title: Acute intravenous synaptamine complex variant KB220™ "normalizes" neurological dysregulation in patients during protracted abstinence from alcohol and opiates as observed using quantitative electroencephalographic and genetic analysis for reward polymorphisms: part 1, pilot study with 2 case reports.
abstract: It is well established that in both food- and drug-addicted individuals, there is dopamine resistance due to an association with the DRD2 gene A1 allele. Evidence is emerging whereby the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may find its place in recovery from reward deficiency syndrome (RDS) in patients addicted to psychoactive chemicals. Utilizing quantitative electroencephalography (qEEG) as an imaging tool, we show the impact of Synaptamine Complex Variant KB220™ as a putative activator of the mesolimbic system. We demonstrate for the first time that its intravenous administration reduces or "normalizes" aberrant electrophysiological parameters of the reward circuitry site. For this pilot study, we report that the qEEGs of an alcoholic and a heroin abuser with existing abnormalities (ie, widespread theta and widespread alpha activity, respectively) during protracted abstinence are significantly normalized by the administration of 1 intravenous dose of Synaptamine Complex Variant KB220™. Both patients were genotyped for a number of neurotransmitter reward genes to determine to what extent they carry putative dopaminergic risk alleles that may predispose them for alcohol or heroin dependence, respectively. The genes tested included the dopamine transporter (DAT1, locus symbol SLC6A3), dopamine D4 receptor exon 3 VNTR (DRD4), DRD2 TaqIA (rs1800497), COMT val158 met SNP (rs4680), monoamine oxidase A upstream VNTR (MAOA-uVNTR), and serotonin transporter-linked polymorphic region (5HTTLPR, locus symbol SLC6A4). We emphasize that these are case studies, and it would be unlikely for all individuals to carry all putative risk alleles. Based on previous research and our qEEG studies (parts 1 and 2 of this study), we cautiously suggest that long-term activation of dopaminergic receptors (ie, DRD2 receptors) will result in their proliferation and lead to enhanced "dopamine sensitivity" and an increased sense of happiness, particularly in carriers of the DRD2 A1 allele. This is supported by a clinical trial on Synaptamine Complex Variant KB220™ using intravenous administration in > 600 alcoholic patients, resulting in significant reductions in RDS behaviors. It is also confirmed by the expanded oral study on Synaptose Complex KB220Z™, published as part 2 of this study. Future studies must await both functional magnetic resonance imaging and positron emission tomography scanning to determine the acute and chronic effects of oral KB220™ on numbers of D2 receptors and direct interaction at the nucleus accumbens. Confirmation of these results in large, population-based, case-controlled experiments is necessary. These studies would provide important information that could ultimately lead to significant improvement in recovery for those with RDS and dopamine deficiency as a result of a multiple neurotransmitter signal transduction breakdown in the brain reward cascade.
authors.affiliation: LifeStream Solutions, Inc., Prescott, AZ, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Miller
authors.forename: Abdalla
authors.initials: A
authors.lastname: Bowirrat
authors.forename: Matthew
authors.initials: M
authors.lastname: Manka
authors.forename: Merlene
authors.initials: M
authors.lastname: Miller
authors.forename: Stanley
authors.initials: S
authors.lastname: Stokes
authors.forename: Debra
authors.initials: D
authors.lastname: Manka
authors.forename: Cameron
authors.initials: C
authors.lastname: Allen
authors.forename: Charles
authors.initials: C
authors.lastname: Gant
authors.forename: B William
authors.initials: BW
authors.lastname: Downs
authors.forename: Andrew
authors.initials: A
authors.lastname: Smolen
authors.forename: Emily
authors.initials: E
authors.lastname: Stevens
authors.forename: Swetha
authors.initials: S
authors.lastname: Yeldandi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Blum
mesh_terms: D000437:Alcoholism / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000483:Alleles; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004569:Electroencephalography / Q000187:drug effects; D005500:Follow-Up Studies; D006556:Heroin Dependence / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000235:genetics; D012201:Reward; D018570:Risk Assessment; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2