LDN. A humble drug

 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:

Fibromyalgia

Ulcerative colitis and Crohn’s Disease

Multiple sclerosis

Rheumatoid arthritis

Chronic pain caused by many conditions

Hashimoto’s thyroiditis

Epstein Barr virus/ Chronic Fatigue Syndrome

Pernicious anemia

Lupus and other auto-immune conditions

Scleroderma

Excess Weight

PCOS

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:

Increase endorphin release by temporarily binding to the MU receptors

Endorphins modulate the immune response

Modulation of the immune system reduces the speed at which unwanted cells grow

Antagonizes TLR: suppressing cytokine modulated immune system

Antagonizes TLR-mediated production of NF-kB: reducing inflammation, potentially down regulating oncogenes

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:

nausea and vomiting

abdominal pain

constipation

decreased appetite

headache

fatigue

insomnia

dizziness

depression

anxiety

 

Who Should NOT Take LDN?

You shouldn’t take LDN if you:

currently take prescribed opioid medications or street drugs

are in an opioid maintenance program and/or are taking suboxone or methadone

are in acute opiate or alcohol withdrawal

have liver problems or abnormal liver tests

if you are currently being treated for or have an alcohol use disorder

you should discontinue LDN before surgery or if you plan to take prescribed opioid medications

you should not take LDN if you are pregnant, plan to become pregnant or are breastfeeding

 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.

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.

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 https://www.restartmed.com/victoza-weight-loss/ 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:

thyroid resistance: reduced conversion of T4 to T3

Increased insulin resistance, weight gain and weight loss resistance

Increased leptin levels leading to weight gain

Increased appetite

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.

 

Sleep

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

Naltrexone for weight loss: Does it work?

 

What is LDN (Low dose naltrexone) & Does it Actually Work?

dr childs

https://www.youtube.com/watch?v=BJhWBGZAOu8

Low Dose Naltrexone: Studies

Low Dose Naltrexone (LDN) is a small or microdose of the drug Naltrexone.

Over the past few years it has become very popular due to its supposed anti-inflammatory and anti-pain effects.

This article explains what LDN is, how it works and who could consider using it.

What is Low Dose Naltrexone and How Does It Work?

Naltrexone works by blocking the receptors that heroin and opiate drugs binds to.

Just like your body’s natural endorphins, this produces a “feel-good” and pain-blocking effect. This can be useful in those who suffer from chronic aches and pains, at least theoretically.

It was originally approved by the U.S. Food and Drug Administration (FDA) in 1984 to treat chronic opioid and alcohol dependence as well as drug detoxification.

Benefits of Microdosing

LDN is a microdose of the original Naltrexone drug, which typically has a daily dose of 50 to 100mg.

An LDN dosage, about 4.5mg, is roughly one-tenth of the typical amount to treat opioid addiction. Interestingly, an opposite effect of the drug is achieved at this smaller dose.

How Does LDN Work?

LDN works by improving inflammation and pain.

It’s hypothesized that LDN causes the body to increase its production of endorphins (chemicals that help promote feelings of euphoria), and also helps boost the immune system.

LDN improves inflammation by blocking the action of Toll-like receptor 4 (TLR4), a receptor found in white blood cells in the immune system. This action can also help lessen pain sensitivity.

Summary: LDN is about 1/10th the dose of Naltrexone, an FDA-approved drug to treat opioid addiction and drug detoxification. In microdoses, the drug creates an opposite effect by increasing the body’s production of endorphins, boosting the immune system and reducing pain sensitivity.

Who Should Consider Using LDN?

Many websites devoted to low dose naltrexone (LDN) rave about its widespread potential health benefits, but most state unsubstantiated claims.

Research looking into the role of LDN for specific conditions like Crohn’s disease (CD), fibromyalgia, multiple sclerosis (MS), Hashimoto’s hypothyroidism and weight loss is only in its early stages. Large-scale, well-designed trials are necessary for us to learn more about its potential effects.

Despite the lack of robust evidence, patients with these chronic conditions have been seeking out LDN in hopes of finding relief from their painful symptoms.

Crohn’s Disease

Crohn’s disease (CD) is a type of autoimmune inflammatory bowel disease (IBD) with gastrointestinal and full-body implications.

Numerous small-scale studies have been published on the use of LDN in CD. Overall, results are promising and no safety concerns have been reported.

The first study in 2007 evaluated 17 active CD patients using 4.5mg LDN, in addition to their standard treatment.

According to quality of life surveys, an impressive 89% showed a positive response to therapy, while 67% achieved disease remission. LDN was well-tolerated, though seven participants noted sleep disturbances (1).

A 2014 pilot study of 14 children with CD receiving placebo or 0.1mg/kg LDN for 8 weeks also reported positive findings. Of those treated with LDN, 25% achieved disease remission and 67% saw improvements in disease activity. The study concluded that LDN is likely safe and helpful for improving CD in children (2).

Furthermore, a randomized, double-blind, placebo-controlled study tested the safety and efficacy of LDN over 12 weeks. Out of 40 CD patients, 80% of those treated with LDN had at least a 70-point decline in their Crohn’s Disease Activity Index score compared to 40% of placebo patients. One-third of the LDN group also experienced disease remission (3).

In a recently published study of 256 Norwegians with IBD, researchers found that the use of LDN led to an overall reduction in other treatment drugs. Such findings imply that LDN may help reduce the number of drugs required for IBD treatment (4).

Summary: There is a lot of compelling evidence that low dose naltrexone can help with crohn’s disease treatement. It’s worth speaking to your doctor about this.

Fibromyalgia

Fibromyalgia is a chronic musculoskeletal pain condition that also causes fatigue, brain fog and sleeping issues.

The condition is challenging to treat because typical anti-inflammatory drugs don’t improve the symptoms. However, two small clinical trials have shown LDN to be an effective treatment.

In a 2009 trial, 10 women with fibromyalgia (not taking opioid medications) took 4.5mg LDN over 8 weeks.

Results showed a 30% improvement over placebo for reducing FM symptoms. Mechanical and heat pain thresholds also improved, with very minimal side effects reported (5).

A later study analyzed 31 women with fibromyalgia also using 4.5mg LDN. Researchers found that the treatment provided specific and clinically beneficial improvements for fibromyalgia pain (6).

Summary: Low dose naltrexone looks promising, but these are small studies.

Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, disabling autoimmune condition impacting the central nervous system.

Symptoms range from mild to severe and include pain, numbness, muscle weakness and fatigue.

A 2008 pilot trial of LDN on 40 patients with primary progressive MS found a significant improvement in spasticity after 6 months. They concluded that LDN is safe and well-tolerated in this population (7).

In another trial, researchers looked at the effect of LDN on other drug treatments in 341 patients with MS. The quasi-experiment found that LDN use did not help reduce the use of other drug treatments (8).

However, a 2010 pilot study of 4.5mg LDN on 60 MS patients over 8 weeks reported significant improvements in mental health quality of life measures. LDN was well-tolerated and no adverse events occurred (9).

Overall, LDN has not shown any disease-modification effects in MS, just improvements in quality of life and pain reduction (10).

Summary: Research indicates low dose naltrexone could be useful for pain management in multiple sclerosis,

Low Dose Naltrexone and Hashimoto’s Hypothyroidism

Hashimoto’s Disease is the most common form of hypothyroidism in Western countries.

It occurs when your immune system mistakenly attacks and damages the thyroid gland, resulting in an underactive thyroid and low thyroid hormone production.

Some alternative health practitioners recommend it for treating hypothyroidism, but research is sparse.

One study of 24 opioid addicts undergoing 50mg of naltrexone treatment (i.e. not low dose naltrexone) found some benefit. Total T3 and the ratio of T4 to T3 conversion improved with increased duration of the naltrexone treatment (11).

Additionally, some theorize that low dose naltrexone helps to normalize the immune system, which could help to improve thyroid antibodies in autoimmune-based thyroid conditions (12).

Again this is theoretical, there is not enough research to make any solid conclusions. If you are looking for weight loss advice with Hashimoto’s I recommend starting here.

Summary: Low dose naltrexone may help with Hashimoto’s disease, at least theoretically. There is hardly any evidence to go by unfortunately.

Low Dose Naltrexone and Weight Loss

There are few rationales explaining why low dose naltrexone (LDN) may help with weight loss.

One idea explores the connection between LDN and appetite. If it helps to reduce appetite, then the theory is that one would consume less calories and therefore lose weight.

A study using 50mg of naltrexone showed that subjects ate less due to decreased palatability of food. However, this has not be replicated in lower-doses of naltrexone. Also, the study did not specifically report on weight change (13).

Another rationale is that LDN impacts insulin and growth-hormone. If it helps to reduce insulin secretions and improve growth-hormone levels, then it may help with weight loss.

A study explored this concept in typical naltrexone doses in 12 obese women and six lean women. It appears that naltrexone did help reduce the insulin response in obese women. However, the study did not use LDN nor did it actually report on its effect on weight change over time (14).

Other rationales include how it helps with sleep and inflammation and therefore weight management. No study designs use LDN and report outcomes specific to weight loss.

While it may be a promising area of research, it does not qualify as one of the 77 weight loss strategies that work.

Summary: Low dose naltrexone does not appear to help with weight loss. Lasting weight loss requires diet and lifestyle change.

Low Dose Naltrexone and Other Conditions

There are other populations starting to gain interest in low dose naltrexone treatment as well.

Those with chronic pain, cancer, depression, lichen planus (an. itchy, painful, scarring hair loss condition) and Hailey-Hailey disease (a rare skin disorder) are finding benefits from LDN (10, 15, 16, 17)

Click here to review a complete list of the current LDN literature for various patient populations.

Low Dose Naltrexone Side Effects

While there’s limited research on LDN, very few adverse effects have been reported so far.

Most commonly, vivid dreams and sometimes nightmares have been observed. Some patients have also reported an increase in headaches compared to placebo, but this hasn’t been statistically validated.

No withdrawal symptoms or interactions with other medications have been noted.

However, long-term safety is not known at this time. Larger and more varied sample sizes are necessary.

Summary: LDN appears to be relatively safe with limited adverse effects, including vivid dreams, nightmares and headaches. Long-term safety is not known.

How to Use It

Keep in mind that LDN is not FDA-approved for the treatment of any medical condition, so there are currently no standardized guidelines for its clinical use.

That doesn’t mean that people aren’t using it, though. Over 250 pharmacies in the U.S. alone have reported compounding LDN.

Because the 4.5mg dose is not available for prescription, many people end up splitting their 50mg tablets and creating their own at-home version. Be aware that this can lead to dosing variability.

It’s advised to take the product on an empty stomach starting with a loading phase of 1.5mg and slowly titrating to 4.5mg over a few days. Most take LDN at bedtime, but if it impairs sleep, some clinicians recommend taking it in the morning.

It can take at least one month and up to two months to start noticing benefits of LDN.

Summary: LDN is not FDA-approved at this time so there are no standard-use guidelines. However, many start with 1.5mg at night and titrate their dose to 4.5mg over a few days. Wait at least one month of use to experience its full effect.

Should You Try Low Dose Naltrexone?

LDN is a fairly safe way to help reduce inflammation and pain for numerous chronic medical conditions.

While the research on LDN appears promising for its efficacy and safety, it’s still in its early phases of study.

More comprehensive and larger-scale research is necessary before this treatment is widely recommended. Talk to your doctor about your interest in trying LDN for the treatment of crohn’s disease, Hashimoto’s hypothyroidism and other chronic pain conditions.

For those interested in weight loss, unfortunately it really doesn’t appear beneficial.

With more time, perhaps more benefits of low dose naltrexone will be discovered and more people will find some much needed relief.