LDN and Toll Like Receptors (TLRs) by Dr Tom Gilhooly

Tuesday, 26 July 2011

The 2nd European LDN conference in Glasgow this year saw the first presentation of a remarkable

study into LDN for the treatment of fibromyalgia by Dr Jarred Younger of Stanford University. This is

the sort of top quality research that we have been crying out for, and perhaps even more remarkable than the results of the study was Dr Younger’s clarity on how LDN works. The vacuum that has existed in LDN research has been filled by lots of myths and legends such as timing of administration and dosage of the drug. Dr Younger explained that LDN is a “racemic mix” of mirror image right and left handed molecules. This is common in chemistry, and most drugs consist of such a natural mix. It is usual for only one of the sides to be biologically active, but in the case of LDN both sides are active. The right handed molecule blocks the opiate receptors, which confer the action which the drug is licensed for i.e. blocking the action of heroin and other illicit opiates.

The more interesting part regards the left handed molecule, which acts on the Toll-like 4 receptors on the surface of immune cells and acts as an immune modulator. Dr Younger studied the effect on microglial cells, a type of immune cells important to the neurological system which become active when the immune system is activated. These cells are important in fibromyalgia, but also in MS , Parkinson’s Disease and several other neurological conditions. The left handed (levo) naltrexone binds to these receptors and reduces the inflammatory chemicals that are pouring out of these cells. This idea makes great sense and fits very well with our findings in the clinic. If this is the mode of action, it fits with the hypothesis of Dr Agrawal and others, and the timing of dose is irrelevant. This is a big discovery, but even Dr Ian Zagon from Penn State who is a big advocate of the opiate hypothesis, states that timing is not an important factor. This would suggest that the opiate-blocking effect of LDN is actually the limiting factor on dose and we should aim to get the highest dose possible that the patient can tolerate, to produce the greatest effect on the immune system. It also puts paid to the idea that LDN is an “immune booster” which should not be used with other immune modulators. In fact it is likely that LDN will be synergistic with these drugs. 

As if this was not enough for one month, along comes the much anticipated double-blind study on Crohn’s Disease by Prof Jill Smith and Ian Zagon from Penn State. This shows a remarkable 83% improvement in the LDN group, with almost half going into remission. Not surprisingly given the participation of Dr Zagon, they ascribe the improvements to increased opiate expression, but the alternative action could be just as viable. In Crohn’s disease and other inflammatory bowel diseases including Coeliac’s disease, there is an increase in Toll Like 4 Receptor numbers on the bowel mucosa. This could explain the rapid and dramatic response to LDN of many patients with these conditions. Added to the results of MS study by Bruce Cree from University of California in San Francisco we already have a bumper year for LDN research. These remarkable studies will inform future practice and research including our soon to be submitted MS study.