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Low Dose Naltrexone: Best Kept Secret in Treating Chronic Disease and Excess Weight?

Wondering why you’ve never heard about LDN, an amazing and inexpensive drug used to alleviate conditions from chronic pain to autoimmunity to weight management?  

Well, you probably haven't heard of low dose naltrexone (LDN) because there’s no billion-dollar pharma conglomerate willing to fork out the big bucks needed to do a large-scale study on LDN.  As a humble drug with an expired patent, and despite over 90 published studies on the various benefits of LDN, from pain management, fibromyalgia, auto-immunity, Crohn's disease, multiple sclerosis, weight management and even cancer, naltrexone has never been picked up by a pharma company willing to pay out the enormous FDA approval costs for a medication they cannot sell exclusively.  So, if no one else has introduced you, we would like you to meet the little engine that could: Low Dose Naltrexone.

Low Dose Naltrexone (LDN) has emerged has an inexpensive and effective treatment for many chronic health conditions including excess weight.  Naltrexone, originally used to help manage opioid use disorders by preventing the euphoria (“high”) caused by opiates, is now recognized as a complimentary treatment for many chronic conditions.  Naltrexone, when used in very low doses, has been found to safely treat a host of conditions and symptoms with minimal side effects.


What is naltrexone?

Naltrexone is a drug that has been used to help people recover from opiate and alcohol use disorders.  However, off-label use of Naltrexone, in much lower doses, has shown benefit in a variety of conditions because of the way naltrexone temporarily binds to opioid receptors in the brain. Binding these receptors promotes the compensatory production of natural endorphins which then have the ability to affect the body’s immune system and slow the production of cells that can negatively influence various medical conditions. 

Low Dose Naltrexone (LDN), in addition to other disease modifying therapeutic modalities, has demonstrated an ability to alleviate a wide variety of medical conditions and symptoms, like:

Growing evidence has demonstrated that our natural endorphins, most commonly known as our natural, pain-killers, also play an important role in immune system regulation among other functions. LDN has been associated with symptom improvement in conditions such as fibromyalgia, Ulcerative Colitis/Crohn’s disease, rheumatoid arthritis, multiple sclerosis, lupus and other auto-immune syndromes, depression, Hashimoto’s Thyroid Disease, complex regional pain syndrome, excess weight and more.


LDN has been found to aid chronic pain by temporarily binding and blocking a mechanism called the MU receptor, which is linked to pain. Blocking the receptor tells our bodies that we aren’t producing enough endorphins (our natural pain relievers), and then releases them.


How does LDN work?

LDN works as an opioid antagonist. LDN can boost the body’s endorphins and enkephalins. In low doses, LDN promotes the release of endorphins over an extended period of time.  This rise in endorphins contributes reduced inflammation and upregulated immune function, and endorphin rise has been attributed to a decrease in symptoms and progression of chronic disease.  

The LDN Trust explains explains LDN’s mechanism of actions occur as Levo and Dextro naltrexone antagonize the opiate/endorphin receptors causing the following:

LDN can also help suppress microglial activity.  Microglia immune cells are the primary immune cells in our central nervous system. They are responsible for inflammatory response due to exposure to pathogens or from injury.  When microglia are activated, they secrete pro-inflammatory cytokines, prostaglandins, nitric oxide and excitatory amino acids. 


How Will LDN Make Me Feel?

Because LDN can increase endorphins, you may feel an overall sense of well-being. Human trials have demonstrated improvement in self-reported depression, wellness and quality of life scores. Feeling well helps lower stress, reduces depression, and increases healing.  Feeling well may also affect over eating and lead to improved weight management.

LDN is typically prescribed at bedtime as the majority of endorphin production in our body occurs while sleeping. Some individuals may experience sleep changes with bed-time dosing and if this occurs, taking LDN during waking hours may be preferable.


Naltrexone, when used in very low doses, has been found to safely treat a host of conditions and symptoms with minimal side effects


What About Side effects?

Side effects of LDN are often minimal and usually transient which makes this medication an easy addition for most patients. Naltrexone may cause the following side effects at maximal doses, however, with low dose regiments these side effects are typically minimal and transient:



Who Should NOT Take LDN?

You shouldn’t take LDN if you:


Remember, LDN is not a treatment for acute conditions.  LDN is for the treatment of chronic disease and, despite over 90 studies published on the various uses of LDN, from pain relief, fibromyalgia, Crohn's disease, multiple sclerosis, systemic sclerosis and even cancer, LDN therapy is considered off-label use and is not FDA approved for use outside of opiate and alcohol use disorder. It’s very important to talk to your healthcare provider before trying LDN to ensure it won’t interact with any other medications you may be taking and you should not stop any of your treatment medications before consulting with your specialist.


How is LDN dosed and monitored?

The most common LDN dosages are 1.5mg, 3mg, and 4.5mg taken at bedtime. LDN may be titrated up or down based on how a person responds to treatment. If a patient is sensitive to medications, providers will often start at an ultra-low dose of just 0.5mg per day and then titrate up gradually to a maximum dose of 4.5mg.  For the treatment of excess weight, doses may be split morning and evening and may be recommended at a slightly higher dosing.

The goal with LDN, as with many medications, is to take the lowest therapeutic dose rather than the highest dose that can be tolerated. LDN is a unique medication and must be individualized.  The right dose for one individual may be 1mg and for another 4.5mg even when both individuals are being treated for the same chronic condition.

Never try to break, alter or manipulate naltrexone tablets to create LDN on your own.  You should always consult a healthcare professional to help you determine which approach is best for your condition and decide on the best LDN dosage to help you combat symptoms.

LDN therapy is just one part of a treatment plan that also includes a balanced lifestyle, good nutrition or auto-immune paleo diet, exercise, and possibly other medications to achieve optimal response.  Regular check-ins with your provider are recommended both to assess your progress and manage dose titration.  You should have an in-person check up at least several times per year while on LDN therapy.


How Thrive Wellness Can Help

LDN is a promising pharmacologic approach for the treatment of chronic diseases and excess weight, and ongoing research supports its use. Since LDN is effective, inexpensive and has few side effects, it is likely that LDN will eventually be regarded as one of the most promising complimentary treatments for many chronic diseases.

At Thrive Wellness, we work closely with our compounding pharmacy partners to ascertain the best dosing strategy for each patient’s particular condition and needs. Response to treatment varies in terms of time and dosing but over treatment course, many have found relief from pain, weight management success and other improvement of long-standing chronic symptoms.

If you think LDN therapy might be right for you, reach out to a Thrive Team Member to schedule a consultation to explore how LDN might benefit your and support your health journey.


How Can LDN Help with Weight Management?


Ways LDN Has Been Found to Aid in Weight Management:

Reduces Insulin Resistance

Curbs Appetite and Reduces Cravings

Can Boost Growth Hormones

Anti-inflammatory Effects

Promotes Better Sleep

Improves Thyroid Function


Although we don’t entirely understand LDN’s mechanism for weight loss, studies have suggested that it may help curb appetite by reducing the appeal of food.  This effect results in a reduction of food cravings.  In addition, LDN may also contribute to a rise in growth hormone levels which can help build lean muscle and burn fat.  In patients with insulin resistance, which contributes to weight gain, belly fat, diabetes, heart disease and other conditions, LDN can improve insulin sensitivity and eventually lower insulin levels making it easier for cells to utilize insulin.


LDN in Combination with Other Medications

LDN with GLP-1 Agonists

LDN combined with a GLP-1 agonist like Saxenda or Wegovy can be beneficial in patients with severe insulin and/or leptin deficiency or resistance. For more information about GLP-1 agonists, read our blog post about GLP-1s for weight management.


How LDN Addresses Weight Loss Resistance

Insulin Resistance and PCOS

In the study Naltrexone effects on insulin sensitivity and insulin secretion in hyperandrogenic women, women using up to 75mg of naltrexone were found to have improved fasting insulin levels which decreased by 40%.  Insulin resistance is related to weight gain and weight loss resistance.  Higher levels of insulin are also associated with an increase in testosterone levels which are commonly found in women with PCOS.  Therefore, addressing insulin resistance is an important factor in the management of PCOS.  Naltrexone’s apparent influence on insulin resistance can explain it’s benefit in weight loss and indirect improvement of PCOS symptoms by the effect of lowering both insulin and testosterone.


Growth Hormone

In the study Influence of chronic Naltrexone treatment on growth hormone and insulin secretion in obese subjects showed that naltrexone exerts an effect that decreases insulin and increases human growth hormone.  GH helps us develop lean muscle mass and improves fat burning capacity which together can lead to weight loss.  It is postulated that as insulin increases, growth hormone decreases.  Naltrexone can help break the cycle of elevated insulin, weight gain and decreased growth hormone by shifting the balance to lower insulin, weight loss and increased growth hormone leading to the ability to develop more lean muscle mass and better calorie burning capabilities.


Inflammation is involved in the pathophysiology of many disease states.  Inflammation is also a big factor that influences weight gain and weight loss resistance.


Anti-Inflammatory Effects and Thyroid Function

LDN is well known for its beneficial effect on thyroid function especially in treating Hashimoto’s thyroiditis. Naltrexone is also well known for exerting anti-inflammatory effects on the body.  In the paper The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain, the authors proposed that LDN demonstrated reduced symptom severity in conditions like fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. The author’s reviewed the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells.  When microglia are activated, they secrete pro-inflammatory cytokines, prostaglandins, nitric oxide and excitatory amino acids. Reducing the activity of microglial cells consequently reduces inflammatory response.  Inflammation is involved in the pathophysiology of many disease states.  Inflammation is also a big factor that influences weight gain and weight loss resistance. 

Inflammation may lead to:

By relieving inflammatory cytokines and markers of inflammation hormone levels become more regulated and balanced which may allow easier weight loss.  Research studies suggest that the use of LDN can help to improve the immune system function and reduce autoantibodies in some autoimmune conditions like Hashimoto’s thyroid disease.  In some studies LDN has been found to increase thyroid hormone levels while reducing thyroid auto-antibodies associated with Hashimoto’s thyroid disease.

Hashimoto’s Thyroid Disease is an autoimmune disease that leads to thyroid gland destruction over time ultimately resulting in hypothyroidism and weight gain or weight loss resistance.



The importance of sleep and its influence on weight loss is huge.  Poor sleep leads to rising inflammation, metabolic issues, hypertension and weight gain which ultimately causes or worsens sleep apnea.

Naltrexone is associated with improved sleep in the majority of patients.  Improving sleep leads to improvements in metabolism, insulin resistance, inflammation and reduced pain.  This is why it is preferred that patients take LDN at bedtime. Some investigators suggest that LDN may be improving sleep through the modulation of neurotransmitter levels or via melatonin precursors. 

We still have a lot to understand about the use of LDN and its effects on weight management especially considering the multiple mechanisms of action as discussed.  Nonetheless, LDN shows amazing promise as a safe, affordable and effective tool in achieving a healthy weight and promoting a state of overall wellness.


Since LDN is effective, inexpensive and has few side effects, it is likely that LDN will eventually be regarded as one of the most promising complimentary treatments for many chronic diseases

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