Current
Drug Abuse Reviews
ISSN: 1874-4737 - Volume 4, 4 Issues, 2011
OPEN ACCESS PLUS
Contents
Review of Topiramate: An Antiepileptic for the Treatment
of Alcohol Dependence, 2009, 2, 135-142
George A. Kenna, Tonya L. Lomastro, Allison
Schiesl, Lorenzo Leggio and Robert M. Swift
[Abstract]
[Full
Text Article]
Why Should We Keep the Cerebellum in Mind When Thinking
About Addiction?, 2009, 2, 26-40
Marta Miquel, Rebeca Toledo, Luis I. García, Genaro
A. Coria-Avila and Jorge Manzo
[Abstract] [Full
Text Article]
Hypothesis-Driven Medication Discovery for the Treatment
of Psychostimulant Addiction, 2008, 1, 303-327
Zheng-Xiong Xi and Eliot L. Gardner
[Abstract] [Full
Text Article]
Cognitive Processes
in Alcohol Binges: A Review and Research Agenda,
2008, 1, 263-279
Matt Field, Tim Schoenmakers and Reinout
W. Wiers
[Abstract] [Full
Text Article]
What Constitutes Prescription Drug Misuse? Problems
and Pitfalls of Current Conceptualizations, 2008,
1, 255-262
Sean P. Barrett, Jessica R. Meisner and
Sherry H. Stewart
[Abstract] [Full
Text Article]
Do Pharmacological Approaches that Prevent Opioid
Tolerance Target Different Elements in the Same Regulatory
Machinery? 2008, 1, 222-238
Javier Garzón, María Rodríguez-Muñoz
and Pilar Sánchez-Blázquez
[Abstract] [Full
Text Article]
The Genetic Components of Alcohol and Nicotine Co-Addiction:
From Genes to Behavior, 2008, 1, 124-134
Isabel R. Schlaepfer, Nicole R. Hoft and Marissa A. Ehringer
[Abstract] [Full
Text Article]
Abstracts
[Back to top]
Review of Topiramate: An Antiepileptic for the Treatment
of Alcohol Dependence
George A. Kenna, Tonya L. Lomastro, Allison
Schiesl, Lorenzo Leggio and Robert M. Swift
[Full
Text Article]
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 2009.
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 alcohol-dependent
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.
[Back to top]
Why Should We Keep the Cerebellum in Mind When Thinking
About Addiction?
Marta Miquel, Rebeca Toledo, Luis I. García, Genaro
A. Coria-Avila and Jorge Manzo
[Full
Text Article]
Increasing evidence has involved the cerebellum in functions
beyond the sphere of motor control. In the present article,
we review evidence that involves the cerebellum in addictive
behaviour. We aimed on molecular and cellular targets in the
cerebellum where addictive drugs can act and induce mechanisms
of neuroplasticity that may contribute to the development
of an addictive pattern of behaviour. Also, we analyzed the
behavioural consequences of repetitive drug administration
that result from activity-dependent changes in the efficacy
of cerebellar synapses.
Revised research involves the cerebellum in drug-induced long-term
memory, drug-induced sensitization and the perseverative behavioural
phenotype. Results agree to relevant participation of the
cerebellum in the functional systems underlying drug addiction.
The molecular and cellular actions of addictive drugs in the
cerebellum involve long-term adaptative changes in receptors,
neurotransmitters and intracellular signalling transduction
pathways that may lead to the re-organization of cerebellar
microzones and in turn to functional networks where the cerebellum
is an important nodal structure. We propose that drug induced
activity-dependent synaptic changes in the cerebellum are
crucial to the transition from a pattern of recreational drug
taking to the compulsive behavioural phenotype. Functional
and structural modifications produced by drugs in the cerebellum
may enhance the susceptibility of fronto-cerebellar circuitry
to be changed by repeated drug exposure. As a part of this
functional reorganization, drug-induced cerebellar hyper-responsiveness
appears to be central to reducing the influence of executive
control of the prefrontal cortex on behaviour and aiding the
transition to an automatic mode of control.
[Back to top]
Hypothesis-Driven Medication Discovery for the Treatment of
Psychostimulant Addiction
Zheng-Xiong Xi and Eliot L. Gardner
[Full
Text Article]
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
drug’s 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.
[Back to top]
Cognitive Processes
in Alcohol Binges: A Review and Research Agenda
Matt Field, Tim Schoenmakers and Reinout
W. Wiers
[Full
Text Article]
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.
[Back to top]
What Constitutes Prescription Drug Misuse? Problems
and Pitfalls of Current Conceptualizations
Sean P. Barrett, Jessica R. Meisner and
Sherry H. Stewart
[Full
Text Article]
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.
[Back to top]
Do Pharmacological Approaches that Prevent Opioid
Tolerance Target Different Elements in the Same Regulatory
Machinery?
[Full
Text Article]
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 G-signalling
(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.
[Back to top]
The Genetic Components of Alcohol and Nicotine Co-Addiction:
From Genes to Behavior
Isabel R. Schlaepfer, Nicole R. Hoft and Marissa A. Ehringer
[Full
Text Article]
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.
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