-
Psychopharmacology Aug 2008Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in... (Review)
Review
RATIONALE
Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable.
OBJECTIVE
The objective of this study was to track how antagonist, agonist, and partial agonist medication approaches influence heroin and cocaine self-administration by rodents, non-human primates, and humans and to compare these results to clinical outcomes.
RESULTS
Across species, heroin self-administration was decreased by all three medication approaches, paralleling their demonstrated clinical utility. The heroin data emphasize the importance of assessing a medication's abuse liability preclinically to predict medication abuse and compliance and of considering subject characteristics (e.g., opioid dependence) when interpreting medication effects. For cocaine, the effects of ecopipam, modafinil, and aripiprazole were consistent in the laboratory and clinic, provided that the medications were administered repeatedly before self-administration sessions. Modafinil attenuated cocaine's reinforcing effects in the human laboratory and improved treatment outcome, while ecopipam and aripiprazole increased the reinforcing effects of cocaine and do not appear promising in the clinic.
CONCLUSIONS
The self-administration model has reliably identified medications to treat opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence. There have been numerous false positives when subjective effects are the primary outcome measure, but not when self-administration is the outcome. Factors relevant to the predictive validity of self-administration procedures include medication maintenance and the concurrent assessment of a range of behaviors to determine abuse liability and the specificity of effect.
Topics: Animals; Cocaine-Related Disorders; Disease Models, Animal; Heroin Dependence; Humans; Primates; Rodentia; Self Administration; Substance-Related Disorders
PubMed: 18283437
DOI: 10.1007/s00213-008-1079-x -
Revue Medicale de Liege 2014Ketamine or -ketamine hydrochloride- is used as an anesthesic and a painkiller. It may also, in some indications, be prescribed in psychiatry and addictology. A... (Review)
Review
Ketamine or -ketamine hydrochloride- is used as an anesthesic and a painkiller. It may also, in some indications, be prescribed in psychiatry and addictology. A literature review was conducted from 2003 to 2013, in PubMed, Google Scholar, Embase, and Psyclnfo, using the following key words (alone or combined): "ketamine", "abuse", "addiction", "dependence" and "misuse". Various studies have shown the benefit of kétamine in some psychiatric conditions such as major depressive episodes and electroconvulsive therapy. Others have demonstrated beneficial effects in alcohol or opiate abstinence maintenance. Ketamine seems to be a promising molecule in psychiatry and in the treatment of addictions, despite the absence of marketing approval for those specific uses. Being a strong psycho-stimulant, ketamine can be the source of abuse and dependence with somatic, psychiatric and cognitive complications.
Topics: Anesthetics, Dissociative; Drug Utilization; Humans; Ketamine; Mental Disorders; Prescription Drug Misuse; Substance-Related Disorders
PubMed: 25158385
DOI: No ID Found -
CNS Drugs Apr 2011Drug dependence is a chronically relapsing disorder that places an enormous strain on healthcare systems. For treatments to have long-term clinical value, they must... (Review)
Review
Drug dependence is a chronically relapsing disorder that places an enormous strain on healthcare systems. For treatments to have long-term clinical value, they must address the causes of relapse. Corticotropin-releasing factor (CRF), a neuropeptide central to the stress response, may be one key to solving the relapse cycle. CRF is hypothesized to mediate the elevated anxiety and negative emotional states experienced during the development of dependence. This review summarizes existing data on changes in the CRF system produced by drugs of abuse and the function of CRF receptors in regulating behavioural responses to drugs of abuse, with an emphasis on drug dependence. Drug-induced changes in neuronal excitability throughout the limbic system, as well as the reversal of these neuroadaptations by CRF receptor antagonists, are also addressed. CRF receptor antagonists, by reducing the motivational effects of drug withdrawal and protracted abstinence, are proposed to be novel therapeutic targets for drug abuse and addiction.
Topics: Animals; Anxiety; Corticotropin-Releasing Hormone; Humans; Mice; Molecular Targeted Therapy; Motivation; Neuropeptides; Rats; Receptors, Corticotropin-Releasing Hormone; Secondary Prevention; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 21425881
DOI: 10.2165/11587790-000000000-00000 -
Drug and Alcohol Dependence May 2010Opioid receptors are critical therapeutic targets for medications development relevant to the treatment of drug dependence and pain. With recent advances in molecular...
Opioid receptors are critical therapeutic targets for medications development relevant to the treatment of drug dependence and pain. With recent advances in molecular neurobiology, it has become evident that the functional activity of opioid receptors, as ligand-regulated protein complexes, is modulated by multifarious intracellular and extracellular events, that there is genetic variation in coding for receptors, and that the activity of endogenous opioid systems may underlie actions common to other addictive disorders. This supplemental issue of Drug and Alcohol Dependence, arising from an invited symposium at the 71st Annual Meeting of the College on Problems of Drug Dependence, provides a series of contemporary reviews focused on recent advances in opioid neuropharmacology. Each speaker provides herein an invited comprehensive review of the state of knowledge on a specific topic in opioid neuropharmacology. Evans and colleagues describe the multi-faceted control of the opioid G-protein coupled receptor as a dynamic "sensor" complex and identify novel targets for drug development. von Zastrow focuses on opioid receptor-mediated events regulated by endocytosis and membrane trafficking through the endocytic pathway and differential responses to opioid agonists. Blendy and colleague provide a review of human association studies on the functional relevance of the mu opioid receptor variant, A118G, and presents data from the A112G knock-in model, an analogous mouse variant to A118G. Finally, Maldonado and colleagues provide a broader systems review from genetic, pharmacologic and behavioral studies implicating the endogenous opioid systems as a substrate for the mediation of substance use disorders spanning pharmacological classes.
Topics: Analgesics, Opioid; Animals; Humans; Neuropharmacology; Opioid-Related Disorders; Receptors, Opioid; Substance-Related Disorders
PubMed: 20378280
DOI: 10.1016/j.drugalcdep.2010.03.001 -
The American Journal of Psychiatry Feb 2013Although tribes differ with regard to the use of alcohol and drugs, substance dependence is one of the primary sources of health problems facing Native Americans.... (Review)
Review
OBJECTIVE
Although tribes differ with regard to the use of alcohol and drugs, substance dependence is one of the primary sources of health problems facing Native Americans. General population studies have demonstrated that substance dependence has a substantially heritable component (approximately 50% of the risk resulting from genetic influences); however, fewer studies have investigated the role of genetics in the risk for substance dependence in Native Americans.
METHOD
The authors present a literature review of the evidence for a genetic component in the etiology of substance dependence in Native Americans, including studies of heritability, linkage analyses, and candidate genes.
RESULTS
Evidence for the heritability of alcohol and drug dependence was found. Linkage analyses revealed that genes influencing risk for substance dependence and related phenotypes, such as body mass index (BMI), drug tolerance, EEG patterns, and externalizing traits, reside on several chromosome regions identified in other population samples. Overlap in the gene locations for substance dependence and BMI suggests that a common genetic substrate may exist for disorders of consumption. Studies of the genes that code for alcohol-metabolizing enzymes have not revealed any risk variants specific to Native American populations, although most Native Americans lack protective variants seen in other populations. Other candidate genes associated with substance dependence phenotypes in Native Americans include OPRM1, CRN1, COMT, GABRA2, MAOA, and HTR3-B.
CONCLUSIONS
Substance dependence has a substantial genetic component in Native Americans, similar in magnitude to that reported for other populations. The high rates of substance dependence seen in some tribes is likely a combination of a lack of genetic protective factors (metabolizing enzyme variants) combined with genetically mediated risk factors (externalizing traits, consumption drive, and drug sensitivity or tolerance) that combine with key environmental factors (trauma exposure, early age at onset of use, and environmental hardship) to produce an elevated risk for the disorder.
Topics: Gene-Environment Interaction; Genes, Overlapping; Genetic Association Studies; Genetic Linkage; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Indians, North American; Inheritance Patterns; Polymorphism, Genetic; Risk Factors; Substance-Related Disorders; United States
PubMed: 23377636
DOI: 10.1176/appi.ajp.2012.12010113 -
Chirurgie (Heidelberg, Germany) Nov 2022The COVID-19 pandemic affects the mental health and professional behavior of surgeons and anesthesiologists and seems to have an impact on substance dependence. (Review)
Review
BACKGROUND
The COVID-19 pandemic affects the mental health and professional behavior of surgeons and anesthesiologists and seems to have an impact on substance dependence.
QUESTION
What are the reasons for the occurrence of substance dependence and burnout in surgeons and anesthesiologists timelessly and during the COVID-19 pandemic and what improvement measures could help in the clinical practice?
MATERIAL AND METHODS
A literature search was conducted in the form of a systematic review of studies and review articles relevant to the topic.
RESULTS
Over the years it has been shown that surgeons and anesthesiologists are prone to drug dependence due to their direct access to medications in the clinical field and work-related stress. In particular, surgeons and anesthesiologists appeared to have an increased propensity for addictive diseases and an increased risk of burnout in the pandemic.
CONCLUSION
Preventive measures in favor of better working conditions in surgery and anesthesia and better drug control (not only for dispensing but also for correct drug testing), as well as more treatment and reintegration programs under psychiatric supervision and in collaboration with a multidisciplinary team are meaningful.
Topics: Humans; COVID-19; Pandemics; Burnout, Professional; Substance-Related Disorders; Anesthesia
PubMed: 35737018
DOI: 10.1007/s00104-022-01675-y -
Drug and Alcohol Dependence Sep 2007We review behavioral- and neuroeconomic research that identifies temporal discounting as an important component in the development and maintenance of drug addiction.... (Review)
Review
We review behavioral- and neuroeconomic research that identifies temporal discounting as an important component in the development and maintenance of drug addiction. First, we review behavioral economic research that explains and documents the contribution of temporal discounting to addiction. This is followed with recent insights from neuroeconomics that may provide an explanation of why drug-dependent individuals discount the future. Specifically, neuroeconomics has identified two competing neural systems that are related to temporal discounting using brain-imaging techniques that examine the relative activation of different brain regions for temporal discounting. According to the competing neural systems account, choices for delayed outcomes are related to the prefrontal cortex (i.e., the "executive system") and choices for immediate outcomes are related to the limbic brain regions (i.e., the "impulsive system"). Temporal discounting provides a useful framework for future imaging research, and suggests a novel approach to designing effective drug dependence prevention and treatment programs.
Topics: Awareness; Brain; Brain Mapping; Choice Behavior; Decision Making; Drug Costs; Humans; Illicit Drugs; Impulsive Behavior; Limbic System; Magnetic Resonance Imaging; Motivation; Prefrontal Cortex; Substance-Related Disorders
PubMed: 17101239
DOI: 10.1016/j.drugalcdep.2006.09.016 -
Journal of Pharmacological Sciences Feb 2005The mesocorticolimbic dopaminergic system plays an important role in the reinforcing effects of drugs of abuse, and the activity-dependent synaptic plasticity of the... (Review)
Review
The mesocorticolimbic dopaminergic system plays an important role in the reinforcing effects of drugs of abuse, and the activity-dependent synaptic plasticity of the system is involved in drug dependence. A DNA microarray screening revealed that the expression levels of tissue plasminogen activator (tPA) mRNA in the nucleus accumbens of morphine- or methamphetamine-dependent rats were significantly increased compared with those in control animals. Since tPA plays a role in synaptic plasticity, we hypothesized that tPA may contribute to the development of drug dependence. Single and repeated morphine treatment as well as repeated methamphetamine treatment induced tPA mRNA expression in the nucleus accumbens, which was associated with an increase in the enzyme activity. Conditioned place preference induced by morphine was markedly reduced in mice with a targeted deletion of the tPA gene (tPA-/- mice), being accompanied by a loss of morphine-induced dopamine release. Similarly, methamphetamine-induced conditioned place preference and locomotor sensitization were reduced in tPA-/- mice. The defects of morphine-induced hyperlocomotion as well as methamphetamine-induced locomotor sensitization in tPA-/- mice were reversed by microinjection of exogenous tPA or plasmin into the nucleus accumbens. These results support our hypothesis that tPA plays a role in long-lasting neuronal changes related to drug dependence.
Topics: Animals; Humans; Neuronal Plasticity; Oligonucleotide Array Sequence Analysis; Substance-Related Disorders; Tissue Plasminogen Activator
PubMed: 15684570
DOI: 10.1254/jphs.cp0040014 -
Neuron Jul 2008Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take drugs and has been linked to dysregulation of brain regions that mediate... (Review)
Review
Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take drugs and has been linked to dysregulation of brain regions that mediate reward and stress. Activation of brain stress systems is hypothesized to be key to the negative emotional state produced by dependence that drives drug seeking through negative reinforcement mechanisms. This review explores the role of brain stress systems (corticotropin-releasing factor, norepinephrine, orexin [hypocretin], vasopressin, dynorphin) and brain antistress systems (neuropeptide Y, nociceptin [orphanin FQ]) in drug dependence, with emphasis on the neuropharmacological function of extrahypothalamic systems in the extended amygdala. The brain stress and antistress systems may play a key role in the transition to and maintenance of drug dependence once initiated. Understanding the role of brain stress and antistress systems in addiction provides novel targets for treatment and prevention of addiction and insights into the organization and function of basic brain emotional circuitry.
Topics: Animals; Brain; Humans; Stress, Physiological; Substance-Related Disorders
PubMed: 18614026
DOI: 10.1016/j.neuron.2008.06.012 -
Neuropsychopharmacology : Official... Jan 2014There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of... (Review)
Review
There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT--is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.
Topics: Animals; Biomarkers, Pharmacological; Cardiovascular System; Cocaine-Related Disorders; Drug Discovery; Humans; Neuroimaging; Substance-Related Disorders; Treatment Outcome
PubMed: 23979119
DOI: 10.1038/npp.2013.210