UK: Low-dose naltrexone as a treatment for chronic fatigue syndrome (2020)

[godlovesatrier]

Low-dose naltrexone as a treatment for chronic fatigue syndrome (2020)

First published: Jan 2021

https://casereports.bmj.com/content/13/1/e232502

Authors:

Authors

• Monica Jane Bolton
• Patient, Manchester, UK
  • http://orcid.org/0000-0002-7972-1841
  • PubMed articlesGoogle scholar articles
• Bryan Paul Chapman
• Patient, West Sussex, UK
  • PubMed articlesGoogle scholar articles
• Harm Van Marwijk
• Department of Primary Care and Public Health, Brighton and Sussex Medical School, Brighton, UK
  • PubMed articlesGoogle scholar articles

Abstract

Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn’s disease, fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone (LDN), no clinical trials exist in people with chronic fatigue syndrome. This condition is characterised by chronic profound fatigue, postexertional malaise, pain and autonomic and neurocognitive disturbances. This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some symptoms only. Treatment doses ranged from 4 to 12 mg. Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.

Treatment Case Studies

Patient’s perspective

Case 1
For me, low-dose naltrexone was truly life changing. From being virtually house bound, always limited by a multitude of symptoms, pain and low energy, I found my life returning. Every treatment or therapy I had tried previously involved effort—pacing myself, training myself, coping with symptoms. With low-dose naltrexone, the improvement just happened—I didn’t have to try, I just got better. I went for walks and started cycling again. The first time I ate out when I was no longer limited by food allergies, I could select from the whole menu—the shock of all that choice! My husband commented I was no longer a shadow of a person but a genuine companion again. From being unable to string sentences together coherently for much of my adult life, I returned to university and gained a distinction in a Master of Research degree, when aged 62!

Case 2
After 25 years of living with the devastating effects of myalgic encephalomyelitis, I was struggling to cope with the limited options for symptom and pain management. Having had many bad reactions to medications, I was hesitant to try a medication that would affect my immune system so I started out at an extremely low dose and slowly increased dosage. While the dreaming was at times disturbing, the positive changes gave me a hope for improvement I had not had in many years. The subsequent improvements have led to a much higher quality of life and I would like to see this medication as an approved option for others in my situation.

Case 3
Since I was 14 (when I had my first chronic fatigue episode), whenever I have had any form of illness I have suffered from depressive episodes, including needing to withdraw socially and becoming very insular. This included the period prior to any illness, where I have felt run down or could tell a cold etc was forming. I started taking low-dose naltrexone when I was 37 and for the first time in 23 years, I have not had a depressive episode linked to colds or any other illness. Low-dose naltrexone has really helped improve my quality of life and also helped in social situations where I am not withdrawing and being insular like I had been previously.

Treatments

Treatment: case 1

She tried various alternative treatments with little improvement. She improved slightly while taking antibiotic combinations including phenoxymethylpenicillin and azithromycin for a year in 2006 but relapsed rapidly on stopping them. She was started on oral vitamin D supplementation in 2009, although this did not improve her symptoms of fatigue. As she has had polymorphic light eruption since her midteens, she remains on colecalciferol 20 000 IU every 2 weeks and now has normal vitamin D levels.
In 2010, she was prescribed LDN, initially at 1.5 mg, slowly increasing the dose over 2 years. She noticed slightly increased energy and reduced food intolerances while taking 4.5 mg/day but needed to reduce the dose to 3 mg due to increased headaches. Ten months later, she started increasing the dose again without recurrence of symptoms, and subsequent stepped dose increases coincided with further improvements in energy, mood and pain. At 9 mg, the frequent episodes of abdominal pain subsided, and she started eating a full diet, including wheat and dairy. Her prescribing doctor suggested experimenting to find the optimum dose of LDN, and after increasing to 7.5 mg two times per day, she settled on 6 mg two times per day, which she has taken for the past 7 years.

Treatment: case 2
Many therapies have been tried, including antiviral agents for reactivated Epstein-Barr virus, with limited success.
She was prescribed LDN in 2014 when 54 years old. Due to known immune hypersensitivity (urticaria), the dose was started very low, at 0.25 mg/day, and increased very slowly over 4 years to the present dose of 4 mg. Initially, her sleep was disturbed by vivid dreaming. At about 6 months, when on 1 mg/day, she noticed improved sleep and lower pain levels, and these symptoms continued to improve as the naltrexone dosage was increased

Treatment: case 3
In 2018, when aged 37, he started LDN, initially at 1 mg/day, increasing to 4.5 mg, which he still takes. He had no side effects starting the drug.

 

[nerd]

Is there any speculation about the mechanism of action yet?

I wish I could remember the opioid receptor CFS/ME mechanism I stumbled across some time ago. I assume this drug has the same interaction.

 

[Rufous McKinney]

I have taken the same dose of 3.5 mgs for several years, running out twice, odd symptoms start to return that for me seem largely inflammatory- thing start swelling up. Alot of heat starts emerging from my body.

but its always been hard to describe exactly what it does. I just know that- when I ran out- I started to worry.

 

[Wishful]

Is there any speculation about the mechanism of action yet?

Since it has different responses in different people, there may be multiple mechanisms at work. For me it just blocked neuropathic pain (very effectively too!). From that I guess that it was the opioid response mechanism, but I can't rule out other possibilities, such as antiinflammatory effects restoring normal neural function.

 

[Hip]

Is there any speculation about the mechanism of action yet?

I don't think anyone has figured out the exact mechanism, but LDN may work for ME/CFS because it:

• Blocks TLR-4 on microglia (anti-inflammatory).
• Inhibits TLR-9 expression.
• Increases levels of met-enkephalin (opioid growth factor) and its receptor.
• Transiently blocks mu-, delta- and kappa-opioid receptors, which is thought then up-regulates endorphins.
• May reduce peroxynitrite and may thereby increase astrocyte glutamate transport.
• Has an effect the nociceptin system.
• Is a prokinetic which helps treat SIBO (some ME/CFS patients have worsened symptoms due to comorbid SIBO).

 

[mitoMAN]

Interestingly, none of the patients my ME/CFS doctor perscribed LDN for ever had any significant improvements.
I've been on it for 8 months without any result. (worked up to 4.5mg over a few months)

 

[Hip]

Interestingly, none of the patients my ME/CFS doctor perscribed LDN for ever had any significant improvements.
I've been on it for 8 months without any result. (worked up to 4.5mg over a few months)

Dr John Chia finds LDN helps only 10% to 20% of his ME/CFS patients, but for those it helps, he says it does so very significantly. Ref: 1 2

 

[godlovesatrier]

This is also a really interesting study:

Low-dose naltrexone therapy improves active Crohn's disease

Objectives: Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues. In an open-labeled pilot prospective trial, the safety and efficacy of low-dose naltrexone (LDN), an opioid antagonist, were tested in patients with active Crohn's disease.

Results: Seventeen patients with a mean CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased significantly (P= 0.01) with LDN, and remained lower than baseline 4 wk after completing therapy. Eighty-nine percent of patients exhibited a response to therapy and 67% achieved a remission (P < 0.001).

You mentioned Th17 @Hip , well LDN appears to work for RA and Chron's which apparently are caused by Th17 levels being raised. Even though the mechanism of action is based on raising endorphin levels to modulate th levels in the body, it looks like those endorphin changes do have an effect on Th17.

 

[Wishful]

May reduce peroxynitrite and may thereby increase astrocyte glutamate transport.

I think that one's unlikely, since peroxynitrite scavengers make my symptoms worse, yet LDN blocked my pain but didn't worsen my other ME symptoms.

 

[lenora]

I have thought about bringing this up with my neurologist, but am a bit reluctant after the Fentanyl fiasco.

Thanks for what you've presented, although I would also like to hear from those who have negative reactions to naltrexone. I have tried it in ointment form (via prescription) and while it has helped, I can't say that it's a remarkable improvement in my pain levels. Still, all comments would be most appreciated. As per usual, I expect that some of us will be helped while it won't make a difference to others. Yours, Lenora.

 

[Rufous McKinney]

am a bit reluctant after the Fentanyl fiasco.

Its not really at all like taking a pain killer. Its - blocking briefly, the opiod receptors. And I take it before bed sometimes I'll notice a odd head ache in the middle of the nite and I wonder if thats: the two hours or so that the receptors are blocked.

its a very small dose.

I didnt' have any side effects nor did I have vivid dream issues- but thats me. Thats unlikely here.

 

[nerd]

Its not really at all like taking a pain killer. Its - blocking briefly, the opiod receptors.

Indeed. It's not comparable at all. If you'd need a comparison, it's more like CBD in that it even helps against opioid addiction. It's like coffeine to the melatonin receptors contrary to taking melatonin.

 

[lenora]

I'm going to bring that up with my neurologist during our next appointment.

I know that naltrexone is also used for bipolar disorder (now that everyone in my family with it, can't be helped), and for suppressed memories. I need to find out all of the pros and cons of this medication.

I've been around long enough to see so-called safe products that b/c real problems for the users. Fortunately, that never occurred to me, but it did make me wary.

 

[pamojja]

I know that naltrexone is also used for bipolar disorder

That's new to me. With naltrexone one also has to consider that it is usually given as a 50 mg/d tablet against opoid-addiction. But used as a immunemodulator only up to 1/10 of that dose (~4.5 mg), usually before sleep.

 

[lenora]

Hello @pamojja. Yes, studies were done on patients with bipolar disorder (& alcoholism) but I haven't looked at them because everyone in my family who was affected, died. Sadly, I may add.

I find myself with insomnia that goes back to the beginning of this illness. Nothing works for long, thus I really haven't taken anything for years now. What's the point?

At first I thought I was also bipolar, but that's not the case. I have been screened by my neurologist, a psychiatrist and see a psychologist when necessary. I have none of the other signs of bipolar disorder, so I was relieved to have that behind me.

Unfortunately lithium does not work for all patients. My family members were among that group...one of the reasons they went on to study naltrexone and the illness. It would be interesting to see where the research stands today. Unfortunately, it's far too late for those I loved. Yours, Lenora.

 

[nerd]

Unfortunately lithium does not work for all patients. My family members were among that group...one of the reasons they went on to study naltrexone and the illness.

May I ask what effect lithium had if any at all, subjectively speaking?

 

[lenora]

The best that I remember is that my family members were bipolar before and after its use. One brother's situation was complicated by drug and alcohol abuse...not so with the others. There are many cases of lithium (an earth salt, as you know) not working for all people. A terrible shame, in reality.

I don't know why you're asking, but I would go forward and use it in good faith if I had been found to have bipolar illness. There are combos of other drugs in use today. Things have probably changed since I first began dealing with it probably 55 yrs. ago, then over the years since.

Believe it or not the only thing that worked in my mother's case, after everything had been exhausted, was electric shock treatments. She was brought out of her state within a few days. And her memory was just fine...no problems whatsoever. That was our gold standard after that incident. She had been hospitalized for over 4 mos. at that point. Drugs were just new on the scene, then. Yours Lenora.

 

[godlovesatrier]

Another study here that links LDN to increased beta-endorphins, which directly modulates t cell action:

Beta-endorphin and the immune system--possible role in autoimmune diseases

Abstract

The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested that the increased cytokine production in immunoinflammatory disorders induces production of beta-endorphins from the pituitary and the lymphocytes; the enhanced level of beta-endorphin causes inhibition of human T helper cell function, which potentially down-regulate the antibody production. Also the beta-endorphin-induced enhancement of the natural killer cell activity may suppress the B cell function. In addition, beta-endorphin also exerts a direct inhibitory effect on the antibody production. Thus, in autoimmune disorders the enhanced cytokine level may via stimulation of the production of beta-endorphins exert a negative feed back on the antibody production and potentially so on the production of autoantibodies.

This does make it sound a bit immunosuppressive though?

 

[sb4]

Is the idea endorphins are upregulated by LDN supported by any evidence?

 

[godlovesatrier]

Study here which measured it in the blood of MS patients with LDN administration:

Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization

3.1. Multiple Sclerosis
The proposal for scientific investigation of LDN as a treatment for multiple sclerosis (MS) has been presented as a medical hypothesis in 2005 [45]. Soon after, a multi-center open label pilot trial involving 40 patients assessed the safety and tolerability of LDN in primary progressive MS for a period of six months [46]. The drug was well tolerated, and a statistically significant decrease in spasticity was noticed (secondary outcome). Levels of β-endorphins in patients’ peripheral blood mononuclear cells increased concurrently with LDN administration, an in vivo proof of concept for one of drug’s mechanism of action.