What Are the Long-Term Side Effects of Low-Dose Naltrexone?

Low-dose naltrexone offers pain relief and immune support, but long-term use may carry side effects that require monitoring.

Low-dose naltrexone (LDN) has emerged as a promising therapy for chronic illnesses that traditional medications often fail to address. Originally approved at a higher dose for treating opioid addiction and alcohol use disorder, LDN therapy involves using a lower dose—typically 0.5 to 4.5 mg—to harness its anti-inflammatory effects and immune-modulating properties. As more patients turn to LDN treatment for conditions like chronic pain, chronic fatigue syndrome, and autoimmune disease, questions naturally arise about the potential long-term side effects. Here’s what you need to know before committing to LDN treatment for the long haul.

What is low-dose naltrexone?

Low-dose naltrexone is a compounded form of naltrexone, a drug originally developed for opioid dependence and medication-assisted treatment. At standard levels (50 mg), it blocks opioid receptors to prevent misuse of opioids or alcohol. At a low dose, however, the drug appears to briefly block these receptors, triggering a rebound effect that increases the production of endogenous opioids—your body’s natural painkillers. This response may help reduce inflammation, regulate immune function, and provide pain relief.

How does low-dose naltrexone work?

When taken in small amounts, low-dose naltrexone creates a temporary blockade of opioid receptors, prompting the body to produce more endorphins. This boost in endogenous opioids may help with pain management, mood regulation, and immune system modulation. Because of these effects, LDN therapy is increasingly used in functional medicine to address conditions like fibromyalgia, chronic pain conditions, autoimmune disorders, and even symptoms of opioid withdrawal in recovery settings.

What are the common short-term side effects of LDN?

Most people tolerate low-dose naltrexone treatment well, but like any medication, there are some common side effects during the adjustment phase. These may include:

• Sleep disturbances or vivid dreams
• Digestive discomfort (nausea, bloating)
• Headaches
• Mood fluctuations

These common side effects are typically mild and temporary, especially when LDN is sourced from a trusted compounding pharmacy and started at a lower dose.

What are the long-term side effects of low-dose naltrexone?

While anecdotal reports suggest that long-term use is generally safe, comprehensive clinical studies are still lacking. However, some potential long-term concerns include:

• Immune dysregulation: In rare cases, prolonged use may alter immune function in unpredictable ways.
• Hormonal fluctuations: Some report changes in thyroid or menstrual function, though findings are inconsistent.
• Sleep issues: Some users experience ongoing vivid dreams or disrupted rest over time.
• Liver function concerns: Though more common at a higher dose, liver enzymes may still be monitored as a precaution.

Because LDN treatment is off-label, ongoing research is needed to better understand the full range of adverse effects associated with extended use.

Long-term use: benefits vs. risks

When considering the long-term use of any treatment or intervention, it’s important to weigh the potential benefits against the possible risks—the same is true of LDN. On the positive side, long-term use of LDN can provide sustained pain relief without the risk of addiction, making it a valuable option for individuals managing a wide range of chronic pain conditions. Additionally, some treatments may offer added benefits, such as supporting mental and immune health, all while causing minimal sedation—an advantage for those seeking to maintain daily functioning. For those who haven’t found success with conventional pain medicine, LDN therapy offers a compelling alternative, but it must be part of a supervised treatment plan.

However, there are also drawbacks to consider. One major concern is the lack of large-scale data on prolonged use of LDN, which means that the full scope of long-term effects remains unclear. There is also the potential for unknown or delayed adverse effects that may not surface until after extended use. Finally, it’s worth noting that the treatment may not be effective for all types of pain or inflammation, limiting its usefulness for some individuals.

Who should use caution with long-term LDN?

While low-dose naltrexone is often well tolerated, certain people should proceed with extra care:

• Those with liver disease or elevated liver enzymes
• People undergoing medication-assisted treatment for opioid dependence
• Pregnant or breastfeeding individuals
• Anyone currently on immunosuppressive drugs

Consulting a licensed provider familiar with functional medicine and LDN treatment is essential for safety and efficacy.

Monitoring your response over time

Monitoring your response to treatment over time is essential for ensuring both safety and effectiveness. To catch any potential issues early, practitioners may recommend regular liver function tests every 6 to 12 months, as well as ongoing tracking of sleep patterns and mood. Keeping a symptom log can also be helpful in evaluating whether the treatment continues to provide relief. If signs of tolerance or side effects begin to emerge, adjustments to your regimen, such as transitioning from daily use to bi-weekly sessions or rotating your dosage, may help maintain benefits while minimizing long-term risks.

Alternatives to long-term LDN therapy

If low-dose naltrexone doesn’t suit you long-term, several other options exist for managing symptoms:

• Behavioral therapy and cognitive behavioral therapy for psychological support
• Non-addictive pain medicine like NSAIDs (with medical oversight)
• Somatic therapies or trauma work, such as EMDR therapy
• Group or couples therapy when emotional health is impacted by chronic pain
• Lifestyle adjustments and integrative care through functional medicine

Each path supports a comprehensive pain management plan that goes beyond medication alone.

How Charlie Health can help

If you’re struggling with your mental health and could use more than once-weekly support, Charlie Health is here to help. Charlie Health’s virtual Intensive Outpatient Program (IOP) provides behavioral health treatment for people dealing with serious mental health conditions, including anxiety, depression, trauma, and more. Our expert clinicians incorporate evidence-based therapies into individual counseling, family therapy, and group sessions. With this kind of holistic online therapy, managing your mental health is possible. Fill out the form below or give us a call to start healing today.