|
OPEN ACCESS PLUS
Accepted articles are published online for free open access for all to view. Open access publishing provides the maximum dissemination of the article to the largest audience. Authors must pay for this service. All corresponding authors will be asked to indicate whether or not they wish to pay to have their paper made freely available on publication. If authors do not select the Open Access option, then their article will be published with standard subscription-based access at no charge.
Authors who opt for Open Access Plus may also self-archive publishers postprints. Bentham Science is compliant with the open access policy for the MRC, Cancer Research UK, NIH, and many other funders. For details, refer to http://www.benthamscience.com/permission.php or email to; openaccess@benthamscience.org.
Contents
2(2): Pp. 135 - 142
George A. Kenna, Tonya L. Lomastro, Allison Schiesl, Lorenzo Leggio and Robert M. Swift
[Open Access Plus] |
|
Despite the availability of currently approved medications and various psychosocial therapies, alcohol abuse and dependence are increasingly prevalent in the United States, and carry a significant socioeconomic burden. Recently, the novel anti-epileptic topiramate has shown great promise as a new treatment for this disorder. The objective of this review is to discuss the limitations of the currently available options for treating alcohol dependence, to review the results of clinical trials assessing the efficacy of topiramate in treating alcohol dependence, and to describe the pharmacological characteristics and mechanisms of action of topiramate as related to this indication. We systematically reviewed Medline, EMBASE, Cochran Reviews and PsycINFO search terms included combinations of the terms “pharmacotherapy” “topiramate”, “alcoholism” and “alcohol dependence.” Searches were last updated 24 October 2008. Currently approved treatments include disulfiram, naltrexone tablets and injection, and acamprosate. Of these, naltrexone has shown the most benefit, however the effect size is small and may reach its most promising potential when combined with medical management. Alternatively, through multiple mechanisms of action, topiramate in clinical trials has demonstrated safety and efficacy in decreasing both craving and withdrawal symptoms and increasing quality of life measures among alcoholdependent individuals. The findings of this review suggest that topiramate is a promising new option for the treatment of alcohol dependence, and may offer substantial benefits over currently approved medications. While the manufacturer will not pursue approval of an indication for the treatment of alcohol dependence, the drug will soon be available generically, making it more affordable for a greater proportion of the public.
|
1(3): Pp. 303 - 327
Zheng-Xiong Xi and Eliot L. Gardner
[Open Access Plus] |
|
Psychostimulant abuse is a serious social and health problem, for which no effective treatments currently exist. A number of review articles have described predominantly ‘clinic’-based pharmacotherapies for the treatment of psychostimulant addiction, but none have yet been shown to be definitively effective for use in humans. In the present article, we review various ‘hypothesis’- or ‘mechanism’-based pharmacological agents that have been studied at the preclinical level and evaluate their potential use in the treatment of psychostimulant addiction in humans. These compounds target brain neurotransmitter or neuromodulator systems, including dopamine (DA), γ-aminobutyric acid (GABA), endocannabinoid, glutamate, opioid and serotonin, which have been shown to be critically involved in drug reward and addiction. For drugs in each category, we first briefly review the role of each neurotransmitter system in psychostimulant actions, and then discuss the mechanistic rationale for each drugs potential anti-addiction efficacy, major findings with each drug in animal models of psychostimulant addiction, abuse liability and potential problems, and future research directions. We conclude that hypothesis-based medication development strategies could significantly promote medication discovery for the effective treatment of psychostimulant addiction.
|
1(3): Pp. 263 - 279
Matt Field, Tim Schoenmakers and Reinout W. Wiers
[Open Access Plus] |
|
Alcohol abuse is associated with a cluster of long-term changes in cognitive processes, as predicted by contemporary models of addiction. In this paper we review evidence which suggests that similar changes may occur during an alcohol binge, and as such they may play an important role in explaining the loss of control over alcohol consumption that occurs during alcohol binges. As a consequence of both acute alcohol intoxication (alcohol ‘priming’ effects) and exposure to environmental alcohol-related cues, we suggest that a number of changes in cognitive processes are likely. These include increased subjective craving for alcohol, increased positive and arousing outcome expectancies and implicit associations for alcohol use, increased attentional bias for alcohol-related cues, increased action tendencies to approach alcohol, increased impulsive decision-making, and impaired inhibitory control over drives and behaviour. Potential reciprocal relationships between these different aspects of cognition during an alcohol binge are discussed. Finally, we discuss the relationship between the current model and existing models of cognitive processes in substance abuse, and we speculate on the implications of the model for the reduction binge drinking and its consequences.
|
1(3): Pp. 255 - 262
Sean P. Barrett, Jessica R. Meisner and Sherry H. Stewart
[Open Access Plus] |
|
Many medications with sedative, anxiolytic, analgesic, or stimulant properties have the potential to be inappropriately used. However, because these substances have beneficial effects, many issues pertinent to understanding prescription drug misuse may differ from those associated with other misused substances. There is currently a lack of consensus about what constitutes prescription misuse and a wide range of operational criteria have been proposed. Inappropriate medication use is frequently defined on the basis of user characteristics (i.e. any non-prescribed use), the reason for use (i.e. use for recreational purposes), the presence of clinically significant symptoms (i.e. meeting diagnostic criteria for abuse and dependence) or on the presence of any of these factors. In cases where multiple criteria are used to define misuse there is often a lack of differentiation among them, while studies that use more specific criteria tend to exclude certain types of misuse from consideration altogether. In addition, in some cases there are a number of potential ways that a single operational criterion can be met and many of these may be associated with substantially different risks, harms, and predictors. Due to considerable variability in the classification of medication misuse both within and between studies, it is currently difficult to interpret the clinical significance of existing findings or to determine the true magnitude of problems associated with any particular form of misuse. In the present review many of the problems and challenges for adequately defining prescription drug misuse will be overviewed and recommendations will be made on how to better characterize this phenomenon.
|
1(2): Pp. 222 - 238
Javier Garzon, Maria Rodriguez-Munoz and Pilar Sanchez-Blazquez
[Open Access Plus] |
|
In the nervous system, the interaction of opioids like heroin and morphine with the G protein-coupled Muopioid receptor (MOR) provokes the development of tolerance to these opioids, as well as physical dependence. Tolerance implies that higher doses of these drugs must be consumed in order to obtain an equivalent sensation, a situation that contributes notably to the social problems surrounding recreational opioid abuse. The mechanisms that promote opioid tolerance involve a series of adaptive changes in the MOR and in the post-receptor signalling elements. Pharmacological studies have consistently identified a number of signalling proteins relevant to morphine-induced tolerance, including the delta-opioid receptor (DOR), protein kinase C (PKC), protein kinase A (PKA), calcium/calmodulin-dependent kinase II (CaMKII), nitric oxide synthase (NOS), N-methyl-D-aspartate acid glutamate receptors (NMDAR), and regulators of Gsignalling (RGS) proteins. Thus, it is feasible that these treatments which diminish morphine tolerance target distinct elements within the same regulatory machinery. In this scheme, the signals originated at the agonist-activated MORs would be recognised by elements such as the NMDARs, which in turn exert a negative feedback on MOR-evoked signalling. This process involves DOR regulation of MORs, MOR-induced activation of NMDARs (probably via the regulation of Src, recruiting PKC and Gα subunits) and the NMDAR-mediated activation of CaMKII. The active CaMKII promotes the sequestering of morphine-activated Gβγ dimers by phosducin-like proteins (PhLP) and of Gα subunits by RGS proteins and tolerance to opioids like morphine develops. Future efforts to study these phenomena should focus on fitting additional pieces into this puzzle in order to fully define the mechanism underlying the desensitization of MORs in neural cells.
|
1(2): Pp. 124 - 134
Isabel R. Schlaepfer, Nicole R. Hoft and Marissa A. Ehringer
[Open Access Plus] |
|
Co-occurrence of alcohol and nicotine addiction in humans is well documented and there is good evidence that common genes may contribute to both disorders. Although genetic factors contributing to tobacco and alcohol problem use have been well established through adoption, twin and family studies, specific genes remain to be identified and their mode of action elucidated. Recent work from human genetics studies has provided evidence that neuronal nicotinic acetylcholine receptors (nAChR) genes may have a role in mediating early behaviors that are risk factors for alcohol and nicotine dependence, such as age of initiation and early subjective responses to the drugs. Converging evidence suggests that the dopaminergic system is likely to be important in mediating the pleasurable feelings of reward when activated by nicotine and /or alcohol consumption. The nAChRs are important components of the dopaminergic reward system because some of the receptors have been shown to activate the release of dopamine, and mice lacking genes for specific nAChR gene subunits show altered behavioral responses to nicotine and alcohol. Furthermore, complex interactions between other neurotransmitter circuits including GABA, glutamate and serotonin may be modulated by nAChRs, leading researchers to study genes involved in neurobiology shared by different drugs. Future studies aimed at understanding the variation among these genes, and their corresponding functional implications, will help elucidate how natural variants in nicotinic receptor genes contribute to these common co-morbid disorders.
|
|
