Search

The current addiction crisis has destroyed a multitude of lives, leaving millions of fatalities worldwide in its wake. At the same time, various governmental agencies dedicated to solving this seemingly never-ending dilemma have not yet succeeded or delivered on their promises. We understand that addictive behavioral seeking is a multi-faceted neurobiological and spiritually complicated phenomenon. However, although the substitution replacement approach, especially to treat Opioid Use Disorder (OUD), has importance for harm reduction in the short term, it does not bring about a harm-free recovery or prevention. Instead, we propose a promising novel approach that uses genetic risk testing with induction of dopamine homeostasis and an objective Brain Health Check during youth. Our model involves a six-hit approach known as the "Reward Dysregulation Syndrome Solution System," which can identify addiction risk and target the root cause of addiction, dopamine dysregulation. While we applaud all past sophisticated neurogenetic and neuropharmacological research, our opinion is that in the long term, addiction scientists and clinicians might characterize preaddiction using tests; for example, administering the validated RDSQuestionarre29, genetic risk assessment, a modified brain health check, or diagnostic framing of mild to moderate Substance Use Disorder (SUD). The preaddiction concept could incentivize the development of interventions to prevent addiction from developing in the first place and target and treat neurotransmitter imbalances and other early indications of addiction. WC 222., Competing Interests: Declaration of Competing Interest KB owns the patents and pending related to GARS and KB220 variants. There are no other conflicts., (Copyright © 2022. Published by Elsevier B.V.)

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.

Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e., a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent JAMA report indicates that non-opioid treatments fare better than chronic opioid treatments. Research demonstrates that over 50 percent of all suicides are related to alcohol or other drug use. In addition to effective fellowship programs and spirituality acceptance, nutrigenomic therapies (e.g., KB220Z) optimize gene expression, rebalance neurotransmitters, and restore neurotransmitter functional connectivity. KB220Z was shown to increase functional connectivity across specific brain regions involved in dopaminergic function. KB220/Z significantly reduces RDS behavioral disorders and relapse in human DUI offenders. Taking a Genetic Addiction Risk Severity (GARS) test combined with a the KB220Z semi-customized nutrigenomic supplement effectively restores dopamine homeostasis (WC 199).

During the current coronavirus disease 2019 epidemic, many outpatient chemical dependency treatment programs and clinics are decreasing their number of in-person patient contacts. This has widened an already large gap between patients with substance use disorders (SUDs) who need treatment and those who have actually received treatment. For a disorder where group therapy has been the mainstay treatment option for decades, social distancing, shelter in place, and treatment discontinuation have created an urgent need for alternative approaches to addiction treatment. In an attempt to continue some care for patients in need, many medical institutions have transitioned to a virtual environment to promote safe social distancing. Although there is ample evidence to support telemedical interventions, these can be difficult to implement, especially in the SUD population. This article reviews current literature for the use of telehealth interventions in the treatment of SUDs and offers recommendations on safe and effective implementation strategies based on the current literature., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Exercise is known to have a myriad of health benefits. There is much to be learned from the effects of exercise and its potential for prevention, attenuation and treatment of multiple neuropsychiatric diseases and behavioral disorders. Furthermore, recent data and research on exercise benefits with respect to major health crises, such as, that of opioid and general substance use disorders, make it very important to better understand and review the mechanisms of exercise and how it could be utilized for effective treatments or adjunct treatments for these diseases. In addition, mechanisms, epigenetics and sex differences are examined and discussed in terms of future research implications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in the world. TBI causes permanent physical, cognitive, social, and functional impairments. Substance use and intoxication are established risk factors for TBI. Data are emerging that also suggest that brain injury might be a risk factor for substance use. Methamphetamine (METH), a highly addictive psychostimulant, has not been thoroughly investigated in the context of TBI exposure. The interplay between the two has been of interest as their pathophysiology intertwines on many levels. However, the knowledge concerning the association between TBI-METH and the impact of chronic METH use on short and long-term TBI outcomes is equivocal at best. In this review of the literature, we postulate that, when combined, these two conditions synergize to result in more significant neuronal damage. As such, chronic exposure to METH before brain trauma may accentuate the pathophysiological signs of injury, worsening TBI outcomes. Similarly, individuals with a history of TBI would be more vulnerable to METH misuse and harmful effects. We, therefore, review the most recent preclinical and clinical data tackling the significant overlap in the pathophysiology of TBI and METH at three levels: the structural level, the biochemical level, and the cellular level. We also highlight some controversial results of studies investigating the outcomes of the interaction between TBI and METH., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Anhedonia is a condition that leads to the loss of feelings pleasure in response to natural reinforcers like food, sex, exercise, and social activities. This disorder occurs in addiction, and an array of related neuropsychiatric syndromes, including schizophrenia, depression, and Post Traumatic Stress Disorder (PTSD). Anhedonia may by due to derangements in mesolimbic dopaminergic pathways and their terminal fields (e.g., striatum, amygdala, and prefrontal cortex) that persist long after the traces of the causative drugs are eliminated (pharmacokinetically). Here we postulate that anhedonia is not a distinct entity but is rather an epiphenomenon of hypodopaminergic states and traits arising from the interaction of genetic traits and epigenetic neurobiological alterations in response to environmental influences. Moreover, dopaminergic activity is rather complex, and so it may give rise to differential pathophysiological processes such as incentive sensitization, aberrant learning and stress-like "anti-reward" phenomena. These processes may have additive, synergistic or antagonistic interactions with the concurrent reward deficiency states leading in some instances to more severe and long-lasting symptoms. Operant understanding of the neurogenetic antecedents to reward deficiency syndrome (RDS) and the elucidation of reward gene polymorphisms may provide a map for accessing an individual's genetic risk for developing Anhedonia. Prevention techniques that can restore homeostatic balance via physiological activation of dopaminergic receptors (D2/D3) may be instrumental for targeting not only anhedonia per se but also drug craving and relapse.

Obesity is damaging the lives of more than 300 million people worldwide and maintaining a healthy weight using popular weight loss tactics remains a very difficult undertaking. Managing the obesity problem seems within reach, as better understanding develops, of the function of our genome in drug/nutrient responses. Strategies indicated by this understanding of nutriepigenomics and neurogenetics in the treatment and prevention of metabolic syndrome and obesity include moderation of mRNA expression by DNA methylation, and inhibition of histone deacetylation. Based on an individual's genetic makeup, deficient metabolic pathways can be targeted epigenetically by, for example, the provision of dietary supplementation that includes phytochemicals, vitamins, and importantly functional amino acids. Also, the chromatin structure of imprinted genes that control nutrients during fetal development can be modified. Pathways affecting dopamine signaling, molecular transport and nervous system development are implicated in these strategies. Obesity is a subtype of Reward Deficiency Syndrome (RDS) and these new strategies in the treatment and prevention of obesity target improved dopamine function. It is not merely a matter of gastrointestinal signaling linked to hypothalamic peptides, but alternatively, finding novel ways to improve ventral tegmental area (VTA) dopaminergic function and homeostasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background The reward deficiency syndrome hypothesis posits that genes are responsible for reward dependence and related behaviors. There is evidence that both bulimia and anorexia nervosa, especially in women, have been linked to a lifetime history of substance use disorder (SUD). There are difficulties in accepting food as an addiction similar to drugs; however, increasingly neuroimaging studies favor such an assertion. Case presentations We are reporting the evidence of comorbidity of eating disorders with SUD found within these case presentations. We show 50 case reports derived from two independent treatment centers in Florida that suggest the commonality between food and drug addictions. In an attempt to provide data from this cohort, many participants did not adequately respond to our questionnaire. Discussion We propose that dopamine agonist therapy may be of common benefit. Failure in the past may reside in too powerful D2 agonist activity leading to D2 receptor downregulation, while the new methodology may cause a reduction of "dopamine resistance" by inducing "dopamine homeostasis." While this is not a definitive study, it does provide some additional clinical evidence that these two addictions are not mutually exclusive. Conclusion Certainly, it is our position that there is an overlap between food- and drug-seeking behavior. We propose that the studies focused on an effort to produce natural activation of dopaminergic reward circuitry as a type of common therapy may certainly be reasonable. Additional research is warranted.

Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA-induced neurotoxicity.

This article focuses on the shared molecular and neurogenetics of food and drug addiction tied to the understanding of reward deficiency syndrome. Reward deficiency syndrome describes a hypodopaminergic trait/state that provides a rationale for commonality in approaches for treating long-term reduced dopamine function across the reward brain regions. The identification of the role of DNA polymorphic associations with reward circuitry has resulted in new understanding of all addictive behaviors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Addiction is a substantial health issue with limited treatment options approved by the FDA and as such currently available. 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., Areas Covered: Through candidate and genome-wide association studies approaches, many gene polymorphisms and clusters have been implicated in drug, food and behavioral dependence linked by the common rubric reward deficiency syndrome (RDS). The results of selective studies that include the role of epigenetics, noncoding micro RNAs in RDS behaviors especially drug abuse involving alcohol, opioids, cocaine, nicotine, pain and feeding are reviewed in this article. New targets for addiction treatment and relapse prevention, treatment alternatives such as gene therapy in animal models, and pharmacogenomics and nutrigenomics methods to manipulate transcription and gene expression are explored., Expert Opinion: The recognition of the clinical benefit of early genetic testing to determine addiction risk stratification and dopaminergic agonistic, rather than antagonistic therapies are potentially the genomic-based wave of the future. In addition, further development, especially in gene transfer work and viral vector identification, could make gene therapy for RDS a possibility in the future.

We have published extensively on the neurogenetics of brain reward systems with reference to the genes related to dopaminergic function in particular. In 1996, we coined "Reward Deficiency Syndrome" (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function. RDS as a useful concept has been embraced in many subsequent studies, to increase our understanding of Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and impulsive behaviors. Interestingly, albeit others, in one published study, we were able to describe lifetime RDS behaviors in a recovering addict (17 years sober) blindly by assessing resultant Genetic Addiction Risk Score (GARS™) data only. We hypothesize that genetic testing at an early age may be an effective preventive strategy to reduce or eliminate pathological substance and behavioral seeking activity. Here, we consider a select number of genes, their polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is evidence for convergence to reward candidate genes. The evidence presented serves as a plausible brain-print providing relevant genetic information that will reinforce targeted therapies, to improve recovery and prevent relapse on an individualized basis. The primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction medicine that embraces the neuroscience of addiction and RDS as a pathological condition in brain reward circuitry that calls for appropriate evidence-based therapy and early genetic diagnosis and that requires further intensive investigation.

Background: Previous attempts to assess the prevalence of drug use in Afghanistan have focused on subgroups that are not generalisable. In the Afghanistan National Urban Drug Use Study, we assessed risk factors and drug use in Afghanistan through self-report questionnaires that we validated with laboratory test confirmation using analysis of hair, urine, and saliva., Methods: The study took place between July 13, 2010, to April 25, 2012, in 11 Afghan provinces. 2187 randomly selected households completed a survey, representing 19 025 household members. We completed surveys with the female head of the household about past and current drug use among members of their household. We also obtained hair, urine, and saliva samples from 5236 people in these households and tested them for metabolites of 13 drugs., Findings: Of 2170 households with biological samples tested, 247 (11·4%) tested positive for any drug. Overall, opioids were the most prevalent drug in the biological samples (5·6%), although prescription drugs (prescription pain pills, sedatives, and tranquilliser) were the most commonly reported in the past 30 days in the questionnaires (7·6%). Of individuals testing positive for at least one substance, opioids accounted for more than 50% of substance use in women and children, but only a third of substances in men, who predominantly tested positive for cannabinoids. After controlling for age with direct standardisation, individual prevalence of substance use (from laboratory tests) was 7·2% (95% CI 6·1-8·3) in men and 3·1% (2·5-3·7) in women-with a national prevalence of 5·1% (4·4-5·8) and a prevalence of 5·0% (4·1-5·8) in Kabul. Concordance between laboratory test results and self-reports was high., Interpretation: These data suggest the female head of household to be a knowledgeable informant for household substance use. They also might provide insight into new avenues for targeted behavioural interventions and prevention messages., (Copyright © 2014 Cottler et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.)

This is the first quantitative analysis of data from urine drug tests for compliance to treatment medications and abstinence from drug abuse across "levels of care" in six eastern states of America. Comprehensive Analysis of Reported Drugs (CARD) data was used in this post-hoc retrospective observational study from 10,570 patients, filtered to include a total of 2,919 patients prescribed at least one treatment medication during 2010 and 2011. The first and last urine samples (5,838 specimens) were analyzed; compliance to treatment medications and abstinence from drugs of abuse supported treatment effectiveness for many. Compared to non-compliant patients, compliant patients were marginally less likely to abuse opioids, cannabinoids, and ethanol during treatment although more likely to abuse benzodiazepines. Almost 17% of the non-abstinent patients used benzodiazepines, 15% used opiates, and 10% used cocaine during treatment. Compliance was significantly higher in residential than in the non-residential treatment facilities. Independent of level of care, 67.2% of the patients (n = 1963; P<.001) had every treatment medication found in both first and last urine specimens (compliance). In addition, 39.2% of the patients (n = 1143; P<.001) had no substance of abuse detected in either the first or last urine samples (abstinence). Moreover, in 2010, 16.9% of the patients (n = 57) were abstinent at first but not at last urine (deteriorating abstinence), the percentage dropped to 13.3% (n = 174) in 2011; this improvement over years was statistically significant. A longitudinal analysis for abstinence and compliance was studied in a randomized subset from 2011, (n = 511) representing 17.5% of the total cohort. A statistically significant upward trend (p = 2.353×10-8) of abstinence rates as well as a similar but stronger trend for compliance ((p = 2.200×10-16) was found. Being cognizant of the trend toward drug urine testing being linked to medical necessity eliminating abusive screening, the interpretation of these valuable results require further intensive investigation.

The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta-analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non-SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Neuroplastic changes in the dorsal striatum participate in the transition from casual to habitual drug use and might play a critical role in the development of methamphetamine (METH) addiction. We examined the influence of METH self-administration on gene and protein expression that may form substrates for METH-induced neuronal plasticity in the dorsal striatum. Male Sprague-Dawley rats self-administered METH (0.1mg/kg/injection, i.v.) or received yoked saline infusions during eight 15-h sessions and were euthanized 2h, 24h, or 1month after cessation of METH exposure. Changes in gene and protein expression were assessed using microarray analysis, RT-PCR and Western blots. Chromatin immunoprecipitation (ChIP) followed by PCR was used to examine epigenetic regulation of METH-induced transcription. METH self-administration caused increases in mRNA expression of the transcription factors, c-fos and fosb, the neurotrophic factor, Bdnf, and the synaptic protein, synaptophysin (Syp) in the dorsal striatum. METH also caused changes in ΔFosB, BDNF and TrkB protein levels, with increases after 2 and 24h, but decreases after 1month of drug abstinence. Importantly, ChIP-PCR showed that METH self-administration caused enrichment of phosphorylated CREB (pCREB), but not of histone H3 trimethylated at lysine 4 (H3K4me3), on promoters of c-fos, fosb, Bdnf and Syp at 2h after cessation of drug intake. These findings show that METH-induced changes in gene expression are mediated, in part, by pCREB-dependent epigenetic phenomena. Thus, METH self-administration might trigger epigenetic changes that mediate alterations in expression of genes and proteins serving as substrates for addiction-related synaptic plasticity., (Published by Elsevier Inc.)

Objectives: The prevalence of substance abuse and other psychiatric disorders among physicians is not well-established. We determined differences in lifetime substance use, and abuse/dependence as well as other psychiatric disorders, comparing physicians undergoing monitoring with a general population that had sought treatment for substance use., Methods: Participants were 99 physicians referred to a Physician's Health Program (PHP) because of suspected impairment, who were administered the Computerized Diagnostic Interview Schedule Version IV (CDIS-IV) to assess the presence of psychiatric disorders. Referred physicians were compared with an age, gender, and education status-matched comparison group from National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Wave 1, in a 1:1 ratio., Results: Although referred physicians did not differ from their counterparts on lifetime use of alcohol, opiates, or sedatives, they did have significantly higher conditional odds of meeting criteria for alcohol, opiate, and sedative The Diagnostic and Statistical Manual of Mental Disorders IV abuse/dependence disorders. Physicians referred to the PHP had significantly lower odds of obsessive-compulsive disorder, major depression, and specific phobia compared with their counterparts., Conclusions: Physicians referred to a PHP have significantly higher odds of abuse/dependence disorders for cannabinoids and cocaine/crack compared with a matched general population sample that had ever sought treatment for substance use, even though physicians were less likely to report use of those substances. Although the rate of alcohol use was similar between the 2 populations, physicians had higher odds of abuse/dependence for opiates, sedatives, and alcohol. More research is needed to understand patterns of use, abuse/dependence, and psychiatric morbidity among physicians.

Motor vehicle crashes are a leading cause of morbidity and mortality in the United States. Drivers with measurable quantities of potentially impairing illicit or prescription drugs in their body fluids are multiple times more likely to be involved in motor vehicle crashes than those without such drugs in their bodies. Drug-related impairment, however, cannot be inferred solely on the basis of the presence of drugs in biological fluids. Thus, for more than a quarter century, there has been a search for drug blood concentrations that are the equivalent of the 0.08 g/dL threshold for alcohol-impaired driving in the United States. We suggest that such equivalents are a mirage, and cannot be determined due to variable drug tolerance, lack of consistent relationships between drug blood concentrations and impairment, innumerable drug combinations and multiple other factors. Thus, while the idea of determining impairing drug concentrations is attractive, it is ultimately unattainable, and withholding drugged driving legislation pending the acquisition of such data is tantamount to a plan for inaction with regard to an important and growing public health and safety problem. We propose specific legislation to address alcohol- and drug-impaired driving in the United States.

Over the past three decades, obesity has become a major public health crisis in the United States. The prevalence of obesity in the United States and in other parts of the world has led to a new word, "globesity," being used to describe the problem. As a result of this increased emphasis on understanding the causes and consequences of obesity, novel theories have stimulated new research aimed to prevent, intervene in and ameliorate the effects and decrease the incidence and medical consequences of globesity. One theory that has gained popularity in recent years, is based on the idea that an excessive intake of highly palatable foods shares similarities with the effects on brain and behavior that are seen with some drugs of abuse. Although this theory is not new, empirically-based translational research has only recently provided strong support for this hypothesis. In the present article, we review the present state of the science in this area and describe some newer clinical and preclinical works that shed light on innovative and interesting overlaps between excessivly palatable food intake and drug use., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The obesity epidemic has led to the postulation that highly palatable foods may be "addictive" for some individuals. This idea is supported by the fact that there are overlaps in brain circuitry that underlie addictive behavior as well as overeating. In this paper, we discuss the utility of the concept of "food addiction" as it may relate to treating certain disordered eating behaviors. Using criteria set forth in the DSM-IV for substance-use disorders, we review data that have emerged from animal models suggesting that overeating, in the form of binge eating, fits some of the criteria for substance abuse. Further, we discuss preclinical data revealing that the addiction-like behavioral changes observed in response to overeating are concomitant with neurochemical changes that are similar to those observed in response to drugs of abuse. With this background and evidence in mind, we conclude this article with a discussion as to how "food addiction" research may translate into clinical strategies and pharmaceutical treatments useful in curtailing overeating.

My work (Mark S. Gold) began in the 70s looking for the mechanisms of drug reinforcement and withdrawal. Through observation and experience, drugs of abuse and the drive for food appeared to be quite related. As pioneered by Bart Hoebel, food can become an object of desire and act in most respects as a drug of abuse. The Gold lab is investigating working models for pathological attachment to eating and food addiction. New pharmacological treatments which interfere with food reinforcement may be the next step., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: It is no surprise that it has taken over four decades to confirm and extend the crucial role of dopamine and related genes and gene deficits in the etiology of risk for drug dependence. Hundreds of studies, enabled by neuroscience neuroimaging and genetic advances, have been reported. While dopamine theories have been reported, confirmed, replicated and replicated again, changes have been slow to move from the bench to the bedside. Unlike penicillin used to target certain infections, addiction requires the consent, motivation and enthusiastic participation of the patient. Clearly, current treatment has not caught up with advances in the science. In-patient and out-patient treatment still relies on detoxification, abstinence and 12 step programs. Addiction is a chronic and relapsing disease. Addiction treatment can be reported as cures at 3 or 6 weeks, only to be clearly failures at 1 or 5 years. The logical standard of care should focus on detoxifying, stabilizing and returning the patient to the pre-loss of control or pre-addiction neurochemical state., Method: Pre-clinical and clinical data on neurochemistry and neurogenetics of Substance Use Disorder (SUD) as it relates to both relapse and drug hunger has been reviewed., Results: We are proposing herein that efforts to physiologically integrate known neural mechanisms with other psychotherapeutic treatment options to combat relapse should be encouraged. It is well known that after prolonged abstinence, recovered addicts are particularly vulnerable to relapse. Individuals who use their drug of choice after abstinence experience a powerful euphoria that can quickly precipitate a full-blown relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed "supersensitivity" might be the result of pre-morbid or state genetic hypodopaminergic polymorphisms., Hypothesis: We are proposing that recent studies have indicated that genetic, personality and environmental factors are predictors of drug use in adolescents. Exploration of various treatment approaches for the most part reveal poor outcomes in terms of relapse prevention and continued drug hunger. The authors are proposing a new paradigm shift in residential, non-residential and aftercare involving the incorporation of genetic testing to identify risk alleles coupled with D2 receptor stimulation using neuroadatogen amino acid precursor enkephlinase--catecholamine-methyltransferase (COMT) inhibition therapy. A natural but therapeutic nutraceutical formulation potentially induces DA release could cause the induction of D2-directed mRNA and proliferation of D2 receptors in the human. We further hypothesize that this proliferation of D2 receptors in turn will induce the attenuation of drug-like craving behavior. Finally, pharmacological therapies have had limited success because these powerful agents have focused on maintenance or interference with drug euphoria rather than correcting or compensating for pre-morbid dopamine system deficits These concepts await further confirmation via required neuro-imaging studies., (Copyright © 2011. Published by Elsevier Ltd.)

Obesity has become a major health problem and epidemic. However, much of the current debate has been fractious and etiologies of obesity have been attributed to eating behavior or fast food, personality issues, depression, addiction, or genetics. One of the interesting new hypotheses for epidemic obesity is food addiction, which is associated with both substance-related disorder and eating disorder. Accumulating evidences have shown that there are many shared neural and hormonal pathways as well as distinct differences that may help researchers find why certain individuals overeat and become obese. Functional neuroimaging studies have further revealed that good or great smelling, looking, tasting, and reinforcing food has characteristics similar to that of drugs of abuse. Many of the brain changes reported for hedonic eating and obesity are also seen in various forms of addictions. Most importantly, overeating and obesity may have an acquired drive like drug addiction with respect to motivation and incentive; craving, wanting, and liking occur after early and repeated exposures to stimuli. The acquired drive for great food and relative weakness of the satiety signal would cause an imbalance between the drive and hunger/reward centers in the brain and their regulation.

The use of methamphetamine (METH) as recreational drugs is a growing problem worldwide with recent concerns that it might cause long-lasting harmful effects to the human brain. METH is an illicit drug that is known to exert neurotoxic effects on both dopaminergic and serotonergic neural systems. Our laboratory has been studying the biochemical mechanisms underlying METH-induced neurotoxic effects both in vivo and in vitro. Our psychoproteomics METH abuse research focuses on the global alteration of cortical protein expression in rats treated with acute METH. In our analysis, an altered protein expression was identified using a multistep protein separation/proteomic platform. Differential changes of the selected proteins were further confirmed by quantitative immunoblotting. Our study identified 82 differentially expressed proteins, 40 of which were downregulated and 42 of which were upregulated post acute METH treatment. In this chapter, we describe the current protocols for the neuronal cell culture in vitro and the in vivo rat model of acute METH treatment (4 x 10 mg/kg) coupled with the description current bioinformatics analysis utilized to analyze the different implicated interaction protein/gene maps that reflected on the altered functions observed. These methods and protocols are discussed in the paradigm of the acute model of METH drug abuse and neuronal cell culture and can be applied on other models of substance abuse such as on MDMA or cocaine.

A sample of 904 physicians consecutively admitted to 16 state Physicians' Health Programs (PHPs) was studied for 5 years or longer to characterize the outcomes of this episode of care and to explore the elements of these programs that could improve the care of other addicted populations. The study consisted of two phases: the first characterized the PHPs and their system of care management, while the second described the outcomes of the study sample as revealed in the PHP records. The programs were abstinence-based, requiring physicians to abstain from any use of alcohol or other drugs of abuse as assessed by frequent random tests typically lasting for 5 years. Tests rapidly identified any return to substance use, leading to swift and significant consequences. Remarkably, 78% of participants had no positive test for either alcohol or drugs over the 5-year period of intensive monitoring. At post-treatment follow-up 72% of the physicians were continuing to practice medicine. The unique PHP care management included close linkages to the 12-step programs of Alcoholics Anonymous and Narcotics Anonymous and the use of residential and outpatient treatment programs that were selected for their excellence.

Methamphetamine (METH) is recognized as one of the most abused psychostimulants in the USA. METH is an illicit drug that is known to exert neurotoxic effects on both dopaminergic and serotonergic neural systems. Our laboratory has been studying the biochemical mechanisms underlying MDMA and METH-induced neurotoxic effects both in vivo and in vitro. Our substance abuse research focuses on the global alteration of cortical protein expression in rats treated with acute METH. Altered protein expression was identified using a multistep protein separation/proteomic platform. Differential changes of the selected proteins were further confirmed by quantitative immunoblotting. Our study identified 82 differentially expressed proteins, 40 of which were downregulated and 42 of which were upregulated post acute METH treatment. Proteins that were shown to be downregulated included collapsin response mediator protein-2 (CRMP-2), superoxide dismutase 1 (SOD 1), and phosphatidylethanolamine-binding protein-1 (PEBP-1). Proteins that were shown to be upregulated included authophagy-linked microtubule-associated protein light chain 3 (LC3), synapsin-1, and Parkinsonism-linked ubiquitin carboxy-terminal hydroxylase-L1 (UCH-L1). This differential protein expression highlights on the neurotoxic mechanism involved in METH exposure as well as to discover potential markers for METH-induced neurotoxicity. In this chapter, we describe the current protocols for the in vivo rat model of acute METH treatment (40 mg/kg) coupled with the description of the multistep separation platform applied. These methods and protocols are discussed in the paradigm of acute model of methamphetamine drug abuse and can be applied to other models of substance abuse such as to MDMA or cocaine.

Comorbidity is the rule rather than the exception for substance use disorders, especially when they involve drugs other than alcohol. A common reaction of physicians to comorbidity is to attribute the substance use of addicted people to "self-medicating" with drugs of abuse. When an individual uses an abused drug nonmedically, he or she is seeking brain reward, not treatment. To confuse this drug-using behavior with treatment is to misunderstand addictive behavior and to encourage a false sense that the primary clinical task is to lower the dysphoria associated with the comorbid condition in order to stop the nonmedical drug use. Even the most effective treatment of comorbid disorders is unlikely to halt the addictive drug use. The best way to handle comorbidity (e.g., depression and alcoholism) is to consider each of the comorbid conditions to be a separate and serious illness deserving of effective and specific treatment and not to consider one to be a "symptom" of the other. While it is desirable to treat all comorbid conditions using the best practices for the treatment of that condition it is not reasonable to assume that one of the comorbid disorders is secondary to the other and therefore that treatment of the "secondary" disorder is irrelevant or unnecessary.

Our study showed that the perception of pain lessens with detoxification from chronic prescription opiate medications. Thus, removal of opiates resulted in less pain, and chronic administration of opiates actually increased pain perceptions. The underlying pathophysiology of increased pain sensitivity from chronic administration is not well understood. However, the enhanced pain from the development of tolerance and dependence is a common phenomenon. Clinicians are advised to limit their prescribing of opiate drugs to patients on a chronic basis. Further, unresolved pain complaints, and continued complaints of pain despite escalating doses of opiate medications suggest addiction and its adverse consequences. Identification of addiction and detoxification is the proper approach to pain management in chronic opiate administration.

Obesity and substance abuse during adolescence have reached epidemic proportions, and both are among the leading major public health problems in the United States. There is a significant amount of weight and Body Mass Index (BMI) gain in adolescent ex-addicts during supervised and confirmed abstinence from drugs and alcohol. The primary purpose of this secondary data analysis was to examine the effectiveness of two interventions implemented to address weight management in residential facilities treating adolescent substance use disorders. The secondary purpose was to establish if the outcome was a function of mandated smoking cessation and prescribed psychotropic medications. The results of the study suggest adolescents experienced weight gain in all groups, however there was no interaction effect for smokers and those adolescents on psychotropic medication for either outcome variable.

We have proposed a novel hypothesis regarding the potential role of occupational or second-hand exposure in physician substance use, abuse, and addiction. While only 5.6% of licensed physicians in Florida are anesthesiologists, nearly 25% of physicians followed for substance abuse/dependence are anesthesiologists. When we sort by drug of choice, anesthesiologists have more opioid abuse and dependence than other physicians and appropriate controls. Abuse of one opioid, fentanyl, appears to be increasing and has been noted among the State of Florida's causes of opioid deaths. Fentanyl and sufentanyl are commonly administered highly potent opioid analgesics, as much as 80-800 times as potent as morphine. We have recent data from the State of Florida impaired physicians database, which has allowed us to categorize all fentanyl abusing and/ or dependent physicians. Just knowing that a physician abuses fentanyl gives you a good clue as to their specialty; 75% are anesthesiologists! While drug abuse researchers, oncologists and others who handle drugs of abuse everyday, have no greater incidence of opioid abuse or dependence, anesthesiologists are at the top of every list. Can this be due to just access and stress? We have proposed an alternative hypothesis of second hand exposure. To test this hypothesis, we developed a sensitive LC/MS/MS assay to measure the intravenous anesthetic and analgesic agents, propofol and fentanyl in air. Not only did we detect propofol and fentanyl in cardiovascular surgery operating room air, we also found the highest concentrations were close to the patient's mouth where anesthesiologists work for hours. Like tobacco, second hand opioid exposure can sensitize and change the brain making abuse, dependence and behavioral disorders more likely. Thus environmental exposure and sensitization may be an important risk factor in physician addiction. Second hand exposure may affect treatment outcome and explain anesthesiologist's inability to return to work in the operating room. We are developing an animal model for second hand exposure and additional studies of the operating room and cardiac anesthesiologists are underway.

Ecstasy use is a growing problem in the United States. Techniques to demonstrate and characterize the toxicity associated with its use have been limited and employed infrequently. In this study, we compare the deleterious effects of ecstasy use in rats with that of methamphetamine and traumatic brain injury. Specifically, we investigate the degradation of structural proteins alphaII-spectrin and tau by the pro-necrotic calpain and pro-apoptotic caspase systems. Ecstasy-induced neurotoxicity is shown after 24 hours, although to a much lesser extent than that of methamphetamine or traumatic brain injury. Neurotoxicity is still evident after 72 hours. Furthermore, apoptosis of the liver is seen 72 hours after ecstasy use. Use of protease inhibitors may be useful in preventing ecstasy-induced toxicity.

A recent federal report indicates that prescription drug abuse is now the second leading category of illicit drug use, following marijuana use. Control strategies typically focus on reducing the diversion of prescription drugs from legitimate sources. The proliferation of unregulated Internet sources, however, has rendered control strategies less effective. This study examines a new approach that focuses on reducing abusability through the use of abuse-resistant drug designs. Drugs with and without such designs are compared and abuse levels assessed using multiple sources. In every instance, drugs employing abuse-resistant designs were found to have significantly lower levels of abuse than comparator drugs without such designs.

Risk of addiction through occupational exposure to drugs of abuse is an important but relatively neglected public health problem. Stress and access may have much less of a role in addiction among certain populations than originally was thought. Risk of addition may be increased dramatically by unintentional exposure in the workplace to potent substances that sensitize the brain. Everyone knows that second-hand inhalation of crack vapors is a very dangerous proposition, but rarely has alarm been raised about exposing anesthesiologists to second-hand fentanyl. Additional studies of the relationship between exposure in the workplace and addiction are necessary. These studies should include biological measures, such as blood levels in exposed workers, and sensitive assays that quantitatively assess levels of exposure in the workplace.

The studies reviewed indicate that brain stress system play an important role in the acquisition and maintenance of drugs of abuse that target the brain's reward centers. In doing so, they may destabilize these areas, making the perception of pleasure more elusive and difficult to attain. Withdrawal from drugs of abuse leads to the activation of brain CRF systems that may produce the anxiogenic response associated with drug withdrawal. More research, however, is needed to investigate the role of brain stress systems and neuropeptides in other drug withdrawal symptoms such as anhedonia. A better understanding of the brain systems underlying drug withdrawal may help in the development of improved pharmacotherapies that can alleviate drug withdrawal symptoms. The second part of the article indicated that there is a very high comorbidity between depression and drug dependence. The reviewed studies suggest that depressed patients initiate drug-taking behavior to self-medicate the symptoms associated with their psychiatric disorder. Chronic use of drugs of abuse, however, may exacerbate the symptoms of pre-existing mental disorders and subsequently increase drug-taking behavior. Conversely, professional treatment of pre-existing psychiatric disorders may decrease the use of illicit substances.

Neurotransmitter release in the nucleus accumbens use has been linked to self-administration and learning following drug use. This endogenous reward system is also activated following food intake or sex. Therefore, rebound hyperphagia following abstinence may be a mechanism to replenish the release of neurotransmitters in this reward system, leading to increased weight gain and a rise in body mass index during recovery from substance abuse. In this report, we examined the relationship between supervised drug abstinence and increased weight gain among adolescents at a residential substance abuse treatment center. Mean weight change over time was followed by repeated analysis of weight and body mass index. Significant weight gain and body mass index increase was observed during supervised and confirmed abstinence from drug use. Furthermore, significant interactions between tobacco use and primary substance use disorder with weight gain was demonstrated by multivariate analysis of variance.

Obesity is among the most pressing health issues affecting developed countries. The etiology of obesity remains unclear despite its associated health risks. We propose a framework for obesity modeled upon overeating as a substance dependence disorder arising from a combination of abnormal cognitive and neuroendocrine processes. While significant work in both of these fields has investigated the body's regulation of satiety signals, fewer studies have focused upon the mechanisms by which these two seemingly disparate systems interact. Although emotional states have been shown to mediate reward processing, the implications for hunger mediating reward have not previously been addressed. We review the interaction between central satiety signals and reward responses to food stimuli and discuss the implications of this research for understanding the causes of obesity.

The primary care physician is in a good position to diagnose, manage and intervene with patients who are undergoing the process of treatment and recovery from alcohol and drug disorders. Medications such as benzodiazepines are effective in the treatment of withdrawal syndromes, and naltrexone and disulfiram can be used to augment relapse prevention. Patients may also participate in psychosocial methods of addiction treatment that can reduce the risk of relapse and improve their psychosocial, health, legal and employment status.

Treatment of withdrawal and postabstinence craving has yielded mixed results in eliminating drug and alcohol use, improving outcomes, and reducing relapse in those patients addicted to alcohol and drugs. To assess the role of "conscious desire" (or craving) for drugs/alcohol during abstinence and withdrawal in continued addictive drug and alcohol use, we analyzed data from 1626 patients voluntarily admitted to a primary rehabilitation center in Minnesota. Eighty-one percent and 71% of all patients completed surveys at 6 and 12 months following discharge. Forty-two percent were diagnosed as alcohol dependent (AD) alone, 28% as alcohol and drug dependent (ADD) other than cocaine, and 25% as cocaine dependent (CD). At 6 months following discharge, the CD group had the lowest abstinence rate for drugs, at 83%, compared to the AD group, at 99%, and for alcohol, at 76%, compared to the AD group, at 75%. The AD group had the best outcomes and the least slippage from 6 to 12 months for drugs and alcohol. In all groups craving was not a major self-reported cause of relapse. For the CD subgroup, impulsive action with no known cause was the most common reason for relapse, while the AD group cited depression. These data agree with other reports in the literature suggesting that relapse is not commonly related to conscious craving. Our experience suggests that craving is rarely the first reason given for relapse. Drug seeking and use are such highly ritualized, automatic behaviors that the addict may appear not to require the intervention of conscious thoughts or distinct craving states to use.(ABSTRACT TRUNCATED AT 250 WORDS)

The association of crack and criminal activity is commonly believed but not well documented or characterized in any systematic studies of crack addicts. In this survey of 200 crack addicts, daily use of crack correlated more with illicit, criminal activities to obtain a supply of crack than to demographic features. Correspondingly, felony and cocaine dealing was associated with total dollars spent on cocaine but not to other demographic features such as level of property or affluence. Moreover, the majority of crack addicts in this sample used cocaine intranasally before starting crack use. The mean age from onset of crack use to seeking help for cocaine addiction is less than 3 years. Severity of crack use and addiction as measured by daily use was associated with psychosocial consequences more than other demographic features.