Does low-dose naltrexone (LDN) work against inflammation?

LDN is attracting attention as an anti-inflammatory agent, but most of the research consists of small studies, cell experiments and animal trials. No large randomised studies have yet convincingly demonstrated its effect in humans. The current findings should therefore be regarded as early, preliminary signals.

The best-described mechanism of action: LDN influences glial cells, the support cells in the brain and spinal cord that also regulate inflammation. In cell studies and small human studies, LDN reduces the release of inflammatory substances from those cells. It is also thought to block an inflammatory receptor and to suppress certain white blood cells. Plausible, but not yet proven in large human research.

The strongest clinical signal comes from small controlled studies in fibromyalgia: participants reported less pain and a better quality of life compared with placebo. In Crohn's disease and multiple sclerosis there are also small studies with positive outcomes. The word 'subjective' matters here: objective measures such as blood values or scans have barely been studied. The groups were always small, so firm conclusions cannot yet be drawn.

For newer applications the evidence is thinner still. A study in 59 Long COVID patients found less fatigue and better sleep, but without a randomised control group. A theoretical article suggested that LDN may reduce blood-clotting problems in COVID-19, but clinical data are entirely lacking. In cell and mouse studies LDN also reduced inflammation and insulin resistance, but that too has not yet been tested in humans.

Regarding safety: several review studies report that LDN is well tolerated and that serious side effects have not been reported. However, long-term data in large groups of people are lacking. In addition, this is off-label use, meaning that doctors prescribe it outside the officially approved indications. Always discuss it with a doctor before considering it.