# Naltrexone (low-dose)

Category: Drugs & Compounds

Also known as: naltrexone, LDN, low-dose naltrexone

Naltrexone, in its low-dose application, is an opioid antagonist that Ray Peat recommended as a short-term intervention to disrupt pathological cycles driven by endorphins. Peat explained that endorphins, the body's endogenous opioids, are produced as a protective emergency…

9 passages · 1 author · 2009–2021 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/naltrexone-low-dose

## Synthesis

**Naltrexone**, in its low-dose application, is an opioid antagonist that Ray Peat recommended as a short-term intervention to disrupt pathological cycles driven by **endorphins**. [Source 1, 3, 6] Peat explained that endorphins, the body's endogenous opioids, are produced as a protective emergency response to stress signals, particularly *lactic acid* generated during hypothyroidism and fatigue. [Source 3, 6] He described these accumulated endorphins as limiting physiological functions in a protective, localized "hibernation" state, and he argued that low-dose naltrexone or naloxone could clear these endorphins, sometimes lifting a person out of depression or a lethargic state within two or three days. [Source 3, 6]

The dosing strategy Peat advocated was sharply distinct from the standard 50 mg dose used for addiction. He consistently cited effective doses of **1 to 4 milligrams**, noting that some individuals find a therapeutic effect with even a hundredth of a milligram. [Source 1, 2, 5] Sarah Murray specified that the effective range is between 2 and 5 milligrams, and Peat confirmed that if the drug is working, the effect is noticeable after the first few milligrams. [Source 1, 8] He emphasized that the treatment should be brief, typically lasting only a few days, and he did not recommend continuous use. [Source 4] Peat advised repeating these short courses only two or three times a year if needed, with a waiting period of two weeks or more to assess whether the process should be repeated. [Source 4, 5]

Mechanistically, Peat connected the need for naltrexone to a fundamental energy deficit. He taught that the hypothyroid state increases *lactic acid* production at the expense of carbon dioxide, and this lactic acid is the primary driver of endorphin production. [Source 1, 3] Therefore, while naltrexone could break the immediate cycle of opioid-driven torpor, Peat considered the basic treatment to be a good diet and thyroid supplementation to restore oxidative metabolism and keep endorphins down. [Source 1, 3, 6] He also noted that exogenous opioids like fentanyl can activate inflammatory histamine pathways, creating a self-perpetuating cycle that a short course of naltrexone can interrupt by blocking the morphine or endorphin effect. [Source 8]

Peat observed that the balance of endorphins could manifest in lateralized physical symptoms, with some individuals developing all their symptoms on one side of the body due to the predominant type of endorphin being produced. [Source 1] He referenced a study where demented patients given large doses of naloxone for several weeks showed cognitive improvement simply from blocking endorphins, and he related this to the way naloxone withdrawal in old rats could cause either exaggerated skin flushing or no flush at all, depending on their baseline body temperature. [Source 6, 9] While Peat considered the drug safe for short-term use, he cautioned against the long-term use of other dopamine agonists like pramipexole, which he did not consider safe. [Source 3, 7]

## People also ask

### How does low-dose naltrexone break a cycle of fatigue?

Peat argued that stress-induced lactic acid triggers protective endorphins that create a lethargic "hibernation" state, and a short course of low-dose naltrexone clears these endorphins, sometimes lifting depression or fatigue within days.

### What dose of naltrexone did Ray Peat recommend?

Peat recommended 1 to 4 milligrams, with some individuals responding to even a hundredth of a milligram, and noted the effect should be noticeable after the first few milligrams.

### Why did Peat consider naltrexone only a short-term fix?

He viewed the underlying cause as a hypothyroid energy deficit that increases lactic acid and endorphins, so while naltrexone could interrupt the cycle, the basic treatment required thyroid supplementation and a good diet to restore oxidative metabolism.

## Related concepts

- [Hypothyroidism](https://bioenergeticoracle.com/md/concepts/hypothyroidism/index.md)
- [Biotin](https://bioenergeticoracle.com/md/concepts/biotin/index.md)
- [Chronic Fatigue Syndrome](https://bioenergeticoracle.com/md/concepts/chronic-fatigue-syndrome/index.md)
- [Estradiol](https://bioenergeticoracle.com/md/concepts/estradiol/index.md)
- [Estrogen-serotonin axis](https://bioenergeticoracle.com/md/concepts/estrogen-serotonin-axis/index.md)
- [Glucose](https://bioenergeticoracle.com/md/concepts/glucose/index.md)

## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — KMUD - October 15, 2021

Ray Peat · Interview · Oct 17, 2021

> **Sarah Murray:** But make sure that if you're going to ask your doctor that you request low-dose naloxone or naltrexone, not the normal dose. The normal dose is 50 milligrams, so you need something more around between 2 and 5 milligrams.
>
> **Ray Peat:** And if it's working, you can tell after the first few milligrams. It can break the cycle in just one day, but sometimes two or three days is okay.
>
> **Caller:** Oh, and how do you spell the two words so that I'm sure to say them correctly to the doctor?
>
> **Ray Peat:** N-A-L-O-X-O-N-E or N-A-L-T-R-E-X-O-N-E.
>
> **Caller:** Okay. And is it given through orally or intravenously?
>
> **Ray Peat:** Orally.
>
> **Sarah Murray:** Orally. Okay. And, in fact, Dr. Peat, you recommend that for anyone who's ever used any opiate medication, a one- to five-day use of low-dose naltrexone to reset the endogenous opiates, opiates our body produces after we come off any type of pain medication that contains opiate.
>
> **Ray Peat:** Yeah, there are numerous types of endogenous opiates or endorphins. Experimenters have shown that a particular balance, The left side of the body and the right side of the body use different endorphins for suppression against injury. Some people who are developing cancer, for example, will have all of their symptoms on one side of the body because of the predominant type of endorphin they're producing.

### Source 2 — Ask the Herb Doctor: Progesterone vs Estrogen, Listener Questions (Part 2)

Ray Peat · Interview · May 18, 2018

> ## Chronic Fatigue Syndrome and Naltrexone
>
> **Shauna (Caller):** Regarding Chronic Fatigue Syndrome (CFS), what is the underlying condition? Is it hypometabolism? Also, is Low Dose Naltrexone (LDN) effective for CFS?
>
> **Ray Peat:** One way of thinking of CFS is that it is very similar to the seizure state in the brain, or the failure state in the heart, under the influence of low progesterone and excess estrogen. It is a deficiency of energy where the cell goes into that swollen, over-excitable state. When a cell is in very bad condition, it can produce histamine. In the hypothyroid, low-progesterone chronic state, the body tends to locally produce a lot of histamine and other inflammatory substances.
>
> **Andrew Murray:** What do you think about Low Dose Naltrexone?
>
> **Ray Peat:** I have experience using Naloxone more than Naltrexone, but they are essentially identical. I found that 1 to 4 milligrams per day of Naloxone would break a depressed condition by suppressing the endorphins, which are induced by lactic acid and fatigue. Endorphins are an emergency measure to turn off excitation. Some people use even a hundredth of a milligram and find a therapeutic effect. I consider 4 milligrams a fairly large dose.

### Source 3 — Ask the Herb Doctor: Thyroid, Polyunsaturated Fats and Oils

Ray Peat · Interview · Apr 1, 2009

> ## Caller: Hashimoto's and Naltrexone
>
> **Caller 3 (Kevin):** I was diagnosed with Hashimoto's disease. Can Dr. Peat speak about that and the use of Low Dose Naltrexone (LDN)?
>
> **Ray Peat:** Hashimoto's was originally defined as infiltration of white blood cells into the inflamed thyroid gland. Since they don't like to cut out a piece of the gland to confirm that, they look for antibodies in the blood. However, anti-thyroid antibodies overlap with many other problems, including arthritis, so they aren't strictly diagnostic. They do indicate inflammation. Since the thyroid is the basic anti-inflammatory hormone, often the thyroid is the main problem. Studies show that supplementing with thyroxine can decrease antibodies. Regarding Naltrexone: When you are hypothyroid and produce lactic acid, you accumulate endorphins. Endorphins limit physiological functions in a protective way, like hibernation. Naltrexone clears those out. Sometimes in two or three days, a person can come out of depression or a lethargic state.
>
> **Caller 3:** Is there any problem with long-term use?
>
> **Ray Peat:** No, but I usually see good results in just two or three days. I think the basic treatment is a good diet and thyroid supplement. Naltrexone is good to try to break up a pattern.

### Source 4 — Ray Peat Email Advice Depository — Post 32

Ray Peat · Email · Feb 6, 2013

> ## Thread 10
>
> **Question:** [Treatments for multiple sclerosis, combined with paranoia in menopause]
>
> **Ray Peat:** For multiple sclerosis, thyroid and progesterone are the most helpful things. Sometimes a very low thyroid function is compensated by extreme nerve excitation, leading to mania or paranoia. Their body temperature might be extremely low, or sometimes the 24 hour cycle is reversed; if the temperature decreases in the morning, that suggests that the stress hormones were very high during the night. [references]
>
> **Question:** [on LDN treatment]
>
> **Ray Peat:** I think it's safe to take 5 or 10 mg of naltrexone daily for a few days, but I don't think it should be used continuously; I have known people who had good results, repeating the short courses two or three times in a year. Estrogen can cause ovarian cysts to develop, and can contribute to the development of skin tags and moles. Its effects on the urethra might help with incontinence, but it can cause problems with the bladder muscle, and cystitis.

### Source 5 — Ray Peat Email Advice Depository — Post 456

Ray Peat · Email · Feb 18, 2018

> **Question:** On Naltrexone dosage to stimulate lutenizing hormone: I have 50mg pills, do you think the low-dose or normal dose is best, and for how long to stimulate LH would you say?
>
> **Ray Peat:** My experience has been with doses of one or two milligrams, repeated for two or three days, when the effect is achieved, then waiting two weeks or more to see if repeating the process is needed.

### Source 6 — Herb Doctors: Thyroid, Polyunsaturated Fats And Oilsnew

Ray Peat · Interview · Apr 1, 2009 · http://l-i-g-h-t.com/files/herb-doctors-thyroid-polyunsaturated-fats-and-oils-new-56-mins.mp4

> **Caller:** One thing I have heard about is taking low-dose naltrexone as a way of helping with the condition. Have you heard of that?
>
> **Ray Peat:** When you are hypothyroid and produce lactic acid too easily, you tend to accumulate endorphins. Endorphins are produced in response to the signal of increased lactic acid to compensate for the stress by acting like morphine equivalents. And the endorphins themselves limit your physiological functions in a protective way, sort of like a localized kind of hibernation. And so, the naloxone or naltrexone will clear those out. Sometimes, in 2 or 3 days, you can see a person come out of depression or a lethargic state. There was a study in California of demented people who were given very big doses of naloxone for several days or several weeks and their dementia improved just by blocking the endorphins.
>
> **Caller:** And how long somebody should be on naltrexone with conditions like Hashimoto's? Is there any problem with long-term use?
>
> **Ray Peat:** No. But I usually see good results in just 2 or 3 days. So I think the basic treatment is a good diet and a thyroid supplement as needed. And then the naloxone and naltrexone is a good thing to try once in a while. If it makes you feel better, then it probably was breaking up a pattern.

### Source 7 — Ray Peat Email Advice Depository — Post 227

Ray Peat · Email · Apr 9, 2016

> **Question:** i asked about how to use naltrexone, and also asked on safety of pramipexole and Ginkgo biloba.
>
> **Ray Peat:** I have seen good results from using naloxone for 3 or 4 days; naltrexone has similar effects. Doses of one milligram or less can sometimes be effective. I don’t consider pramipexole to be safe. Ginkgo is fairly safe.

### Source 8 — KMUD - October 15, 2021

Ray Peat · Interview · Oct 17, 2021

> **Caller:** Yes, I'm in Hawaii, and my question is about effects. During a surgery two years ago, my husband had an aggressive surgery to remove a large tumor in his colon, and during the five weeks in the hospital, he was given fentanyl for four weeks and then total anesthesia three times and also a CAT scan and an MRI. After coming home... 80% of the time, he experiences various degrees of heaviness in his body. His arms, legs, chest, and mouth feel like they're full of cottony lead. And during these times, he also feels partially anesthetized, as if observing his body but not quite in it. 20% of the time, his energy is up, he's present and normal, although the cottony mouth never goes away. So also, several times a day, electric-like shocks that last one second pass through various parts of his body, leaving an itch that he scratches for 10 to 15 minutes to relieve. So, to us, this appears to be lingering damage from the fentanyl and the anesthesia residue. He feels as if his body is poisoned. Do you know of anything that might help this situation?
>
> **Ray Peat:** Fentanyl, that's an opioid? Yeah. I would guess that a short use of naloxone or naltrexone might break the cycle. One of the effects of morphine or most of the opioids is to activate inflammatory, especially histamine pathways. And the histamine keeps the opioid effect going. And just a short one or two or three days dosing of naloxone or naltrexone can break that cycle by stopping the morphine or endorphin effect.

### Source 9 — Hot flashes, energy, and aging

Ray Peat · Article · 2013 · https://raypeat.com/articles/articles/hot-flashes-energy-aging.shtml

> In young rats, sudden morphine withdrawal caused by injecting the anti-opiate naloxone, causes the tail skin to flush, with a temperature increase of a few degrees, and causes the core body temperature to fall slightly. However, old animals respond to the withdrawal in two different ways. One group responded to the naloxone with an exaggerated flushing and decrease of core temperature. The other group of old rats, which already had a lower body temperature, didn't flush at all (Simpkins, 1994). I think this provides an insight into the reason that menopausal treatment with estrogen can relieve some hot flashes--estrogen treatment might create a flush resistant state similar to that of the cooler old animals in Simpkins' experiment.
>
> It has been known for a long time, from studies in animals and people, that estrogen lowers body temperature, and that this involves a tendency to increase blood flow to the skin in response to a given environmental temperature, that is, the temperature "set-point" is lowered by estrogen. Besides increasing heat loss, estrogen decreases heat production. These physiological effects of estrogen can be seen in the normal menstrual cycle, with progesterone having the opposite effect of estrogen on metabolic rate, skin circulation, body temperature, and heat loss. This causes the familiar rise in temperature when ovulation occurs. Occasionally, young women will experience hot flashes during the luteal phase of their menstrual cycle because of insufficient progesterone production, or at menstruation, when the corpus luteus stops producing progesterone.
>
> Estrogen increases the free fatty acids circulating in the blood, and this shifts metabolism away from oxidation of glucose to oxidation of fat, and it also reduces oxidative metabolism, for example by lowering thyroid function (Vandorpe and Kühn, 1989). These changes are analogous to those of fasting, in which metabolism shifts to the oxidation of fatty acids for energy, causes decreased body temperature, and in some animals leads to a state of torpor or hibernation.
>
> Despite decreasing oxidative metabolism, estrogen stimulates the adrenal cortex, both directly and indirectly through the brain and pituitary, increasing the production of cortisol. Cortisol, by increasing protein turnover, can increase heat production, but this effect isn't necessarily sufficient to maintain a normal body temperature. It increases blood glucose, mainly by blocking its use for energy production, but the glucose is derived from the breakdown of muscle protein.

_Generated 2026-07-20 from the Bioenergetic Oracle corpus._