LDN therapy has become more accepted in medicine. However, many practitioners of LDN therapy operate from the conventional wisdom of LDN for autoimmune disorders using 1.5 mg to 4.5 mg. However, the original article interviewing Dr. Bihari focus on LDN as an agent that can normalize immune system. Recent articles point to the mechanism by which normalizing immune system including modulation of glial cell function via Toll like receptor 4 (TLR4). Understanding the mechanism of TLR4 opens up whole new clinical implications not considered at this time. The clinical use for utilizing ultra low dose naltrexone or microgram dosing of naltrexone will be reviewed. Lastly, combination therapy with other therapeutic modalities including CBD oil and acupuncture will be discussed.