1. Low Dose Naltrexone in the Treatment of Autism Spectrum Disorders Phillip C. DeMio, MD 320 Orchardview Ave. Suite 2 Seven Hills, OH 44131 216-901-0441 www.drdemio.com © Phillip C. DeMio, MD 2005

2. Low Dose Naltrexone (LDN) Orginally for heroin addiction/opiate addiction. (Depade®, formerly Trexan®, ReVia® Concept behind such treatment –Opiate receptors –Drugs –Endorphins/opiate peptides © Phillip C. DeMio, MD 2005

3. Low Dose Naltrexone (LDN) cont. “side” effects of such treatment –Depressed mood –Respiratory symptoms “hidden” immune toxicity Other abnormal immune symptoms: brain; others “sub clinical” rise in endorphins –…but fully blocked by the high dose of Naltrexone »This led to the syndrome of opiate/endorphin withdrawal -agitation -respiratory (SOB, huffing, stuffy, cough) -diarrhea/cramps -“crawling skin”/gooseflesh © Phillip C. DeMio, MD 2005

4. Opiate Peptides, Naltrexone, and the Immune Connection T-Lymphocytes –Are white blood cells (WBC’s) –Eg. Th-1 and Th-2 Excess Th-2 activity means autoimmunity, allergy, and lowered healthy immunity Peptides –Those from gluten, casein, and others (“exorphins”) cause peptide-specific Th-2 stimulation (increased activity) –That makes people sick! (symptoms in: ASD, MS, ALS, IBD, HIV, RA, SLE, asthma, allergy, and cancer to name a few) © Phillip C. DeMio, MD 2005

5. Immune Connection cont. Endorphins –Compete with exorphins –So endorphins redirect Th-2 WBC’s away from allergy/autoimmunity –Endorphins also stimulate healthy immunity (by heightening Th-1 activity) Endorphins are abnormally and strikingly low in children and adults who have ASD (and MS, ALS, IBD, HIV, RA, SLE, asthma, allergy, and cancer) (c) Phillip C. DeMio, MD 2005

6. Low-Dose Connection Recall the rise in endorphins with full dose Naltrexone –“side effects can be good” (a clue, a foot in the door) But full dose Naltrexone blocks the endorphins © Phillip C. DeMio, MD 2005

7. Low-Dose Connection, cont. Why the low dose? –Naltrexone at low dose retains it abliity to cause an endorphin rise –If the dose is low enough, the endorphin- blocking effect of Naltrexone is gone in as little as two hours So most of the day yields higher endorphins They are not blocked They are free to “do good” (immune; other) © Phillip C. DeMio, MD 2005

8. Low-Dose Connection, cont. Great benefit for ASD (and MS, ALS, IBD, HIV, RA, SLE, asthma, allergy, and cancer) The dose: –Less than one tenth the orginal dose used for addiction. –Currently the target doses are: 3mg/24 hours if less than 45kg 4.5mg/24 hours if over 45kg We will revisit “the”dose © Phillip C. DeMio, MD 2005

9. LDN in Clinical use for ASD Immune dysfunction, autoimmunity and, allergy in ASD affects: –Brain/nerves –Gi tract/dysbiosis –Lungs/respiratory/sinus systems –Thyroid (and other hormonal organs) –Frequent severe infections/fever –Other/adult immune problems as mentioned –Allergy (skin, respiratory, food) © Phillip C. DeMio, MD 2005

10. Clinical use, cont. This connects to variants of ASD: –OCD –Tics/Tourette Syndrome –Immunity/autoimmunity/allergy (asthma) –Clinical and laboratory abnormalities –Parents, siblings, and other relatives of persons with ASD (“later onset”) © Phillip C. DeMio, MD 2005

11. Clinical Use, cont. Preparations –Topical or oral Currently, same dose for each Swallowing, taste, and timing issues 11pm dose Maybe oral is better if: –Constipated –Crampy Diarrhea: start with topical What about gluten and casein? –Make exorphins –LDN may cause withdrawal if not gf/cf But may actually cause improvement –We will revisit the dose © Phillip C. DeMio, MD 2005

12. Clinical Use, cont. Sources –Coastal Compounding Pharmacy (topical) –Lee-Silsby Compounding Pharmacy (topical or oral) –Others (experience/communication) Dr. McCandless after Dr. Bihari: Many responders More science and numbers than Dr. Kanner! © Phillip C. DeMio, MD

13. What to Expect in Clinical Use “Effects” –Bowels and brain –Immune system –They overlap! “Side” effects –Bowels and brain –Immune system –Stimulation “good”: endorphins/transient “not good” –Die-off –Excess blockade of endorphins –Constipation/agitation/sensory issues © Phillip C. DeMio, MD 2005

14. Other Clinical Issues Itching and rash Unique situations –Opiate drugs Pain Anesthesia –Clonidine/guanabenz –Enzymes Long term –Will effects sustain? –Experience outside of ASD © Phillip C. DeMio, MD 2005

15. Revisiting the Dose Kids/adults can get the “not good” responses Some patients may not sustain Revisiting the dose –Unsustained group Raise the dose (chasing your tail?) Pulse dose –Kids on gf/cf diet Ultra-low-dose Naltrexone –Start low and slow © Phillip C. DeMio, MD 2005

16. LDN Conclusion Ultimately, as with other treatments –Naltrexone helps many persons –May help a little or a lot –“effects” vs “side” effects Q and A © Phillip C. DeMio, MD 2005