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Why Should I Take Low-Dose Naltrexone at Night?

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According to the UK-based LDN Research Trust Charity, low-dose naltrexone (LDN) is a safe and effective medication that is not an opioid and is not addictive. It may help relieve pain, control autoimmunity, and reduce inflammation. Naltrexone is approved for treating alcohol and opioid use disorders.1 It is prescribed at a higher dose, which can cause several unpleasant side effects. In the 1980s, Dr. Bernard Bihari used LDN to treat symptoms associated with acquired immune deficiency syndrome (AIDS) by using LDN to boost the immune response. He found that LDN worked better than the traditional higher dose. Since then, clinical uses have continued to increase.2

LDN’s manufacturer does not specify when it should be taken, but many people take it in the morning to reduce insomnia, one of the potential side effects.3 Other people take LDN at night because it may cause drowsiness, fatigue, and dizziness, making it hazardous to drive or operate heavy equipment. It has historically been prescribed for nighttime use because most endorphins are produced at night.3 However, studies show the same effect occurs during the daytime. Depending on potential side effects and what works best with your schedule, take LDN in the morning or at night.

Should Low-dose Naltrexone(LDN) Be Taken On An Empty Stomach?

Some people experience nausea when taking LDN. Taking LDN with a meal can help reduce this. 

What Dose Of LDN Should I Take? 

The best answer to this question is the dose that is prescribed for you. The typical LDN dosage is 1.5 mg to 5 mg daily.3 Many people start at an even lower dose than the recommended dose because of side effects and need to slowly titrate their dosage upward. LDN does not work quickly and may take some time before you notice any noticeable changes in your symptoms.

What Are The Side Effects Of LDN?

Side effects from LDN are uncommon, and when they occur, they are typically mild. Reported side effects from LDN include: 

  • Difficulty sleeping
  • Nightmares
  • Unusual dreams
  • Nausea
  • Weight loss
  • Prolonged erections
  • Headaches

Starting out with a low dose of naltrexone and slowly increasing it helps your body get used to it and reduces side effects. 

pharmacist looking at a drug label

What Is LDN Used For?

Naltrexone is a life-saving medication for people with opioid addiction. Scientists are still learning about all the ways low-dose naltrexone (1/10th the dose) can be used to treat medical conditions. Low-dose naltrexone is used to treat:4,5 

  • Weight loss
  • Cancer
  • Chronic fatigue syndrome
  • Fibromyalgia
  • Autoimmune thyroid disorders
  • Multiple sclerosis
  • Crohn’s disease
  • Rheumatoid arthritis
  • Psoriasis
  • Skin conditions
  • Pain control
  • Autism
  • Stress

These uses are off-label. While no clinical trials have been conducted to demonstrate its efficacy, researchers found that patients’ pain and other symptoms improved more on lower doses of naltrexone than on the higher doses used to treat opioid addiction. This is counterintuitive because, typically, we assume higher doses will yield more benefits.

Researchers need to separate true effects from placebo when evaluating drug effects. A drug with more benefits at a lower dose suggests the effects are true. However, LDN lacks high-powered clinical trials to test its safety and efficacy.

Who Should Not Take LDN?

LDN is contraindicated for anyone taking opioids or other pain medications. LDN is a pure opioid antagonist. Taking LDN while taking opioids could cause a serious and dangerous withdrawal reaction. Do not take LDN if you have hepatitis or liver failure. People who have had organ transplants and are taking immunosuppressive drugs permanently are cautioned against using LDN.

Examples of opioids: 

  • Heroin
  • Codeine
  • Morphine
  • Oxycodone
  • Tramadol
  • Hydrocodone
NOM Infographic

How Does LDN Work? 

LDN works by temporarily binding and blocking opioid mu receptors. These receptors are found throughout the nervous system, the gastrointestinal tract, and lymphocytes. LDN binds for about one hour, and the effects last for 4 to 6 hours. When the receptor is temporarily blocked, your brain responds by producing more opioids. An increase in opioids has many effects on the body. The most significant is reducing pain. Increased opioid levels persist in the body for about 18 to 24 hours.6 

LDN blocks toll-like receptor (TLR)-4 receptors found on immune cells (macrophages) and reduces inflammation. Activated microglial cells in the brain produce pro-inflammatory chemicals called cytokines.3 Inflammatory chemicals increase blood flow and cause swelling, redness, and pain. The inflammatory response is meant to fight pathogens, but when activated unnecessarily, the inflammatory process causes you to feel ill without the benefits. 

Many of the benefits associated with LDN are due to increased natural opioid release and decreased inflammation. More research is needed in this area.

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Does Low-dose Naltrexone(LDN) Make You Gain Weight?

LDN can cause decreased appetite and cravings, which can cause weight loss. Weight gain is not typically a side effect associated with LDN. 

LDN may help people lose weight by reducing insulin resistance, restoring growth hormone levels, controlling appetite, improving sleep, and optimizing thyroid hormone. 7

  • Insulin resistance is when the body cannot effectively convert carbohydrates into energy
  • Low-dose naltrexone may help restore growth hormone to physiological levels
  • Low-dose naltrexone helps you resist cravings for unhealthy foods
  • Sleep and weight loss are interconnected. Poor sleep causes fatigue, low energy, lower motivation to exercise and resist unhealthy food choices. Weight gain can increase the risk of sleep apnea, which alters sleeping patterns
  • Low-dose naltrexone may help optimize thyroid function

LDN is a safe and effective medication that naturally increases opioids and decreases inflammation. It is prescribed off-label because there are few clinical trials showing its benefits. This is likely because LDN is a cheaper, generic medication, which makes it difficult to get the financial support necessary to fund a clinical trial. Another potential drawback of using LDN is that the only currently available form is a 50-mg tablet, unless you are prescribed LDN and a compounding pharmacy fills it. 

From The Expert: Maybell Nieves, M.D.

Low-dose naltrexone (LDN) is sometimes used for chronic pain and autoimmune conditions, though it’s not FDA-approved for these uses. It’s thought to work by briefly blocking opioid receptors, which may then lead to an increase in the body’s natural opioid production and a reduction in inflammation. Typical doses for LDN range from 0.5 mg to 4.5 mg daily, often taken at night. While generally well-tolerated, common side effects can include sleep disturbances and vivid dreams, especially when starting treatment.

It’s crucial to avoid LDN if you are taking opioid medications, as it can block their effects and potentially trigger opioid withdrawal symptoms. Always discuss all your medications with your doctor before starting LDN. If you experience severe side effects or your condition worsens, seek medical attention promptly. The evidence supporting LDN for many conditions is still developing, and more research is needed.

Written by

Leann Poston M.D.
Leann Poston M.D.
Licensed Physician and Medical Content Reviewer
Dr. Leann Poston is a licensed physician in the state of Ohio who holds an M.B.A. and an M. Ed. She is a full-time medical communications writer and educator who writes and researches for Invigor Medical. Dr. Poston lives in the Midwest with her family. She enjoys traveling and hiking. She is an avid technology aficionado and loves trying new things.

Medically Reviewed By

Maybell Nieves, M.D.
Maybell Nieves, M.D.
General Surgery / Medical Reviewer
Dr. Maybell Nieves is an internationally trained general and breast surgeon—graduate of the European Oncology Institute and University of Milan—who serves as academic coordinator and breast surgeon at the Universitary Hospital of Caracas, manages high-volume oncologic care and fellow training, pioneered a breast surgery unit, and partners with nonprofits on early detection and awareness.
Medical Review Process
Every article on Invigor Medical is reviewed by licensed medical professionals to ensure accuracy, clarity, and clinical relevance. Our editorial team works closely with practitioners to verify that content reflects current research, guidelines, and best practices.
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Medical treatments discussed on this site may not be appropriate for everyone. All medications require a prescription from a licensed healthcare provider following an appropriate telehealth consultation, and treatment decisions should be made on an individual basis.
Leann Poston M.D.
Leann Poston M.D.
Licensed Physician and Medical Content Reviewer
Dr. Leann Poston is a licensed physician in the state of Ohio who holds an M.B.A. and an M. Ed. She is a full-time medical communications writer and educator who writes and researches for Invigor Medical. Dr. Poston lives in the Midwest with her family. She enjoys traveling and hiking. She is an avid technology aficionado and loves trying new things.

Medication Disclaimer

Important Safety Information

Maybell Nieves, M.D.
Maybell Nieves, M.D.
General Surgery / Medical Reviewer
Dr. Maybell Nieves is an internationally trained general and breast surgeon—graduate of the European Oncology Institute and University of Milan—who serves as academic coordinator and breast surgeon at the Universitary Hospital of Caracas, manages high-volume oncologic care and fellow training, pioneered a breast surgery unit, and partners with nonprofits on early detection and awareness.