Low-Dose Naltrexone: Drug Interactions to Be Aware Of

Low-dose naltrexone is becoming more and more recognizable for its off-label use in managing a wide range of chronic conditions. They include fibromyalgia, autoimmune diseases, and even multiple sclerosis.

While being able to help with various symptoms, low-dose naltrexone isn’t self-contained. It may interact with other medications, and understanding those interactions is the key to developing a safe and effective treatment strategy.

What Is Low-Dose Naltrexone?

Naltrexone is typically used when treating opioid and alcohol use disorders. This FDA-approved medication works to suppress the euphoric effect caused by opioids and alcohol, resulting in reduced cravings. Standard doses of naltrexone vary between 50 and 100 mg.

Low-dose naltrexone (LDN) typically falls between 0.5 mg and 5 mg. It’s commonly known for its off-label use in treating such conditions as:

• fibromyalgia;
• inflammatory diseases;
• immune-related conditions;
• chronic fatigue syndrome (CFS);
• endometriosis;[1]
• complex regional pain syndrome (CRPS);
• depression;
• certain types of cancer.

The exact way low-dose naltrexone works hasn’t been fully studied yet. With that said, some studies show that LDN can positively affect the body’s natural endorphin production, which may help promote anti-inflammatory responses.[2] Low-dose naltrexone is also believed to regulate the immune cells that may trigger the inflammatory response, such as macrophages and lymphocytes. This typically leads to reduced inflammation.

Because LDN interacts with key immune and nervous system pathways, it is important to understand how it may affect (or be affected by) other medications. Certain combinations may lead to reduced effectiveness or even adverse effects.

Opioids and Low-Dose Naltrexone Interaction

It is crucial to avoid taking low-dose naltrexone if you have already been using opioid medications. While opioid medications act on opioid receptors, LDN can bind to them. Even at low doses, by binding to opioid receptors, LDN can reduce or even block the effects of opioid medications.

This means low-dose naltrexone, when combined with opioids, may potentially:

• trigger severe opioid withdrawal symptoms;
• reduce the effectiveness of opioids used to manage chronic pain;
• increase the risk of relapse in patients managing opioid dependency.

When the opioid receptor balance is disrupted, patients may also experience mood changes. The opioid withdrawal symptoms may include nausea/vomiting, excessive sweating, chills, diarrhea, muscle pain, insomnia, and anxiety.[3]

LDN should only be started at least 10-14 days after your last opioid dose. It is also essential to avoid taking opioid-based medications once you’ve started your low-dose naltrexone treatment. It may take a few weeks for LDN to achieve noticeable results, so any setbacks can be quite disruptive.

Close monitoring is crucial when transitioning from opioids to low-dose naltrexone. On top of that, proper timing is one of the key elements that can help avoid complications and ensure a safe use of LDN.

Can LDN Affect Immunosuppressant Use?

Low-dose naltrexone works as an immune modulator, temporarily blocking opioid receptors and thus potentially helping regulate the immune response. This means its mechanism is opposite to the immunosuppressant use. That’s why, despite these two types of medication being generally safe in their interactions, it’s still necessary to proceed with caution and ensure thorough monitoring throughout the treatment.

When a patient is required to combine immunosuppressants with LDN, the key is to introduce low-dose naltrexone gradually. Additionally, regular blood work is recommended. Any signs of a potential autoimmune flare or new symptoms must be reported to your healthcare provider.

Some Cough and Antidiarrheal Medications

Most cough and antidiarrheal medications (especially over-the-counter ones) are safe to use with LDN. With that said, there are exceptions that you should be aware of. Specifically, medications that contain opioids. While they are only available by prescription, it’s crucial to ask a healthcare professional about the potential side effects of their interaction with LDN.

The examples of the medications to use with caution include:

• cough syrups containing codeine (i.e., Promethazine, Tuzistra XR);
• antidiarrheal oral tablets that contain diphenoxylate (i.e., Lomotil, Lonox);
• cough relievers containing hydrocodone (i.e., Tussionex, Obredon, Hycodan);
• Loperamide (most commonly known by the brand name Imodium), which is an over-the-counter antidiarrheal medication that’s an FDA-approved synthetic opioid;[4]
• cough medications containing dextromethorphan (often over-the-counter) (i.e., Delsym, Vicks Formula 44).

To sum up, you should not combine LDN with any opioid-based medications. Always make sure to read the label carefully and ask your doctor about the opioid-free alternatives. When starting a new medication while on low-dose naltrexone, make sure you begin with the lowest dose and increase it gradually.

If you notice any unexpected symptoms or changes in your health, be sure to notify your healthcare provider immediately.

Low-Dose Naltrexone and Recreational Drugs

Low-dose naltrexone can interact with recreational drugs, especially those that affect the nervous system or opioid receptors. Therefore, combining LDN with recreational drugs is very risky and can lead to unpredictable results.

Any form of opioids has to be avoided. They include opium, heroin, hydrocodone, oxycodone, morphine, fentanyl, tramadol, etc. Their interaction with even the smallest doses of naltrexone may precipitate opioid withdrawal.

Aside from potentially triggering a rapid set-off of withdrawal symptoms, LDN may also reduce the pleasurable effects of recreational drugs. This includes not only opioids but psychedelics as well (i.e., LSD, mescaline, DMT, etc.). This can be very dangerous, as some users may increase their dosage to achieve a euphoric sensation. This, consequently, may increase the risk of overdose.

There’s not enough proof that LDN can directly interact with cannabis (both THC and CBD). Nonetheless, there is anecdotal evidence that low-dose naltrexone may either reduce or heighten the effects of cannabis. If you are prescribed medical cannabis while taking LDN, make sure to notify your doctor. The safest approach is to start with very low doses of cannabis and correct your treatment based on your body’s reactions.

Other Interactions

Even though the combination of LDN and alcohol is believed to be generally safe, it is recommended to avoid alcoholic beverages when taking low-dose naltrexone. Consuming alcohol may trigger or aggravate certain side effects (including headaches and nausea).

Alcohol may also impact the effectiveness of your LDN treatment. At the same time, LDN may reduce the effects of alcohol, which often makes people increase their intake, leading to potentially dangerous levels of intoxication.

It’s also worth mentioning herbal supplements. While most are considered safe in combination with LDN, some require special attention. For instance, herbs that may affect mood or the immune system, like St. John’s wort and echinacea, may interfere with LDN’s effects. Always let your physician know if you take any natural supplements.

The Bottom Line

Low-dose naltrexone has a lot of potential in treating several challenging conditions, from chronic pain to autoimmune diseases. But despite being very promising, this medication does carry some risks. Make sure you have an open conversation with your healthcare provider regarding any other medications you’re currently taking, as some of them may interact with low-dose naltrexone.

Frequently Asked Questions About Low-Dose Naltrexone Drug Interactions