Plain Language Summary: Naltrexone Utilization Along Its Dosing Spectrum- A Literature Review

✎ Dr. Ebony King, PharmD, RPh

ORCiD: 0009-0002-6190-3935

Original Article: https://www.scriptumpharm.org/1-2f

Abstract

Naltrexone, a widely recognized opioid receptor antagonist, has been primarily used at standard doses of 50–100 mg daily to treat opioid and alcohol use disorders. Recent studies, however, reveal its versatility across a broader dosing spectrum. This review examines the therapeutic effects and safety profiles of naltrexone across three dosing strategies: standard doses for substance use disorders, low-dose naltrexone (LDN, 1–5 mg/day) for chronic pain and  autoimmune diseases, and ultra-low-dose naltrexone (ULDN, microgram levels) as a  complement to opioid therapy. However, naltrexone’s role in reducing opioid misuse among those with a history of dependency remains limited. Our results serve to highlight naltrexone’s expanding clinical applications and highlights the need for further research to optimize its use across diverse dosing regimens and conditions. 

Plain Language Summary:

Naltrexone is like a talented actor, able to step into completely different roles depending on what the script calls for. Put it in the spotlight, and it takes command. Shift it into a supporting role, and it still brings exactly what the scene calls for. What makes it so versatile is not the drug itself, but how much of it you use. 

In its most familiar role, naltrexone helps individuals on the path to stopping opioids or alcohol. At its full strength, it helps by blocking the parts of the brain that usually respond to these substances with a rush of reward. Without that chemical reinforcement, the desire to use begins to fade. It is like turning off the sound during a dramatic scene. The moment still happens, but it no longer holds the same pull. 

But when the dose is turned down, naltrexone begins to behave differently. At lower doses, it may help individuals with conditions like fibromyalgia, Crohn’s disease, or multiple sclerosis by calming an overactive immune system. In these conditions, the body often stays on high alert , sending out pain and inflammation signals long after any real threat has passed. Low-dose naltrexone, or LDN, helps quiet that response. It works more like a gentle reset, giving the body a chance to find balance without causing sedation or long-term side effects.

At ultra-low doses, where amounts are measured in micrograms, naltrexone plays a different role entirely. When used alongside opioid medications for pain, ultra-low-dose naltrexone (ULDN) may help those medications work more effectively and last longer. Many patients may be able to take lower doses of their opioid medication while still experiencing meaningful pain relief. This could also lead to fewer common side effects, like drowsiness, constipation and a reduced need for increasing doses over time. ULDN operates seamlessly behind the scenes, ensuring everything runs smoothly without drawing attention to itself. 

What is remarkable is that this is all the same medication, adapting its actions based on the amount used. Naltrexone can block cravings, restore balance, or support safer pain care, all depending on the dose. 

These lower-dose versions are not yet available at most pharmacies, but compounding pharmacies can prepare them when prescribed. Ongoing research continues to uncover how this approach can help more people across different health conditions. 

Naltrexone reminds us that healing is not always about doing more. Sometimes, the best results come from doing just enough, in the right way, at the right time.

Reference

1. Gray C, Gabriel K, Gorman J. Naltrexone utilization along its dosing spectrum: a literature review. J Scrip Pharm. Published online October 1, 2024. doi:10.70390/G6MR