Treatment Options

How Long Does Low Dose Naltrexone Stay in Your System: Understanding Its Effects, Benefits, and Duration in the Body

January 22, 2026

Low Dose Naltrexone (LDN) has gained widespread attention for its unique ability to regulate the immune system, reduce inflammation, and help manage chronic pain, autoimmune diseases, and certain mental health conditions. Originally developed to treat opioid and alcohol dependence at standard doses of 50 milligrams, naltrexone in low doses—typically between 1.5 and 4.5 milligrams—works differently in the body, offering therapeutic benefits beyond addiction treatment. A common question patients ask before starting treatment is how long does low dose naltrexone stay in your system and what that means for dosing, side effects, and overall results. Understanding how LDN works, how it’s metabolized, and how long it remains active can help patients and healthcare providers tailor treatment for maximum effectiveness and safety.

What Is Low Dose Naltrexone (LDN)?

Naltrexone is an opioid receptor antagonist, meaning it blocks the effects of opioids in the brain. In standard doses, it’s used to help people recovering from opioid or alcohol dependence by preventing the euphoric effects of those substances. At low doses, however, naltrexone behaves differently. Instead of continuously blocking opioid receptors, LDN briefly inhibits them, which triggers a rebound effect that increases the body’s production of endorphins and enkephalins—natural chemicals that reduce pain, enhance mood, and regulate the immune system.

This temporary receptor blockade is what makes LDN useful for conditions beyond addiction. It’s often prescribed for:
• Autoimmune diseases such as multiple sclerosis, lupus, and rheumatoid arthritis.
• Chronic pain conditions like fibromyalgia and neuropathy.
• Inflammatory bowel diseases including Crohn’s disease and ulcerative colitis.
• Thyroid disorders, particularly Hashimoto’s thyroiditis.
• Mental health conditions such as depression and anxiety related to inflammation.

Because of its broad range of potential benefits, LDN is considered a promising therapy for people who have not found relief from conventional treatments.

How Low Dose Naltrexone Works in the Body

At low doses, naltrexone temporarily blocks the body’s opioid receptors for a few hours. This short-term interruption stimulates the brain and immune system to increase natural endorphin production. Endorphins not only reduce pain and improve mood but also regulate immune responses and reduce inflammation throughout the body.

This mechanism makes LDN particularly useful for chronic illnesses involving immune dysfunction or inflammatory processes. Unlike standard pain medications or immunosuppressants, LDN works by supporting the body’s own regulatory systems rather than shutting them down.

How Long Does Low Dose Naltrexone Stay in Your System?

The answer to how long does low dose naltrexone stay in your system depends on several factors, including dosage, metabolism, and individual health status. The drug’s half-life—the time it takes for half of the medication to leave the bloodstream—is approximately 4 to 6 hours. However, the physiological effects of LDN last much longer, often extending for 18 to 24 hours after a single dose.

Even though the medication itself clears from the bloodstream within about a day, the boost in endorphin production it triggers can persist for 24 to 36 hours. This means that while the chemical presence of LDN is short-lived, its biological impact continues well beyond the time it’s physically in your system.

Pharmacokinetics of Low Dose Naltrexone

To understand how long it stays active, it helps to look at how LDN moves through the body:

Absorption: LDN is rapidly absorbed after oral ingestion, reaching peak blood levels within 1 to 2 hours.
Distribution: It’s distributed throughout body tissues, particularly in the liver and brain, where it binds to opioid receptors.
Metabolism: The liver metabolizes naltrexone primarily into an active metabolite called 6-beta-naltrexol, which contributes to its overall effects.
Elimination: Both naltrexone and its metabolites are excreted mainly through urine, with smaller amounts passing through feces.

Because of this quick metabolism and excretion, most of the drug is cleared from the body within 24 hours. However, some people with slower liver function or higher body fat percentages may retain small traces slightly longer.

How Long the Effects Last

Although the medication’s presence in the body is brief, the biological changes it triggers persist much longer. The increased endorphin and enkephalin levels last for approximately one full day after each dose, which is why LDN is typically prescribed once daily, usually at bedtime. The nighttime dosing schedule allows endorphin production to peak in the early morning hours when the body naturally produces these compounds.

Patients who take LDN often report improvements in pain, fatigue, and mood within 2 to 6 weeks of consistent use, although some conditions may take several months to show significant progress.

Does LDN Build Up in the System?

Unlike many medications, LDN does not accumulate in the body over time. Its short half-life and rapid elimination prevent buildup. That said, the effects of regular dosing can compound over time, as endorphin levels stabilize and inflammation gradually decreases. This is one reason patients are encouraged to continue treatment consistently for several weeks before assessing results.

Factors That Affect How Long LDN Stays in Your System

Several factors influence how long LDN remains active in the body:
• Liver Function: Because the liver metabolizes naltrexone, people with impaired liver function may process it more slowly.
• Age and Metabolism: Younger patients with faster metabolic rates clear the medication more quickly.
• Dosage: Although doses are small (1.5–4.5 mg), slightly higher doses may take longer to metabolize.
• Body Composition: Individuals with higher body fat percentages may retain the medication a bit longer since naltrexone is lipid-soluble.
• Frequency of Use: Taking LDN daily leads to consistent endorphin regulation but doesn’t cause the drug itself to accumulate.

Common Side Effects and Duration

LDN is well-tolerated by most patients, but mild side effects can occur, especially during the first few days of treatment. These can include:
• Sleep disturbances or vivid dreams.
• Headaches.
• Digestive discomfort.
• Temporary fatigue or restlessness.

These side effects typically resolve within one to two weeks as the body adjusts to the medication. Because LDN leaves the body quickly, any unwanted effects usually subside within 24 hours after discontinuation.

Interactions and Precautions

LDN should not be taken with opioid pain medications (such as morphine, hydrocodone, or oxycodone) because it blocks their effects and can trigger sudden withdrawal. Patients must be opioid-free for at least 7 to 10 days before starting LDN. It’s also important to consult your healthcare provider before using LDN if you have liver disease, are pregnant, or are taking other prescription medications.

How to Take Low Dose Naltrexone Safely

LDN is typically compounded by a pharmacy because it’s not commercially available in low-dose form. It can come as a capsule, liquid, or tablet, with doses tailored to each patient’s needs. The most common dosing schedule is:
• 1.5 mg nightly for the first week.
• 3.0 mg nightly for the second week.
• 4.5 mg nightly as a maintenance dose thereafter.

Your provider may adjust this based on your response or condition. Because the effects of LDN last roughly 24 hours, consistent daily dosing ensures stable endorphin levels and maximum therapeutic benefits.

How Long It Takes for LDN to Leave the Body Completely

Most of the medication is eliminated within 24 hours after the last dose. However, complete clearance—including metabolites—typically occurs within 48 to 72 hours. If you need to stop LDN for surgery, opioid treatment, or another reason, your doctor will usually recommend waiting at least three days before starting opioid-based medications to prevent interference.

What Happens After You Stop Taking LDN

Because LDN doesn’t build up in the system, stopping it doesn’t cause withdrawal symptoms. However, the benefits it provides—such as pain relief and immune regulation—will gradually diminish as endorphin levels return to baseline. Some patients notice increased fatigue, pain, or inflammation within a few days of discontinuing LDN. For this reason, many doctors recommend tapering off slowly rather than stopping abruptly.

The Long-Term Benefits of LDN

Although its physical presence in the body is brief, LDN’s ability to recalibrate immune and neurological systems can have lasting positive effects. Long-term users often report:
• Reduced pain and inflammation.
• Improved mood and mental clarity.
• Better sleep quality.
• Fewer flare-ups of autoimmune symptoms.
• Enhanced overall quality of life.

Unlike opioids or steroids, LDN does not cause dependency or suppression of natural body functions. It promotes balance rather than replacement.

Actionable Takeaways

• The answer to how long does low dose naltrexone stay in your system is about 24 hours, though its effects last longer due to endorphin stimulation.
• LDN’s half-life is 4–6 hours, and it’s fully cleared from the body within 48–72 hours.
• The medication’s therapeutic benefits can persist for a day or more after dosing.
• Daily use maintains steady endorphin levels and maximizes results.
• LDN does not accumulate in the system or cause dependency.
• Side effects are generally mild and temporary, resolving as the body adjusts.

Conclusion

So, how long does low dose naltrexone stay in your system? The medication itself typically clears within one day, but its positive biological effects—like increased endorphins and reduced inflammation—can last for up to 24 hours or more. This is why most people take LDN once daily, often at night, to maintain consistent benefits. While short-acting in the bloodstream, its influence on the immune and nervous systems can lead to long-term improvements in pain, mood, and overall well-being. If you’re considering low dose naltrexone therapy, consult a healthcare provider who understands LDN’s unique mechanisms. With proper dosing and guidance, this small daily medication can make a big difference in restoring balance and health naturally.