The recommendation for the scientific research of LDN to treat multiple sclerosis (MS) was initially presented as a medical theory in 2005. Shortly after, an open-label multi-centered pilot trial including 40 patients evaluated the tolerability and safety of LDN in the initial progression of MS for six months. The medicine was well-tolerated by the patients, and a statistically notable reduction in spasticity was observed. β-endorphin levels in subjects’ peripheral blood mononuclear cells elevated simultaneously with administration of LDN and proved the concept of one of the LDN’s mechanisms of action.

After some time, a retrospective study assessed 215 patients among which, 87% had relapsing-remitting MS and 10% with secondary progressive MS, who were given LDN. The average disease duration was ten years, and the LDN therapy was given for a median period of 804 days. Despite some hold of recall bias, 77% of subjects experienced no side effects at any point of LDN therapy. 6% reported insomnia, and 5% complained of having vivid dreams. 60% of subjects reported less weakness while using LDN, and just four persons mentioned it oppositely. More than half of the subjects confirmed an improvement in overall quality of life.


Moreover, two placebo-controlled randomized trials, seventeen-week long and eight-week long, determined the impact of LDN therapy on the quality of life of MS patients have been declared before in the study mentioned above. The seventeen-week-long study comprised 96 patients, and no analytical variation was observed between the groups. The eight-week-long trial was carried out on 60 patients, and researchers saw a considerable improvement in mental health elements of these patients and improved overall quality of life.

Preliminary investigations in autoimmune encephalomyelitis-induced mice, a standard MS model, manifested proof of opioid growth factor signaling as a prominent characteristic in the pathophysiology of Multiple Sclerosis. Before any other symptoms were observed, there was a decrease in the mice’s circulating opioid growth factors. After the administration, LDN restored the levels of opioid growth factors. Former in vitro experiments proved that LDN or opioid growth factor could suppress the proliferation of B and T cells, a mechanism that can benefit autoimmune states. An earlier investigation in the same mouse model also proved the advantages of opioid growth factor and low dose naltrexone in inhibiting the progression of the disease, modifying neurological defects, and considering postponing the onset of neurological dysfunction. Diminished levels of serum opioid growth factor were also seen in humans with MS, and LDN therapy reverted the discrepancy in these patients.

Such conclusions led researchers to recognize LDN’s therapeutic implications.