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A Guide to Low-Dose Naltrexone Benefits (& Is it Safe?)

Though It’s Relatively Safe, Low-Dose Naltrexone Needs Further Study

If you struggle with an autoimmune condition, chronic pain, or another chronic disease, you may have run across the medication low-dose naltrexone, or LDN. Low-dose naltrexone is a popular drug among alternative healthcare providers who typically prescribe it for chronic pain or inflammatory bowel disease (IBD), as well as chronic infections such as Lyme disease. 

However, like any medication, LDN isn’t a cure-all, and it seems to work for some but not for many others. In this article, I’ll lay out the benefits of low-dose naltrexone, examine the research we have so far, and review the potential side effects and safety profile. (Spoiler: It seems quite safe overall!) 

If you’re considering LDN as part of your treatment plan, read on for my comprehensive review of this increasingly popular medication. 

What is Low-Dose Naltrexone (LDN)?

Naltrexone is a type of medication called an opioid antagonist that, at its higher doses, counteracts the effects of opioid drugs [1]. The Food and Drug Administration has approved oral naltrexone for the treatment of opioid-use or alcohol-use disorders [2]. Naltrexone helps with these disorders by reducing the appeal and effectiveness of substance misuse [2]. For these purposes, it’s typically given at doses of at least 50 mg [2]. 

But, when given at a much lower dose (aka low-dose naltrexone, referring to doses of 0.5–4.5 mg), naltrexone can have different effects, such as reducing pain and inflammation [3]. The LDN Research Trust says popular uses of LDN include treating cancers, autoimmune diseases, chronic pain, and mental health issues [4].

Though we don’t yet fully understand how it works, some scientists theorize that LDN can increase the activity of neurotransmitters, like endorphins or dopamine, both of which can improve mood and well-being [3]. Endorphins have the added benefit of being analgesics (pain relievers) and stress reducers. 

If the endorphins theory is accurate, it may help explain some of LDN’s anti-inflammatory effects [3], since endorphins can calm immune cells that are typically overactive in autoimmune disorders [5], like Crohn’s disease. However, some recent research has called the endorphins theory into question [6].

Another possible mechanism of action behind its anti-inflammatory effects is that LDN may block certain receptors involved in inflammation, which could reduce pain induced by inflammation [3]. On the other hand, LDN might help chronically activated microglial cells (immune cells in the brain) by calming their activity without suppressing the immune system [3].

However it works, in the 1980s, an AIDS doctor began using LDN (1.5–3 mg) as an off-label drug (used for something other than what the FDA approves it for) to improve AIDS treatment. Since then, LDN has become a popular go-to for many in alternative and functional medicine [2]. But the drug lacks the rigorous study of large-scale clinical trials (possibly due to its off-label nature), so there is less evidence behind its use for now [2].

However, LDN may fall under the category of safe and cheap enough to try for pain management or immune-mediated conditions, and then you can assess the benefits for yourself.

Key Takeaway: Low-dose naltrexone is an off-label and less-studied version of the prescription drug naltrexone. LDN is typically prescribed for chronic pain and autoimmune conditions, such as Crohn’s disease.

Uses and Benefits of LDN

Given the limited available research, the most likely science-backed benefit of LDN is pain relief [7, 8, 9, 10]. But there’s also evidence to suggest that LDN has the potential to be helpful for some other conditions.

Let’s break down the most science-backed uses of LDN so far. 

LDN for Chronic Pain

Some evidence in systematic reviews suggests that LDN is safe and that it may reduce pain in people with chronic pain conditions like fibromyalgia and complex regional pain syndrome [7, 8, 9]. 

A clinical trial (though one weakened by the lack of a placebo group) compared LDN to amitriptyline (an antidepressant used to relieve pain), and found they were similarly effective, yet LDN had far fewer side effects [10]. 

That said, two recent randomized placebo-controlled trials found that LDN was no better than placebo for reducing pain in people with fibromyalgia or other chronic pain [11, 12]. That doesn’t exactly negate the pro-pain research, but it does offset it somewhat and indicate that we still need more clinical studies to tell us how effective LDN really is.

If LDN is good for relieving pain, it might do so by influencing the body’s opioid receptors and exerting anti-inflammatory effects on the central nervous system [3].

This might suggest that those who benefit from taking LDN have a condition stemming from nervous system dysfunction, and LDN might relieve their symptoms by taking pressure (i.e. inflammation) off the nervous system. More research is needed here, but it’s interesting to consider, especially as we learn more about the nervous system’s role in many chronic and autoimmune conditions, like Crohn’s and fibromyalgia.

LDN for Crohn’s Disease

One systematic review suggests that taking LDN for 8–12 weeks may help improve symptoms and intestinal inflammation in people with active Crohn’s disease [1]. More research is necessary, but if you have Crohn’s and are looking for an alternative to harsher medications such as biologic drugs, LDN may be worth a shot. 

Many people struggling with IBD may also struggle with a dysregulated nervous system [13]. In those cases, LDN might help calm the nervous system, consequently improving gut symptoms and overall quality of life.

LDN for Skin Conditions

Some evidence suggests that LDN might be a safe and effective treatment for certain skin conditions, including Hailey-Hailey disease (a rare genetic condition that causes skin blisters and cracks), lichen planopilaris (scarring on the scalp followed by hair loss), and severe itching related to various conditions [14].

LDN for Depression

A very small randomized placebo-controlled trial (not much evidence, but promising enough to encourage more study) found that people with major depression who took LDN with their antidepressants had some reductions in depression scores compared to those who took a placebo [15]. 

When people report feeling happier overall while taking LDN, it could be related to the placebo effect or greater levels of dopamine circulating in the body while the drug is active, as well as increased endorphins and reduced inflammation [3]. LDN’s effects on mood warrant further study as we seek alternatives to antidepressants like SSRIs, which attempt to correct depression by increasing serotonin levels in the brain. 

Conditions That May Not Benefit from Taking LDN

The effects of LDN on opioid-use disorder, chronic fatigue syndrome (CFS), and hypothyroidism have all been studied to some extent. Large randomized controlled trials have shown that LDN is not better than other drugs, like buprenorphine, for helping people detox from opioids enough to start high-dose naltrexone [16, 17]. But the research for LDN’s effects on CFS [18] and hypothyroidism [19] is extremely limited and has not yet found promising results for these conditions. Ideally, more and better research is on the way.

How Long to See Benefits of Low-Dose Naltrexone?

If you start LDN, your provider will likely have you start at a lower dose of 0.5 mg or 1 mg, and scale up to 1.5–4.5 mg over about a month [20]. Once you are at your target dose, it may take another 8 weeks to notice benefits from the medication [20]. As with most medications, some people notice a difference in days to weeks, while others need longer to see a change in their symptoms. And still others won’t see any effect at all. 

Sometimes the changes are so subtle that you won’t notice them unless you stop LDN for a week and see symptoms come back [20]. Just make sure to stay in communication with your doctor and let them know of any positive or negative changes you notice with LDN.

Key Takeaway: Some research supports the use of LDN to manage chronic pain, certain autoimmune conditions, skin conditions, and clinical depression. More research is needed, but the drug may treat these conditions by increasing endorphins and dopamine, lowering inflammation, and regulating the immune and nervous systems.

Potential Risks and Side Effects of LDN

In general, LDN is a remarkably safe medication with a low side-effect profile. LDN may interfere with certain blood tests and opioid medications, and you should avoid taking it if you have liver disease, are pregnant, or are breastfeeding [21]. 

But otherwise, all doses (low to high) of naltrexone appear to be safe and unlikely to cause serious negative side effects for up to 1 year [1, 8, 22]. Longer-term data are lacking, but I know of prescribing clinicians who have kept their patients on the drug for years without issue. 

The most common side effects appear to be mild abdominal pain, diarrhea, constipation, nausea, and vivid dreams [8]. Many of these side effects may be reduced by taking the medication in the morning [23] (as opposed to before bed, to avoid potential sleep disturbance) and taking it before a meal [24]. 

Key Takeaway: LDN has relatively few side effects. Some have reported mild abdominal pain, diarrhea, constipation, nausea, and vivid dreams, but it’s possible to minimize these side effects by taking LDN in the morning instead of at night. Taking it with food might help, too.

How to Get LDN

According to the LDN Research Trust, LDN is a prescription medication a qualified healthcare provider will need to prescribe [25]. You can typically get a prescription for LDN from a functional medicine MD, or from a naturopathic doctor who works with a prescribing clinician. Once you begin taking LDN, you’ll have to get your prescription renewed periodically by checking in with your doctor, just like with any other medication. 

Insurance won’t cover LDN since it is an off-label use of the drug naltrexone. However, LDN is quite inexpensive even without insurance—it typically costs between $20–$30 per month [26]. Your provider will need to call in an LDN prescription to your local compounding pharmacy, where they can tailor the medication to your specified dose. 

Key Takeaway: Low-dose naltrexone has to be prescribed by a doctor and refilled regularly, like any medication. It’s relatively inexpensive, costing around $20 to $30 a month.

With Its Low Side-Effect Profile, LDN May Be Worth the Experiment

While research into its effects is ongoing, low-dose naltrexone therapy is a viable option to try for conditions like chronic pain, Crohn’s disease, and perhaps other autoimmune conditions that are driven by inflammation and a dysregulated immune system. 

Though we need more research to be certain, low-dose naltrexone appears to be remarkably safe and well-tolerated by most people. Those who notice a benefit report both a reduction in symptoms and a general increase in well-being. If you’re interested in LDN as a treatment option, discuss a trial of it with your healthcare provider. 

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➕ References
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