Low-Dose Naltrexone, Receptors, & Lupus

Naltrexone is best known for helping treat drug and alcohol addiction. But, low-dose naltrexone treatment may also reduce lupus pain and inflammation.

Medications are designed to impact the body in a particular way, towards a particular goal.  What they do in the body, the drug action, is known as pharmacodynamics. Generally speaking, there are 2 ways that a medication can cause a change. A medication can be an:

1. Agonist

   1. Stimulate and activate receptors

2. Antagonist (blockers)

   1. Stop agonists from activating receptors

Active receptors either trigger a particular response from the body or trigger the release of hormones (which in turn trigger the desired response). Receptors are located in the cell membrane or inside a given cell. The active ingredient in a medication attaches to the receptor using a specific type of chemical bond depending on the drug (covalent, ionic, hydrogen, hydrophobic).

How naltrexone works

Naltrexone is an opioid antagonist, so it attaches to the opioid receptors in the body. Unlike methadone or suboxone, naltrexone doesn’t do the opioid’s job. Instead, it blocks opioids from binding to these receptors, preventing them from having any effect. Opioids and their receptors are involved in pain relief and feelings of pleasure. These feelings are very strong and are a part of why it can be very difficult to quit using opioids or alcohol (which is linked to the endogenous opioid system).Naltrexone is usually taken in doses of 250-300mg. At that dosage, it prevents the pain-relieving and pleasant effects of drugs and alcohol by competing for, and then blocking, the opioid receptors in the brain. This reduces the positive effects of opioids or narcotics (though the precise mechanism of action is unknown) and some side effects.

Low-dose naltrexone and lupus

Small doses of naltrexone have been taken by people with lupus to help reduce pain and regulate the immune system.We naturally produce neuropeptides that bond to the opioid receptors in the brain. They are endorphins and enkephalins. A lot of endorphins and enkephalins are produced during exercise, which is why exercise can be so good for Lupus Warriors in pain. They are also produced when you are injured, happy, relaxed, or believe that something can help you. (In fact, that is a part of how the placebo response works!) At a low dose, naltrexone blocks a few of the opioid receptors in the body. This make the body less sensitive to the pain-relieving and other effects of endorphins and enkephalins. While the blocking isn’t usually enough for you to feel, it is enough for your body to detect. In response, the body tries to make up for it by producing more endorphins and enkephalins and, also, producing more opioid receptors. When the small amount of naltrexone wears off, the combination of higher amounts of natural painkillers and more-sensitive cells reduce the sensation of pain.

More than pain management

The small flood of endorphins and enkephalins also trigger receptors throughout the cells of the immune system and help to reign it in. Endorphins and enkephalins are a major part of how the immune system functions. They are involved in antibody creation and the ability of the body to hunt down and kill cancer cells. They might also help "police" the immune system, preventing it from attacking the body's own cells inappropriately -- the basis for autoimmune disease.  Low-dose naltrexone also interacts with glial cells, the “glue” of the brain, to stop pain. When these cells are activated, they help promote inflammation and are also involved in chronic pain, including fibromyalgia. Low-dose naltrexone may protect glial cells from irritation and prevent them from activating.

The research on low-dose naltrexone

A 2014 review in the journal Clinical Rheumatology reviewed the use of low-dose naltrexone (LDN). They looked at the trials that have been published so far and, despite finding mainly small trials with low sample sizes, they determined that LDN holds a lot of promise for people with lupus, and others who suffer from autoimmune disease and chronic pain. Naltrexone is already approved by the FDA and safe at high doses – it’s been tested at up to 600mg a day for a week. Because it is given at such tiny doses, low-dose naltrexone will have fewer side effects than the usual dose while still providing a pain-relieving and immune-boosting benefits. As an anti-addiction drug, naltrexone doesn’t create dependence, either.This means that low dose naltrexone can give Lupus Warriors an option for treatment that doesn’t increase disease vulnerability, has a low risk of side effects and helps with pain.Researchers suggest that the best use of LDN may be before a flare (or during times of lower symptoms) or before serious damage to organs. This is because it may help to prevent flares or more severe symptoms. LDN is likely less effective at treating more severe or progressed lupus.

Things to know before starting low-dose naltrexone

Naltrexone does have side effects. Normal dose or high dose naltrexone can lead to both minor side effects and more serious ones. Minor side effects include:

• nausea

• decreased appetite

• abdominal pain and/or constipation

• headaches

• fatigue

• insomnia

• dizziness

• anxiety

• depression

 Major side effects to be aware of include:

• confusion

• hallucinations

• blurred vision

• vomiting

• diarrhea

 Low-dose naltrexone interferes with opioid medications, preventing them from working properly and making them less effective. Though low dose naltrexone is a painkiller, it will have the opposite effect if taken with opioid analgesics.Low dose naltrexone also requires a functioning and healthy liver and kidney to be processed properly. If the organs are weakened, it can cause damage to those organs. Already existing organ damage from systemic lupus erythematosus or lupus nephritis can make it unsafe to take naltrexone, even at low doses.

Updating the regimen?

As with any medication or treatment, speak with your lupus treatment team to see if LDN may be right for you. If you aren’t taking an opioid painkiller and have a healthy liver and kidneys, it may be a good option for you.Even with the risks, low-dose naltrexone is a potential aid for chronic pain and inflammation. It may be able to help keep flares at bay without leaving you open and vulnerable to other diseases, and with a low risk of side effects.