Neurological correlates of brain reward circuitry linked to opioid use disorder (OUD): Do homo sapiens acquire or have a reward deficiency syndrome?

Abstract

The extant literature confirms that an array of polymorphic genes related to- neurotransmitters and second messengers govern the net release of dopamine in the Nucleus Accumbens (NAc) in the mesolimbic region of the brain. They are linked predominantly to motivation, anti-stress, incentive salience (wanting), and wellbeing. Notably, in 2000 the Nobel Prize was awarded to Carlsson, Greengard, and Kandel for their work on the molecular and cellular function of dopaminergic activity at neurons. This historical psychopharmacological work involved neurotransmission of serotonin, endorphins, glutamate, and dopamine, and the seminal work of Blum, Gold, Volkow, Nestler, and others related to neurotransmitter function and related behaviors. Currently, Americans are facing their second and worst opioid epidemic, prescribed opioids, and easy access drive this epidemic of overdoses, and opioid use disorders (OUDs). Presently the clinical consensus is to treat OUD, as if it were an opioid deficiency syndrome, with long-term to life-long opioid substitution therapy. Opioid agonist administration is seen as necessary to replace missing opioids, treat OUD, and prevent overdoses, like insulin is used to treat diabetes. Treatment of OUD and addiction, in general, is similar to the endocrinopathy conceptualization in that it views opioid agonist MATs as an essential core to therapy. Is this approach logical? Other than as harm reduction, is using opioids to treat OUD therapeutic or harmful in the long term? This historical Trieste provides a molecular framework to understand the current underpinnings of endorphinergic/dopaminergic mechanisms related to opioid deficiency syndrome and generalized reward processing depletion. WC 249.

Early Life Stress and Risks for Opioid Misuse: Review of Data Supporting Neurobiological Underpinnings

“…This condition may be innate or acquired and is clinically manifested as anhedonia, numbing, apathy, or decreased motivation for natural reinforcers [ 324 , 325 ]. According to the hypothesis, opioid/endorphin deficiency increases a person’s vulnerability for OUD by disrupting interactions between midbrain opioid and DA neurotransmitter systems [ 326 ]. This has been supported by evidence that ELS alters µ- and k-receptor mRNA levels [ 62 , 63 , 64 ] and decreases downstream DA signaling [ 63 , 65 ] in a way that may alter the reinforcing and antinociceptive effects of opioids.…”

Opioid, Cocaine and Methamphetamine Overdose Crisis and Deaths in 2021

“…Volkow has suggested that evidence-based prevention and treatment interventions can reduce overdose mortality by 40%. However, opioid use disorder (OUD) is a chronic relapsing disorder that, while initially driven by brain reward activation, increasingly engages anti-reward neurocircuits [20] that drive adverse emotional states and relapse [21].…”

“…Discontinuation of MAT is associated with high rates of relapse and an increased risk of overdose. Relapsing patients are often given the same MAT treatments again and again and again [20]. The risk of overdose and relapse remains even after years of stable recovery.…”

A Novel Precision Approach to Overcome the “Addiction Pandemic” by Incorporating Genetic Addiction Risk Severity (GARS) and Dopamine Homeostasis Restoration

“…Neurologically, MATs may induce persistent changes that compromise endorphin, dopamine, and other brain systems. Long-term agonist treatments may be necessary for lack of other options, but we caution that data on long-term use vs. short-term harm reduction is lacking [ 4 ].…”

“…During the current viral pandemic, there is also a profound, pre-existing, and growing worldwide epidemic of addiction to opioids, psychostimulants, alcohol, and cannabis. Treatments themselves, like long-term agonist treatments for opioid use disorder (OUD), may also cause Reward Deficiency Syndrome (RDS) [ 4 ], resulting in harm and deadly consequences that rival and might eclipse the magnitude of the current viral issue.…”