What is Naltrexone?

Naltrexone is an FDA approved drug used as an opiate antagonist for treating opiate drug and alcohol addiction since the 1970s, available in generic form as well as in the brand name ReVia in 50mg tablets. At regular dosing to treat addiction, usually 50mg to 150mg a day, it blocks the euphoric response to opiate drugs such as heroin or morphine as well as alcohol.

Opioids are known to operate as cytokines, the principal communication signalers of the immune system, creating immunomodulatory effects through opioid receptors on)immune cells. A popular immune classification method is referred to as the Thl/Th2 balance: Th1 cells promote cell-mediated tmmun~ty, while Th2 cells induce humoral immunity. Simplistically, the inability to respond adequately with a Thl response can result in ~hronic infection and cancer; an overactive Th2 response can contribute to allergies and various syndromes and play a role in autoimmune diseas~, which most autism spectrum children show on immune testing. The November 13, 2003 issue of the New England Journal of Medicine notes: “Preclinical evidence indicates overwhelmingly that opioids alter the development, differentiation, and function of immune cells, arid that both innate and adaptive systems are affected An Italian study done in 1996 by Scifo and Marchetti attempted to correlate immunolgical determinations and behavioral performance in treatment with naltrexone in 10, 20, and 30mg doses in autistic children, with significant reduction of autistic symptoms noted in 7 out of 12 children. The behavioral improvement was accompanied by alterations in the distribution of the major lymphocyte subsets, with significant increase in normalization of the CD4/CDB (Tl) ratio and an inverse ratio of changes in NK cell activity to plasma beta-endorphin levels. A large body of research in the last two decades has pointed repeatedly to our endogenous opioid secretions as playing the central role in the beneficial orchestration of the immune system.

The full and optimum dose of Low-Dose Naltrexon (LDN) for children is 3mg, and pharmacies make It in 3 ml syrlnges at 6mg per ml, with 1/2 ml being the regular dos~ (3 mg), or 6 doses in each syringe. To try to avoid the side effects of the initial immune transition and probable latent viral activation some parents have been using tiny doses (as recommended by some p rents: in the early study and upon my subsequent recommendation). As we continue with this grand experiment, I am now starting to think the tiny doses are great for some of the behavioral responses (more sociability, language, etc.) but that we need to push on to the higher dose to get the optimum immune enhancement/modulation we are ultimately looting for (which would of course help the sociability/cognition language issues also). Ann Brasher had that intuition (and she is very wise) while I was still being intimidated by parents' unhappiness with their kids' symptoms, especially painful when they have kids who have “never been sick before." However, I have noted that these hyperimmune kids who never get sick continue to have autism, and the fact hat many kids I test may have at first very high NK cytotoxicity score but ultimately the majority have very low NK values.

Recently I have heard hat adult autoimmunity patients reported that Dr. Bihari himself encouraged them to push on to the full dose to get optimum immune benefit in spite of initial negative effects, and as they did so they start d feeling better than they had in years, and continue to feel wonderful This dedicated physician/researcher has had many more years experience with LDN than anyone else, and even though I believe all of his work has been with adults, autoimmune issues are definitely art 9f our kids' disorder (Singh's studies showed over 70% of ASD kids have elevated brain tissue antibodies) and a recent very elegant autopsy study by Vargas done on brains of autistic children (the majority died from drowning {Note: Please teach your child how to swim } showed almost everyone of them showed brain inflammation (autoimmu~itY/9xidative stress in my mind) whereas the non-ASD kids showed none.

Some parents are so P1ased: With the increase in affect and cognition that I understand their reluctance to move to higher doses, and since all answers are not in I think we have to see how the kids who stay at low doses ultimately d compared to the ones that go on to full dose. It also may be that the die-off does go slower with the tiny doses and some kids can handle 0ly a little at a time (how much parents can bear is significant also). However, with viral replication being what it is, and enhanced by the presence of metals that most of our kids have, I think I would want t sooner rather than later eventually move up to the optimum dose, and some of our kids who are adult size are going up to 4mg and a few even t 4.5 in my practice with good results. Some of the kids who have the worst responses end up being the ones who make the most outstanding progress, and I certainly am tempted to think that the immune activation is lowering their viral load with accompanying die-off symptoms. My a assumption (and my prayer) is that they are moving more toward a normal immune functioning system that will mount the usual defenses against viral and other infections. I plan in the clinical research study starting in January to get participants to move up to the full dose by the first 4 weeks of the study so there will be 12 weeks at full dose before retesting.

Bernard Bihari, MD,New York physician studying the immune responses in AIDs patients, di covered that a very low dose of naltrexone, approximately one-tenth the usual dosage, boosts the immune system and helps fight diseases characterized by inadequate immune function. The temporary inhibition of brain endorphins when given a very tiny dose 01 naltrexone apparently results in a reactive increase in the production of endorphins, tending to normalize the immune system with this elevation, and accomplished its results with virtually no side effects or toxicity; naltrexone is considered very safe and has never been reported as being addicting. When LDN is given between 9 p.m. and midnight, the body attempt~ to overcome the opioid block and the endorphins rise, to stay elevated throughout the next 18 hours. Studies in human cancer patients show that LDN acts to increase natural killer cells and other healthy immune defenses, and hundreds of multiple sclerosis patients have totally halted progression of their disease for up to 8-10 years or more with regular use of this medication. Restoration of the body's normal production of endorphins in those with cancer or autoimmune diseases is the major therapeutic action of LON, which needs to be given only once a day between 9pm and l-2am.

The use of LDN for children: with autism spectrum disorders was previously studied in the 1990s, with researchers using from 5 to 50mg daily or every other day. In these trials, researchers were looking for opioid antagonism. Pankseppi Shattock and other researchers noted better results with low doses; studies on higher doses were more equivocal in children, and non-compliance due to the bitterness of the drug posed a problem for children who could not swallow capsules.

For my private clinical studies, Dr. Tyrus Smith at Coastal Compounding created a very effective transdermal cream. This allowed easy adjustment of dosing (some ~f the smaller kids did better with only 1­1/2mg), the bitter taste was no problem, and the cream could be put on the children's bodies while they slept. The cream is put into syringes, with ~ cc providing 3mg for children or 4.5mg for adults; most adults prefer capsules; both are equally effective.

For my private clinical studies, Dr. Tyrus Smith at Coastal Compounding created a very effective transdermal cream. This allowed easy adjustment of dosing (some ~f the smaller kids did better with only 1­1/2mg), the bitter taste was no problem, and the cream could be put on the children's bodies while they slept. The cream is put into syringes, with ~ cc providing 3mg for children or 4.5mg for adults; most adults prefer capsules; both are equally effective

I completed a preliminary eight-week informal study on 15 of my autism patients May-June 2006 applying 3mg of LDN transdermally between 9 and 12 p.m. Several adults participated also, one with Crohn's Disease and one with Chronic Fatigue Syndrome using 4.5mg nightly. Parents and participating adults reported weekly on the results of the treatment.

Eight of the 15 children in this study had positive responses, with five of these eight having results considered quite phenomenal according to their parents. The primary positive responses have been in the area of mood, cognition, language, and socialization. Two small children responded better when changed to 1-1/2mg dosing. No allergic reactions were noted, and the primary negative side effect was insomnia and earlier awakening, usually fairly short-lived. The two adults in the study had very positive responses, with the Crohn's participant reporting that she has been' in remission since starting LON (almost 10 months at this writing).

All of the children in my study were on well-controlled dietary restriction. I have received reports from the e-lists I monitor of about 5-10% of other children (not my patients) having side effects such as irritability, agitation, and restlessness, subsiding as soon as the drug is withdrawn. I queried these parents about gluten/casein/soy in the children's diets, as this response is very likely indicative of withdrawal symptoms of opioid block even though brief. I suspect that children on a strict GF/CF/SF diet are less apt to show this response; this has yet to be tested.

The immediate positive mood/cognitive/relating effects seen in many children starting this intervention is unlikely to be from immune enhancement showing up so quickly. For other autoimmune studies using LDN, the evidence is that the optimum immune response can take four to six months. In private correspondence with earlier autism researchers Ors. Panksepp and Shattock, they postulated that the LDN therapeutic effect with the rebound of endogenous opioids in the brain "loosens up" the opioid social-reward systems so children who were not connecting to the many known opioid \based, social rewards in the environment begin to respond to those rewards. Both these researchers emphasized the importance of positive social reactions being reinforced and enhanced substantially by social support and encouragement, helping the new behavior become part of positive behavior modification. A significant proportion of children upon starting LDN show not only some increased hyperactivity and sleep changes, but a bout of what seems like "viral activation" in the form of a cold, fever blister, and other infections. These are usually short-lived, followed by a burst of improved language, cognition, and socially seeking behavior. Now, instead of immediately lowering the dose, I am asking parents to use the full dosage, which seems to: cut ~own this time of adjustment for most of the children. Some do need to go down in dosage, but I urge parents to try to stay the course if possible as I suspect the maximum immune benefits occur with full dose, whereas the immediate social-reward and cheerfulness effects occur on ultra-tiny doses.

As an effective, non-toxic, non-addicting, and inexpensive behavioral and immunomodulating i6tervention, LDN is joining our biomedical arsenal to help more and more children recover from autism as well as helping anyone with autoimmune diseases and cancer. As an FDA approved medication, it must be pres6ribed and must also be compounded for the tiny dosing required.

Note: I am currently conducting a clinical study aimed at not only ASO children but their parents, as it is well known that autoimmunity has a strong genetic component. 80 adults and 26 children are in this 16 week study. Dr. Vojdani at Immunosciences Labs helped me work out an extensive immune pan~l for determining what LDN will do to important immune and autoimmune markers along with weekly tracking of behavior, mood, and physiological functions. Results of this study will be reported by June 2006. ! For more information, see www.lowdosenaltrexone.org or join Autism_LON@yahoogroups.com.