title: Varenicline in Autism: Theory and Case Report of Clinical and Biochemical Changes.
abstract: To explore the potential benefits of varenicline (CHANTIX®), a highly specific partial agonist of neuronal α4β2 nicotinic acetylcholine receptors (nAChR), for autistic symptoms, and present resulting biochemical changes in light of dopamine-related genotype.
  
  
  
  The clinical and biochemical changes exhibited by a 19-year-old severely autistic man following the use of low-dose varenicline in an ABA experiment of nature, and his genotype, were extracted from chart review. Clinical outcome was measured by the Ohio Autism Clinical Impression Scale and 12 relevant urine and saliva metabolites were measured by Neuroscience Laboratory.
  
  
  
  With varenicline, this patient improved clinically and autonomic biochemical indicators in saliva and urine normalized, including dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), epinephrine, norepinephrine, taurine, and histamine levels. In addition, with varenicline, the dopamine D1 receptor (DRD1) antibody titer as well as the percent of baseline calmodulin-dependent protein kinase II (CaM KII) activity dropped significantly. When varenicline stopped, he deteriorated; when it was resumed, he again improved. Doses of 0.5, 1, and 2 mg daily were tried before settling on a dose of 1.5 mg daily. He has remained on varenicline for over a year with no noticeable side effects.
  
  
  
  This report is, to the best of our knowledge, only the second to demonstrate positive effects of varenicline in autism, the first to show it in a severe case, and the first to show normalization of biochemical parameters related to genotype. As with the previous report, these encouraging results warrant further controlled research before clinical recommendations can be made.
authors.affiliation: 1 Tufts University School of Medicine , Boston, Massachusetts.
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Mostafavi
authors.affiliation: 2 Hardy Healthcare, PLLC , Peterborough, New Hampshire.
authors.forename: Paul
authors.initials: P
authors.lastname: Hardy
authors.affiliation: 3 Department of Psychiatry, Nisonger Center, Ohio State University , Columbus, Ohio.
authors.forename: L Eugene
authors.initials: LE
authors.lastname: Arnold
mesh_terms: D001321:Autistic Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D008297:Male; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000187:drug effects; D000068580:Varenicline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D004298:Dopamine; D000068580:Varenicline
keywords: autism; nicotine; nicotinic receptors; treatment; varenicline; α4β2 receptors