I have read a lot on LDN and dextromethorphan being used to slow progression of neurological diseases. Not that I understand it all but there seems to be a difference of opinion between the Dr. Bihari people and the NIH group on how these opioid antagonists work. The NIH group seems to believe these drugs work by suppressing neuroinflammation caused by over activated microglial (killer) cells which destroy dopamine producing neurons. In any event, they all seem to believe that these drugs work at very low doses. The research doctor in the email below says not to exceed 10mg a day on naltrexone. If we assume DM and LDN dosages are equivalent, to combine LDN and DM at a combined dose below 10mg may not be risky but no one knows. From what I've seen here, DM seems to have the added benefit of reducing PD symptoms by boosting dopamine production. Maybe LDN has the same effect but there are so few taking LDN for PD, I've never seen that mentioned as a plus.
It seems the drug companies are doing a lot of research on very expensive new drug thearpies that we may or may not see anytime soon. It's a shame that they don't pick up on old established drugs like DM and naltrexone and look at the the work that has come out of Dr. Hong's group at the NIH.
Ashley
Below is an email exchange with one of the developers of LDN. I don't know if it's appropriate to name him, so I guess I shouldn't:
Jan 06
If I could ask you, do you accept the basic claims of Dr. Bihari on the method of action and (probable) effectiveness of LDN?
Response: Low dose naltrexone may have a variety of actions. One certainly is that it works through the Opioid Growth Factor (OGF)- OGF receptor (OGFr) axis. OGF is an inhibitory growth peptide that appears to stablize cells/tissues. This can occur in tissue culture (cells are grown outside the body) and in animals/humans. When we discovered all of this about 25 years ago, the basis for the action naltrexone at low doses is that it acts for 6-8 hours. During this time the naltrexone does not allow the enkephalins/endorphins (opioids) of the body to interact with the opioid receptors on cells/tissues. The cells/tissues compensate for the deprivation of natural endorphins/enkephalins by making more of these opioids, and also making more opioid receptors. Now the trick - if you only block with naltrexone for 6-8 hours, for the remaining 18 hours or so you have high levels of opioids interacting with the opioid receptors and you get a supersensitive reaction. OGF is probably the best example of how naltrexone does its thing. OGF can repress cells, but most probably has effects on the immune system under in vivo (entire animal/human) situations.
Would you recommend LDN to a friend if they had a disease in which LDN could stop progression?
Response: The only legitimate study that I have (we are talking about statistics, etc) for low dose naltrexone is one that I know about - this is concerning Crohn's disease. And even this is a preliminary report. The internet is filled with claims about LDN - including some from doctors. Please be aware that science is not serving as underpinnings for these claims.
Now, in saying this, please let me say that LDN has many potentially terrific effects. But all of this should be done under a physician's supervision. Take the LDN once a day - in our patent on this
we recommended dosages of 3-10 mg of naltrexone/daily. I believe many now are using 4.5 mg/day - that is fine and was derived from our claims. Do not take this more than once a day. Do not take this if you are using opioid-based pain medications. Have a doctor examine the patient prior to beginning medication, making special assessment of the signs/symptoms that you want to treat. Have a follow-up visit in one month, and again in the 2nd month. Compare the outcomes to the original data. If nothing changes - or things decline - try a new medication.
I've viewed your many publications (not that I can really understand them) and noticed that most of your work now is in Opioid Growth Factor. Is that in any way related to how LDN works? Have you given up on naltrexone (LDN) as a disease treatment?
Response: Our discovery of LDN (we call it intermittent opioid receptor blockade) was made in a serendipity fashion, while looking for agents to alter growth (e.g., cancer, development). In actuality, LDN is really not doing anything to growth/biological activity. It is really interrupting the body with its natural chemicals - the enkephalins/endorphins. Therefore, our mission has to identify the precise opioid in the body that influences biological activities - this is methionine enkephalin - what is called opioid growth factor (OGF) to distinguish it from methionine enkephalin's role as a neurotransmitter in the nervous sytem. We then went on to identify the receptor for OGF - this is now called the OGF receptor (OGFr). We then went on to clone and sequence the gene for OGFr - it is one of the 20,000 genes in humans, and we know its chromosomal location. In fact, OGF is now being used in phase II clinical trials (we already passed phase I and have a publication in a journal on this) by our group to treat pancreatic cancer. How the OGF-OGFr axis does its thing - the mechanisms - as well as using this now to help patients, really is our focus.