Low Dose Naltrexone (LDN)
Background
The use of low (micro doses) of the drug Naltrexone has in recent years been found useful in correcting immune system imbalances. It has been used primarily in adults with Crohn's Disease or Multiple Sclerosis. Some dramatic improvements have been noted in a relatively short time with the use of LDN.
The mechanism of action is blocking of endorphins during their critical production phase; usually during the hours of 9 pm to 3 am. If endorphins are blocked at that time, the body compensates by producing 2-3 times the amount of endorphins during the next 24 hours. This has an immune balancing effect.
In the past, Naltrexone was used in 25 or 50 mg doses with autistic children. It was primarily used to block the opioid effects from gluten and casein. However, studies in adults (Naltrexone is used to help fight alcohol and heroin addiction) have shown that such doses block too many endorphins, and may lead to depression as well as gastrointestinal upset. However, the low dose use, does not usually cause such problems.
The dose used in children is usually 1.5 to 3 mg given between the hours of 9 pm and 3 am. It may be given orally, or in a transdermal cream. This treatment is a PRESCRIPTION, and thus needs a doctor's order. It will also need to be carefully compounded by a compounding pharmacy. Most pharmacies who compound the oral form use lactose as the filler, so you will need to specify 'no lactose' if that will be a problem. Other fillers are readily available. A transdermal form has also been developed which may be applied late at night while the child sleeps. This form offers a bit more flexibility in dosing, but is not as well established as a treatment form as the oral.
What to expect during use?
During the first week or so, some restlessness and difficulty sleeping may be noted. This can be lessened by giving the dose as late as possible, but in any case, it usually does not last more than one week. GI upset is a rare side effect, and also only lasts a few days.
After the initial adjustment phase, improvements in all areas of immune/behavioral function may be noted. Improved cognition, speech, gut health and decreased stimming may be noted. It takes 2-3 months for maximum effects to be noted. It also appears that LDN must be continued indefinitely for the effects to be continued. In the adult cases, return of symptoms usually occur within weeks of stopping the drug. However, a missed dose NOW AND THEN does not seem to be a problem.
Any additional questions should be addressed with your doctor.
Recommended link for further information on LDN
http://www.lowdosenaltrexone.org/
Autism One Radio - Presentation on LDN with Dr DeMio
Recent informal study on Transdermal LDN in children with Autism
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LOW-DOSE NALTREXONE: INFORMAL CLINICAL STUDY REPORT
July 1st 2005
JAQUELYN McCANDLESS, M.D.
Certified by American Board of Psychiatry & Neurology
21800 Marylee St., #48, Woodland Hills, CA 91367
Telephone (818) 716-0565 Fax (818) 337-7338
www.starvingbrains.com
What is Naltrexone?
Naltrexone is an FDA-approved drug called Revia used as an opiate antagonist, and has been used to treat opiate drug addiction. At full dose, usually 50-150mg a day, it blocks the response to opiate drugs such as heroin or morphine.
I as well as many other DAN! Doctor's have tried Naltrexone as an opioid blocker hoping to offset the opioid effects of the large peptides in wheat and milk that are thought to affect our kids adversely.
However, I never found it to be useful for that purpose, and I haven't heard of many others who have. Some studies were actually done on autistic children by researchers to try to study this, but results were not encouraging. I occasionally hear of it being used for SIB, but I do not now its effectiveness in that regard.
However, it has been shown that opioids can operate as cytokines, operating through opioid receptors on immune cells and producing immunomodulatory effects. The quality of an individual's immune system can be evaluated through the balance of cytokines (e.g. interleukins and interferons) it is producing. Cytokines are the principal communication signalers of the immune system. A popular classification method is referred to as the Th1/Th2 balance; Th1 cells promote cell-mediated immunity while Th2 cells induce humoral immunity. While cellular immunity (Th1) directs Natural Killer T-cells and macrophages to attack abnormal cells and microorganisms at sites of infection inside the cells, humoral immunity (Th2) results in the production of antibodies used to neutralize foreign invaders and substances outside of the cells. The inability to respond adequately with a Th1 response can result in chronic infection and cancer; an overactive Th2 response can contribute to allergies, various syndromes and play a role in autoimmune disease, which probably all of our ASD children have to some extent.
A Manhattan, New York physician, Dr. Bernard Bihari, studying the immune responses in a group of AID?s patients, discovered that a very low dose of Naltrexone in less than one-tenth the usual dosage boosts the immune system and helps fight any disease that is characterized by inadequate immune function. As an effective up-regulator of the immune system, he termed this new therapy Low-Dose Naltrexone (LDN) and has described remarkable responses in those with AID?s, cancer, and autoimmune diseases such as Multiple Sclerosis (MS).
LDN tends to normalize the immune system by elevating the body's endorphin levels but also accomplishes its results with virtually no side effects or toxicity.
I first got the idea of trying this on ASD children from hearing of its benefits in halting the usual progression in MS disease, reading of many first-hand reports of no recurrence for up to 5 and 6 years in some of these people using a nightly tiny dose of Naltrexone. In reviewing the literature, the lowest dose Naltrexone that had been used in autistic children was 12.5mg, and the researchers were looking for its use as an opioid antagonist, not an immune system stimulant. Since the endorphins are an integral part of the immune system, when a tiny dose of Naltrexone (3mg for children, 4.5mg for adults) is given between 9-12pm at night (11pm is ideal) there is an attempt for the body to overcome the opioid block and the endorphins rise, to stay elevated throughout the next 18 hours.
I have just completed an 8-week informal clinical study on 15 of my ASD patients using low-dose Naltrexone, or LDN. Several adults participated also, one with Crohn's Disease, one with Chronic Fatigue Syndrome, and Jack and myself as controls, not having any immune disorder that we know about. The dose Dr. Bihari found most efficacious was between 3-4.5mg, so the children were given 3mg and the adults or children over 100 lbs 4.5mg. This medication is terribly bitter (causing subjects from previous studies to drop out), and needs to be given once daily only between 9-12pm (ideally 11pm, which is usually about the time parents go to bed).
I worked with Dr. Tyrus Smith at Coastal Compounding; he at first created capsules in these two strengths, but then we decided on a transdermal (TD) cream which parents could put onto their kids just before parents go to bed ? hopefully the kids are long asleep. That way we could adjust the dose easily (some of the tinier kids did better with only 1-1/2mg), the bitter tastewas no problem, and it could be put on their bodies while they slept.
It has worked wonderfully and was brilliantly executed by Tyrus, with whom I have worked closely on many compounds for ASD kids over the years. A month's supply is $30, a two-month supply is $55.
I asked parents to report weekly on: Sleep, Appetite, Stools,
Relating, General Activity, Cognition, and Language. 8 of the 15 children have had positive responses, and five of these 8 have been nothing short of phenomenal according to their parents. The primary positive responses have been in the area of mood, cognition, language, and relating. 5 of the children had equivocal results, some good responses interspersed with complications with gut infections and treatments, so it was difficult to know just what was doing what. One child dropped out because of no response after 4 weeks (my Chelsey, of course, a notorious non-responder), one child dropped out because of vacations and trips,
and another stopped because of personal family issues.
No allergic reactions were noted to the cream. The primary side effect was that in the first few days of taking this medicine, the child might have some insomnia and wake up earlier. Even then, most woke up in better mood. Quite a few of the kids had early hyperactive/hyper-awake effects, and this was temporary (3-5 days) except for two of the tiny kids, who finally got much better when their dose was decreased. One of these ended up doing very well with only a tiny bit (almost immeasurable) each night, yet it had a definite effect. I would say the most consistent positive report has been happiness and good mood in the kids. I now recommend everyone start with ¼ cc, or 1.5mg for a few nights before going on to the ½ cc, which is 3mg. The adults will stay on 4.5mg, though 3 may be plenty for some of them.
The two adults in the study, one with Crohn's and the other with Chronic Fatigue Syndrome, have had very positive responses, and the Crohn's participant says shehas not had any problems with her gut since taking this. Dr. Bihari has announced a study with 15 Crohn's with all 15 having a very positive and sustained excellent reaction to the therapy. Other than feeling a little more erotic (this has been reported in some of the MS patients), Jack and I have not noticed any side effects from the use at 4.5mg nightly. We feel pretty good on it; the mood elevation is pretty universal with everyone who takes it, and increased socialization had even been noted in some earlier studies which used much bigger doses. No one else has done a study of ASD kids with these tiny doses, and no one to my knowledge has used the transdermal application at night for the endorphin rush (pulse) that takes place about 2-4 am. All participants who completed the study have indicated they wish to continue.
This very small and very preliminary study has been positive enough to warrant amore formal study, and I am trying to get Dr. Vojdani at Immunosciences interested in participating with some immune testing to verify the supposed T2 to T1 shift that I believe is happening for at least some of the children. However, the doses are tiny, the application is easy, it is non-toxic at these doses, and it is relatively inexpensive, so I suspect we will get lots of informal clinical data from those who will be starting to use it now long before we get a formal study conducted. This is by no means a magic bullet, but I am adding it to my armamentarium to try to get the children as immune-efficient as possible. I would appreciate parents reporting on the lists I monitor; for questions, please do not post or phone me personally, but I will try to address questions on the CSB e-list if other parents or your doctors cannot.
To those of you who participated in the study; please feel free to share on the lists any of your feelings, impressions, and results, good, bad, or indifferent ? the more we know the better for everyone. I THANK ALL OF YOU SO MUCH for being trusting enough to go along with me in trying something new, and I thank Dr. Tyrus Smith for helping devise a successful form to use in our children. BTW, he has as usual offered to share his formula with any other compounding pharmacy who wishes to call him, 912-354-5188.
Jaquelyn McCandless, M.D. 7-2-05