Igor Elman

Cooper Hospital · Psychiatry

The North American opioid epidemic has resulted in over 800,000 related premature overdose fatalities since 2000, with the United States leading the world in highest opioid deaths per capita. Despite increased federal funding in recent years, intended to address this crisis, opioid overdose mortality has continued to increase. Legally prescribed op...

ince the seminal discovery reported by Drs Kenneth Blum & Ernest P. Nobles in JAMA 1990 of the association of the DRD2 Taq A1 allele and severe alcoholism, the field of Psychiatric Genetics was born, and the understanding of the relationships between DNA polymorphisms and epigenetic insults exploded [1]. Nature vs. nurture is now thought to be 50/5...

Since 2000 there have been 915,515 people who have died from a drug overdose in the United States (US). This number continues to increase and in 2021 drug overdose deaths reached a record high of 107,622, and opioids specifically were responsible for 80,816 of those deaths. This unprecedented rate of drug overdose deaths is the direct result of inc...

In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individ...

Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In our previous research, we examined th...

Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In our previous research, we examined th...

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those at risk for at least alcohol use disorder (AUD), a subset of rew...

Reward Deficiency Syndrome (RDS) is defined as a breakdown of reward neurotransmission that results in a wide range of addictive, compulsive, and impulsive behaviors. RDS is caused by a combination of environmental (epigenetic) influences and DNA-based (genetic) neurotransmission deficits that interfere with the normal satisfaction of human physiol...

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 neur...

Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known...

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum’s group developed the Genetic Addiction Risk...

Excessive alcohol intake, e.g., binge drinking, is a serious and mounting public health problem in the United States and throughout the world. Hence the need for novel insights into the underlying neurobiology that may help improve prevention and therapeutic strategies. Therefore, our group employed a darkness-induced alcohol intake protocol to def...

Background There is a shortage of clinical studies examining the efficacy of Nicotinamide Adenine Dinucleotide and Enkephalinase infusions (IV1114589NAD) in treating Substance Use Disorder (SUD). Objective This study aims to provide evidence that IV1114589NAD infusions significantly attenuate substance craving behavior. Methods The study cohort c...

This brief commentary aims to provide an overview of the available and relatively new precision management of reward deficiencies manifested as substance and behavioral disorders. Current and future advances, concepts, and the substantial evidential basis of this potential therapeutic and prophylactic treatment modality are presented. Precision Beh...

The nucleus tractus solitarius (NTS), is a key brainstem structure relaying interoceptive peripheral information to the interrelated brain centers for eliciting rapid autonomic responses and for shaping longer‐term neuroendocrine and motor patterns. Structural and functional NTS’ connectivity has been extensively investigated in laboratory animals....

While opioids are a powerful class of drugs that inhibit transmission of pain signals, their use is tarnished by the current epidemic of opioid use disorder (OUD) and overdose deaths. Notwithstanding published reports, there remain gaps in our knowledge of opioid receptor mechanisms and their role in opioid seeking behavior. Thus, novel insights in...

Reward Deficiency Syndrome (RDS) encompasses many mental health disorders, including a wide range of addictions and compulsive and impulsive behaviors. Described as an octopus of behavioral dysfunction, RDS refers to abnormal behavior caused by a breakdown of the cascade of reward in neurotransmission due to genetic and epigenetic influences. The r...

The Autonomic Nervous System (ANS) is a critical part of the homeostatic machinery with both central and peripheral components. However, little is known about the integration of these components and their joint role in the maintenance of health and in allostatic derailments leading to somatic and/or neuropsychiatric (co)morbidity. Based on a compre...

In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some...

A variety of behavioral disorders are associated with addictions, impulsivity, obsessive-compulsive behaviors, and some personality disorders, which are collectively known as reward deficiency syndrome. These disorders are also associated with diverse digestive disorders. The enteric nervous system, a complex subdivision of the peripheral nervous s...

Basic pain research has shed light on key cellular and molecular mechanisms underlying nociceptive and phenomenological aspects of pain. Despite these advances, [[we still yearn for] the discovery of novel therapeutic strategies to address the unmet needs of about 70% of chronic neuropathic pain patients whose pain fails to respond to opioids as we...

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 prescrip...

Millions of Americans experience pain daily. In 2017, opioid overdose claimed 64,000 lives increasing to 84,000 lives in 2020, resulting in a decrease in national life expectancy. Chronic opioid use results in dependency, drug tolerance, neuroadaptation, hyperalgesia, potential addictive behaviors, or Reward Deficiency Syndrome (RDS) caused by a hy...

It is well established that migraine is a multifactorial disorder. A deep understanding of migraine should be based upon both the underlying traits and the current states affected by different physiological, psychological, and environmental factors. At this point, there is no framework fully meeting these criteria. Here, we describe a broader view...

This article describes a unique therapeutic precision intervention, a formulation of enkephalinase inhibitors, enkephalin, and dopamine-releasing neuronutrients, to induce dopamine homeostasis for detoxification and treatment of individuals genetically predisposed to developing reward deficiency syndrome (RDS). The formulations are based on the res...

Background Chronic pain is prevalent among patients with rare diseases (RDs); however, little is understood about the integration of biopsychosocial mechanisms as they relate to the unique set of clinical features and therapeutic challenges inherent in the pain conditions of patients with RDs. Methods This review presents examples of major disease...

In 2019, the US Center for Disease Control and Prevention provided vital statistics related to drug overdoses in the United State1. They concluded that in the USA the number of deaths at almost 72,000 was due to 66.6% of opioid overdoses. In fact, the rate is alarming and increasing yearly. To make 2021 even more scary is the daunting effect on inc...

Introduction Polymorphic gene variants, particularly the genetic determinants of low dopamine function (hy-podopaminergia), are known to associate with Substance Use Disorder and a predisposition to PTSD. Addiction research and molecular genetic applied technologies supported by the National Institutes of Health (NIH) have revealed the com-plex fun...

Although unconscious processing is a key element of mental operation, its neural correlates have not been established. Also, clinical observations suggest that unconscious processing may be involved in the pathophysiology of post-traumatic stress disorder (PTSD), but the neurobiological mechanisms underlying such impairments remain unknown. The pur...

Background: The prevalence of tobacco cigarette smoking in the US has declined to approximately 15%, yet, it remains over 90% among individuals with opioid use disorder regardless of whether they are currently using opioids illicitly or as opioid substitution therapy. This disparity raises the question of whether opioids facilitate smoking among in...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Metabolic hormones stabilize brain reward and motivational circuits, whereas excessive opioid consumption counteracts this effect and may impair metabolic function. Here we addressed the role of metabolic processes in the course of the agonist medication-assisted treatment for opioid use disorder (OUD) with buprenorphine or methadone. Plasma lipids...

Post-traumatic stress disorder (PTSD) is a severe polygenic disorder triggered by environmental factors. Many polymorphic genes, particularly the genetic determinants of hypodopaminergia (low dopamine function), associate with a predisposition to PTSD as well as substance use disorder. Support from the National Institutes of Health for neuroimaging...

Opioid use disorder (OUD) is a mounting public health problem with substantial morbidity and mortality. Stress involvement in the course of OUD is generally accepted, but little is understood about the underlying neurobiological mechanisms in part due to a lack of laboratory-based models for chronic stress exposure. Post-traumatic stress disorder (...

Worldwide daily, millions of people are unable to combat their frustrating and even fatal romance with getting high; for some, “high” may be just experiencing feelings of well-being. The neuroscience community conducts and funds, outstanding research using sophisticated neuroimaging and molecular-genetic applied technology to improve understanding...

Abstract In patients with post-traumatic stress disorder (PTSD), a decrease in the brain reward function was reported in behavioral- and in neuroimaging studies. While pathophysiological mechanisms underlying this response are unclear, there are several lines of evidence suggesting over-recruitment of the brain reward regions by aversive stimuli re...

Neurological soft signs (NSSs) are highly prevalent among patients with schizophrenia, but their pathophysiological significance remains unclear. The present study employed perceptual-motor and visuospatial processing tests that have not yet been attempted in this patient population. Patients with schizophrenia or schizoaffective disorder (n = 42)...

The United States are amid an opioid overdose epidemic; we are challenged to provide non-addicting/non-pharmacological alternatives to assist in pain attenuation. There are proven strategies available to manage chronic pain effectively without opioids. Utilization review providers for insurance companies often ignore medicine based scientific peer-...

It is well recognized that, despite similar pain characteristics, some people with chronic pain recover, whereas others do not. In this review, we discuss possible contributions and interactions of biological, social, and psychological perturbations that underlie the evolution of treatment-resistant chronic pain. Behavior and brain are intimately i...

Blum's laboratory first showed the benefits of naloxone or narcotic antagonists in the treatment of alcohol dependence. This seminal work published in Nature in the early 70's, in conjunction with many other studies, later served as the basis for the development of the narcotic antagonist (NTX) now used to treat both alcohol and opioid dependence....

Background: Opioid addiction remains a major public health problem bearing enormous societal costs including death by overdose in about 90 Americans every day. The increase in opioid mortality rate over the past few years has been attributed to multiple factors, including overprescribing of prescription opiates, the emergence of high potency opioid...

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 derang...

The brain regions tied to pleasure can be triggered by engaging in sex, eating tasty food, watching a movie, accomplishments at school and athletics, consuming drugs, and noble efforts to help the community, the country, and the world. It is noteworthy that research suggests that the latter type of satisfaction, supporting the community, may result...

Pain is essential for avoidance of tissue damage and for promotion of healing. Notwithstanding the survival value, pain brings about emotional suffering reflected in fear and anxiety, which in turn augment pain thus giving rise to a self-sustaining feedforward loop. Given such reciprocal relationships, the present article uses neuroscientific conce...

By unconscious or covert processing of pain we refer to nascent interactions that affect the eventual deliverance of pain awareness. Thus, internal processes (viz., repeated nociceptive events, inflammatory kindling, reorganization of brain networks, genetic) or external processes (viz., environment, socioeconomic levels, modulation of epigenetic s...

Objective: Olanzapine, an atypical antipsychotic, is associated with glucoregulatory abnormalities, but the nature of this link is not fully elucidated. This is the first olanzapine oral glucose tolerance test (oGTT) study to consider treatment dose and duration, and to compare complementary indices respectively assessing insulin sensitivity (Mats...

Background: Chronic opioid misuse is associated with reduced sensitivity to natural rewards and social motivation deficits that include impaired caregiving. The neurobiological mechanisms underlying these deficits and their response to treatment are not well understood. Baby schema (Kindchenschema) is a set of juvenile physical features, which is...

Background Excessive gambling is considered to be a part of the addiction spectrum. Stress-like emotional states are a key feature both of pathological gambling (PG) and of substance addiction. In substance addiction, stress symptomatology has been attributed in part to “anti-reward” allostatic neuroadaptations, while a potential involvement of ant...

While olanzapine is frequently associated with glucoregulatory abnormalities, the underlying pathophysiological mechanisms remain unclear. Because olanzapine’s superior therapeutic profile frequently renders switching to more metabolically-safe antipsychotics a clinically undesirable option, understanding how olanzapine is involved in metabolic dis...

Background: Parallel to the ongoing expansion of legalized gambling activities is a growing concern about rising occurrence of uncontrollable gambling. People with preexisting gambling and/or chemical addictions may be particularly vulnerable, but the extent of such co-occurring conditions and their demographic and clinical characteristics have no...

Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypo...

Chronic pain is a common squealae of military- and terror-related injuries. While its pathophysiology has not yet been fully elucidated, it may be potentially related to premorbid neuropsychobiological status, as well as to the type of injury and to the neural alterations that it may evoke. Accordingly, optimized approaches for wounded individuals...

While chronic pain is considered by some to be a CNS disease, little is understood about underlying neurobiological mechanisms. Addiction models have heuristic value in this regard, because both pain and addictive disorders are characterized by impaired hedonic capacity, compulsive drug seeking, and high stress. In drug addiction such symptomatolog...

Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its utility could be hampered by poor adherence. To gain a better insight into this phenomenon, we utilized blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) in conjunction with a validated cue-induced...

There is an ongoing public debate about the new graphic warning labels (GWLs) that the Food and Drug Administration (FDA) proposes to place on cigarette packs. Tobacco companies argued that the strongly emotional images FDA proposed to include in the GWLs encroached on their constitutional rights. The court ruled that FDA did not provide sufficient...

Olanzapine (OLZ), a commonly prescribed second generation antipsychotic drug, is associated with obesity and metabolic syndrome and may contribute to increased cardiovascular morbidity and mortality. Opioidergic neurotransmission may be implicated in the development of these metabolic disturbances. The objective of this study was to assess the effe...

Although cerebellar alterations have been consistently noted in the addiction literature, the pathophysiology of this link remains unclear. The cerebellum is commonly classified as a motor structure, but human functional neuroimaging along with clinical observations in cerebellar stroke patients and anatomical tract tracing in non-human primates su...

In general, the invention provides methods and compositions for treating sequela of weight gain or pain insensitivity, e.g., in a subject suffering from a psychiatric disorder, such as schizophrenia. The combinations employed in the invention include a second generation antipsychotic agent and an opioid receptor antagonist.

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system's role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we p...

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displ...

Evaluating external and internal stimuli is critical to survival. Potentially tissue-damaging conditions generate sensory experiences that the organism must respond to in an appropriate, adaptive manner (e.g., withdrawal from the noxious stimulus, if possible, or seeking relief from pain and discomfort). The importance we assign to a signal generat...

Drug cues play an important role in relapse to drug use. Naltrexone is an opioid antagonist that is used to prevent relapse in opioid dependence. Central opioidergic pathways may be implicated in the heightened drug cue-reactivity, but the effects of the opioid receptors' blockade on the brain responses to drug cues in opioid dependence are unknown...

Blockade of opioidergic neurotransmission contributes to reduction in body weight. However, how such blockade affects body weight gain (BWG) attributed to second generation antipsychotic agents (SGAs) has not yet been established. Here we examined the effects of an opioid receptor antagonist, naltrexone (NTX), on food intake and BWG associated with...