key: cord-1015211-8svwn4ui
authors: Braverman, Eric R.; Dennen, Catherine A.; Gold, Mark S.; Bowirrat, Abdalla; Gupta, Ashim; Baron, David; Roy, A. Kenison; Smith, David E.; Cadet, Jean Lud; Blum, Kenneth
title: Proposing a “Brain Health Checkup (BHC)” as a Global Potential “Standard of Care” to Overcome Reward Dysregulation in Primary Care Medicine: Coupling Genetic Risk Testing and Induction of “Dopamine Homeostasis”
date: 2022-04-30
journal: Int J Environ Res Public Health
DOI: 10.3390/ijerph19095480
sha: a7c761921e7de8397e9a049b25505e525201e3f8
doc_id: 1015211
cord_uid: 8svwn4ui

In 2021, over 100,000 people died prematurely from opioid overdoses. Neuropsychiatric and cognitive impairments are underreported comorbidities of reward dysregulation due to genetic antecedents and epigenetic insults. Recent genome-wide association studies involving millions of subjects revealed frequent comorbidity with substance use disorder (SUD) in a sizeable meta-analysis of depression. It found significant associations with the expression of NEGR1 in the hypothalamus and DRD2 in the nucleus accumbens, among others. However, despite the rise in SUD and neuropsychiatric illness, there are currently no standard objective brain assessments being performed on a routine basis. The rationale for encouraging a standard objective Brain Health Check (BHC) is to have extensive data available to treat clinical syndromes in psychiatric patients. The BHC would consist of a group of reliable, accurate, cost-effective, objective assessments involving the following domains: Memory, Attention, Neuropsychiatry, and Neurological Imaging. Utilizing primarily PUBMED, over 36 years of virtually all the computerized and written-based assessments of Memory, Attention, Psychiatric, and Neurological imaging were reviewed, and the following assessments are recommended for use in the BHC: Central Nervous System Vital Signs (Memory), Test of Variables of Attention (Attention), Millon Clinical Multiaxial Inventory III (Neuropsychiatric), and Quantitative Electroencephalogram/P300/Evoked Potential (Neurological Imaging). Finally, we suggest continuing research into incorporating a new standard BHC coupled with qEEG/P300/Evoked Potentials and genetically guided precision induction of “dopamine homeostasis” to diagnose and treat reward dysregulation to prevent the consequences of dopamine dysregulation from being epigenetically passed on to generations of our children.

Addiction is a global pandemic that has negatively affected millions of people [1] . Although addiction itself is not a diagnostic term in the International Classification of Diseases 10th revision (ICD-10), it is still widely used by professionals and the public [1] . When it comes to diagnostic terminology, "addiction" was previously classified as substance abuse and substance dependence in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) [2] . The DSM-5 consolidated the terminology into substance use disorder (SUD) with a severity scale [3] . However, federal agencies continue to use different/multiple terms such as SUD, alcohol use disorder (AUD), opioid use disorder (OUD), addiction, substance dependence, substance abuse, and experimental gateway, etc. [4] [5] [6] [7] [8] . For the purpose of this paper, SUD is all-encompassing.

The National Center for Drug Abuse Statistics (NCDAS) reports that~12% of Americans over the age of 12 use illicit drugs, and if alcohol and tobacco are included, then the percentage increases to~60 [9] . In the United States (US),~50% of teenagers have misused a drug at least once and~61% of teenagers have abused alcohol by 12th grade [10, 11] . In addition, 70% of users who experiment with illegal drugs before age 13 develop SUD within the next 7 years, compared to 27% of those who experiment with illegal drugs after age 17 [9] . Furthermore, many individuals with SUD also suffer from polysubstance abuse. For example, according to the Substance Abuse and Mental Health Services Administration (SAMHSA),~35% of adults with illicit drug use disorder also have AUD [12] . Alcohol is one of the most commonly used drugs, and AUD is the most common type of SUD in the US [13, 14] . The lifetime prevalence of AUD is~29%, the prevalence of binge drinking in young adults (age 18-25) is~31%, and~70% of Americans report having alcohol in the past year [9, 10, 15] . SUD global severity, by country, is also underreported and inconsistent, ranging from 5 to 20%, depending on the agency [16] [17] [18] [19] [20] [21] [22] .

SUD reporting is underestimated in the US due to stigma, confusion, lack of precision in reporting medical causes of death, poor self-reporting, and confusing/lack of uniform terminology, etc. [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] . Patients with SUD often have co-occurring neuropsychiatric/medical disorders, and thus, their deaths can be attributed to any one of their comorbidities, leading to death certificate discrepancies. Furthermore, SUD is often the tipping point to death in patients with medical comorbidities [36] . Drug overdose deaths are often reported as accidents (cars, machinery, military, prescription mistakes, etc.), heart attacks, sudden cardiac deaths, strokes, etc. [23] [24] [25] [26] . In 2019, SUD was reported as the third and/or tenth leading cause of death classified as accidental or suicide, respectively [37] . Approximately 50% of all death certificates and 20-30% of drug overdose death certificates that the CDC receives are inaccurate or have incomplete causes of death [25, 35] . These inaccuracies result in the underreporting of deaths attributed to SUD. SUD mortality will likely continue to increase until a more accurate and reliable system is implemented [35] . Finally, we believe that in those cases with the presence of DNA antecedent polymorphisms across the brain reward circuitry, it might suggest that SUD is not easily reversed and may indeed be a life-long condition if untreated. Nevertheless, our new knowledge related to the role of environment and epigenetic influence on gene expression that includes acetylation (positive expression) and methylation (negative expression), the presence of SUD in an individual could become a reversable phenotype if the epigenetic repair becomes a life-style change, including induction of brain circuitry homeostasis.

Therefore, we believe that the US medical system, especially pediatrics, must implement and utilize standard neuropsychiatric metrics and imaging in the diagnosis and treatment of SUD until the number of SUD deaths becomes zero.

During the COVID-19 pandemic, reported opioid youth deaths increased by 25%, from~75,000 to~100,000, with an average age of 24,~70% men [38] [39] [40] [41] . SUD is estimated to cost the US~1 trillion dollars, i.e., 700 billion National Institute on Drug Abuse (NIDA), 300 billion National Institute on Alcohol Abuse and Alcoholism (NIAAA), but 

NIDA defines SUD as a chronic relapsing disorder. As a result, the long-term success rate of Alcoholics Anonymous (AA) and rehab groups is very low, except on the rare occasion when patients follow treatment guidelines [6, 181, 182] . According to NIDA, the relapse rate for SUD is 40-60% and "resembles those of other chronic diseases such as diabetes, hypertension, and asthma" [183] . Therefore, longitudinal studies must follow patients with SUD over the course of years (we recommend at least five) or even a lifetime for verified results [184, 185] . Furthermore, a placebo response may last as long as a year with the buoyant attention of a healthcare practitioner [186] .

Neuropsychiatric disorders are common in the US, and according to the National Institute of Mental Health, nearly one in five US adults has a mental illness [187] . In addition,~45% of individuals with SUD have co-occurring neuropsychiatric disorders [12] . Neuropsychiatric disorders and SUD influence each other, and their combined presentation can result in more severe functional impairment, poorer treatment outcomes, higher treatment costs, and increased mortality and morbidity [188] . Many individuals with SUD and/or neuropsychiatric disorders do not receive treatment [187, 188] . In a study by Han et al., only~9% of adults with SUD and co-occurring neuropsychiatric disorders received both mental health care and substance use treatment, while~52% received neither form of treatment [188] . Additionally, they reported that~3-13% received only substance use treatment, and~34-44% received only mental health care [188] . These findings reveal a significant disparity between the prevalence of SUD and co-occurring neuropsychiatric disorders prevalence and treatment rates.

Solving the SUD pandemic would resolve the US economic crisis, including debt service. One important dilemma related to the treatment of opioid dependence is the widespread use of opioids to specifically treat the unfortunate victims of OUD. While the prescribing of opioids (i.e., Buprenorphine) has reduced harm, it does not result in prophylaxis [189] . To achieve some reasonable solution in terms of treatment, relapse prevention, and prophylaxis, one novel therapeutic should include genetic risk assessment and induction of dopamine balance [190] . Many addiction programs are opting for the use of the non-addicting and relatively safe narcotic antagonist Naltrexone despite its associated poor compliance, even in the injectable form [191] [192] [193] . An analysis conducted at Stanford University suggested that the number of unwanted deaths from prescription opioids and street heroin will continue to increase if no changes are made to the currently available treatment, prevention, and public health approaches [194] .

Studies have shown that Naltrexone is beneficial by attenuating cravings via "psychological extinction" and reducing relapse. In addition, research performed by Blum's group has shown that Buprenorphine is the current medication-assisted treatment (MAT) of choice, but injectable Naltrexone plus an agent to enhance dopaminergic function and tone may rekindle interest amongst addiction physicians and patients [195] . Previously, an open-label investigation in humans showed improvement in Naltrexone compliance and outcomes with dopamine augmentation using the pro-dopamine regulator referred to as KB220 (262 days) compared to naltrexone alone (37 days) [195] . This well-studied complex consists of amino-acid neurotransmitter precursors and enkephalinase inhibitor therapy compared to standard treatment [196] . Consideration of this novel paradigm shift may assist in not only addressing the current opioid epidemic but also the broader issue of reward dysregulation.

It is important to recognize that SUD may also occur with certain palatable foods such as sugar and may also become highly addictive to the individual. It is well known that over 90 percent of people with obesity have an abnormal romance with carbohydrates. It is also well-known that there is strong evidence that common neurochemical mechanisms are observed in both animal and human imaging studies [48, 180] .

SUD is widely recognized as a neurological disorder. However, despite this, there are currently no standard, routine, objective brain assessments being performed, and without standardization, patients with neurological/brain disorders/dysfunction will not be able to receive the treatment they need. For example, it took approximately 40 years to obtain a core set of cardiac tests, e.g., electrocardiogram (EKG), echocardiogram, and blood tests, etc., which ultimately halted the bypass cardiac pandemic. Brain health needs to have a similar stepwise approach that parallels those used to treat cardiac disease because, without routine objective assessments, clinical studies lack reliability, accuracy, dependability, and reproducibility (Table 3) . Therefore, utilizing the currently available inexpensive objective testing of premorbid memory, attention, and neuropsychiatry, with the possible addition of supplemental imaging and genotyping, would greatly improve brain/mind health and help combat the addiction pandemic (Table 3 ) [180, 197] . 

Based on the literature review, it is our opinion that a novel, cost-effective Brain Health Checkup that involves the domains: Memory, Attention, Neuropsychiatry, and Neurological Imaging may become the new standard of care in pediatric medicine, starting with children aged five and especially following Genetic Addiction Risk Score (GARS) testing (for curiosity or especially in a family tree robust with Reward Deficiency Syndrome (RDS) behaviors such as AUD, etc.). This checkup would be referred to as a "Brain Health Checkup" (BHC). Utilizing primarily PUBMED, the current paper herein, reviews over 36 years of virtually all the computerized and written-based assessments of Memory, Attention, Neuropsychiatry, and Neurological imaging. This research found the following tests to be the most beneficial for each of the aforementioned domains and recommends their use in the BHC: Central Nervous System Vital Signs (Memory), Test of Variables of Attention (Attention), Millon Clinical Multiaxial Inventory III (Neuropsychiatric), Quantitative Electroencephalogram/P300/Evoked Potential (Neurological Imaging). Obviously, these denoted domains should not be limited but in our opinion be included in any BHC to be effective in diagnoses in primary care and reward dysregulation.

SUD is a total brain disorder that causes brain injury, delayed processing, decreased memory, attention abnormalities, neuropsychiatric disturbance, and MRI results that parallel dementia/mild cognitive impairment (MCI) ( Table 4 ) . Brain atrophy/damage is found in MCI, moderate cognitive impairment (MoCI), and dementia . MRI results can be confusing if not performed serially, as the worsening of atrophy is more predictive of dementia. SUD may cause more injury to the dorsal lateral prefrontal cortex and mesial temporal lobe [198] . Additionally, studies have shown that SUD may cause slightly greater damage than MCI . The mechanism of SUD brain atrophy is the same as dementia, called retrogenesis, which is the opposite of neurogenesis [198, [227] [228] [229] [230] [231] [232] [233] [234] [235] . Ventral Tegmental Area REF: Out of all the memory tests reviewed, the Central Nervous System Vital Signs (CNSVS) assessment was found to be the best. The CNSVS is a computerized neuropsychological test used to evaluate the neurocognitive status of patients, which includes mental processes that range from simple motor performance, attention, and memory to executive functions [236, 237] . It includes 10 normed objective neurocognitive tests: verbal memory, visual memory, finger tapping, symbol digit coding, shifting attention, continuous performance, perception of emotions, Stroop test, non-verbal reasoning, and four-part continuous performance [236, 237] . CNSVS was found to be the best memory test because it is SOC2 certified, registered with the FDA, available globally, economical at~USD 35, has greater than 99% compliance, and only takes~30 min to complete [236] [237] [238] [239] [240] . CNSVS has high appeal because complex attention correlates with better SUD function and possible prevention [236, 238, 239, 241, 242] . CNSVS has no practice learning effect (test-retest probability) and becomes a reliable indicator of deterioration or improvement over time [236] . The presidential Montreal Cognitive Assessment (MoCA) test correlates well with CNSVS results [242] .

Attention deficits are common in SUD patients [243] [244] [245] [246] . In fact, research has shown that of adults presenting with SUD, 20-30% have concurrent ADHD, and 20-40% of adults diagnosed with ADHD also have a history of SUD [180, [243] [244] [245] [246] . Therefore, the Test of Variables of Attention (TOVA), which is an attention screening test, would be useful in the diagnosis and subsequent treatment of SUD. The TOVA measures omission errors (inattention), commission errors (impulsivity), response time, response time variability (consistency), commission error response time, post-commission error response time, anticipatory responses, embedded performance validity, inattentiveness, impulsivity, sustained attention, and vigilance [247, 248] . It can successfully diagnose ADHD subtypes, including inattention, impulsivity, attentional failure due to depression or psychomotor retardation, and inconsistency [248, 249] . TOVA is currently the best attention test because it is FDA approved, economical at~USD 15, has greater than 99% compliance, and only takes~22 min to complete [249] . In addition, TOVA does not have a significant practice effect, is easy to supplement with Conners' checklist, and allows for diagnostic heterogeneity [247, 249, 250] .

Virtually all SUD patients have some form of neuropsychiatric/global dopamine dysfunction in life. Premorbid neuropsychiatric medical findings that predict progression to SUD are not widely screened for or even known ( Table 2 ). The range of neuropsychiatric consequences of SUD are extremely diverse and cannot be accurately or reliably measured without standardization of testing (Table 5 ). This results in the absence of early identification of high-risk individuals across primary care and the various specialties. If a BHC were a mandated part of neuropsychiatric medicine, then the premorbid states would be characterized. For example, cardiovascular disease has been greatly controlled by testing premorbid patients with no heart disease or only early disease (hypertension or hyperlipidemia), i.e., EKG, labs, and echocardiogram. This approach engages the patient in their treatment and has been repeated in diabetes (hemoglobin A1c), obesity (body mass index, bioimpedance), breast cancer (mammogram/ultrasound), cervical cancer (pap smear), asthma (pulmonary function tests), and routine blood work for anemia, kidney, liver disease, etc. In addition, the BHC would help destigmatize SUD brain disorders, which is a key step towards medical parity [30, 31] . The individual brain function tests could also be called BFTs to parallel liver function tests (LFTs), thyroid function tests (TFTs), pulmonary function tests (PFTs), and kidney function tests (KFTs), etc. [30,31]. The Millon Clinical Multiaxial Inventory-III (MCMI-III) is a diagnostic tool that can quickly and efficiently screen patients for neuropsychiatric disorders ( Table 6 ). The MCMI-III provides a measure of 24 Axis I and II disorders and clinical syndromes for adults undergoing psychological or psychiatric assessment/treatment [252, 253] . It has 175 questions and 27 scales with 99% compliance [252, 253] . Assessed MCMI 1-4 correlates with the DSM [252] [253] [254] [255] . MCMI-III contains a lifetime interpretation guide that captures many past and future predictions of behavior [256] . Non-psychiatrists should ideally use MCMI-III because DSM 5 has over 500 diagnoses/severity, which makes it difficult for non-psychiatrists to use. Additionally, psychiatrists' use of the DSM typically results in one to two diagnoses for SUD patients, which is often inaccurate and misleading because SUD patients are typically worse than any one or two diagnoses alone. The most common finding of the MCMI-III test is the rate of depression,~10-20% [257] . We studied the impact of SUD on brain electrophysiology and found that SUD significantly worsens normal temporal lobe abnormalities [257] . The bitemporal injury of SUD increases mood disorders [257] . Our MCMI-III data have been shown to have a high predictive value of suicide rates and secondary mood and psychiatric disturbances [257] . Conventional data suggest that at least 25% of adolescents have a psychiatric disorder. This by far underestimates the problem, which is that adolescents have closer to 50% Axis 1 diagnoses and~90% have an Axis 2 trait. The continued dumping of SUD patients to psychiatrists demonstrates the current health care system's failure to coordinate brain health and medical comorbidities [36]. 

SUD should be recognized as a brain disorder, and thus, neurological imaging should be implemented in its diagnosis and treatment. It is known that imaging is a very useful tool to help understand neurotransmitter interaction at regions of interest (ROI) in the brain, and over the past 40 years, electrophysiology has become the standard and most costeffective method (Table 7 ) [258] [259] [260] [261] [262] [263] [264] . In fact, of all imaging methods, decreased p300 amplitude/latency, increased theta wave on qEEG, and abnormal evoked potential on visual and auditory processing are most established with electrophysiology (Table 7 ) [257, [264] [265] [266] [267] [268] [269] [270] [271] [272] . Therefore, in terms of imaging, Quantitative Electroencephalogram (qEEG)/P300/Evoked Potential (EP) should become the standard in the diagnosis/treatment of SUD patients. [198, 251, 257, [264] [265] [266] [267] [268] [269] [270] [271] [272] [273] [274] [275] [276] [277] Long-term successful treatment in medicine is accomplished with precision biological markers [257, 278, 279] . When all practitioners use the same test, e.g., EKG, echocardiogram, and cholesterol, etc., we obtain the best results [280] [281] [282] . The most common neuropsychiatric diagnosis in the US is depression, which only worsens with SUD [257, 265, 266] . Our laboratory showed that patients with both depression and SUD synergistically induce an exacerbated infraction in P300 metrics (Figure 1 ). Since SUD is a neurological disorder, talk therapy is an adjunct to spiritual and rehab therapeutics [182, [259] [260] [261] [262] [263] [264] [283] [284] [285] [286] [287] . 

Addiction is a substantial health issue with limited treatment options approved by the FDA and, as such, currently available. It is known that cognitive circuitry and reward circuity overlap in the brain and share similar "light switches" [292] . The advent of neuroimaging techniques that link neurochemical and neurogenetic mechanisms to the reward circuitry brain function provides a framework for potential genomic-based therapies [293] .

A search of the current literature (9-26-21) via PUBMED provides descriptions of promising new targets, alternatives such as animal models of gene therapy, addiction treatment and relapse prevention, and nutrigenomic and pharmacogenomic methods to manipulate transcription and gene expression [294] . In our opinion, while developing a cost-effective methodology to help primary care physicians incorporate the proposed BHC, we recognize the clinical benefit of early genetic testing to determine addiction risk stratification and dopaminergic agonistic (in subjects with hypodopaminergia) and antagonistic (in subjects with hyperdopaminergia) therapies. Adoption of these actionable targets, especially in the promotion of precision medicine, is potentially the genome-based wave of the future. In addition, further development, especially in gene transfer work (gene editing) and viral vector identification, could be the future of gene therapy for RDS. This could be accomplished through candidate and genome-wide association studies. Many gene clusters and polymorphisms implicated in drug, food, and behavioral dependence are linked by the common rubric RDS [293, 294] .

Since SUD is widely correlated with neuropsychiatric, medical, and social consequences, methods are reviewed to identify comorbidities and their high risk (Tables 1, 2, 4 and 5) [36]. One very critical area of assessment must include a detailed family history of familiar SUD. The premorbid risk factors include virtually any neuropsychiatric/sleep disorders, traumatic brain injury, concussion, head trauma, family history of addiction, 

Addiction is a substantial health issue with limited treatment options approved by the FDA and, as such, currently available. It is known that cognitive circuitry and reward circuity overlap in the brain and share similar "light switches" [292] . The advent of neuroimaging techniques that link neurochemical and neurogenetic mechanisms to the reward circuitry brain function provides a framework for potential genomic-based therapies [293] .

A search of the current literature (9-26-21) via PUBMED provides descriptions of promising new targets, alternatives such as animal models of gene therapy, addiction treatment and relapse prevention, and nutrigenomic and pharmacogenomic methods to manipulate transcription and gene expression [294] . In our opinion, while developing a cost-effective methodology to help primary care physicians incorporate the proposed BHC, we recognize the clinical benefit of early genetic testing to determine addiction risk stratification and dopaminergic agonistic (in subjects with hypodopaminergia) and antagonistic (in subjects with hyperdopaminergia) therapies. Adoption of these actionable targets, especially in the promotion of precision medicine, is potentially the genome-based wave of the future. In addition, further development, especially in gene transfer work (gene editing) and viral vector identification, could be the future of gene therapy for RDS. This could be accomplished through candidate and genome-wide association studies. Many gene clusters and polymorphisms implicated in drug, food, and behavioral dependence are linked by the common rubric RDS [293, 294] .

Since SUD is widely correlated with neuropsychiatric, medical, and social consequences, methods are reviewed to identify comorbidities and their high risk (Tables 1, 2, 4 and 5) [36]. One very critical area of assessment must include a detailed family history of familiar SUD. The premorbid risk factors include virtually any neuropsychiatric/sleep disorders, traumatic brain injury, concussion, head trauma, family history of addiction, neurotransmitter and second messenger polymorphisms, hormonal abnormalities, and other areas of dysfunction (Table 2 ). Early identification of genetic risk for all reward dysregulation, either deficit or surfeit in terms of dopaminergic activity, is critical prior to any initiation of unwanted substances or even non-substance seeking as a preventive step [295] .

Dopamine genotyping is critical for pediatrics because "an increase in dopamine levels is typical of all addictive drugs (final common SUD pathway) and sufficient to trigger forms of synaptic plasticity underlying adaptive behaviors" [296] [297] [298] . Genotyping predicts a higher probability of SUD in pediatric patients, but SUD is not completely determined by genes at any age [196, [294] [295] [296] . Genes are a risk factor, particularly when young, but as individuals age, they transcend genetics with epigenetics. Therefore, the BHC is more essential long term.

Drug and alcohol experimentation is almost endless, from bath salts to psychedelics (Table 8 ) [299] [300] [301] [302] [303] . Currently, despite the existence of the GARS test and possibly other viable genetically based panels, most clinicians involved in addiction medicine fail to identify SUD appropriately and objectively in patients of all ages. This conundrum translates to lack of psychometrics for evaluating the premorbid risks of SUD as part of primary care standard medicine [180] . Subjective medical histories of SUD and even medical patients alone are unreliable; for example, patients misreport their current height by 0.5-4 inches [333] [334] [335] [336] [337] [338] . Testing of reward dysregulation such as SUD is marked by underreporting of patients not willing to testify against themselves, and moreover, there is difficulty in identifying the number of substances being used through standard testing, e.g., urine drug screens, breathalyzers, blood alcohol levels, etc. It is known that, for example, patients that carry the DRD2 A1 allele are more likely to deny or lie about their SUD issue [338] . Specifically, Comings et al. investigated the dopamine D2 receptor (DRD2) gene haplotypes, identified by the allele-specific polymerase chain reaction of two mutations (G/T and C/T) 241 base pairs apart, in 57 of the ATU subjects and 42 of the controls [338] . They reported that subjects with the one haplotype tended to show a decrease in mature and an increase in neurotic and immature defense styles compared to those without the one haplotype. These results suggest that the DRD2 locus is one factor controlling defense styles (lying).

The pediatric population will also benefit from a BHC. Currently, there is inadequate subjective and virtually no objective psychometrics to analyze the premorbid risks of SUD in the pediatric population (Table 3) . However, according to NCDAS,~50% of teenagers have experimented with illicit drugs at least once [12] . Early drug use/abuse has been shown to correlate with SUD later in life, and according to the gateway hypothesis, this early experimentation can escalate into more addictive illicit drugs later in adulthood [12, 300, 301, 339] . Each episode of experimentation likely injures the brain to some degree, and eventually, these injuries accumulate, resulting in SUD [299] [300] [301] 340] . Of interest in terms of a gateway hypothesis to SUD, Kandel and Kandel [339] describe how marijuana and other illicit drug use are preceded by tobacco or alcohol use. Additionally, using their mouse model, they were able to identify biological processes, showing that nicotine is a gateway drug that exerts a priming effect on cocaine through epigenetically increased global acetylation in the striatum [339] .

It is noteworthy that it may be difficult in some cases to misdiagnose SUD with other conditions, and even careful following of DSM-5 may not provide the best possible manner to determine SUD compared with other neurological diseases. However, with the coupling of a strong family history and genetic addiction risk assessment, this might be a way to prevent misdiagnosis. Nevertheless, if we could agree that SUD is just a subset of a more major umbrella terminology such as reward deficiency, then it may not be such a real issue due to overall common reward circuitry dysregulation in general.

Once a person is in rehab or detox, it is the equivalent of their first stroke or heart attack, and by then, treatment is too late. The tools to prevent the progression of SUD are available and must be utilized; otherwise, the deaths attributed to addiction will continue to rise. The approach to brain health and addiction needs to be reexamined, and a new approach must be implemented by the medical community as a whole. At least three decades of clinical research reviewed here establishes a "Brain Health Check" based on precision medicine for the SUD phenotype centered around precision neuropsychiatric testing, i.e., Memory (CNSVS), Attention (TOVA), Neuropsychiatric (MCMI-III), Neurological Imaging (qEEG/P300/EP). The BHC establishes a set of objective assessments for brain health that parallel those used to treat cardiac disease and provides a form of standardization that is desperately needed. This approach would greatly improve the brain/mind health of all and help stop/prevent the rise of SUD with early detection and treatment, thus bringing an attenuation to the current addiction pandemic.

Moreover, The Carter Center has estimated that if the addiction crisis continues at the same rate, by the year 2030, it will cost America approximately 16 trillion dollars. The current status of our precious youth has been compromised by not only the COVID pandemic but also by the unfortunate state of an unwanted global opioid crisis, especially in America. Hundreds of thousands of people have succumbed to deadly opioid type drugs, a rate that is increasing yearly. The neurodevelopment of our children has been compromised by not only the victimization of mothers using opioids and other drugs during pregnancy but also by a high rate of DNA polymorphic antecedents as well as methylation on specific important genes related to normal brain function via known epigenetic insults. Along with these genetic antecedent insults affecting normal mRNA transcription and loss of required proteins to induce normal brain function, normal brain development in our youth is very complex.

It is generally accepted that myelination in the frontal cortex is quite delayed in our youth, especially as it relates to executive function and decision making. However, we embrace positive thinking, especially as it relates to neurotheology. An understanding of this short circuiting in brain development, along with potential high antecedent polymorphic risk variants or alleles and generational epigenetics, provides a clear rationale to embrace the Brain Research Commission (BRC) suggestion to mimic fitness programs with an adaptable Brain Health Check-up. This can be implemented in America and other countries' educational systems. Adoption of this proposal may reduce juvenile criminal activities and potential attenuation of relapse to RDS behaviors. 

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Randomised Sham-Controlled Study of High-Frequency Bilateral Deep Transcranial Magnetic Stimulation (DTMS) to Treat Adult Attention Hyperactive Disorder (ADHD): Negative Results

The Effectiveness of Neurofeedback and Stimulant Drugs in Treating AD/HD: Part II

Manor, I. The Placebo Response in Adult ADHD as Objectively Assessed by the TOVA Continuous Performance Test

Attention-Deficit/Hyperactivity Disorder (ADHD) in Children

ADHD in the Elderly: An Unexpected Diagnosis

Clinical Assessment and Diagnosis of Adults with Attention-Deficit/Hyperactivity Disorder

Neurogenetic Interactions and Aberrant Behavioral Co-Morbidity of Attention Deficit Hyperactivity Disorder (ADHD): Dispelling Myths. Theor

The possibilities of neurostimulation (sympathetic correction) in the treatment of amnestic (Korsakoff's) psychosis

Psycho-Education for Substance Use and Antisocial Personality Disorder: A Randomized Trial

CDC Guideline for Prescribing Opioids for Chronic Pain-United States

Substance Use Disorder and Risk of Suicidal Ideation, Suicide Attempt and Suicide Death: A Meta-Analysis

Reductions in Cannabis Use Are Associated with Improvements in Anxiety, Depression, and Sleep Quality, but Not Quality of Life

Effects of Fexofenadine, Diphenhydramine, and Placebo on Performance of the Test of Variables of Attention (TOVA)

Allergic Rhinitis

Beclomethasone in Steroid-Dependent Asthma. Effective Therapy and Recovery of Hypothalamo-Pituitary-Adrenal Function

Resilience Intervention for Young Adults with Adverse Childhood Experiences

Global DNA Methylation Levels in White Blood Cells of Patients with Chronic Heroin Use Disorder. A Prospective Study

Platelet to Lymphocyte Ratio (PLR) in Alcohol Use Disorder

Patients with Diabetes Respond Well to Contingency Management Treatment Targeting Alcohol and Substance Use

Relationship between Diabetes and Mortality among Persons with Co-Occurring Psychotic and Substance Use Disorders

Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms

Obesity 2021: Current Clinical Management of a Chronic, Serious Disease

Neuropsychiatric Symptoms Are Early Indicators of an Upcoming Metabolic Decline in Alzheimer's Disease

Endogenous Sex Hormones and Metabolic Syndrome in Aging Men

Hypothalamic Function in Response to 2-Deoxy-D-Glucose in Long-Term Abstinent Alcoholics

Prevalence of Osteoporosis and Proxy Clinical Indicators of Osteoporosis in Patients on Long Term Risperidone

Subjective, Psychomotor, and Physiological Effects of Pregabalin Alone and in Combination with Oxycodone in Healthy Volunteers

Efficacy and Safety of Propranolol for Treatment of Temporomandibular Disorder Pain: A Randomized, Placebo-Controlled Clinical Trial

HIV Clinic-Based Buprenorphine plus Naloxone versus Referral for Methadone Maintenance Therapy for Treatment of Opioid Use Disorder in HIV Clinics in Vietnam (BRAVO): An Open-Label, Randomised, Non-Inferiority Trial

Alcohol Use Disorder Tied to Development of Chronic Kidney Disease: A Nationwide Database Analysis

Differential DNA Methylation Following Chemotherapy for Breast Cancer Is Associated with Lack of Memory Improvement at One Year

Self-Detection Remains a Key Method of Breast Cancer Detection for U.S. Women

Strength and Temporal Variance of the Default Mode Network to Investigate Chronic Mild Traumatic Brain Injury in Service Members with Psychological Trauma

BIONIC study group. Trajectories in Health Recovery in the 12 Months Following a Mild Traumatic Brain Injury in Children: Findings from the BIONIC Study

Is Computerized Cognitive Testing Useful in Children and Adolescents with Moderate-to-Severe Traumatic Brain Injury?

Examining Microstructural White Matter in Active Duty Soldiers with a History of Mild Traumatic Brain Injury and Traumatic Stress

Compromised Hippocampus-Striatum Pathway as a Potential Imaging Biomarker of Mild-Traumatic Brain Injury and Posttraumatic Stress Disorder. Hum. Brain Mapp

Test or Rest? Computerized Cognitive Testing in the Emergency Department after Pediatric Mild Traumatic Brain Injury Does Not Delay Symptom Recovery

Cognition in the Emergency Department as a Predictor of Recovery after Pediatric Mild Traumatic Brain Injury

Neuropsychological Outcome and Its Correlates in the First Year after Adult Mild Traumatic Brain Injury: A Population-Based New Zealand Study

Frequency and Impact of Recurrent Traumatic Brain Injury in a Population-Based Sample

Neurocognition in the Emergency Department after a Mild Traumatic Brain Injury in Youth

Diagnostic Confirmation of Mild Traumatic Brain Injury by Diffusion Tensor Imaging: A Case Report

A Phase I Study of Low-Pressure Hyperbaric Oxygen Therapy for Blast-Induced Post-Concussion Syndrome and Post-Traumatic Stress Disorder

A Review of the Validity of Computerized Neurocognitive Assessment Tools in Mild Traumatic Brain Injury Assessment

20-Year Mortality after Discharge in a Cohort of 1,099 Former Trauma Inpatients with and without Substance Use Disorders

Violent and Nonviolent Suicide in Veterans with Substance-Use Disorders

Sexual Risk Behaviors among Teens at an Urban Emergency Department: Relationship with Violent Behaviors and Substance Use

Pragmatic Randomised Controlled Trial to Evaluate the Effectiveness and Cost Effectiveness of a Multi-Component Intervention to Reduce Substance Use and Risk-Taking Behaviour in Adolescents Involved in the Criminal Justice System: A Trial Protocol (RISKIT-CJS)

Developmental Epidemiological Courses Leading to Antisocial Personality Disorder and Violent and Criminal Behavior: Effects by Young Adulthood of a Universal Preventive Intervention in First-and Second-Grade Classrooms

What's the Influence of Social Interactions on Substance Use and Treatment Initiation? A Prospective Analysis among Substance-Using Probationers

Results of a Pilot Randomized Controlled Trial of Buprenorphine for Opioid Dependent Women in the Criminal Justice System

Changes in Daily Substance Use among People Experiencing Homelessness and Mental Illness: 24-Month Outcomes Following Randomization to Housing First or Usual Care: Substance Use and Housing First: Results of a Randomized Trial

Therapeutic Mechanisms of Mindfulness-Oriented Recovery Enhancement for Internet Gaming Disorder: Reducing Craving and Addictive Behavior by Targeting Cognitive Processes

Acute Urinary Retention Secondary to Buprenorphine Administration

Distinctive Aspects of Peptic Ulcer Disease, Dieulafoy's Lesion, and Mallory-Weiss Syndrome in Patients with Advanced Alcoholic Liver Disease or

Risk Factors for Aspiration Pneumonia after Definitive Chemoradiotherapy or Bio-Radiotherapy for Locally Advanced Head and Neck Cancer: A Monocentric Case Control Study

Splenic Function and Alcohol Addiction

Peripheral Blood and Bone Marrow Findings in Chronic Alcoholics with Special Reference to Acquired Sideroblastic Anemia

Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances

Fernández, I. Influence of Substance Use on the Erectile Response in a Sample of Drug Users

The Effects of Alcohol and Drug Abuse on the Skin

Crusted Scabies in a Patient with Methamphetamine Abuse

Disease in Women: Clinical Perspectives

Drug Abuse Relapse Rates Linked to Level of Education: Can We Repair Hypodopaminergic-Induced Cognitive Decline with Nutrient Therapy?

Predicting Relapse after a First Episode of Non-Affective Psychosis: A Three-Year Follow-up Study

Precision Behavioral Management" (PBM): It Is a Generational Family Affair

Attention-Deficit/Hyperactivity Disorder and Risk of Substance Use Disorder: Developmental Considerations, Potential Pathways, and Opportunities for Research

Understanding the Relationship between Amphetamines and Psychosis

Brain Interrupted: Early Life Traumatic Brain Injury and Addiction Vulnerability

American College of Obstetricians and Gynecologists. Opioid Use and Opioid Use Disorder in Pregnancy

Hypothesizing Las Vegas and Sutherland Springs Mass Shooters Suffer from Reward Deficiency Syndrome: "Born Bad

Substance-Use Disorders and Poverty as Prospective Predictors of First-Time Homelessness in the United States

Embracing the Unknown in the Diagnosis of Traumatic Encephalopathy Syndrome

Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

The Molecular Neurobiology of Twelve Steps Program & Fellowship: Connecting the Dots for

Relative Efficacy of Mindfulness-Based Relapse Prevention, Standard Relapse Prevention, and Treatment as Usual for Substance Use Disorders: A Randomized Clinical Trial: A Randomized Clinical Trial

Medications for Smoking Cessation: Guidelines from the

Activation Instead of Blocking Mesolimbic Dopaminergic Reward Circuitry Is a Preferred Modality in the Long Term Treatment of Reward Deficiency Syndrome (RDS): A

Do Patients with Alcohol Dependence Respond to Placebo? Results from the COMBINE Study

Department of Health and Human Services. (n.d.). Nimh Mental Illness. National Institute of Mental Health

Treatment, and Unmet Treatment Needs of US Adults with Mental Health and Substance Use Disorders

Opioid Substitution Therapy: Achieving Harm Reduction While Searching for a Prophylactic Solution

Molecular Neuro-Biological and Systemic Health Benefits of Achieving Dopamine Homeostasis in the Face of a Catastrophic Pandemic (COVID-19): A Mechanistic Exploration

Extended-Release Naltrexone Opioid Treatment at Jail Reentry (XOR)

Adherence Monitoring in Naltrexone Pharmacotherapy Trials: A Systematic Review

Long-Term Follow-up Study of Community-Based Patients Receiving XR-NTX for Opioid Use Disorders

Supply: How We Must Tackle the Opioid Epidemic

Improving Naltrexone Compliance and Outcomes with Putative Pro-Dopamine Regulator KB220, Compared to Treatment as Usual

Pro-Dopamine Regulator (KB220) A Fifty Year Sojourn to Combat Reward Deficiency Syndrome (RDS): Evidence Based Bibliography (Annotated)

Resting State Activity and Connectivity of the Nucleus Basalis of Meynert and Globus Pallidus in Lewy Body Dementia and Parkinson's Disease Dementia

Neuropsychological Consequences of Chronic Drug Use: Relevance to Treatment Approaches. Front

Infratentorial Abnormalities in Vascular Dementia

Left Anterior Temporal Lobe Sustains Naming in Alzheimer's Dementia and Mild Cognitive Impairment

Lewy Body Disease: Thalamic Cholinergic Activity Related to Dementia and Parkinsonism

Improved Social Interaction and Increased Anterior Cingulate Metabolism after Group Reminiscence with Reality Orientation Approach for Vascular Dementia

Atrophy Rates of the Cingulate Gyrus and Hippocampus in AD and FTLD

Ventral Tegmental Area Disruption in Alzheimer's Disease. Aging

A Tensor Based Morphometry Study of Longitudinal Gray Matter Contraction in FTD

Atrophy of the Putamen in Dementia with Lewy Bodies but Not Alzheimer's Disease: An MRI Study

Object Alternation: A Novel Probe of Medial Frontal Function in Frontotemporal Dementia

Network-Selective Vulnerability of the Human Cerebellum to Alzheimer's Disease and Frontotemporal Dementia

Tau Accumulation in the Nucleus Accumbens in Tangle-Predominant Dementia

Patterns of Olfactory Functional Networks in Parkinson's Disease Dementia and Alzheimer's Dementia

Amyloid-β-Related and Unrelated Cortical Thinning in Dementia with Lewy Bodies

Exploring the Patterns of Acupuncture on Mild Cognitive Impairment Patients Using Regional Homogeneity

11C] PIB Binding in Parkinson's Disease Dementia

Cingulate Cortex Structural Alterations in Substance Use Disorder Psychiatric Inpatients

Cerebral Correlates of Psychotic Symptoms in Alzheimer's Disease

Frontal Lobe Dementia and Subcortical Vascular Dementia: A Neuropsychological Comparison

Occipital Lobe and Posterior Cingulate Perfusion in the Prediction of Dementia with Lewy Body Pathology in a Clinical Sample

Hippocampus and Parahippocampal Gyrus Linear Measurements Based on Magnetic Resonance in Alzheimer's Disease

1H MRS in Stroke Patients with and without Cognitive Impairment

Different Patterns of N-Acetylaspartate Loss in Subcortical Ischemic Vascular Dementia and AD

Functional Connectivity Alterations of the Temporal Lobe and Hippocampus in Semantic Dementia and Alzheimer's Disease

Midbrain Atrophy in Subcortical Ischemic Vascular Dementia

Subchronic Duloxetine Administration Alters the Extended Amygdala Circuitry in Healthy Individuals

Dementia Associated with Disorders of the Basal Ganglia

Magnetic Resonance Imaging Texture of Medial Pulvinar in Dementia with Lewy Bodies

Prefrontal Cortex Atrophy Predicts Dementia over a Six-Year Period

Testing the White Matter Retrogenesis Hypothesis of Cognitive Aging

Harnessing Neurogenesis and Neuroplasticity with Stem Cell Treatment for Addictive Disorders

Adult Hippocampal Neurogenesis in the Pathogenesis of Addiction and Dual Diagnosis Disorders

Deficient Plasticity in the Hippocampus and the Spiral of Addiction: Focus on Adult Neurogenesis

Neural Stem Cells, and Adult Neurogenesis

Alcohol and Adult Neurogenesis: Roles in Neurodegeneration and Recovery in Chronic Alcoholism

Alcohol and Cocaine Combined Substance Use on Adult Hypothalamic Neural Stem Cells and Neurogenesis

Synergistic Effects of Social Isolation and Morphine Addiction on Reduced Neurogenesis and BDNF Levels and the Resultant Deficits in Cognition and Emotional State in Male Rats

Hippocampal Deficits in Neurodevelopmental Disorders

Reliability and Validity of a Computerized Neurocognitive Test Battery, CNS Vital Signs

Computerized Screening for Cognitive Impairment in Patients with COPD

Estimation of the Contribution of Norketamine to Ketamine-Induced Acute Pain Relief and Neurocognitive Impairment in Healthy Volunteers

Comparative Neuropsychological Effects of Carbamazepine and Eslicarbazepine Acetate

Factor Structure of the CNS Vital Signs Computerized Cognitive Battery in Youth with Neurological Diagnoses

Polymorphisms of Apolipoprotein E Gene and Cognitive Functions of Postmenopausal Women, Measured by Battery of Computer Tests-Central Nervous System Vital Signs

The International Collaboration on ADHD and Substance Abuse (ICASA): Mission, Results, and Future Activities

Bar-Shalita, T. Attention-Deficit/Hyperactivity Disorder Symptoms, Sensation-Seeking, and Sensory Modulation Dysfunction in Substance Use Disorder: A Cross Sectional Two-Group Comparative Study

Delayed P300 Latency Correlates with Abnormal Test of Variables of Attention (TOVA) in Adults and Predicts Early Cognitive Decline in a Clinical Setting

Test of Variables of Attention (TOVA) as a Predictor of Early Attention Complaints, an Antecedent to Dementia

Neural Mechanisms of Affective Instability and Cognitive Control in Substance Use

Performance on the Continuous Performance Test in Children with ADHD Is Associated with Sleep Efficiency

Effects of Comorbid Disorders on Reward Processing and Connectivity in Adults with ADHD

Störungen durch Substanzkonsum und begleitende psychische Störungen bei Jugendlichen: Zahlen aus einer Spezialambulanz für Suchterkrankungen

Impact of Adolescent Marijuana Use on Intelligence: Results from Two Longitudinal Twin Studies

Millon Clinical Multiaxial Inventory-III Subtypes of Opioid Dependence: Validity and Matching to Behavioral Therapies

Contributions to the Dimensional Assessment of Personality Disorders Using Millon's Model and the Millon Clinical Multiaxial Inventory (MCMI9-III)

Millon Clinical Multiaxial Inventory: I & II

Evolution of the Millon Clinical Multiaxial Inventory

Global Millon Clinical Multiaxial Inventory III Corrections Interpretive Report (MCMI-III)

Substance Use Disorder Exacerbates Brain Electrophysiological Abnormalities in a Psychiatrically-Ill Population

A Multicenter Effectiveness Trial of QEEG-Informed Neurofeedback in ADHD: Replication and Treatment Prediction

Drug Misuse and Addiction

Overcoming QEEG Abnormalities and Reward Gene Deficits during Protracted Abstinence in Male Psychostimulant and Polydrug Abusers Utilizing Putative Dopamine D 2 Agonist Therapy: Part 2

Molecular Imaging of Opioid and Dopamine Systems: Insights into the Pharmacogenetics of Opioid Use Disorders. Front

Heightened Dopaminergic Response to Amphetamine at the D3 Dopamine Receptor in Methamphetamine Users

Altered Functional Connectivity of the Nucleus Accumbens Subdivisions in Amphetamine-Type Stimulant Abusers: A Resting-State FMRI Study

EEG Biofeedback as a Treatment for Substance Use Disorders: Review, Rating of Efficacy, and Recommendations for Further Research

Exploring the Relationship between Depressive and Anxiety Symptoms and Neuronal Response to Alcohol Cues

P300 Development across the Lifespan: A Systematic Review and Meta-Analysis

Menopause Analytical Hormonal Correlate Outcome Study (MAHCOS) and the Association to Brain Electrophysiology (P300) in a Clinical Setting

P300 (Latency) Event-Related Potential: An Accurate Predictor of Memory Impairment

Use of Growth Hormone in Elderly Individuals

Preliminary Investigation of Plasma Levels of Sex Hormones and Human Growth Factor(s), and P300 Latency as Correlates to Cognitive Decline as a Function of Gender

Plasma Growth Hormones, P300 Event-Related Potential and Test of Variables of Attention (TOVA) Are Important Neuroendocrinological Predictors of Early Cognitive Decline in a Clinical Setting: Evidence Supported by Structural Equation Modeling (SEM) Parameter Estimates

Neurosteroid Levels in Patients with Bipolar Disorder and a History of Cannabis Use Disorders

Late Whiplash Syndrome: Correlation of Brain SPECT with Neuropsychological Tests and P300 Event-Related Potential

Evoked Potentials and Memory/Cognition Tests Validate Brain Atrophy as Measured by 3T MRI (NeuroQuant) in Cognitively Impaired Patients

Preliminary Findings Demonstrating Latent Effects of Early Adolescent Marijuana Use Onset on Cortical Architecture

Recent Tobacco Use Has Widespread Associations with Adolescent White Matter Microstructure

Evoked Potentials and Neuropsychological Tests Validate Positron Emission Topography (PET) Brain Metabolism in Cognitively Impaired Patients

Central and Peripheral Biomarkers of Stress Response for Addiction Risk and Relapse Vulnerability

Identifying Biological Markers for Improved Precision Medicine in Psychiatry

The Low Impact of Screening Electrocardiograms in Healthy Individuals: A Prospective Study and Review of the Literature

Usefulness of Combined History, Physical Examination, Electrocardiogram, and Limited Echocardiogram in Screening Adolescent Athletes for Risk for Sudden Cardiac Death

Cholesterol Screening among Children and Their Parents

NIDA-Drug Addiction Treatment Outcome Study (DATOS) Relapse as a Function of Spirituality/Religiosity

Our Beliefs

Inclusion of Family Therapy in Rehabilitation Program of Substance Abuse and Its Efficacious Implementation

Delivering Remote Measurement-Based Care in Community Addiction Treatment: Engagement and Usability over a 6-Month Clinical Pilot. Front

Neurochemical Substrates and Neuroanatomical Generators of the Event-Related P300

Resting EEG and ERPs Findings in Methadone-Substituted Opiate Users: A Review

The P300 Event-Related Potential and Its Possible Role as an Endophenotype for Studying Substance Use Disorders: A Review

Event-Related Potentials in Substance Use Disorders: A Narrative Review Based on Articles from 1984 to 2012: A Narrative Review Based on Articles from 1984 to 2012

Overlapping Neural Systems Represent Cognitive Effort and Reward Anticipation

Pre-Clinical Models of Reward Deficiency Syndrome: A Behavioral Octopus

Neurogenetics and Gene Therapy for Reward Deficiency Syndrome: Are We Going to the Promised Land? Expert Opin

Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) during Adolescent Brain Development

Coupling Genetic Addiction Risk Score (GARS) and pro Dopamine Regulation (KB220) to Combat Substance Use Disorder (SUD)

Coupling Genetic Addiction Risk Score (GARS) with Electrotherapy: Fighting Iatrogenic Opioid Dependence

Synaptic Mechanism Underlying Serotonin Modulation of Transition to Cocaine Addiction

Neurobiologic Advances from the Brain Disease Model of Addiction

Gateway Hypothesis" and Early Drug Use: Additional Findings from Tracking a Population-Based Sample of Adolescents to Adulthood

The Social Exigencies of the Gateway Progression to the Use of Illicit Drugs from Adolescence into Adulthood

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Potential Therapeutic Effects of Psilocybin

Effects of a Behavioral Intervention That Emphasizes Spices and Herbs on Adherence to Recommended Sodium Intake: Results of the SPICE Randomized Clinical Trial

Evidence for Sugar Addiction: Behavioral and Neurochemical Effects of Intermittent, Excessive Sugar Intake

The Effects of Drug Abuse on the Human Nervous System

Synthetic and Non-Synthetic Cannabinoid Drugs and Their Adverse Effects-A Review from Public Health Prospective

Heroin Addicts with a History of Glue Sniffing: A Deviant Group within a Deviant Group

Strong Feelings: Emotion, Addiction, and Human Behavior

Violent Behaviors in Drug Addiction: Differential Profiles of Drug-Addicted Patients with and without Violence Problems: Differential Profiles of Drug-Addicted Patients with and without Violence Problems

Exploring the Consumption of Ultra-Processed Foods and Its Association with Food Addiction in Overweight Children

Clinical Studies of Cyclazocine in the Treatment of Narcotic Addiction

Bath Salts and Synthetic Cathinones: An Emerging Designer Drug Phenomenon

Tolerance, and Addiction to Benzodiazepines: Clinical and Pharmacokinetic Considerations

Addiction to Barbiturates and the Barbiturate Abstinence Syndrome

Emerges from the Murky Waters of Addiction. Abuse Trends of an Old Drug

Psychedelics and Mental Health: A Population Study

Safety and Side-Effects of Buprenorphine in the Clinical Management of Heroin Addiction

Food Addiction, Saturated Fat Intake, and Body Mass Index in Peruvian Adults: A Cross-Sectional Survey

Abuse Liability of Barbiturates and Other Sedative-Hypnotics

Psychiatric Side Effects Induced by Supraphysiological Doses of Combinations of Anabolic Steroids Correlate to the Severity of Abuse

Sex Addiction as a Disease: Evidence for Assessment, Diagnosis, and Response to Critics

Treatment of Nicotine Addiction: Present Therapeutic Options and Pipeline Developments

Inhalant Addiction. In Textbook of Addiction Treatment

Is Caffeine Addictive?-A Review of the Literature

Potential Human Neurotoxicity of MDMA ('Ecstasy'): Subjective Self-Reports, Evidence from an Italian Drug Addiction Centre and Clinical Case Studies

Bourges-Rodríguez, H. Does Salt Addiction Exist?

Abuse Potential of Carbohydrates for Overweight Carbohydrate Cravers

Alcohol Addiction (Alcoholism) and the Opioid System

Managing Terrorism or Accidental Nuclear Errors, Preparing for Iodine-131 Emergencies: A Comprehensive Review

Mitragyna Speciosa): Friend or Foe? Prim. Care Companion CNS Disord

Kava in the Pacific Islands: A Contemporary Drug of Abuse?

Self-Reported Weight and Height: Implications for Obesity Research

Detection of Drugs of Abuse in Exhaled Breath Using a Device for Rapid Collection: Comparison with Plasma, Urine and Self-Reporting in 47 Drug Users

Inaccuracies in Survey Reporting of Alcohol Consumption

Meta-Analysis of Self-Reported Substance Use Compared with Laboratory Substance Assay in General Adult Mental Health Settings: Self-Reported Substance Use Compared with Laboratory Substance Assay

Inconsistencies in Self-Reported Drug Use by Adolescents in Substance Abuse Treatment: Implications for Outcome and Performance Measurements

Dopamine D2 Receptor Gene (DRD2) Haplotypes and the Defense Style Questionnaire in Substance Abuse, Tourette Syndrome, and Controls

The Gateway Hypothesis of Substance Abuse: Developmental, Biological and Societal Perspectives

Cognitive Functioning Related to Binge Alcohol and Cannabis Co-Use in Abstinent Adolescents and Young Adults