Abstract

Willuhn et al., observed that habitual cocaine use was correlated with reductions in D2/D3 receptors linked to decreased cue activation in occipital cortex and cerebellum. Dopamine agonist therapy maintains dopamine function and is a relapse prevention tactic focused on psychoactive drug and behavioral addictions. Medication Assisted Treatment (MAT) with emphasis on glutaminergic medications fails in the long-term treatment of Reward Deficiency Syndrome Behaviors (RDS). While the careful use of “dopamine antagonist-therapy” short-term is supported, the research-based concept of “dopamine agonist therapy” in long-term is proposed. Neurogenetics and epigenetics are important in understanding treatment response and clinical outcomes. The neuro–mechanisms involving “dopamine homeostasis” are key to understanding recovery from drug and non–drug addictive behaviors. For example, patients who carry the DRD2 A1 allele (30-40 less D2 receptors) should consider Neuronutriant–Amino-Acid therapy (KB220 variants) a prevention modality. DRD2 A1 allele carriers show amplified striatal function of L-amino acid decarboxylase, prior to dopamine biosynthesis. Another example is the effect of Acute Tyrosine Phenylalanine Depletion (ATPD) on decision-making and reward found carriers with amino-acid deficiency (ATPD). They experienced attenuated reward and reduced decision-making ability as quantified by Iowa Gambling Task (IGT). Future research should be directed at asking the question; Would “dopamine agonist therapy” using KB220 variants reduce methylation and increase acetyl groups to enhance DRD2 expression especially in DRD2 A1 allele carriers and lead to increased dopamine function and a reduction of drug and non-drug seeking behaviors?

Keywords: Dopamine homeostasis, dopamine resistance, neuronutrient–amino-acid therapy, neurogenetics, epigenetics, enkephalinase inhibition, KB220 variants.