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

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 R E N

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

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

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

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

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

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

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

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

Clinical Use, cont. Preparations What about gluten and casein? 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

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

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

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

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

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