Neurobiology Of Addiction Research Articles

Comparison of impulsivity in non-problem, at-risk and problem gamblers.

As a non-substance addiction, gambling disorder represents the model for studying the neurobiology of addiction without toxic consequences of chronic drug use. From a neuropsychological perspective, impulsivity is deemed as a potential construct responsible in the onset and development of drug addiction. The objective of this study was to investigate the associations between impulsivity and gambling status in young adults with varying severity of gambling. A sample of 1120 college students, equally divided into non-problem, at-risk and problem gamblers, were administered multiple measures of impulsivity including the UPPSP Impulsive Behaviors Scale (UPPSP), the Barratt Impulsiveness Scale-11 (BIS-11), and the Delay-discounting Test (DDT). Compared with non-problem gamblers, both at-risk gamblers and problem gamblers displayed elevated scores on Negative Urgency, Positive Urgency, Motor Impulsiveness, and Attentional Impulsiveness. Problem gamblers showed higher scores than at-risk gamblers on Positive Urgency. Logistic regression models revealed that only Negative Urgency positively predicted both at-risk gambling and problem gambling compared to non-problem gambling. These results suggest that dimensions of impulsivity may be differentially linked to gambling behavior in young adults, with Negative Urgency putatively identified as an important impulsivity-related marker for the development of gambling disorder, which may provide a better understanding of the pathogenesis.

Update in the neurobiology of addiction

<p align="left">Addiction is a major global health concern. Up to date, underlying the possible mechanisms of addiction have begun to yield fundamentally important insights to discover the novel therapeutics as there are very few effective treatments for addiction. This review article is designed to outline the underlying mechanisms of addiction.</p>

The neurobiology of addiction: the perspective from magnetic resonance imaging present and future.

Background and AimsAddiction is associated with severe economic and social consequences and personal tragedies, the scientific exploration of which draws upon investigations at the molecular, cellular and systems levels with a wide variety of technologies. Magnetic resonance imaging (MRI) has been key to mapping effects observed at the microscopic and mesoscopic scales. The range of measurements from this apparatus has opened new avenues linking neurobiology to behaviour. This review considers the role of MRI in addiction research, and what future technological improvements might offer.MethodsA hermeneutic strategy supplemented by an expansive, systematic search of PubMed, Scopus and Web of Science databases, covering from database inception to October 2015, with a conjunction of search terms relevant to addiction and MRI. Formal meta‐analyses were prioritized.ResultsResults from methods that probe brain structure and function suggest frontostriatal circuitry disturbances within specific cognitive domains, some of which predict drug relapse and treatment response. New methods of processing imaging data are opening opportunities for understanding the role of cerebral vasculature, a global view of brain communication and the complex topology of the cortical surface and drug action. Future technological advances include increases in MRI field strength, with concomitant improvements in image quality.ConclusionsThe magnetic resonance imaging literature provides a limited but convergent picture of the neurobiology of addiction as global changes to brain structure and functional disturbances to frontostriatal circuitry, accompanied by changes in anterior white matter.

How to study sex differences in addiction using animal models.

The importance of studying sex as a biological variable in biomedical research is becoming increasingly apparent. There is a particular need in preclinical studies of addiction to include both sexes, as female animals are often excluded from studies, leaving large gaps in our knowledge of not only sex differences and potential prevention and treatment strategies but also with regard to the basic neurobiology of addiction. This review focuses on methodology that has been developed in preclinical studies to examine sex differences in the behavioral aspects and neurobiological mechanisms related to addiction across the full range of the addiction process, including initiation (acquisition), maintenance, escalation, withdrawal, relapse to drug seeking and treatment. This review also discusses strategic and technical issues that need to be considered when comparing females and males, including the role of ovarian hormones and how sex differences interact with other major vulnerability factors in addiction, such as impulsivity, compulsivity and age (adolescent versus adult). Novel treatments for addiction are also discussed, such as competing non-drug rewards, repurposed medications such as progesterone and treatment combinations. Practical aspects of conducting research comparing female and male animals are also considered. Making sex differences a point of examination requires additional effort and consideration; however, such studies are necessary given mounting evidence demonstrating that the addiction process occurs differently in males and females. These studies should lead to a better understanding of individual differences in the development of addiction and effective treatments for males and females.

Brain Stimulation in Addiction.

Localized stimulation of the human brain to treat neuropsychiatric disorders has been in place for over 20 years. Although these methods have been used to a greater extent for mood and movement disorders, recent work has explored brain stimulation methods as potential treatments for addiction. The rationale behind stimulation therapy in addiction involves reestablishing normal brain function in target regions in an effort to dampen addictive behaviors. In this review, we present the rationale and studies investigating brain stimulation in addiction, including transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Overall, these studies indicate that brain stimulation has an acute effect on craving for drugs and alcohol, but few studies have investigated the effect of brain stimulation on actual drug and alcohol use or relapse. Stimulation therapies may achieve their effect through direct or indirect modulation of brain regions involved in addiction, either acutely or through plastic changes in neuronal transmission. Although these mechanisms are not well understood, further identification of the underlying neurobiology of addiction and rigorous evaluation of brain stimulation methods has the potential for unlocking an effective, long-term treatment of addiction.

Drug Courts - Just the Beginning: How to Get Other Areas of Public Policy in Sync? Addressing Continuing Collateral Consequences for Drug Offenders

In 2003, I prepared an article for the Middle Eastern-Mediterranean Summer Institute on Drug Use: “Drug Courts – Just the Beginning: Getting Other Areas of Public Policy in Sync” which highlighted five areas of public policy in the U.S., unconnected to the criminal justice, that imposed significant ― and generally lifetime ― sanctions on drug court graduates regardless of their successful completion of a drug court program and termination from criminal justice supervision. At that time, the extensive research corroborating the effectiveness of drug courts in reducing drug use, recidivism and promoting long term recovery was just beginning to be disseminated, along with scientific findings relating to the neurobiology of addiction, its effects on the brain and cognitive functioning ― all confirming that drug use was a symptomatic of a chronic disease and far more than a “behavioral” issue and/or moral failing. Given these extensive research findings, as well as over a decade of drug court experience at the time, it was therefore discouraging, but not unexpected, that the impact of the research had not yet affected public policy and practice in sectors not directly involved with drug offending and/or treatment. Given the commonly held premise that it takes seventeen years for research to affect practice, I prepared this “update” to determine the degree to which these research findings have now “infiltrated” practice. The intention in preparing this “Update” ten years later was to document progress made in reducing these areas of stigma ― come to be known as “collateral consequences” ― in light of the tremendous growth of drug courts since the article was first published in 2003, both in the U.S. and abroad, the widely documented effectiveness of these programs in stemming continued drug use and crime, and the growing body of research documenting addiction as a chronic disease for which treatment has proven effective and incarceration in and of itself to be counter-effective. The expectation was that progress in removing stigma associated with addiction would have been significant during these years. The results, however, have been the opposite. While there has been some progress, it has been slow and spotty, and the situation in 2014 can be characterized by continued stigma imposed by multiple sectors of public policy on individuals who have successfully completed drug court programs and which, in many instances, extend for their lifetime. Not only do the major areas of stigma described in the 2003 article continue but, in addition, the preparation of this “Update” has uncovered numerous additional “collateral consequences” that hadn’t formally surfaced in 2003 ― exclusions regarding the right to adopt children, grounds for divorce, and a host of professional license requirements.

Qu’apporte la neurobiologie aux addictions ?

Addictions are multifactorial, and there are no experimental models replicating all aspects of this pathology. The development of animal models reproducing the clinical symptoms of addictions allows significant advances in the knowledge of the neurobiological processes involved in addiction. Preclinical data highlight different neuroadaptations according to the routes of administration, speeds of injection and frequencies of exposure to drugs of abuse. The neuroadaptations induced by an exposure to drugs of abuse follow dynamic processes in time. Despite significant progresses in the knowledge of neurobiology of addictions allowing to propose new therapeutic targets, the passage of new drugs in clinical is often disappointing. The lack of treatment efficacy reported in clinical trials is probably due to a very important heterogeneity of patients with distinct biological and genetic factors, but also with different patterns of consumption that can lead to different neuroadaptations, as clearly observed in preclinical studies.

Critical needs in drug discovery for cessation of alcohol and nicotine polysubstance abuse

Polysubstance abuse of alcohol and nicotine has been overlooked in our understanding of the neurobiology of addiction and especially in the development of novel therapeutics for its treatment. Estimates show that as many as 92% of people with alcohol use disorders also smoke tobacco. The health risks associated with both excessive alcohol consumption and tobacco smoking create an urgent biomedical need for the discovery of effective cessation treatments, as opposed to current approaches that attempt to independently treat each abused agent. The lack of treatment approaches for alcohol and nicotine abuse/dependence mirrors a similar lack of research in the neurobiology of polysubstance abuse. This review discusses three critical needs in medications development for alcohol and nicotine co-abuse: (1) the need for a better understanding of the clinical condition (i.e. alcohol and nicotine polysubstance abuse), (2) the need to better understand how these drugs interact in order to identify new targets for therapeutic development and (3) the need for animal models that better mimic this human condition. Current and emerging treatments available for the cessation of each drug and their mechanisms of action are discussed within this context followed by what is known about the pharmacological interactions of alcohol and nicotine. Much has been and will continue to be gained from studying comorbid alcohol and nicotine exposure.

The American Psychiatric Publishing Textbook of Substance Abuse Treatment, Fifth Edition

Back to table of contents Previous article Next article Book ForumFull AccessThe American Psychiatric Publishing Textbook of Substance Abuse Treatment, Fifth EditionChristian Thurstone, M.D.Christian ThurstoneSearch for more papers by this author, M.D.Published Online:1 Oct 2015https://doi.org/10.1176/appi.ajp.2015.15060812AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail edited by Marc Galanter, M.D., Herbert D. Kleber, M.D., and Kathleen T. Brady, M.D., Ph.D. Washington, D.C., American Psychiatric Association Publishing, 2015, 980 pp., $199.00 (hardcover).Given the pace of research in the field, an update to the last edition published in 2008 is much anticipated. Overall, this edition is an important contribution. It is comprehensive and updated. The editors, who are on the cutting edge of the field, have lined up a list of contributors who are also impressive. Anyone who reads this text will be well-prepared for a certification examination and will have a good fund of knowledge for patient care.The textbook is divided into various sections starting with the bio-psycho-social basis for addiction. It then progresses to a discussion of specific drugs of abuse and treatment options. The text concludes with special topics including adolescents, pregnant women, and prevention. Each chapter is authored or coauthored by an expert in that particular area. Another helpful feature of the book is a list of recommended readings at the end of each chapter for those who want more details.The textbook also includes important updates. For example, it uses new DSM-5 terminology. It also incorporates some of the latest neurobiology and clinical science of addiction. Specifically, the chapters on marijuana include the latest neurobiology of the endocannabinoid system as well as an excellent review of the latest behavioral and pharmacological treatments. Additionally, the chapter on the neurobiology of addiction lays an excellent foundation, and the chapter on preventing prescription drug abuse is especially well updated and practical.The main limitation of the text is a lack of precision and detail in certain areas. For example, the chapter on motivational enhancement cites the latest edition of the book on motivational interviewing but does not explain specifically how motivational interviewing has been substantially changed or updated.Another example of the lack of precision and detail is found in the chapters on marijuana. The chapter on marijuana treatment (Chapter 24) states that cannabidiol (CBD) is a CB1 and CB2 receptor antagonist but later states that CBD potentiates the effects of Δ9-tetrahydrocannabinol (THC) via a CB1 receptor-dependent mechanism. At the same time, other research not included in the chapter shows that CBD has a very low affinity for the CB1 receptor and that it may sometimes inhibit or potentiate the effect of THC, depending on the specific outcome being measured (1). In this case, clarification and precision are needed to avoid confusion. Furthermore, the chapters on marijuana would also benefit from specific details on practical and relevant topics such as edibles, butane hash oil, dabbing, and the different strains of marijuana, including Cannabis indica and Cannabis sativa.In summary, the revised Textbook of Substance Abuse Treatment is a welcome and much-needed update. Its readers will have a good fund of knowledge from experts in the field. However, many chapters require additional detail to help the reader clearly understand the subject. In view of this limitation, those who are interested in the topic may want to compare this text with the recently updated ASAM Principles of Addiction Medicine to see which text meets their needs better.Dr. Thurstone is affiliated with the Department of Psychiatry, University of Colorado Health Sciences Center, Denver.The author reports no financial relationships with commercial interests.Reference1 McPartland JM, Duncan M, Di Marzo V, et al.: Are cannabidiol and Δ(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br J Pharmacol 2015; 172:737–753Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 172Issue 10 October 01, 2015Pages 1028-1029 Metrics PDF download History Accepted 1 July 2015 Published online 1 October 2015 Published in print 1 October 2015

The Roles of Dopamine and α1-Adrenergic Receptors in Cocaine Preferences in Female and Male Rats.

Cocaine dependence is characterized by compulsive drug taking and reduced involvement in social, occupational, or recreational activities. Unraveling the diverse mechanisms contributing to the loss-of-interest in these 'non-drug' pursuits is essential for understanding the neurobiology of addiction and could provide additional targets for treating addiction. The study objectives were to examine changes in cocaine-induced dopamine (DA) overflow in the nucleus accumbens (NAc) over the course of self-administration and determine the roles of α1- and β-adrenergic receptors (AR) in the loss-of-interest in food rewards following the development of an addicted phenotype in male and female rats. Subjects were given access to cocaine and palatable food pellets in a choice self-administration paradigm to identify 'addicted' cocaine-preferring (CP) individuals and resistant pellet-preferring (PP) individuals based on their patterns of self-administration over 7 weeks. Cocaine-induced DA overflow in the NAc was examined with microdialysis early and late during self-administration (weeks 2 and 7). Subjects were treated in counter-balanced order with propranolol (β-AR antagonist), terazosin (α1-AR antagonist), or vehicle for an additional 3 weeks of self-administration. CP rats displayed increased motivation for cocaine and attenuated motivation for pellets following the development of cocaine preferences. In females, the estrous cycle affected pellet, but not cocaine, self-administration. CP rats displayed attenuated cocaine-induced DA overflow in the NAc. Propranolol enhanced cocaine reinforcement and reduced pellet intake, whereas terazosin enhanced motivation for pellets and reversed preferences in a subset of CP rats. The implications of these results for the treatment of addiction are discussed.

Alcohol addiction: a molecular biology perspective.

Alcohol misuse represents worldwide an important risk factor for death and disability. Excessive alcohol consumption is widely diffused in different ethnicities and alcohol use is part of the lifestyle of both young and old people. The genetic basis of alcohol dependence concerning ethanol metabolism and the pathways of reward circuits are well known. The role of genetic variants in the neurobiology of addiction as well as in response to medication in alcoholism therapy still represents an intriguing argument that needs to be deeply analyzed and explained. The molecular approach to the study of these aspects could be difficult because of the large number of genes and variations involved. Our work is intended to offer an overview of genes and variants involved in alcohol addiction and pharmacogenetics. Our aim is to delineate a molecular approach strategy to look at alcohol dependence from a genetic and applicative point of view. The indications provided in this work should be of help for those who wish to undertake a molecular study of this multifactorial disease.

OR08-2 * COMBINING ELEMENTS OF CBT INTO A 3 CIRCLE RECOVERY PLANNING MODEL FOR THE TREATMENT OF PROCESS ADDICTIONS

In light of recent research into the neurobiology of addiction (Volkow, Wolfe et al) the evidence is becoming clearer that addiction is a primary, chronic and progressive brain disease which encompasses not just the abuse of substances but also a number of destructive and addictive dopamine reinforcing ‘behaviours’ or ‘processes.’ The current paper explores the use of Three Circle recovery plans combined with CBT principles to create a treatment modality which addresses risky behaviours which may not be best treated through an abstinence based model, for example, sex and food addictions. Three Circle/CBT Recovery Plans are able to be adapted to treat both chemical and process addictions and can be implemented, reviewed and completed as a whole in a shorter time span than completing 12 Steps. The working model discussed applies tailored and individualised treatment pathways including monitored medication regimes, where appropriate, whilst still maintaining abstinence from harmful behaviours. Previous work has shown a theoretical basis for the combination of twelve step principles and CBT (Brown, 2012) and has shown a significant treatment effect for clients who are attending treatment of this type (Brown, 2013). The current paper explores the theoretical and practical underpinnings of a combined Three Circles/CBT approach.

How the Brain Disease Paradigm Remoralizes Addictive Behaviour

In recent decades, addiction has been medicalized anew through the rise of an influential ‘brain disease paradigm’. This questions the equivalence of addiction to drug dependence by re-emphasizing loss of self-control over unhealthy impulses as the disease locus. While showing continuities with the nineteenth-century vision of addictions as ‘diseases of the will’, neurobiology objectifies disease as disrupted neurochemical transmission and lasting neuroadaptation. The brain disease paradigm emerged together with rapid advances in neuroimaging technology as well as intensified research efforts to confirm cigarette smoking as nicotine addiction. After smoking achieved such recognition in the late 1980s, numerous other unhealthy impulses and appetites have likewise come under neurobiological investigation as prospective cases of addiction. Despite its technoscientific sophistication, neurobiology's biomedicalization of addiction remains as partial and ambiguous as past medicalizations. By confirming moral self-transformation anew as an indispensable component of treatment and recovery, neurobiology revives addiction as a moral disease in the process of its objectification. Furthermore, through its rediscovery of a classic nineteenth-century ‘liberal disease’ at the molecular level, the neurobiology of addiction is acting as a vital moralizing resource in the biomedicalization of health and illness more generally today.

"Mourning" a lost opportunity.

"Mourning" a lost opportunity.

Prenatal cocaine exposure initiates the release of TIMP‐1 and MMP‐9 in primary neuronal and glial cell cultures (651.21)

Drug addiction is a complex phenomenon that is mediated by biochemical events sequential to repeated exposure to a drug. The mechanisms underlying drug addiction include processes similar to those operating in forms of synaptic plasticity. Recently, pro‐addicitve cytokines, tissue inhibitors of matrix metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) have been shown to influence neuronal plasticity consequent to repeated cocaine injections in animal models. The present study was designed to investigate the role of TIMP‐1 and MMP‐9 in the addiction neurobiology of offspring exposed to cocaine during gestation. Time pregnant Sprague‐Dawley rats were treated with 40 mg/kg of cocaine HCl on gestational day (GD) 10‐21. On postnatal day (PND) 2, the brain tissue of the pups was harvested to yield mixed primary neuronal and glial cell cultures. Primary cell cultures were also exposed to a second sub‐lethal dose of cocaine in vitro and their response was measured. An increase in TIMP‐1 and MMP‐9 expression was observed in prenatally exposed primary neuronal and glial cell cultures. Through in vivo and in vitro studies, these findings suggest that exposure to cocaine in utero initiates the release of pro‐addictive cytokines increasing the incidence of addiction in the affected offspring.Grant Funding Source: NIH‐NIMHD G12MD007582

Corticotropin releasing factor: A key role in the neurobiology of addiction

Drug addiction is a chronically relapsing disorder characterized by loss of control over intake and dysregulation of stress-related brain emotional systems. Since the discovery by Wylie Vale and his colleagues of corticotropin-releasing factor (CRF) and the structurally-related urocortins, CRF systems have emerged as mediators of the body's response to stress. Relatedly, CRF systems have a prominent role in driving addiction via actions in the central extended amygdala, producing anxiety-like behavior, reward deficits, excessive, compulsive-like drug self-administration and stress-induced reinstatement of drug seeking. CRF neuron activation in the medial prefrontal cortex may also contribute to the loss of control. Polymorphisms in CRF system molecules are associated with drug use phenotypes in humans, often in interaction with stress history. Drug discovery efforts have yielded brain-penetrant CRF1 antagonists with activity in preclinical models of addiction. The results support the hypothesis that brain CRF-CRF1 systems contribute to the etiology and maintenance of addiction.

The Addicted Human Brain: An Overview of Imaging Studies and Their Treatment Implications

Addiction is characterized by loss of control over substance use, often operationally defined as continued use of substances despite knowledge of adverse consequences. The exact cause of addiction is not known, but it’s hypothesized that both environmental and genetic factors play a crucial role in the predisposition of this disease. When an individual abruptly stops using a drug or an addictive substance, withdrawal symptoms often take place, which include vomiting, nausea, loss of appetite and depression. Not much is known about the neurobiology of addiction and treatment remains a huge challenge. Current research aims at identifying the neurological circuit of addiction as well as the key neurotransmitters and biological markers involved in this disease. In this paper, I will first begin by giving you an overview of the major substances that cause addiction as well as the most common addictive behavior patterns. Second, I will discuss the major findings that have been done using animal models of addiction, and describe in more details the role that brain imaging technology plays in improving our understanding of drug abuse. Finally, a closer look will be taken at the behavioral and pharmacological approaches frequently employed to treat addiction.

EPA-1759 - Brain structural abnormalities in medial temporal lobe are associated with mood and anxiety in methadone maintenance treatment

Several brain circuits are relevant in the neurobiology of addiction. Here we want to highlight symptoms related to the domains of mood, anhedonia and anxiety that may precede drug abuse and represent a specific risk factor for addiction. The mood regulation circuit that contributes to regulation of stress reactivity and the interoception circuit that contributes to awareness of drug craving and mood also participate in addiction but their involvement in the human brain has been much less investigated. Here we aim to investigate mood and anxiety in opiate dependent, treatment-seeking patients receiving Methadone Maintenance Treatment, to test hypothesis of regional grey matter reduction correlating with mood and anxiety. Cambridge Gambling Task (CGT) data were acquired from 30 patients receiving MMT and 23 controls. T1 weighted Magnetic Resonance Images were acquired from a representative subset of these volunteers. MMT patients exhibited grey matter reductions in the orbito-medial prefrontal cortex and basal ganglia. Additionally, patients exhibited significant abnormalities in the clinical rating scales BDI, Anhedonia, HAD-Anxiety, IDS and Snaith Hamilton. Increased BDI, HAD-Anxiety and IDS correlated with grey matter reductions in the hippocampus, amygdala, bed nucleus of stria terminalis and insula. Increased Snaith Hamilton correlated with grey matter reductions in periaqueductal gray, ventral tegmental area and nucleus caudate. These findings support an interpretation of a neurobiological underpinning of mood and addiction. However, the anatomically restricted correlates with mood and anxiety suggest that a rationale for adopting a mood addiction model should be further investigated.

The Development of a Preference for Cocaine over Food Identifies Individual Rats with Addiction-Like Behaviors

RationaleCocaine dependence is characterized by compulsive drug taking that supercedes other recreational, occupational or social pursuits. We hypothesized that rats vulnerable to addiction could be identified within the larger population based on their preference for cocaine over palatable food rewards.ObjectivesTo validate the choice self-administration paradigm as a preclinical model of addiction, we examined changes in motivation for cocaine and recidivism to drug seeking in cocaine-preferring and pellet-preferring rats. We also examined behavior in males and females to identify sex differences in this “addicted” phenotype.MethodsPreferences were identified during self-administration on a fixed-ratio schedule with cocaine-only, pellet-only and choice sessions. Motivation for each reward was probed early and late during self-administration using a progressive-ratio schedule. Reinstatement of cocaine- and pellet-seeking was examined following exposure to their cues and non-contingent delivery of each reward.ResultsCocaine preferring rats increased their drug intake at the expense of pellets, displayed increased motivation for cocaine, attenuated motivation for pellets and greater cocaine and cue-induced reinstatement of drug seeking. Females were more likely to develop cocaine preferences and recidivism of cocaine- and pellet-seeking was sexually dimorphic.ConclusionsThe choice self-administration paradigm is a valid preclinical model of addiction. The unbiased selection criteria also revealed sex-specific vulnerability factors that could be differentiated from generalized sex differences in behavior, which has implications for the neurobiology of addiction and effective treatments in each sex.

The Archaeology of Mind

The Archaeology of Mind