Evidence for low-dose naltrexone (LDN) as a treatment for ME/CFS
'The evidence is poor' doesn't mean what you'd expect.
While researching LDN, I read an account by an ME/CFS patient whose GP refused to prescribe the drug because ‘the evidence for it is poor’. You'd expect this to mean: ‘research shows the drug isn't very good’, but that isn't the case. Research suggests that, while it isn't a cure, LDN brings improvement of some symptoms for some patients. For people with an illness as debilitating as ME/CFS, even a partial improvement could be a very big deal.
In fact, 'the evidence is poor' doesn't mean the drug is poor, it means the research is.
A 2019 study of 218 ME/CFS patients who received LDN found that 74% saw some improvement in their symptoms1. But this study is considered to be of poor quality because there was no blinding and no case control; the study was based on medical records of patients from a clinic.
And a 2021 study found that naltrexone restored function to natural killer (NK) cells2. People with ME/CFS have been consistently found to have poor NK cell function, and it’s believed that this plays a role in the disease. But this study was carried out in the lab, so it’s not certain that the same process would take place in the bodies of human beings.
There’s also a 2019 report of three people with ME/CFS who all showed some improvement on LDN - but this is also considered ‘poor quality evidence’3.
The problem with ME/CFS is that we never get high-quality research, because the organisations that allocate funds for medical research - such as the NIH in the US, and the Wellcome Trust in the UK - consistently choose not to allocate the same kind of funding to ME/CFS as for similarly devastating diseases such as cancer, multiple sclerosis or HIV. The kinds of studies that are considered to be of high quality - case control studies with large numbers of participants - cost millions. That kind of money is almost never allocated to ME/CFS research.
I think that when GPs look down their noses at the ‘poor quality evidence’ for LDN they’re assuming that the system works as it should: that if a drug is promising there will be a few small studies, and if these have good results they’ll be followed in the natural course of things by proper clinical trials. It might work that way for other diseases, but it doesn’t work that way for ME/CFS, which is so neglected by funders that there are hardly any clinical trials at all.
In fact a clinical trial of LDN in ME/CFS patients was announced in 2016. It was put on hold and eventually cancelled, without anyone having been given the drug. I don’t know what happened with that trial, but I imagine that funding difficulties came into it4. Another research group has announced a trial of LDN in Long Covid patients5, but the results of that trial won’t apply to those who have had ME/CFS since before the pandemic.
Some doctors do prescribe LDN off-label to patients with ME/CFS, but they’re hard to find. Here in the UK it seems to be very difficult to find an NHS doctor willing to prescribe it, with the result that only those who can afford to go private have access to the medication.
LDN is an old drug, and is considered safe, although it can cause nausea and insomnia which usually go away with time.6
Immune Effects of Low-dose Naltrexone in ME/CFS at clinicaltrials.gov
Low-dose Naltrexone for Post-COVID Fatigue Syndrome at clinicaltrials.gov