From InterAction 105, published September 2020
Retired GP Dr Monica Bolton shares her experience of low dose naltrexone (LDN), and reviews the evidence, having recently returned to university to investigate research about M.E. and LDN.
If specialist doctors treating people with M.E. had to choose just one drug for a clinical trial, what would it be? The answer given recently by a group of USA specialists was low dose naltrexone (LDN).
What is it?
Naltrexone was discovered in the 1960s and has been available on the NHS since the 1980s, but only to treat drug addiction and alcoholism. Like a lot of other medicines, naltrexone has different effects on body systems at different doses. At standard doses it blocks the effects of morphine and heroin but also our own body’s morphine-like compounds called endorphins, and this is why it helps in addiction.
Naltrexone has been used in lower doses, again since the 1980s, anecdotally benefitting a wide range of conditions. Sadly, there has been very little clinical research (but some interesting lab-based work) to document whether it works or not.
At low doses, naltrexone reduces inflammation and pain, probably by improving immune cell function, including in the brain (www.tinyurl. com/LDNreview2014).
A recent small Australian study reported that naltrexone improved an important cell function in immune cells from people with M.E. If other researchers confirmed these results, working with a larger number of people with M.E., this would be a very promising advance in M.E. research.
Is it effective?
Anecdotally, there are stories, such as mine (see below), which suggest it can help symptoms in some people with M.E. But looking at the research side (such as clinical trial results), the answer is that we just don’t know.
There are small scale clinical trials of LDN showing some benefit in illnesses involving the immune system, such as Crohn’s disease, rheumatoid arthritis, MS and HIV infection. Published research from Norway, using their central prescription database, has shown that using LDN led to reductions in prescriptions for other drugs normally dispensed for rheumatic disease and for Crohn’s disease. It might seem odd that one drug appears effective in so many illnesses – but endorphins are a fundamental part of the body’s response systems so altering their balance in a sick body might benefit a wide range of conditions.
Although there have been no clinical trials of LDN in M.E., there are several published clinical trials in people with fibromyalgia, a condition which often overlaps with M.E. These showed that symptoms such as pain or fatigue were reduced in some people, and about half of those taking LDN felt generally better. However, these were all small trials, so larger, longer trials are still needed to confirm these results.
A Finnish doctor recently published his retrospective experience of using LDN in clinical practice to treat more than 200 people with M.E. over several years; 74% of the sample had some response to LDN, although for the majority this was partial, with improvements in only one or two symptoms.
Is it safe?
So far, clinical experience and long term safety data suggest LDN is very safe, as long as you are not taking any pain-killers from the morphine family, as these interact with naltrexone.
A paper by myself and a group from the University of Manchester used statistics to show that naltrexone is as safe as placebo (ie. dummy pills with no active ingredients) in clinical trials). In two blinded fibromyalgia clinical trials, i.e. where participants didn’t know what medication they were taking, the LDN groups experienced side-effects of head-aches and vivid dreams. Some people do report being troubled by side-effects when starting LDN, although reducing the dose for a few weeks usually helps.
What if someone wanted to try LDN?
Please remember that LDN is an unlicensed medicine. (Licensed medicines have been assessed extensively by the UK regulatory authorities and passed for a particular use in a particular illness; this means both safety and effectiveness have been well studied.)
People wanting to try LDN will need a prescription from their NHS doctor (GP or specialist) or a private doctor. Many NHS doctors are not prepared to prescribe it as it is unlicensed. Do not buy off the internet; there are unscrupulous online pharmacies selling counterfeit medicines! If your GP would like to learn more, the LDN Research Trust offers an information pack. You could also refer him or her to the published research highlighted in this piece. You must not take naltrexone if you are currently taking any painkillers from the morphine family (including codeine, dihydrocodeine and tramadol) – always check with your doctor.
Some people feel improvements immediately after they start taking LDN, although others take up to two months to respond. I think it is rare to get a very good response, like I had (though I do take a slightly higher dose than most people – the optimum dose is still not known).
What’s your experience?
Have your tried LDN? We would love to hear about your experience, and share it in the next issue of InterAction. We will also go onto look at other symptom management approaches that people with M.E. tell us they have found helpful, starting with CBD oil.
To tell us about your experience of any of the above, please get in touch (see p 2).
Please note
Action for M.E. does not recommend any individual treatments or management approaches. Instead, we offer information to allow you to make informed decisions about what is right for you. Because we don’t yet understand the biology of M.E., there are no targeted treatments that work for the majority. This differentiates M.E. from other conditions where better understood biomarkers can offer clearer treatment pathways and protocols. So a treatment approach that you find effective may or may not have a different impact on someone else with the illness, and vice versa.
My story
I was very ill with M.E. for over 20 years, and have now returned to normal health, which I believe was due to LDN. My illness started in 1988 with viral meningitis, causing severe M.E. – I was bed-bound with a multitude of symptoms, and unable to self-care for several years. I did improve slowly, but then relapsed again in 1999 due to gastroenteritis. This time I was never able to care for myself, and used a motorised wheelchair on the few occasions I went out.
In 2010, after several years of trying various alternative treatments, I was prescribed LDN. I obtained the prescription through Dicksons chemist in Glasgow, as they list doctors prescribing LDN privately. The improvement with LDN was quite different to anything I had tried previously. I just improved – no effort was needed on my part. I found my widespread pain lessened, sleeping improved and my energy and stamina increased. My frequent gastrointestinal pains faded away, and the food allergies and intolerances I had developed after the gastroenteritis all cleared up. Now I was able to eat a full diet.
My mind woke up fully for the first time since the meningitis. I started walking further, and then cycling. I came off all disability benefits. I still have some brain damage from the meningitis, and don’t fight infections so well (though much better than before I started LDN). Apart from that, I now have an active and full life.
With my new-found health, I have been trying to find a way of organising a clinical trial of LDN in people with M.E. in the UK, with the eventual aim of making LDN available on the NHS. I returned to university, gained distinction in a Master of Research degree and published two papers as a result, one of which included my case history.
But the sad news is that it really is incredibly difficult to run a clinical trial well, and even more difficult in people with M.E. Clinical trials are expensive, and without major funding (usually provided by the drug company while the drug is still under patent), they are impossible to conduct. No large drug company is interested in researching naltrexone as it is cheap and out of patent, so any research group is dependent on grants from public bodies, or very generous donors – the cost will be several million pounds even for an exploratory trial.
Despite this, I am encouraged that the speed of research, particularly in the USA, is picking up all the time, and I believe research will eventually lead to new treatments that work for us all.
