5+ Reasons Low Dose Naltrexone (LDN) May Work for Your Pain

Naltrexone is a patent medicine invented in the 1960s to block opiates and prevent people from abusing them. If someone takes Naltrexone, then heroin, opium, codeine, morphine, and so forth, just don’t work. They can’t get high. They can’t even get pain relief; Naltrexone is stronger at blocking the receptors and keeps the drugs from binding. The problem is, like many drugs, it works too well! In fact, it works so well, it doesn’t even let the natural endorphins bind to their normal receptors – they’re blocked-out! So, people taking it could never feel good, and quit taking the medication. LDN stands for Low Dose Naltrexone. Since the standard dose is 50 mg the lower doses must be compounded by a compounding pharmacist in doses from 0.5 mg to 4.5 mg.

Endorphins

Endorphins are peptide (short protein) hormones made in the pituitary gland that bind to opiate receptors. It is not one, but several different peptides. When they attach to a receptor it causes a reaction that blocks pain and makes people feel good – among many other actions. These receptors are found on all cells of the body and can have different effects depending on their location. The effect on a pain nerve, or muscle cell is different from that of a lymphocyte or immune cell. It is important to note that if you take morphine or any opiate medication, it lowers your production of endorphins,[1] preventing you from getting all their good effects.

Morphine

Human cells make their own morphine,[2] which is identical to the process found in the opium poppy. When there is damage, they can suppress the pain both locally, and in the central nervous system. Studies show that women with higher levels of endorphins have less pain with childbirth, for example.[3] When a person takes morphine (or any opiate) it suppresses the body’s own production, making people more sensitive to pain, which is why people get “hooked” on, or tolerant of, pain medications – without the medication they can’t even feel normal. This is just the opposite of LDN.

How does LDN work?

Don’t get NALTREXONE confused with NALOXONE, which is similar, but fast-acting; NALTREXONE may take a couple hours to work. The very low dose of naltrexone means it won’t last long in the body. If people take it at night, while they sleep, it works, and it’s gone by the time they get up. As naltrexone blocks the opiate receptors, the system is trying to stimulate those receptors. The natural reaction of the body is to make more endorphins to make up for the lack of stimulation. This is exactly the opposite of what people hooked on opiate drugs do. While those taking drugs get more and more pain as endorphins decline, those who take LDN are increasingly able to create internal pain control. Moreover, the naltrexone binds to receptors on the immune cells, preventing them from releasing inflammatory cytokines that stimulate the immune response. So, LDN has a double benefit – more pain relief, and lower inflammation.[4] LDN can increase your production of endorphins by as much as 300%![5]

What is LDN good for?

• Chronic Pain
• Inflammation
• Multiple Sclerosis
• Fibromyalgia
• Crohn’s Disease
• Chronic Fatigue
• Chronic infections (yeast, EBV, Lyme, etc.)
• Depression and Anxiety
• Autoimmune disease

LDN for DEPRESSION and ANXIETY

Endorphins are made in the brain when there is stress and anxiety. In fact, it comes from the same hormone that causes your adrenal glands to produce stress hormones, ACTH. Endorphins affect the levels of serotonin,[6] which are directly related to anxiety and depression. In a case report by doctors experienced in the use of LDN the authors conclude: “without successful LDN treatment of fibromyalgia, remission of depression may be unlikely.” [7]

LDN for AUTOIMMUNE DISEASE:

• Endorphin receptors are found on the lymphocytes, regulating immune function and antibody production.[8]They also decrease the cytokines that stimulate immune response, as well as increasing the cytokines that decrease the immune response.
• There are several studies that have shown a benefit in Hashimoto’s thyroid disease.[9]
• LDN seems to be more beneficial for inflammatory arthritis than degenerative arthritis,[10][11] meaning rheumatic or inflammatory arthritis may respond better to LDN therapy. [12] This makes sense because degenerative arthritis is not caused by an overactive immune response.

LDN for CHRONIC PAIN

Chronic pain and inflammation in Multiple Sclerosis, Fibromyalgia, Crohn’s Disease, and Other Chronic Pain Disorders are mediated by the immune system as well as the autonomic nervous system. If a person is low in endorphins, they can be much improved by LDN. Endorphins lower stress hormones and help lower the pain threshold.

LDN for PARKINSON’S DISEASE

PARKINSON’S DISEASE is caused by low dopamine. Endorphins stimulate opiate receptors which increase dopamine. There have been several studies to show that some people with Parkinson’s disease may respond to LDN.[13]

LDN for CHRONIC INFECTIONS

Yeast, Lyme, Epstein-Barr virus, and so forth are common infections. Some people get chronic infections because their immune system is not functioning properly. The issue is not the presence of the infectious organism, by itself, but rather the fact that the host is immune deficient. So, even though endorphins are shown to lower pain, they also increase the number of T cells, improving the immune response.

Who should take LDN?

The bottom line is that if you have an autoimmune disease, or a chronic pain syndrome, or fatigue, anxiety or depression you should consider trying LDN. It definitely does NOT work for everyone, in fact, most research shows that across the spectrum of illness, only about 30% of people are helped by it. So, how do you know? Try it. There is no downside. There are few, if any, side effects, and if you have any side-effects they will go away quickly when the medication is stopped. If you have low endorphins, you may benefit greatly from LDN. If your endorphins are not low, then you are not likely to notice any difference. However, if your body is low in endorphins, you may find a remarkable improvement over time.

One way to know if you are low in endorphins is to take a dose of an opiate medication such as codeine, morphine, hydrocodone, or oxycodone. If it calms and relaxes you, and you feel “normal” for a few hours, then you probably lack endorphins. You may do well on LDN.

How to take LDN

Since it is such a low dose, many physicians start with 3mg or even 4.5mg. The problem with this is that it is more likely to have side-effects. It is simple to just start with 0.5mg and increase after one week. Gradually increase by 0.5mg each week. The stopping point is either when you feel the symptoms have resolved, or when you get side effects. If you have difficulty sleeping, the most common side effect, it is a good idea to continue the same dose for a few days since the symptoms generally resolve by then. If not, then go down on the dose. Most people will feel best between 3 and 4.5mg. If it is not helping at 4.5mg, then it probably isn’t for you.

There is one interesting caveat to LDN therapy. While taking the LDN it is a good idea to avoid milk and milk products, including cheese. Milk contains proteins that act like endorphins when they are processed in a certain way.[14] (Some people crave milk because they get “high” from it.) These can interfere with the natural production of endorphins.

Now, let’s consider other options:

Making your own (how to increase your endorphins without a prescription)

There are many ways to make endorphins: studies indicate that exercise, meditation, sex, and laughter all increase endorphin levels in the blood.[15]  Also, surgery, stress, and acupuncture increase endorphins. Many people use food to increase their endorphins. Some things can be healthy, others not so much, I would like to just evaluate some healthy ways to increase endorphins. You can, and should, consider doing some or all these even if you are doing LDN. Don’t expect that the LDN is going to fix everything.

EXERCISE

Sustained exercise more than 30min. enough to sweat and get tired increases endorphins. Exercising with others may increase your endorphins more than exercising alone.

I had a patient who was a middle-aged woman with a teenage son that played soccer with my kids. Her husband was a police officer. She came to my office regularly for chronic pain. One day she admitted that she had multiple doctors giving her pain medications which she used between her doses of IV heroin to keep her from getting withdrawals. She wanted to get off all opiates, so we tried various medications that are used to wean off, or prevent withdrawals, or calm the anxiety… but nothing worked. She couldn’t overcome it, and gave up. One day, a few years after our last visit, I went into a business, and there she was, the human resources director. I asked, “How are you doing?”

Knowing what I was referring to, a big smile came across her face, and she said, “Clean and sober for over a year!”

“After all we tried, I’m amazed and need to know… How did you do it?”

She responded quietly. “Have you ever heard of a runner’s high?”

“Of course!”

“When I need a hit, I go for a run, pushing hard, hoping to hit ‘The wall’ so I can push through it, and when I do… I feel great! And the great thing is, that I don’t get anxious or worried about where my next “fix” will come from so I no longer have anxiety!”

MEDITATION

Having a time for a focused mind helps to lower pain and anxiety, releasing endorphins.

COLD THERAPY

There are many ways to do cold therapy. Some places have a chamber cooled by liquid nitrogen that people sit in, another way is to take cold showers or ice baths.

Wim Hof has a whole program to improve function of the autonomic nervous system which induces endorphins.[16]He uses breathing techniques with cold water to modulate the normal response to environmental changes. It isn’t just being cold, but relaxing in the cold with deep breathing that gives the greatest benefit. This both increases endorphins, and the receptors so your body gets more benefit from the endorphins you have.

FASTING

One study indicated that endorphin levels are increased during the first few days of fasting, but not with longer fasts.[17] However, the great benefit of fasting is to have more sensitivity to your natural morphine, to help you relax and have less pain.

The question of “Who should try LDN” is not simple to answer. LDN can be a great way to increase endorphins to get rid of pain and fatigue, but it doesn’t work for everyone, even if they have the “same illness.” We also indicated other methods that don’t require a prescription, and work in multiple ways, not just to improve the endorphin system, but also other neurological and metabolic functions of the body. Rather than using drugs, working with your body’s own natural mechanisms to relieve pain, anxiety, stress, depression, and so forth will bring much more benefit in the long run.

 

 

Sources:

[1] Int J Mol Sci. 2021 Jan; 22(1): 338. Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism, Alexander Pilozzi, Caitlin Carro, and Xudong Huang
[2] https://ui.adsabs.harvard.edu/abs/2004PNAS..10114091P/abstract
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796446/#B87-ijms-22-00338
[4] Int J Mol Sci. 2021 Jan; 22(1): 338.Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism. Alexander Pilozzi, Caitlin Carro, and Xudong Huang*
[5] https://fight-parkinsons.org/wp-content/uploads/2018/06/LDN.pdf
[6] Int J Mol Sci. 2021 Jan; 22(1): 338. Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism. Alexander Pilozzi, Caitlin Carro, and Xudong Huang*
[7] Case Reports Cureus. 2022 Feb 28;14(2):e22677. doi: 10.7759/cureus.22677. eCollection 2022 Feb. Depression in Fibromyalgia Patients May Require Low-Dose Naltrexone to Respond: A Case Report.  Jagoda Siembida, Brian Johnson
[8] Review Fed Proc. 1985 Jan;44(1 Pt 1):92-4. Enkephalins and endorphins as modifiers of the immune system: present and future. J Wybran; PMID: 2981735
[9] https://ldnresearchtrust.org/hashimoto-thyroiditis-and-low-dose-naltrexone-ldn-paula-johnson
[10] PLoS One. 2019 Feb 14;14(2):e0212460. doi: 10.1371/journal.pone.0212460. eCollection 2019. Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study. Guttorm Raknes, Lars Småbrekke
[11] https://ldnresearchtrust.org/what-forms-arthritis-can-ldn-help
[12] https://www.myrateam.com/resources/low-dose-naltrexone-for-rheumatoid-arthritis
[13] https://fight-parkinsons.org/wp-content/uploads/2018/06/LDN.pdf
[14] Review Biopolymers. 1997;43(2):99-117. doi: 10.1002/(SICI)1097-0282(1997)43:2<99::AID-BIP3>3.0.CO;2-V. Milk protein-derived opioid receptor ligands.  H Teschemacher 1, G Koch, V Brantl
[15] https://en.wikipedia.org/wiki/Endorphins#cite_note-pmid15383669-17
[16] https://www.wimhofmethod.com/
[17] Horm Res. 1990;33(6):239-43. doi: 10.1159/000181525. Plasma beta-endorphin during fasting in man. G Komaki 1, H Tamai, H Sumioki, T Mori, N Kobayashi, K Mori, S Mori, T Nakagawa