports of lesion clearance, reduced inflammation, and improved quality of life

Example studies

  • Treatment of Hailey-Hailey Disease with LDN (Albers et al.)
  • LDN Therapy for Psoriasis (Weinstock et al.)

Post-Viral Syndromes & Fatigue

Conditions studied

  • Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS)
  • Post-acute sequelae of COVID-19 (Long COVID)

Key findings

  • Improvements in fatigue, sleep, cognitive function, and overall functional status in some patients
  • Ongoing clinical trials underway

Example studies

  • LDN Use for Post-Acute Sequelae of COVID-19 (Bonilla et al.)
  • LDN in Chronic Fatigue Syndrome (Bolton et al.)

Psychiatric & Neurobehavioral Conditions

Conditions studied

  • Major depressive disorder (adjunctive)
  • Excoriation (skin-picking) disorder

Findings

  • Early evidence suggests potential benefit in select cases
  • Further controlled trials needed

Important Context & Limitations

  • LDN use in these studies is off-label
  • Study quality varies (case reports → randomized trials)
  • Not all studies show benefit
  • Optimal dosing and patient selection remain active areas of research

Despite these limitations, the breadth and consistency of investigation across immune, inflammatory, and neuroimmune conditions has driven continued clinical interest.

Suggested footer disclaimer (important legally)

This page is for educational purposes only and summarizes published research. It does not constitute medical advice or guarantee clinical outcomes. Individual responses to LDN vary.