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.<\/p>\n
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Disclaimer:<\/em><\/strong> 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.<\/em><\/p>\n Before the concept of low-dose naltrexone was born, high doses of this drug were used in conventional medicine for completely different purposes.<\/p>\n Naltrexone is a drug that blocks the activity of opioids<\/a> in the brain. Your body normally produces endorphins<\/a> and enkephalins<\/a>, natural opioids that contribute to feel-good sensations. In fact, these chemicals are the body\u2019s most powerful reward and pleasure system [R<\/a>, R<\/a>].<\/p>\n Opioid drugs can provide relief from chronic, intense pain. But they don\u2019t come without risks: high doses can slow or even stop breathing and exaggerate feelings of calm, euphoria, and pleasure when abused.<\/p>\n Opioid drugs include both prescription painkillers like Vicodin and Percocet, as well as drugs of abuse like fentanyl.<\/p>\n Although we are currently seeing the disastrous effects of the opioid epidemic – from doctors over-prescribing opioid painkillers to extremely potent opioids like fentanyl reaching the streets – the concept of reversing opioid activity dates back to a time before this crisis began [R<\/a>, R<\/a>, R<\/a>].<\/p>\n The opioid blocker naltrexone was synthesized in the 60s and approved in the 80s for treating opioid addiction [R<\/a>].<\/p>\n Doctors gave naltrexone to opioid addicts in recovery to prevent relapse. The rationale was to completely shut off the \u2018high\u2019 of abused narcotics. By blocking all receptors in advance, naltrexone renders narcotics powerless.<\/p>\n The dosage needed to achieve opioid blockage is high, ranging from 50 – 100 mg\/day [R<\/a>, R<\/a>].<\/p>\n Note<\/em><\/strong>: Naltrexone shouldn\u2019t be confused with naloxone<\/em> (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 [R<\/a>, R<\/a>].<\/p>\n 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.<\/p>\n By attempting the impossible – using an opioid blocker to enhance the immune response in people with an \u201cuntreatable\u201d disease – Dr. Bihari spurred a lot of attention.<\/p>\n 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<\/a>. Few would stay on it [R<\/a>].<\/p>\n To re-wind: opioid-like endorphins are not only released to help us cope with everyday social situations free of fear, pain, and anxiety<\/a>. They also play an important role in acute stress<\/a> and the fight-or-flight response [R<\/a>].<\/p>\n Interested in the drug\u2019s 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.<\/p>\n Surprisingly, it turned out that a small naltrexone dose (3 – 5 mg) increased endorphins to the same extent as a high dose [R<\/a>].<\/p>\n 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 [R<\/a>].<\/p>\n However, it wasn\u2019t 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.<\/p>\n 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 [R<\/a>].<\/p>\n Despite some encouraging findings and anecdotes, we still know less than we don\u2019t about LDN. Proper, large-scale trials are lacking. Most of the data relies on Dr. Bihari\u2019s observations, small-scale studies, and clinical and personal experiences. Because of this, there\u2019s still insufficient evidence to recommend LDN for any indication.<\/strong><\/p>\n The mechanism outlined here and proposed by Dr. Bihari is considered to be a controversial scientific hypothesis<\/strong>. It hasn\u2019t 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\u2019s claims.<\/p>\n With this in mind, let\u2019s take a look at how LDN is hypothesized to work.<\/p>\n 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% [R<\/a>, R<\/a>].<\/p>\n 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\u2019s thought to increase the activity of opioids [R<\/a>, R<\/a>].<\/p>\n In comparison, high dose naltrexone doses raise endorphins but keeps the receptors constantly blocked, reducing<\/em> their activity as the end result [R<\/a>, R<\/a>].<\/p>\n Dr. Bihari believed that the rise in endorphin levels remains for as long as a person is taking the low dose every night.<\/p>\n Beta-endorphin, one of our main natural opioids, has a long half-life of about 20 hours in the body. It\u2019s unknown for how long other endorphins stay high in the blood.<\/p>\n Endorphins act on different opioid receptors [R<\/a>, R<\/a>, R<\/a>]:<\/p>\n There are several other receptor types that may be important for the action of LDN, but these two appear to play the largest role [R<\/a>].<\/p>\nWhat is Naltrexone?<\/strong><\/span><\/h2>\n
The Story of Opioids<\/strong><\/span><\/h3>\n
The Discovery of LDN<\/strong><\/span><\/h3>\n
Snapshot<\/span><\/h3>\n
Proponents<\/h4>\n
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Skeptics<\/strong><\/h4>\n
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Proposed Mechanism<\/strong><\/span><\/h3>\n
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