Brief Discovery of Low Dose Naltrexone

The increasingly prevalent use of low dose naltrexone and its efficacy in a myriad of diseases have stimulated questions about its effects and mechanisms among prescribers and patients today. A brief history into its discovery may yield answers regarding how this progressive medication works in the treatment of various health conditions such as chronic fatigue, multiple sclerosis, and autoimmune thyroid diseases.

In 1984, naltrexone was first introduced as the FDA-approved drug Trexan as a 50-mg dose to help patients overcome their addiction to heroin. Its mechanism of action involves blocking opioid receptor sites, thus inhibiting the negative effects of opioids. However it also blocked the positive effects of endorphins, which is the body’s own opioid-like hormones that help relieve pain, fear, and anxiety. Due to its blockade of both opioids and endorphins together, its use as an anti-addiction drug failed largely due to its inhibition of the positive effects of endorphins, imparting adverse effects such as extreme tiredness, stomach pains, anxiety, and joint and muscle pain.

In 1985, Dr. Bernard Bihari, a Harvard Medical School graduate treating HIV-infected patients, discovered that his patient population had less than 20% of the normal levels of endorphins, and consequently this low level of endorphins contributed to the weakened immune system in his patients. He made it his goal to find a drug that can raise endorphin levels without completely blocking the opioid receptors. Having closely followed the research and development of naltrexone, he had an idea that naltrexone, being a competitive antagonist of the body’s opioid receptors, might completely block opioid receptors at a high dose of 50mg, but may only be a transient, or temporary, receptor blocker at lower doses.

Through his research, Dr. Bahari found that the body’s highest production of endorphins occurred during the night, between 2:00am and 4:00am specifically. His experiments with varying doses of naltrexone from 1mg to 4.5mg, administered at night before bed, would galvanize the body’s generation of endorphins, healing and boosting the body’s immune system as we sleep. With low doses of naltrexone at a fraction of the dose recommended to treat addicts, the low dose naltrexone boosted endorphin levels by 200 to 300%.

In the aftermath of his discovery, Dr. Bihari performed a placebo-controlled trial with 50 patients infected with HIV, where one group was given low dose naltrexone and the other half placebo. After about 9 months, those who received low dose naltrexone resulted in fewer deaths (8% vs 33% death rate) and fewer opportunistic infections compared to the group who received the placebo.

In his excitement to publicize his discovery, Dr. Bihari met with other physicians treating HIV-infected patients in New York and San Francisco, convincing them to use this novel treatment amongst their own patients. However, the measure of the effectiveness of any HIV treatment at that time was an increase in the CD4 cell count, which is an indication of the health of the immune system. Low dose naltrexone would stop the ongoing decline of CD4 cells in HIV patients, but it would not increase its production. Due to this misunderstood result, low dose naltrexone was not seen as a valid treatment for HIV, and so it was never popularized as a mainstream treatment for autoimmune diseases.

Fortunately, a small but growing population of prescribers and patients are recognizing Dr. Bihari’s discovery of low dose naltrexone and seeing its merits as a possible treatment for diseases of the immune system. Throughout the world, low dose naltrexone has become the cornerstone for current and future clinical studies in the treatment of various autoimmune diseases such as multiple sclerosis, fibromyalgia, and Crohn’s disease, only to name a few. Despite our poor comprehension of its exact mechanism of action, healthcare practitioners are starting to understand that the positive effects of LDN on endorphin levels can be an effective therapy for diseases and conditions that have never before been treated with LDN. Although the clinical research for LDN is still in its infancy, the evidence for the efficacy of LDN will continue to grow as prescribers and patients embrace its clinical utility as a possible treatment approach for autoimmune conditions today.