Naltrexone, traditionally prescribed in high doses (50 mg or more) to help individuals overcome opioid or alcohol dependence, has recently gained attention for its other uses, including its potential in weight loss. Low dose naltrexone (LDN) means taking a dose of naltrexone that is up to one-tenth, or 10%, of the dose that is usually taken for opioid addiction.
How LDN Works
LDN’s mechanism is unique. It temporarily blocks opioid receptors in the brain for a few hours, triggering a rebound effect that increases the body’s endorphin production. This is called a paradoxical effect. At low dosages, naltrexone appears to “trick” the brain into producing more natural opioids (these are called endogenous opioids). It does this by binding briefly to opioid receptors, blocking our naturally occurring opioids from binding. Our body counteracts this by producing more naturally occurring opioids to "wash off" the low dose naltrexone. 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.
Low dose naltrexone also appears to have anti-inflammatory effects by regulating microglial cells which have a key role in general and nerve inflammation. When microglial cells are activated, they produce pro-inflammatory cytokines, free radicals (reactive oxygen species), and nitric oxide - all of these substances have been associated with pain, inflammation, fatigue, feeling rundown or like you have come down with something.
LDN and Weight Loss: The Potential Benefits
It is possible that low dose naltrexone may help with weight loss because lower dosages of naltrexone are thought to curb hunger and food cravings. Here's how it may contribute to weight management:
- Controls Appetite: LDN can help control your appetite. It works on the part of the brain that tells you when you’re hungry or full. LDN influences opioid receptors involved in food cravings and addictive eating behaviors.
- Reduces Inflammation: Inflammation in the body can make it hard to lose weight. Chronic inflammation contributes to obesity, insulin resistance, and metabolic syndrome.
- Improves Insulin Sensitivity: If your body uses insulin better, you’re likely to store less fat.
- Better Sleep: Good sleep is important for losing weight. Poor sleep can mess up hormones that control hunger and weight. Many patients report improved sleep quality on LDN, which can further reduce inflammation, stabilize mood, and support metabolism.
LDN vs. Contrave and Wegovy
Contrave is a long-acting tablet that contains 8mg of naltrexone and 90mg of bupropion that is FDA approved for weight loss in people who are overweight or obese with at least one weight-related condition such as high blood pressure or type 2 diabetes. In clinical trials, 36% to 48% of patients taking Contrave lost at least 5% of body weight.
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Wegovy, one brand name for semaglutide, has also emerged as a promising option in the battle against obesity. Originally used as a treatment for type 2 diabetes under the name Ozempic, semaglutide has shown remarkable effectiveness in promoting weight loss.
How Wegovy Works
- Appetite Suppression: Wegovy helps reduce appetite by acting on the brain regions responsible for hunger.
- Slows Down Stomach Emptying: Semaglutide slows the rate at which food leaves the stomach, increasing feelings of fullness.
Both medications require medical supervision and should be part of a comprehensive weight management plan that includes dietary changes and increased physical activity. Wegovy, by contrast, might be more fitting for individuals with a BMI of 30 or higher, or 27 with an additional weight-related condition, who can tolerate the initial side effects and afford the higher cost. Ultimately, the choice between LDN and Wegovy should be guided by a healthcare provider and tailored to the individual’s health profile, weight loss goals, and lifestyle. LDN also pairs well with GLP-1 agonists (e.g., Saxenda, Wegovy), particularly for patients with PCOS or leptin resistance. Leptin is the hormone that tells your brain when you’re full and regulates fat storage. Many overweight individuals develop leptin resistance, meaning their brain doesn’t recognize signals to stop eating.
Considerations and Precautions
Low dose naltrexone blocks opioid receptors and can precipitate opioid withdrawal, so it is important that you do not take any opioid (narcotic) pain relieving drugs at the same time as low dose naltrexone. Tell your doctor or other health care provider of any recent use of opioids or any history of opioid dependence before starting low dose naltrexone to avoid having an opioid withdrawal. If you are on opioids long term for conditions such as chronic fatigue and do not want to stop them, then you cannot take low dose naltrexone.
Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during therapy. If you think you have become pregnant while using this medicine, tell your doctor right away.
Do not take naltrexone and bupropion combination with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]). Do not start taking naltrexone and bupropion combination during the 2 weeks after you stop a MAO inhibitor. Wait 2 weeks after stopping naltrexone and bupropion combination before you start taking a MAO inhibitor. If you take them together or do not wait 2 weeks, you may have confusion, agitation, restlessness, stomach or bowel symptoms, a sudden high body temperature, an extremely high blood pressure, or severe seizures.
Read also: Weight Loss with Semaglutide
Do not use naltrexone and bupropion combination if you are also using Zyban® to quit smoking or Aplenzin® or Wellbutrin® for depression, because they also contain bupropion. Also, do not take this medicine if you are using or have used narcotic drugs (eg, buprenorphine, methadone, or other habit-forming painkillers) within the past 7 to 10 days.
This medicine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell the doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. If you or your caregiver notice any of these side effects, tell your doctor right away.
You have a higher risk of accidental overdose, serious injury, or death if you use heroin or any other narcotic medicine while you are being treated with naltrexone and bupropion combination. Also, naltrexone prevents you from feeling the effects of heroin if you use it.
Do not stop taking this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely. This is to decrease the chance of having certain side effects when you stop the medicine, such as agitation, anxiety, dizziness, a feeling of constant movement of self or surroundings, headaches, increased sweating, nausea, trembling or shaking, trouble with sleeping or walking, or unusual tiredness.
Your blood pressure might get too high while you are using this medicine. This may cause headaches, dizziness, or blurred vision. You might need to measure your blood pressure at home. If you think your blood pressure is too high, call your doctor right away.
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This medicine may cause a serious allergic reaction, including anaphylaxis, which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, swelling of the face, tongue, or throat, trouble breathing, or chest pain.
Serious skin reactions (eg, Stevens-Johnson syndrome) can occur with this medicine. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, red skin lesions, severe acne or skin rash, sores or ulcers on the skin, or fever or chills with this medicine.
Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.
Check with your doctor right away if blurred vision, eye pain, or any other change in vision occurs during or after treatment. Your doctor may want your eyes be checked by an ophthalmologist (eye doctor).
This medicine may increase the risk of hypoglycemia (low blood sugar) in patients with diabetes. Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms of low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. You should check your blood sugar before you start treatment and while you are taking this medicine.
Drinking alcoholic beverages should be limited or avoided, if possible, with this medicine.
Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.
Side Effects of LDN
Side effects with low dose naltrexone are uncommon because the dose is so low and have been reported by less than 8% of people. Low dose naltrexone is unlikely to cause the same side effects as high dose naltrexone. Difficulty sleeping initially was reported by approximately 8% of people receiving low dose naltrexone but this resolved within two weeks in most people. 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. The long term side effects of low dose naltrexone are unknown because research has not investigated what happens to people who take the medication long term.
LDN Dosage
Typical LDN doses range from 1.5mg to 4.5mg per day. Providers often start at a low dose (0.5mg) and slowly titrate up to find the individual’s optimal dose. It may take up to 8 to 10 weeks for low dose naltrexone to work. Important: Never attempt to split or crush a full-strength naltrexone tablet. At Thrive Wellness, we partner with reputable compounding pharmacies to ensure your LDN dose is tailored to your condition, lifestyle, and goals.
LDN for Other Conditions
Most studies investigating low dose naltrexone have been small with most reporting a favorable effect for conditions such as fibromyalgia, Crohn's disease, and pain.
Two, separate small clinical trials investigated low dose naltrexone for fibromyalgia. A 28.8% reduction in baseline pain and a decrease in symptoms such as general satisfaction with life and improved mood (but not improved fatigue or sleep) was reported by 31 women in one trial.
88% of people assigned low dose naltrexone (4.5mg/day) had at least a 70-point decline in the Crohn’s Disease Activity Index score (CDAI) after 12 weeks compared to 40% of placebo-treated patients (n=40). There was also a 5-point decline in the Crohn’s disease endoscopy index severity score in 78% of people taking low dose naltrexone compared with 28% taking placebo.
User reviews for low dose naltrexone has been mostly favorable with an average rating of 7.0 out of 10 from a total of 61 ratings for using low dose naltrexone for the off-label treatment of Fibromyalgia. 62% of reviewers reported a positive experience, while 25% reported a negative experience. Comments included "Naltrexone has been a Godsend for me", "I have Lupus, Fibromyalgia and severe arthritis in my neck. Naltrexone is the only drug that has worked", and "Naltrexone has changed my life in almost every way! Cured: fibromyalgia, rheumatoid arthritis, and Cushing disease!
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