The following is not intended to be medical advice. If you have questions about low-dose naltrexone, please speak to your doctor.
The drug Narcan, or naloxone, has been in the news for the last five to ten years due to its effective use as an opioid-reversal agent. If someone is overdosing, a spray of naloxone in the nose will keep the person safe until emergency personnel arrive. It’s often confused with its cousin, naltrexone. Naltrexone is used to help people who are in opioid-use disorder (OUD) or alcohol-use disorder (AUD) treatment remain off substances. How did a medication used to help people remain sober become a medication to help treat pain? The answer lies in the brain (as most answers do).
How opioids work
To understand how naltrexone, an opioid antagonist, works, it is helpful to understand how opioid agonists (usually just called opioids) work and effect the brain.
The brain has receptors for endorphins. Endorphins are most commonly known as the feel-good proteins that the body produces during and after exercise. They can also be produced after other exciting activities. When these endorphins are made, they attach to receptors (called mu [pronounced like mew] receptors) in the brain, and that’s what causes the “feel-good” feeling after a good workout or surviving a sky dive.
These receptors are also where opioid molecules like to bind. Opioids are different than endorphins, but they use the same receptors to help dull pain and make whoever is taking them feel relaxed, calm, or “high.” The mu receptors are also involved in opioid dependence (which is different than addiction) as well as respiratory functions. This is why people who take too many opioids can stop breathing (Dhaliwal and Gupta).
One of the ways to help people who have overdosed on opioids is to give them Narcan (naloxone). Narcan is an opioid antagonist, which means it attaches to those mu receptors as well, blocking the opioids’ ability to do so. Without the opioid molecules attaching to the receptors, the symptoms of overdose, like shallow breathing, cold skin, and excessive sleepiness, start to go away. (Pro tip: if you ever administer Narcan, call 911 immediately after, as the person who has overdosed will need more medical attention.)
What is naltrexone?
Naltrexone was discovered in 1963 by Dr. Joseph Volpicelli, who saw its potential as a treatment for AUD. (Alcohol also interacts with the mu receptors.) Naltrexone was patented in 1967 and was approved for medical use in the United States in 1984. Since it is an opioid antagonist, “naltrexone blocks the euphoric and sedative effects of opioids such as heroin, morphine, and codeine,” explains the Substance Abuse and Mental Health Services Administration (SAMHSA). Taking naltrexone helps someone who is in recovery from AUD or OUD not crave opioids or alcohol. The mu receptors have naltrexone attached, and the naltrexone blocks the ability of the opioids or alcohol to get to the mu receptors.
Naltrexone comes in two forms: an oral pill and an intramuscular injection. (A third form, called Contrave, is naltrexone combined with the antidepressant bupropion and used to treat obesity.) Both forms of naltrexone can be used for those recovering from AUD, but the intramuscular version is preferred for those recovering from OUD. The pill is taken daily, while the injection is given by a medical professional once per month. It is started once the patient has gone through withdrawal and is used for several months to help the patient continue with sobriety.
What is low-dose naltrexone (LDN)?
In the 1980s, Dr. Bernard Behari, a neurologist and psychiatrist, was working with patients who had AIDS. He found that at low doses, naltrexone could cause the body to produce endorphins but wasn’t a large enough dose to block the mu receptors completely. These new endorphins found their way to the mu receptors and attached (Alternative Therapies). Because endorphins play a role in pain regulation, having these extra endorphins hanging out on the mu receptors helped patients feel less pain and that feel-good feeling endorphins are known for.
There have been some studies done about LDN, looking at what conditions it might help. Most of the conditions LDN seems to work best for are autoimmune. They include Crohn’s disease, multiple sclerosis, fibromyalgia, and neuropathic corneal pain. When doctors and patients learned of the effects of LDN on pain and anxiety—and that it was a non-opioid option–they began trying it to help with cancer pain, chronic fatigue syndrome/myalgic encephalomyelitis, chronic pain, Gulf War syndrome, diabetic neuropathy, long COVID, and more.
Using LDN
Patients usually start at 1.5 mg daily of naltrexone (though some start as low as 0.1 mg) and titrate up to a dose that works for them. This is how Janelle A., a user of LDN, started her course. When she started LDN in 2019, she was diagnosed with fibromyalgia, which, in 2024, she learned was actually hypermobile Ehlers-Danlos syndrome. “I was started at the lowest dose and then stepped up. At first, I didn’t feel there was much of an effect, but that changed in the first couple months of taking it,” she said in a recent interview. Effective doses and the time it can take to feel the effects vary from patient to patient, and no one dose or schedule can be recommended for everyone.
Many people who have body-wide chronic pain get some relief using low-dose naltrexone, though, unfortunately, like every medication, it doesn’t work for everyone. Often, after years of suffering through pain and trying a variety of drugs and other therapies, LDN is suggested as a “well, it can’t hurt” option. “I had tried Cymbalta, Lyrica, and gabapentin as ongoing maintenance meds for my chronic pain prior to LDN,” said Janelle. She reports that LDN is the most effective at treating her baseline daily pain with the least amount of side effects. She still gets pain flares for which she takes other medication, but daily, LDN manages her pain.
Drawbacks of LDN
While LDN may seem like a wonder drug, there are a few drawbacks. As previously mentioned, there have been several studies done on LDN, but most of the ones about how well LDN works have small sample sizes and are focused on a single condition, disease, or patient case. More research is coming; according to PubMed, there have been 39 published papers about LDN in 2024 (as of the writing of this article).
Additionally, while naltrexone has been approved by the Federal Drug Administration (FDA) for use in AUD and OUD treatment, low-dose naltrexone hasn’t been approved for treating anything. It would need to be prescribed “off-label,” a term meaning “for treating an issue that it wasn’t intended for.” Many drugs are prescribed this way, but some insurers will not pay for drugs that aren’t being used in an FDA-approved way.
The LDN also needs to be made in a compounding pharmacy because naltrexone comes in 50 mg pills. It’s difficult to split that in 4.5 mg with an at-home pill splitter. Since LDN isn’t FDA approved, LDN pills can’t be manufactured. A compounding pharmacy will make individualized capsules containing the correct dose of naltrexone and is able to change the amount as the patient needs. Prices for one month’s supply of LDN can cost from $20 to $67 and potentially more since there are no pharmaceutical companies or benefit managers to set the price. And, of course, it can cause side effects like any medication and can interact with other medications, especially opioids.
It’s not recommended to use LDN and opioids at the same time. The LDN and the opioids will fight for the same receptors, and the LDN will win if it’s present in the body. This becomes a problem for some people when they have surgery or if LDN isn’t helping. However, “it seems the decision to avoid LDN ahead of surgery is more cautious than anything else,” Janelle explained, in reference to an upcoming surgery of her own. “The dosage of LDN is significantly lower than the dosage of naltrexone used to treat addiction.” Therefore, there may be room on the receptors in the brain for both, but there have been no conclusive scientific studies to support that theory.
Other types of pain medications, like non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and topical analgesics, will not negatively interact with LDN. (Ask your doctor first because they might interact with something else.) Additionally, a patient can choose to stop LDN two to three days before surgery to use opioids for pain control. Once the patient stops the opioids, they should wait two days to resume using LDN (LDN Research Trust). Again, follow the advice of the medical professionals who know your unique medical situation.
While the field of pain medicine has a long list of pills and procedures to treat pain, it’s common for a patient to reach the end of the list and still not have their pain management needs met. Therapies like LDN give hope to the patients for whom it works and to the possibility that other treatments for pain may be closer than we realize.
Kate Schultz
November 2024
