- Everything You Need to Know about Low-Dose Naltrexone
- What is Naltrexone and What Makes Low-Dose Naltrexone (LDN) So Special?
- What are the Potential Benefits of Low-Dose Naltrexone (LDN)?
- LDN has anti-inflammatory effects
- LDN is relatively low cost
- LDN causes minimal side effects
- LDN has no known abuse potential
- What are the Risks of Low-Dose Naltrexone?
- It can be tricky to find the best dose
- There isn’t a lot of evidence about long-term safety
- Patients may inappropriately create their own dosage forms
- What conditions can LDN be used to treat?
- How can I try Low-Dose Naltrexone (LDN)?
- What is Low Dose Naltrexone (LDN)? + Side Effects
- The Story of Opioids
- The Discovery of LDN
- Proposed Mechanism
- Does it Block or Stimulate Endorphins?
- The Missing Link Between Cancer, Autoimmunity, and Depression?
- Is It Legal?
- LDN Dosage
- Typical Protocol & Dosage
- Ultra-low Dosage
- Potential Synergies (Lifestyle & Supplements)
- LDN Side Effects and Interactions
Everything You Need to Know about Low-Dose Naltrexone
How did a drug used to treat opioid addiction become a potential breakthrough medication for managing symptoms of over 15 different conditions? Read on for the interesting story and everything else you need to know about low-dose naltrexone (LDN).
What is Naltrexone and What Makes Low-Dose Naltrexone (LDN) So Special?
Originally, naltrexone came to market as a drug used to treat heroin and opioid addiction. Naltrexone works by blocking opioid receptors throughout the body so that heroin and other opioids can’t latch onto them. Without making contact with the opioid receptors, opioids can’t produce the feeling of getting “high.”
Naltrexone has been around for decades. The U.S. Food and Drug Administration (FDA) first approved naltrexone back in 1984.
Not until years later did a doctor discover that a much lower dose of naltrexone (~1/10th the typical treatment dose) had even more potential benefits for patients with HIV, cancer, and autoimmune diseases.
What are the Potential Benefits of Low-Dose Naltrexone (LDN)?
Both patients and health care providers are excited about the potential uses of LDN. what experts know so far, these are a few of the benefits of LDN:
LDN has anti-inflammatory effects
At very low dosages, naltrexone can relieve pain and inflammation. LDN has been used to treat chronic pain conditions such as fibromyalgia and inflammatory conditions such as Crohn’s disease.
LDN is relatively low cost
LDN is relatively inexpensive. This is great for patients since insurance companies do not cover the cost of LDN.
LDN causes minimal side effects
In general, side effects from LDN are mild, and severe side effects are uncommon. In research studies, one of most common side effects reported was vivid dreams. Other side effects may include nausea, constipation, diarrhea, insomnia, and/or fatigue. Usually side effects disappear quickly, but rarely, they may last several weeks to months.
LDN has no known abuse potential
Un some other anti-abuse drugs, health care providers have not seen dependence, tolerance, misuse, or abuse of LDN so far. Also, it seems that when LDN therapy is stopped, withdrawal is not a concern.
What are the Risks of Low-Dose Naltrexone?
There are several advantages to LDN therapy, but LDN therapy presents a few challenges also.
It can be tricky to find the best dose
Because clinical studies are still ongoing, the best LDN dose for treating certain conditions isn’t known yet. This means your health care provider may have to experiment with different doses until he or she finds the best dose for you.
There isn’t a lot of evidence about long-term safety
Experts know a lot about full-dose naltrexone, but not as much about LDN. This is because large, long-lasting studies have not been conducted yet. Even though smaller studies and real-world experience suggest LDN is well-tolerated, the long-term safety is yet to be determined. To date, no serious concerns have been reported.
Patients may inappropriately create their own dosage forms
Because LDN is not an FDA-approved dosage form, some patients try to “create” the low dose by splitting 50 mg naltrexone tablets into very small pieces. This leads to very inconsistent dosing and increases the risk of unintentional overdoses, side effects, and serious complications.
LDN should only be compounded by trained health care professionals the knowledgeable pharmacists at The Compounding Center in Leesburg, VA!
What conditions can LDN be used to treat?
Experts don’t know everything about LDN yet since LDN research in still ongoing. However, LDN has been used in patients for years. These are just a few of the conditions for which LDN use has been tested in clinical trials:
- Autoimmune diseases
- Various types of cancer
- Lyme disease
- Crohn’s Disease and Ulcerative Colitis
- Post-Traumatic Stress Disorder (PTSD)
- Chronic pain
- Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD)
- Multiple sclerosis (MS)
- Parkinson’s disease
- Dissociative disorder
How can I try Low-Dose Naltrexone (LDN)?
While the knowledgeable pharmacists at The Compounding Center do our best to share with you the most accurate scientific information, we also understand that first-hand accounts from actual patients are also valuable.
On the LDN Research Trust website, you will find accounts of patients’ experiences LDN to manage their conditions. We encourage you to talk to your doctor about whether LDN might be appropriate for you to try.
If you live in any of the states we’re licensed in, our trained pharmacy staff will compound your specific LDN dose with a prescription from your doctor.
The Compounding Center in Leesburg prepares LDN as immediate-release capsule with no fillers or binders to interfere with the drug’s absorption. Plus, you can be sure we take your allergies and dietary concerns into consideration. We make sure our compounded LDN capsules are free of common allergens gluten, lactose, and dyes.
We’ll even ship it to you if you can’t get to the store!
Give us a call to get a quote.
The Compounding Center
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What is Low Dose Naltrexone (LDN)? + Side Effects
The serendipitous discovery of low-dose naltrexone (LDN) spurred a revolution in the background of medicine. Read on to understand its unique mechanism and side effects.
Disclaimer: LDN is not FDA-approved for pain or any other indication. It is still a highly experimental approach. The aim of this post is to outline scientific research for informational purposes only. If you are interested in LDN, it is important to talk to your healthcare provider about its possible effectiveness, side effects, and risks.
The Story of Opioids
Before the concept of low-dose naltrexone was born, high doses of this drug were used in conventional medicine for completely different purposes.
Naltrexone is a drug that blocks the activity of opioids in the brain. Your body normally produces endorphins and enkephalins, natural opioids that contribute to feel-good sensations. In fact, these chemicals are the body’s most powerful reward and pleasure system [1, 2].
Opioid drugs can provide relief from chronic, intense pain. But they don’t come without risks: high doses can slow or even stop breathing and exaggerate feelings of calm, euphoria, and pleasure when abused.
Opioid drugs include both prescription painkillers Vicodin and Percocet, as well as drugs of abuse fentanyl.
Although we are currently seeing the disastrous effects of the opioid epidemic – from doctors over-prescribing opioid painkillers to extremely potent opioids fentanyl reaching the streets – the concept of reversing opioid activity dates back to a time before this crisis began [3, 4, 5].
The opioid blocker naltrexone was synthesized in the 60s and approved in the 80s for treating opioid addiction .
Doctors gave naltrexone to opioid addicts in recovery to prevent relapse. The rationale was to completely shut off the ‘high’ of abused narcotics. By blocking all receptors in advance, naltrexone renders narcotics powerless.
The dosage needed to achieve opioid blockage is high, ranging from 50 – 100 mg/day [1, 6].
Note: Naltrexone shouldn’t be confused with naloxone (Narcan), although both drugs are opioid blockers. You may have heard about naloxone kits (spray or injection) that can save lives in opioid overdose.
Naloxone is a better choice for reversing overdose because it starts to act faster and lasts for a shorter time, as is desirable in emergency situations.
Naltrexone, on the other hand, takes a couple of hours just to kick in [7, 8].
The Discovery of LDN
Around the same time when naloxone was being used for opioid addiction in mainstream clinics, New York-based physician Dr. Bernard Bihari started using the drug in very low doses in the midst of the first AIDS epidemic.
By attempting the impossible – using an opioid blocker to enhance the immune response in people with an “untreatable” disease – Dr. Bihari spurred a lot of attention.
He was initially working with opiate addicts when he observed that high-dose naltrexone seemed to make the body triple endorphin production. However, it caused too many side effects, such as insomnia and the inability to handle stress. Few would stay on it .
To re-wind: opioid- endorphins are not only released to help us cope with everyday social situations free of fear, pain, and anxiety. They also play an important role in acute stress and the fight-or-flight response .
Interested in the drug’s immune effects, Dr. Bihari started prescribing a range of naltrexone doses to HIV patients. His goal was to find the best dose that would boost endorphins without causing negative effects.
Surprisingly, it turned out that a small naltrexone dose (3 – 5 mg) increased endorphins to the same extent as a high dose .
Next, he ran a 9-month LDN trial in people with AIDS and described the results as promising. After realizing the immune-normalizing potential of LDN for AIDS, Dr. Bihari hypothesized its application for a wide range of autoimmune diseases .
However, it wasn’t until 2007 that the first low-dose naltrexone (LDN) clinical trial was published. All the while, science has been gaining a lot of insight into the intricate workings of endorphins and opioids in the body.
Some small LDN studies have been published and LDS has gained attention as a potential complementary approach to many chronic diseases. Yet the opinions about its clinical use are mixed, and rightly so .
Despite some encouraging findings and anecdotes, we still know less than we don’t about LDN. Proper, large-scale trials are lacking. Most of the data relies on Dr. Bihari’s observations, small-scale studies, and clinical and personal experiences. Because of this, there’s still insufficient evidence to recommend LDN for any indication.
- Used off-label for autoimmune diseases, chronic pain, and inflammation
- Claimed to increase natural opioids and balance the immune system
- Limited studies suggest side effects are mostly rare and mild
- ly few drug interactions
- Large-scale studies lacking
- Not enough data to rate effectiveness
- Unapproved, unofficial use (off-label)
- Dosing usually has to be adjusted to each individual
- Use largely relies on clinical expertise
- Long-term safety unknown
The mechanism outlined here and proposed by Dr. Bihari is considered to be a controversial scientific hypothesis. It hasn’t been confirmed in large trials or, therefore, accepted by most medical doctors and experts. Proper clinical studies have yet to verify most of Dr. Bihar’s claims.
With this in mind, let’s take a look at how LDN is hypothesized to work.
Dr. Bihari considered that low naltrexone doses block opioid receptors for a short time – about 3 hours. In response, the body seems to increase the production of endorphins. According to Dr. Bihari, a small late-evening dose of naltrexone will boost endorphin production by 300% [9, 1].
He said that although naltrexone is cleared away by the morning, endorphins stay high all the next day. The endorphin blockage from low-dose naltrexone is described as mild and short. Essentially, it’s thought to increase the activity of opioids [9, 1].
In comparison, high dose naltrexone doses raise endorphins but keeps the receptors constantly blocked, reducing their activity as the end result [9, 1].
Dr. Bihari believed that the rise in endorphin levels remains for as long as a person is taking the low dose every night.
Beta-endorphin, one of our main natural opioids, has a long half-life of about 20 hours in the body. It’s unknown for how long other endorphins stay high in the blood.
Endorphins act on different opioid receptors [9, 10, 11]:
- Mu receptors are in the brain and help with pain relief.
- Delta receptors may play a role in cancer and the immune system.
There are several other receptor types that may be important for the action of LDN, but these two appear to play the largest role .
Does it Block or Stimulate Endorphins?
The concept of “stimulating by blocking” is not an easy one. Let’s dive a bit deeper.
The hypothalamus is a structure in the base of the brain and part of the limbic system, which orchestrates emotions, motivation, and learning. Low-dose naltrexone is thought to block opioid receptors in the hypothalamus .
In response to the short-term blockage, Dr. Bihari said that the brain begins producing more of a prohormone called proopiomelanocortin during the night. Next, this hormone is broken up into 3 others in the pea-sized “master gland” called the pituitary:
- Adrenocorticotropic hormone (ACTH)
- Melanin-stimulating hormone
Aside from these direct effects on the brain, Dr. Bihari thought that LDN may also signal the adrenals to make more enkephalin via another prohormone called proenkephalin.
This is a normal response, as the body interprets blocked receptors as a signal that endorphins are low. To compensate, it increases their production. For this reason, Dr. Bihari would say that LDN increases natural opioids – endorphins and enkephalins – by blocking.
He said that if the receptors are blocked by a high dose, they don’t get to recover and stay shut off. According to him, the ideal dose should maximally increase endorphins while minimally blocking them .
The Missing Link Between Cancer, Autoimmunity, and Depression?
To understand how LDN might work, some scientists are trying to get to the bottom of how complex diseases cancer, autoimmunity, and mood imbalances may be connected to endorphins. Their work is still in the early stages and nobody yet has any conclusive answers.
According to one theory that has yet to be verified, low blood levels of endorphins might contribute to immune deficiencies, and this link has been implicated in cancer and autoimmune diseases. Similarly, HIV/AIDS is accelerated by a deficiency of endorphins. Of course, they are not the only potential cause, but might be a piece of the puzzle .
Low endorphins are highly unly to be the only causative factor of autoimmune problems, mood disorders, or any other complex disease. These diseases always involve multiple possible factors–including the body’s chemistry, environment, health status, and genetics–that often vary from one person to another.
Another interesting scientific concept is the so-called “sickness response” or “sickness behavior.” When people are faced with a disease – be it cancer or depression – they tend to isolate themselves while the body increases inflammation and alters the immune response .
To draw a parallel, sickness behavior is well-known to scientists in the animal world: animals will isolate themselves for a short period of time when faced with an infection or disease to avoid contaminating others.
Sickness behavior can become devastating if it stops to serve a purpose and turns into chronic low mood and energy. It turns out that low endorphins may be the culprit of this complex psychological and emotional response in humans, at least according to certain research groups .
By boosting endorphins, LDN is hypothesized to help reverse this kind of behavior while also balancing the immune system. However, this hypothesis has yet to be tested in clinical trials [12, 13].
Is It Legal?
LDN is an experimental approach. Despite ongoing scientific efforts, there’s not enough clinical data about its effectiveness. Thus, it is often thrown into the “alternative treatments” bucket, but it is not illegal.
Naltrexone is a drug licensed and approved by the FDA, meaning that doctors can prescribe it. However, it’s not approved for the indications we focus on in this article. That makes the use of LDN “off-label.”
Consult with your physician before taking low-dose naltrexone. This medication requires a prescription and should only be used under the guidance of a qualified healthcare professional.
Typical Protocol & Dosage
- LDN is usually taken only once a day before bedtime as 90% of endorphins are hypothesized to be made during the night .
- The dosage typically ranges from 1.5 mg to 5 mg/day*.
- Slow/timed-release naltrexone and LDN capsules that contain calcium carbonate filters should be avoided .
- Pills are the most common form, but topical creams and patches have also been developed; they may work better for children or people who have difficulty swallowing.
- Naltrexone is commercially available only at a 50mg dose, which means that people need to get their prescribed low-dose formulation from a compounding pharmacy .
*Dr. Bihari considers that the dose should be no less than 1.75 – 2 mg/day and no higher than 4.5 – 5 mg/day. He used to say that 3 mg/day is a good dose that works for most people .
This is where the confusion kicks in, as some studies used so-called “ultra low-doses,” ones that range from 0.125-0.5 mg/day. On the other hand, borderline doses of 0.5-1 mg/day are considered “very low-dose” .
There is no clear benefit to very or ultra-low doses, the published studies. However, each person is different and your doctor may consider that doses in this range will work better for you.
Potential Synergies (Lifestyle & Supplements)
There are many natural factors that may increase internal opioids. In theory, these may work in synergy with low-dose naltrexone – but this synergy was never tested in trials.
The following is purely theoretical. Mostly studies on cells or animals, these factors are hypothesized to either increase the activation and sensitivity of receptors or boost endorphin production:
Depending on your health concerns and lifestyle, some of these may work better than others. Make sure to speak to your doctor before making any changes to your lifestyle or supplements regime.
You may try the additional strategies listed above if you and your doctor determine that they could be appropriate. None of these strategies should ever be done in place of what your doctor recommends or prescribes.
LDN Side Effects and Interactions
This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects.