Page 63 - ITPS-7-2

INNOSC Theranostics and
Pharmacological Sciences Youth brain health check and dysregulation

should be emphasized that these findings stem from case compliance remains a deterring issue. The approved drug
12
studies, and it is improbable for individuals to carry all acamprosate, an NMDA receptor antagonist and a positive
putative risk alleles. Based on the previous research and allosteric modulator of GABAA receptors, also disrupts
our qEEG studies, we cautiously suggest that long-term dopaminergic signaling. The growing acceptance of the
13
activation of dopaminergic receptors may increase their RDS concept, introduced by Blum in 1995, facilitates the
proliferation, leading to enhanced “dopamine sensitivity” common mechanism hypothesis for substance and non-
and a heightened sense of happiness, particularly in substance addiction. Understanding the in-common
carriers of the DRD2 A1 allele. 2 neuromodulating features of neurotransmission and its
The intravenous administration of the Synaptamine disruption through chronic exposure to substance and
Complex Variant KB220 in >600 alcoholic patients resulted non-substance addictions requires the utilization of an
14
in a significant reduction in RDS behaviors; this effect approach that involves “dopamine homeostasis.”
was further supported by an expanded study involving 3. Review of evidence
3
oral KB220Z and functional magnetic resonance imaging
conducted on abstinent heroin addicts. For a deeper The “out of the box” approach involves coupling genetic
4
understanding, future studies, including functional positron risk polymorphic testing with a safe and well-researched
emission tomography scanning, are required to determine complex, KB220Z. The KB220Z is customized to match
the acute and chronic effects of oral KB220Z on the the presence of resultant alleles and provide a precision
number of D2 receptors and its interaction with the nucleus nutraceutical with known prodopamine regulatory
2,15
accumbens (NAc). In addition, further confirmation of pharmacological properties. High-tier publications
these findings through large, population-based, and case- strongly support a shared neuromechanism underlying
controlled experiments could ultimately lead to significant both substance and non-substance addiction, such as
improvements in the treatment and recovery of patients with alcohol, opioids, gambling, and food.
RDS and dopamine deficiency resulting from disruptions in In the 1970s, Blum’s laboratory developed an amino-
the transduction of multiple neurotransmitter signals within acid-based enkephalinase inhibitory pro-dopamine
the Brain Reward Cascade (BRC). 5 regulator with the KB220 nutraceutical complex as its
Moreover, recent neuroimaging studies have highlighted cornerstone ingredient, now validated by over 45 clinical
the potent effects of KB220Z, underscoring the importance studies published in peer-reviewed journals. 16,17 The
17
of Pro-dopamine regulation along the BRC (Figure 1). basis of this complex is its ability to mimic the BRC, an
established model of reward processing. The most striking
It is also possible that ACH neurons at the NAc ACH
can stimulate both muscarinic (red hash) and nicotinic feature is the activation of BOLD by the KB220Z across
the BRC, including the NAc, anterior cingulate gyrus,
18
(green hash) receptors. Finally, glutamate neurons in the anterior thalamic nuclei, hippocampus, prelimbic, and
VTA will project to dopamine neurons through NMDA infralimbic parts of the prefrontal cortex (PFC). Evidence
receptors (green equal sign) to preferentially release
dopamine at the NAc (shown as a bullseye), indicating of genetic vulnerability as an antecedent to unwanted
euphoria or a “wanting” response. The result is that when RDS behaviors may be a determining factor, which could
be identified early in life. Based on previously published
dopamine release is low, there can be a state of unhappiness literature, the role of reward gene polymorphisms puts
characterized by endorphin deficiency. At the same time, individuals at an increased risk for various forms of RDS
general (usual) happiness depends on the dopamine 19,20
homeostatic tonic set point. In addition to the coronavirus behaviors, including anhedonia. This insight spurred the
6
disease 2019 pandemic, there is a global addiction crisis. development of the patented genetic addiction risk severity
While being highest in the US, the devastation and deaths (GARS) test, aimed at identifying genetic risk for these
from drug overdose are global issues requiring “out of behaviors. Specifically, published studies have illustrated
the coupling of GARS with KB220Z formulations of semi-
the box” thinking. Even in the face of harm reduction,
7
relying on opioids to treat issues caused by other potent customized precision pro-dopamine regulators tailored
21
opioids seems counterintuitive and perpetuates unwanted to one’s GARS profiles. The biological approach of this
22
addictions. Several investigative groups have been system enhances the effectiveness of RDS treatment.
8
cognizant that addressing the root cause is one of the Balancing the BRC or achieving “dopamine
approaches to reducing harm. Another approach is homeostasis” is generally preferred and considered a
9,10
using a narcotic antagonist (like naltrexone) to induce commendable objective, as opposed to interventions
“psychological extinction” through blocking D2 receptors. that involve blocking natural dopamine or administering
11
The latter approach appears more acceptable; however, potent opioids to overcome opioid addiction. In the face
21
Volume 7 Issue 2 (2024) 3 doi: 10.36922/itps.1472