A reader asked me to assemble information from studies on Low Dosage Naltrexone. For conditions like Fibromyalgia, we have 49 studies with good or no effects.  I speculate that the effectiveness is dependent upon the microbiome prior to starting.

A lot of the published literature are case-reports (i.e. on individuals). My general impression from larger studies is that it is a 50-50 toss of the coin if improvement will happen. There is an absence of literature on its impact on different bacteria in the microbiome.

• Efficacy and Safety of Low Dose Naltrexone for Chronic Pain [2024]
  • “Seven (23%) reported side effects. LDN was associated with a statistically significant reduction in PEG in adult chronic pain patients, however the clinical significance is unclear as over 75% of patients discontinued LDN due to lack of benefit.”
• Low-Dose Naltrexone Improves post-COVID-19 condition Symptoms [2024]
  • “The relative hazard of improvement for those taking low-dose naltrexone was 5.04 (95% CI, 1.22-20.77; P = 0.02) compared with physical therapy alone. Both fatigue and pain were improved in patients taking low-dose naltrexone”
• Low-dose naltrexone use for the management of post-acute sequelae of COVID-19 [2023]
  • “The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status.”
• A systematic literature review on the clinical efficacy of low dose naltrexone and its effect on putative pathophysiological mechanisms among patients diagnosed with fibromyalgia [2023]
  • “One study reported baseline erythrocyte sedimentation rate (ESR) predicted LDN response (≥30% reduction in fibromyalgia symptoms) and a second study showed plasma concentrations of inflammatory biomarkers were lower after LDN treatment.”
• Complex Presentations, Identification and Treatment of Mast Cell Activation Syndrome and Associated Conditions: A Case Report [2023]
  • “The patient was ultimately deemed to have other associated conditions including a mast cell-mediated disorder as well as joint hypermobility due to her response to antihistamine and mast cell stabilizing agents. Final outcomes include immense improvement upon mast cell stabilization with ketotifen, and remission of SIBO with low-dose naltrexone (LDN).”
• Low-dose naltrexone as a treatment for chronic fatigue syndrome [2020] – Three(3) Case Reports
  • “it was clear she was stable and well, and could walk, and more recently, cycle, without problems. Prior to starting LDN, her intellectual and cognitive functioning was very limited. “
  • “She no longer requires acupuncture for symptomatic pain relief. However, her functional level did not improve with LDN. also continues with other symptoms of myalgic encephalomyelitis including postexertional neuroimmune exhaustion, periodic muscle weakness, orthostatic intolerance, symptomatic sinus tachycardia, urticarial rashes and susceptibility to bacterial infections”
  • “His functional level improved from being mild–moderately limited on a daily basis (60%–70% on a functional activity scale) to mild limitations (80%–90% on a functional activity scale). “
• Repurposing low-dose naltrexone for the prevention and treatment of immunothrombosis in COVID-19 [2022] “we hypothesize that the immune-modulating and known pharmacologic properties of LDN could be leveraged as a novel therapeutic strategy in COVID-19.”
• Low-dose Naltrexone Therapy for Psoriasis [2020]
  • Three adverse events included insomnia, diarrhea, and self-limited headache. Marked improvement was seen by 53% of the 15 patients. Low-dose naltrexone regulates lymphocyte responses, reduces cytokine production, and likely reduces mast cell activity.
• Low Dose Naltrexone in Dermatology [2019]
• Pharmacology Update: Low-Dose Naltrexone as a Possible Nonopioid Modality for Some Chronic, Nonmalignant Pain Syndromes [2019]
  • “When used in doses of 1 to 5 mg it acts as a glial modulator with a neuroprotective effect via inhibition of microglial activation. It binds to Toll-like receptor 4 and acts as an antagonist, therefore inhibiting the downstream cellular signaling pathways that ultimately lead to pro-inflammatory cytokines, therefore reducing inflammatory response. Low-dose naltrexone (LDN) may also have utility in improving mood disorders and the potential to enhance the quality of life”
• 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 [2018]
  • “Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn’s disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited.”
• Low dose naltrexone for induction of remission in Crohn’s disease [2018]
  • “The results of the study in adult patients suggest that low dose naltrexone may provide a benefit in terms of clinical response (i.e. an improvement in disease symptoms) and endoscopic response (i.e. a reduction in inflammation of the gut as shown by examining the gut with a scope)”
• Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment [2018]
• The Effect of Low-Dose Naltrexone on Medication in Inflammatory Bowel Disease: A Quasi Experimental Before-and-After Prescription Database Study [2018]