Low Dose Naltrexone

Naltrexone was synthesized in 1963 as an orally active competitive opioid receptor antagonist. Naltrexone HCl was approved by FDA in 1984 for the treatment of opioid addiction.

Low-dose naltrexone (LDN) is a medication that has gained attention for its potential therapeutic benefits in various medical conditions. Naltrexone is an opioid receptor antagonist, which means it blocks the effects of opioids and can be used to treat opioid addiction.

However, when used at a much lower dose than the standard dose for addiction treatment, LDN has shown some interesting effects that have generated interest in the medical community. LDN is used at a significantly lower dose (typically 1-5 mg) compared to the standard dose used for opioid addiction treatment (50 mg).

It may take up to 8 to 10 weeks for low dose naltrexone to work. It is important to keep taking it until at least then to know if it works for you.

The idea behind LDN is to harness its potential immune-modulating[1] and anti-inflammatory properties. LDN is often used off-label for various autoimmune diseases[2], such as multiple sclerosis[3], rheumatoid arthritis[4], Crohn’s disease[5], and Hashimoto’s thyroiditis[6]. Some individuals with chronic pain conditions, including fibromyalgia[7] and complex regional pain syndrome[8], have reported improvements with LDN.

LDN may have potential benefits in conditions like depression and bipolar disorder, although more research is needed in this area. There is ongoing research into LDN’s potential role in cancer treatment, particularly for certain types of tumors.

You should not use low dose naltrexone treatment if you:
  • Are receiving opioid (narcotic) analgesics
  • Are addicted to opioids
  • Are withdrawing from opioids or have symptoms of opioid withdrawal
  • Have failed a naloxone challenge test[9] or have a positive urine screen for opioids
  • Have acute hepatitis but may be allowed in patients with stable or compensated cirrhosis after considering the risks versus benefits
  • Are allergic to or have had a hypersensitivity reaction to naltrexone, polylactide-co-glycolide (PLG)[10], or any other diluent or inactive ingredient in the product.

LDN is believed to work by briefly blocking opioid receptors, which in turn stimulates the body to produce more endorphins[11]. This increase in endorphins may help regulate the immune system and reduce inflammation. The use of LDN is considered experimental, and its efficacy is not universally accepted.

Low dose naltrexone is usually well tolerated with few side effects. Some people need a more gradual increase in their dosage to help them tolerate the drug. Low dose naltrexone should be started at an extremely low dose, such as 1 to 1.5mg/day, and the dosage should be increased by 1mg every week to a maximum of 4.5 mg/day.

Some individuals have reported symptom improvements, particularly in autoimmune diseases, chronic pain, and mood disorders. Research on LDN is ongoing, and more studies are needed to establish its effectiveness in various conditions. LDN is generally well-tolerated when used at low doses. Common side effects are usually mild and may include sleep disturbances, vivid dreams, and mild gastrointestinal symptoms.

Low dose naltrexone has a very short half-life – around 4 to 6 hours – which means its binding effects wear off quickly, but this is long enough to boost levels of naturally occurring opioids for 18 to 24 hours. Endogenous opioids[12] are natural pain relievers and having more of these around in the body is one of the ways low dose naltrexone is thought to work.

LDN should not be taken in conjunction with opioids or opioid-containing medications, as it can block their effects and lead to withdrawal symptoms. Consult with a healthcare provider before using LDN if you are pregnant or breastfeeding. LDN may interact with other medications, so inform your doctor of any other drugs you are taking. Patient affinity for LDN may be driven somewhat by the “low-dose” preface,

which can be agreeable to individuals who have experienced negative side effects from other medications. Clinicians prescribing LDN should be aware that many patients will come into the treatment with considerable expectations which could drive placebo effects. Patients may even approach a clinician with a specific request to be prescribed LDN.

The totality of the basic and clinical research to date suggests that LDN is a promising treatment approach for chronic pain conditions thought to involve inflammatory processes.

Some of the most common side effects of naltrexone include headache, loss of appetite, fatigue, constipation, and vivid dreams.

Conditions that can be treated with LDN
  • Autoimmune cardiomyopathy
  • Diabetic myopathy
  • Multiple sclerosis
  • Eczema 
  • Psoriasis
  • Cushing’s syndrome
  • Crohn’s disease
  • Hashimoto’s thyroiditis
  • Diabetes mellitus type 1
  • Hypothyroidism
  • Celiac disease
  • Inflammatory bowel disease
  • Ulcerative colitis
  • Hepatitis C
  • Epstein Barr virus
  • Vitiligo
  • HIV
  • Lyme disease
  • Certain types of cancers
  • Multiple myeloma
  • Guillain-Barre syndrome
  • Kawasaki’s disease
  • Autism
  • Anxiety disorders
  • Lupus
  • Post-traumatic stress disorder
  • Emphysema
  • POEMS syndrome
  • Fibromyalgia
  • Rheumatoid arthritis
  • Vasculitis
  • Endometriosis
  • Infertility
  • Polycystic ovary syndrome
  • Traumatic brain injuries
  • Skin Diseases

  1. Immune modulation refers to the process of altering or regulating the activity of the immune system, often with the goal of achieving a balanced and appropriate immune response. This can involve enhancing the immune system’s defenses against infections or cancer while also reducing autoimmune reactions or excessive inflammation. Immune-modulating interventions may include the use of medications, such as corticosteroids, immunosuppressants, or immunomodulators, as well as lifestyle changes, diet, and other therapies aimed at optimizing immune function to maintain health. The concept of immune modulation is important in the context of various medical conditions, particularly autoimmune diseases and inflammatory disorders, where the immune system’s actions need to be carefully regulated. [Back]
  2. Autoimmune diseases are a group of disorders in which the immune system mistakenly targets and attacks the body’s own cells and tissues, leading to chronic inflammation and damage. These conditions can affect various organs and systems, and they often result from a complex interplay of genetic, environmental, and immunological factors. Common autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, and celiac disease, among many others. The immune system, which is designed to defend against external threats like infections, becomes dysregulated in autoimmune diseases, leading to an attack on healthy tissues. Treatment typically focuses on suppressing the immune response and reducing inflammation to manage symptoms and prevent further damage. [Back]
  3. Multiple sclerosis (MS) is a chronic and often disabling autoimmune disease of the central nervous system, characterized by inflammation, demyelination (damage to the protective myelin sheath surrounding nerve fibers), and the formation of scar tissue. This complex neurological disorder can lead to a wide range of symptoms, including fatigue, muscle weakness, impaired coordination, sensory disturbances, and cognitive impairments. The exact cause of MS is not fully understood, but it is believed to involve a combination of genetic predisposition and environmental factors. There is no cure for MS, but various treatments, including disease-modifying medications, can help manage symptoms, slow the progression of the disease, and improve the quality of life for those affected by this condition. [Back]
  4. Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints, leading to inflammation, pain, and joint damage. In RA, the body’s immune system mistakenly attacks the synovium, the lining of the membranes that surround the joints. This abnormal immune response causes inflammation, which can result in joint swelling, pain, stiffness, and eventually joint deformities. RA is a systemic disease, meaning it can affect other organs and systems beyond the joints, leading to complications such as cardiovascular issues, lung problems, and fatigue. While the exact cause of RA is not fully understood, genetic and environmental factors are believed to play a role in its development. Treatment for RA aims to reduce inflammation, relieve symptoms, and slow the progression of the disease, often involving a combination of medications, physical therapy, and lifestyle modifications. [Back]
  5. Crohn’s disease is a chronic inflammatory bowel disease (IBD) characterized by inflammation and damage in various parts of the digestive tract, most commonly the small intestine and colon. It is an autoimmune condition where the immune system mistakenly attacks the gastrointestinal tract, leading to a range of symptoms including abdominal pain, diarrhea, weight loss, and fatigue. Crohn’s disease is associated with periods of flares and remissions, and it can result in complications such as strictures, fistulas, and malabsorption of nutrients. While the exact cause of Crohn’s disease remains unclear, it is thought to involve genetic predisposition and environmental factors. Treatment typically focuses on managing inflammation, alleviating symptoms, and improving the quality of life for individuals with the condition. [Back]
  6. Hashimoto’s thyroiditis, also known as chronic lymphocytic thyroiditis, is an autoimmune disorder that primarily affects the thyroid gland. In Hashimoto’s, the body’s immune system mistakenly attacks the thyroid tissue, leading to chronic inflammation and progressive damage to the gland. This results in an underactive thyroid (hypothyroidism), which can cause a range of symptoms including fatigue, weight gain, cold intolerance, and depression. Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the United States and is more common in women than in men. While the exact cause of Hashimoto’s is not fully understood, it is thought to involve a combination of genetic and environmental factors. The condition is typically managed with thyroid hormone replacement therapy to restore normal thyroid function. [Back]
  7. Fibromyalgia is a complex and chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, and often accompanied by sleep disturbances, cognitive difficulties, and mood disturbances. It is considered a central sensitization disorder, where the central nervous system becomes hypersensitive to pain signals, amplifying pain sensations throughout the body. The exact cause of fibromyalgia is not fully understood, but it is believed to involve a combination of genetic, environmental, and neurological factors. Diagnosing fibromyalgia can be challenging as it is primarily based on clinical symptoms and the exclusion of other medical conditions. Management typically includes a multimodal approach that may include medication, physical therapy, and lifestyle modifications to improve the quality of life for those affected. [Back]
  8. Complex Regional Pain Syndrome (CRPS), formerly known as Reflex Sympathetic Dystrophy (RSD), is a chronic and debilitating neurological condition characterized by severe, continuous pain that is out of proportion to the initial injury, often accompanied by sensory changes, skin color and temperature abnormalities, and motor dysfunction. CRPS is believed to result from abnormal responses of the sympathetic nervous system to trauma or injury, leading to a vicious cycle of pain and dysfunction. This condition can affect any part of the body and may lead to long-term disability if not properly managed. Early diagnosis and a multimodal treatment approach, which may include physical therapy, medications, and sympathetic nerve blocks, are crucial for improving the outcomes for individuals with CRPS. [Back]
  9. A naloxone challenge test is a medical procedure used to diagnose opioid dependence or assess a patient’s physical dependence on opioids. It involves the administration of naloxone, an opioid receptor antagonist, which quickly reverses the effects of opioids and can precipitate withdrawal symptoms in opioid-dependent individuals. If a patient exhibits withdrawal symptoms, such as sweating, anxiety, and other signs of opioid withdrawal, following naloxone administration, it suggests physical dependence on opioids. The naloxone challenge test can help healthcare professionals evaluate a patient’s opioid dependence and guide appropriate treatment strategies, such as medication-assisted treatment for opioid use disorder. [Back]
  10. Polylactide-co-glycolide (PLG) is a biodegradable and biocompatible copolymer commonly used in the pharmaceutical and medical fields. It is synthesized by combining polylactic acid (PLA) and polyglycolic acid (PGA) monomers. PLG’s unique properties, such as controlled biodegradability, tunable degradation rates, and minimal toxicity, make it an excellent material for drug delivery systems, including microspheres, nanoparticles, and implantable devices. These drug delivery systems can be designed to release therapeutic agents gradually over time, enhancing drug efficacy and reducing side effects. PLG has found extensive applications in the development of sustained-release formulations for a wide range of pharmaceutical and medical applications, from vaccines to tissue engineering. [Back]
  11. Endorphins are natural chemicals produced by the body that act as neurotransmitters in the brain. They are often referred to as “feel-good” or “pain-relieving” molecules because they have the ability to reduce pain and induce a sense of well-being. Endorphins are released in response to various stimuli, such as exercise, stress, pain, and pleasurable activities. They bind to the body’s opioid receptors, leading to pain relief and a boost in mood. The term “endorphin” is derived from “endogenous morphine,” emphasizing their morphine-like properties. Endorphins play a crucial role in the body’s natural pain management system and are associated with the “runner’s high” experienced during vigorous exercise, as well as the relief from stress and discomfort. [Back]
  12. Endogenous opioids, often referred to as endorphins, enkephalins, and dynorphins, are naturally occurring molecules within the human body that act as neurotransmitters and neuromodulators. They are part of the body’s endogenous pain control system and play a crucial role in modulating pain perception, mood, and stress responses. Endogenous opioids bind to specific receptors in the central and peripheral nervous systems, influencing various physiological and psychological processes, including pain relief and mood regulation. These molecules are produced in response to stress, pain, and pleasurable activities, and their effects are similar to exogenous opioids like morphine, providing a sense of well-being and analgesia. The interaction between endogenous opioids and their receptors is a complex and tightly regulated system that is essential for maintaining overall homeostasis in the body. [Back]

Further Reading


Author: Doyle

I was born in Atlanta, moved to Alpharetta at 4, lived there for 53 years and moved to Decatur in 2016. I've worked at such places as Richway, North Fulton Medical Center, Management Science America (Computer Tech/Project Manager) and Stacy's Compounding Pharmacy (Pharmacy Tech).

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