Promoting Precision Addiction Management (PAM) to Combat the Global Opioid Crisis

Abstract

It is universally agreed that dopamine is a major neurotransmitter in terms of reward dependence, however, there remains controversy regarding how to modulate its role clinically to treat and prevent relapse for both substance and non-substance-related addictive behaviors. It is also agreed by most that there is a need to provide early genetic identification possibly through a novel researched technology referred to Genetic Addiction Risk Score(GARS).™ The existing FDA-approved medications promote blocking dopamine, however, we argue that a more prudent paradigm shift should be biphasic-short-term blockade and long-term upregulation, enhancing functional connectivity of brain reward. It is critical to understand that the real phenotype is not any specific drug or non -drug addictive behavior, but instead is Reward Deficiency Syndrome (RDS). Thus the true phenotype of all addictive behaviors is indeed RDS. Finally, we are suggesting that one way to combat the current out of control Opioid /Alcohol crisis worldwide is to seriously reconsider treating RDS by simply supplying powerful narcotic agents (e.g. Buprenorphine). This type of treatment will only keep people addicted. A more reasonable solution involving genetic testing, urine drug screens using Comprehensive Analysis of Reported Drugs (CARD) and dopamine homeostasis we call " Precision Addiction Management" ™ seems parsonomiuos.

Keywords: Genetic addiction risk score; Hypo dopaminergic; Pro-dopamine regulation; Reward deficiency syndrome.

Figure 1:

Brain Reward Cascade [6,7], In this cascade, the stimulation of the serotonergic system within the hypothalamus, through innervation, stimulates delta/mu receptors via the release of enkephalin. Further activation of the enkephalinergic system leads to inhibition of GABA transmission in the striatum via enkephalin stimulation of mu receptors upon GABA neurons. This inhibition allows the fine-tuning of GABA activity. Additionally, this provides the normal release of dopamine at the projected area of the NAc. Dopamine is a neurotransmitter with multiple essential functions including behavioral effects such as “pleasure” and “stress reduction.” Without the typical function of dopamine, an individual will suffer from cravings and may have difficulty coping with stress.