Chronic inflammation? You might need low dose naltrexone

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Enhancing immunity. Resolving inflammation. Reducing pain. Increasing endorphins. These are some of the potential benefits of low dose naltrexone.

So what is low dose naltrexone?

First, let’s talk about naltrexone. Naltrexone is a drug that has been approved by the FDA for the treatment of opioid and alcohol dependence. It works by blocking opioid receptors in the body. For people who have opioid dependence, it basically blocks some of the key effects of the medication—so if you take opioids, you don’t get their upsides, and are less likely to use them. For people with alcohol dependence, it seems to reduce craving. In both cases, the idea is that treatment can help maintain abstinence. For these uses, naltrexone is usually dosed at 50 mg.1,2

But we’re talking about low dose naltrexone here. And by low dose, I mean a lot lower: ten to 100 times lower.  

At these low doses, LDN is basically a different therapy, and it works in slightly different ways. LDN isn’t the only therapy that is like this—vitamin C, for example, also works in very different ways at low and high doses. The result is that LDN has the effect of modifying the immune system while also creating anti-inflammatory effects.

How does it do all these things? There are at least three ways.

The first is pretty straightforward—it can block opioid receptors, just like regular doses of naltrexone can. But it does this only for a short period of time, and it doesn’t do so completely. The result is that the body compensates by increasing the production of endorphins. Endorphins are the body’s natural version of opioids. You might think about these with a runner’s high, but they play a role in many pleasurable activities, like eating and social interactions. In addition to their role in pain, endorphins are involved in stress response, immune function, and mood.3

The second is closely related to the first. LDN can increase Opioid Growth Factor, or OGF. OGF is also like an endorphin – it’s an endogenous (meaning “made in the body”) opioid that interacts with a particular receptor, appropriately named the Opioid Growth Factor receptor (OGFr). This pathway plays a key role in cellular growth, and OGF is being studied for its role in slowing cancer growth and reducing symptoms in autoimmune disease.4

The third is related to the brain. LDN can reduce inflammation in the brain through its action on a particular type of brain cell, called microglia.  Microglia are the immune cells of the brain. When they are in balance, they help keep things running smoothly by clearing out old cells and debris. When microglia are activated by an injury or infection, they respond by increasing inflammation, producing reactive oxygen species and cytokines (which are small proteins that the immune system use to communicate with its cells). This is all well and good in the short term, but if microglia are always activated, the chronic inflammation that results can cause problems—things like fibromyalgia, Alzheimer’s Disease, and multiple sclerosis.5,6 LDN helps bring microglia back into balance, and it does so by blocking something called Toll-like receptor 4 (TLR4), which results in the decrease of pro-inflammatory cytokines.7   

What conditions might LDN help? While the studies are still early, it is being explored in a variety of conditions rooted in chronic inflammation. For example, LDN has been shown to reduce pain and inflammation in patients with multiple sclerosis, potentially improving quality of life. In fibromyalgia, it may help manage chronic pain and inflammation. In inflammatory bowel diseases, like Crohn’s disease, it may help reduce symptoms and inflammation, even in patients who are resistant to other therapies. In complex regional pain syndrome, it helps with pain. In several skin conditions, it seems to improve symptoms.8–12 It may also be helpful in long COVID. In one study that followed patients with long COVID taking LDN over two months, patients had significant improvement in energy, pain, concentration, and sleep, as well as several other markers of quality of life. Another study found that LDN as part of a supplement combination significantly improved fatigue, and a third found that LDN was associated with fewer symptoms and improved function. These were all small studies, but they are very promising.13–15 LDN has been studied in a variety of cancer as well, including bladder, breast, liver, lung, colon, ovarian, and cervical cancers, where it seems to reduce cancer growth (though these studies are also early, and more studies are needed).16,17 In reality, the list of conditions that might benefit from LDN is quite long—anything rooted in chronic inflammation (which is most, if not all, chronic conditions).

What are the downsides to LDN? In general, there aren’t too many. It is usually well tolerated, and the most common side effect is probably sleep disturbance. Some people experience vivid dreams. Other symptoms include headache, mild nausea, and constipation. These are usually short-lived.18

How do you dose LDN? I usually start low and go slow. For most people, I start at 1 mg and slowly increase over the course of several weeks to 4 or 5 mg. For people who are more sensitive to medications or supplements, I may start at 0.5 and increase by 0.5 per week (maybe splitting it up into two doses per day). If a patient develops symptoms, I’ll decrease the dose.

In summary, LDN is an intriguing therapy that may enhance immunity, resolve inflammation, reduce pain, and increase endorphins. It may have a role in whole host of chronic conditions, including multiple sclerosis, inflammatory bowel disease, long COVID, and fibromyalgia. It tends not to have major side effects. And some people feel much better when they take it. Perhaps it could be helpful for you.

References

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2.         DailyMed - NALTREXONE HYDROCHLORIDE tablet, film coated. Accessed June 19, 2024. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=21b43dab-015c-c82f-ba6e-27da0ec12fc5

3.         IJMS | Free Full-Text | Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism. Accessed June 19, 2024. https://www.mdpi.com/1422-0067/22/1/338

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5.         Aguzzi A, Barres BA, Bennett ML. Microglia: Scapegoat, Saboteur, or Something Else? Science. 2013;339(6116):156-161. doi:10.1126/science.1227901

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8.         Patten DK, Schultz BG, Berlau DJ. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn’s Disease, and Other Chronic Pain Disorders. Pharmacother J Hum Pharmacol Drug Ther. 2018;38(3):382-389. doi:10.1002/phar.2086

9.         Ekelem C, Juhasz M, Khera P, Mesinkovska NA. Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions: A Systematic Review. JAMA Dermatol. 2019;155(2):229-236. doi:10.1001/jamadermatol.2018.4093

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12.       Lie MRKL, van der Giessen J, Fuhler GM, et al. Low dose Naltrexone for induction of remission in inflammatory bowel disease patients. J Transl Med. 2018;16(1):55. doi:10.1186/s12967-018-1427-5

13.       O’Kelly B, Vidal L, McHugh T, Woo J, Avramovic G, Lambert JS. Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study. Brain Behav Immun - Health. 2022;24:100485. doi:10.1016/j.bbih.2022.100485

14.       Isman A, Nyquist A, Strecker B, et al. Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19. Brain Behav Immun - Health. 2024;36:100733. doi:10.1016/j.bbih.2024.100733

15.       Bonilla H, Tian L, Marconi VC, et al. Low-dose naltrexone use for the management of post-acute sequelae of COVID-19. Int Immunopharmacol. 2023;124(Pt B):110966. doi:10.1016/j.intimp.2023.110966

16.       Couto RD, Fernandes BJD. Low Doses Naltrexone: The Potential Benefit Effects for its Use in Patients with Cancer. Curr Drug Res Rev. 2021;13(2):86-89. doi:10.2174/2589977513666210127094222

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18.       Ploesser J, Weinstock LB, Thomas E. Low dose naltrexone: side effects and efficacy in gastrointestinal disorders. Int J Pharm Compd. 2010;14(2):171-173.