חיפוש מאמרים

Cocaine Cues and Dopamine in Dorsal Striatum: Mechanism of Craving in Cocaine Addiction
Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Logan, J., Childress, A. R., & Wong, C. Journal of Neuroscience 26.24 (2006): 6583-6588.
Abstract The ability of drugs of abuse to increase dopamine in nucleus accumbens underlies their reinforcing effects. However, preclinical studiesRead More...

Abstract

The ability of drugs of abuse to increase dopamine in nucleus accumbens underlies their reinforcing effects. However, preclinical studies have shown that with repeated drug exposure neutral stimuli paired with the drug (conditioned stimuli) start to increase dopamine by themselves, which is an effect that could underlie drug-seeking behavior. Here we test whether dopamine increases occur to conditioned stimuli in human subjects addicted to cocaine and whether this is associated with drug craving. We tested eighteen cocaine-addicted subjects using positron emission tomography and [11C]raclopride (dopamine D2 receptor radioligand sensitive to competition with endogenous dopamine). We measured changes in dopamine by comparing the specific binding of [11C]raclopride when subjects watched a neutral video (nature scenes) versus when they watched a cocaine-cue video (scenes of subjects smoking cocaine). The specific binding of [11C]raclopride in dorsal (caudate and putamen) but not in ventral striatum (in which nucleus accumbens is located) was significantly reduced in the cocaine-cue condition and the magnitude of this reduction correlated with self-reports of craving. Moreover, subjects with the highest scores on measures of withdrawal symptoms and of addiction severity that have been shown to predict treatment outcomes, had the largest dopamine changes in dorsal striatum. This provides evidence that dopamine in the dorsal striatum (region implicated in habit learning and in action initiation) is involved with craving and is a fundamental component of addiction. Because craving is a key contributor to relapse, strategies aimed at inhibiting dopamine increases from conditioned responses are likely to be therapeutically beneficial in cocaine addiction.

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Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research
Stoops, W. W., & Rush, C. R. Expert review of clinical pharmacology 7.3 (2014): 363-374.
Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. InnovativeRead More...

Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. Innovative strategies are necessary to develop successful pharmacotherapies for stimulant use disorders. This manuscript reviews human laboratory studies and clinical trials to determine whether one such strategy, use of combination pharmacotherapies, holds promise. The extant literature shows that combination pharmacotherapy produced results that were better than placebo treatment, especially with medications shown to have efficacy as monotherapies. However, many studies did not compare individual constituents to the combination treatment, making it impossible to determine whether combination treatment is more effective than monotherapy. Future research should systematically compare combined treatments with individual agents using medications showing some efficacy when tested alone.

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Pharmacological approaches to methamphetamine dependence: a focused review
Karila, L., Weinstein, A., Aubin, H. J., Benyamina, A., Reynaud, M., & Batki, S. L. British journal of clinical pharmacology 69.6 (2010): 578-592.
Abstract Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronalRead More...

Abstract

Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double‐blind placebo‐controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d‐amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.

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Efficacy of central nervous system stimulant treatment for cocaine dependence: a systematic review and meta‐analysis of randomized controlled clinical trials
Castells, X., Casas, M., Vidal, X., Bosch, R., Roncero, C., Ramos‐Quiroga, J. A., & Capellà, D. Addiction 102.12 (2007): 1871-1887.
Aims  To evaluate the efficacy of central nervous system (CNS) stimulants compared with placebo for the treatment of cocaine dependence. Methods  ARead More...

Aims  To evaluate the efficacy of central nervous system (CNS) stimulants compared with placebo for the treatment of cocaine dependence.

Methods  A systematic review and meta‐analysis was carried out. Bibliographic databases were searched, reference lists of retrieved studies were hand‐searched and the first authors of each study were contacted. All randomized controlled clinical trials (RCCT) comparing the efficacy of any CNS stimulant with placebo in cocaine‐dependent patients were included. Quantitative data synthesis was performed for each single CNS stimulant and for all CNS stimulants.

Results  Nine RCCT met the inclusion criteria. These RCCT included 640 patients and compared five CNS stimulants: mazindol, dextroamphetamine, methylphenidate, modafinil and bupropion with placebo. No CNS stimulant improved study retention [RR = 0.94 (0.81–1.09)] or cocaine use [RR = 0.90 (0.79–1.02)]. An exploratory analysis using indirect estimations of cocaine use showed that the proportion of cocaine‐positive urine screens was lower with dexamphetamine than with placebo [RR = 0.73 (0.60–0.90)] and that all CNS stimulants pooled together also suggested a significant decrease of cocaine use [RR = 0.87 (0.77–0.99)]. Data on craving could not be meta‐analysed due to heterogeneity, but no RCCT found differences in cocaine craving between active drug and placebo except one, whose outcome favoured dexamphetamine. No serious adverse event (AE) was reported. Average of AE‐induced dropouts was low and was greater for CNS stimulants than placebo: 4.4% versus 1.3% (P = 0.03).

Conclusion  The main outcomes of this study do not support the use of CNS stimulants for cocaine dependence. Nevertheless, secondary analyses provide some hopeful results that encourage further research with these drugs, mainly with dexamphetamine and modafinil.

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Advances and challenges in pharmacotherapeutics for amphetamine-type stimulants addiction
Cao, D. N., Shi, J. J., Hao, W., Wu, N., & Li, J. European journal of pharmacology 780 (2016): 129-135.
Abstract Addiction to amphetamine-type stimulants (ATS) is a serious worldwide public health problem with major medical, psychiatric and socioeconomic consequences.Read More...

Abstract

Addiction to amphetamine-type stimulants (ATS) is a serious worldwide public health problem with major medical, psychiatric and socioeconomic consequences. However, no approved pharmacological therapies are available to treat ATS addiction. Based on the neurobiological mechanisms underlying ATS addiction, the recent research works about pharmacological strategies have been focused on monoamine, glutamate, endogenous opioid peptide and γ-amino butyric acid (GABA) systems. This review summarizes the recent advances in the medications being developed to treat ATS addiction and discusses the remaining challenges. Although no substantial evidence for efficacious medications has emerged, some of these agents, including bupropion, naltrexone and mirtazapine, have demonstrated promise in clinical studies. Moreover, some challenges, such as the development of new preclinical animal models of drug addiction, the design of large-scale clinical trials with strict quality control, and the distinction of patients' genetic polymorphisms, need further attention. Despite the lack of success to date, much effort is being made to develop efficacious medications for treating ATS addiction.

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A systematic review of cognitive and behavioural therapies for methamphetamine dependence
Lee, N. K., & Rawson, R. A. Drug and alcohol review 27.3 (2008): 309-317.
Introduction and Aims. The use of methamphetamine is widespread and poses significant challenges for treatment providers. Much of the treatmentRead More...

Introduction and Aims. The use of methamphetamine is widespread and poses significant challenges for treatment providers. Much of the treatment knowledge about this group has been extrapolated from studies of treatment for cocaine dependence. Medications have been shown to be of limited effectiveness for methamphetamine users, making psychological interventions the treatment of choice.

Approach. This paper describes a systematic review of cognitive–behavioural and behavioural interventions for methamphetamine users. A systematic search of published literature was undertaken focusing only on randomised trials.

Key Findings. There were a relatively small number of intervention studies that compared cognitive–behavioural or behavioural interventions using randomised trial methodology. Most commonly, studies examined cognitive–behaviour therapy (CBT) and/or contingency management (CM). Treatment with CBT appears to be associated with reductions in methamphetamine use and other positive changes, even over very short periods of treatment (two and four sessions). CM studies found a significant reduction of methamphetamine during application of the procedure, but it is not clear if these gains are sustained at post‐treatment follow‐up.

 Implications. The review highlights that there are effective treatments for methamphetamine dependence. Alcohol and other drug (AOD) clinicians are familiar with these types of interventions and should use them and convey to clients that they are effective. Services and policy makers should ensure that best practice interventions are implemented within AOD services.

 Conclusion. Psychological intervention is effective in addressing methamphetamine use and dependence. CBT and contingency management are two accessible interventions that are implemented easily within current AOD services. There is still more work to conduct in improving methamphetamine treatment, however, and further research into cognitive–behavioural and behavioural treatments for methamphetamine users is required, with a focus on improving longevity of the effect of intervention and improving effectiveness among more complex presentations.a

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Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis
De Crescenzo, F., Ciabattini, M., D’Alò, G. L., De Giorgi, R., Del Giovane, C., Cassar, C., & Cipriani, A. PLoS medicine 15.12 (2018): e1002715.
Background Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear whichRead More...

Background

Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear which intervention, if any, should be offered first. We aimed to estimate the comparative effectiveness of all available psychosocial interventions (alone or in combination) for the short- and long-term treatment of people with cocaine and/or amphetamine addiction.

Methods and findings

We searched published and unpublished randomised controlled trials (RCTs) comparing any structured psychosocial intervention against an active control or treatment as usual (TAU) for the treatment of cocaine and/or amphetamine addiction in adults. Primary outcome measures were efficacy (proportion of patients in abstinence, assessed by urinalysis) and acceptability (proportion of patients who dropped out due to any cause) at the end of treatment, but we also measured the acute (12 weeks) and long-term (longest duration of study follow-up) effects of the interventions and the longest duration of abstinence. Odds ratios (ORs) and standardised mean differences were estimated using pairwise and network meta-analysis with random effects. The risk of bias of the included studies was assessed with the Cochrane tool, and the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We followed the PRISMA for Network Meta-Analyses (PRISMA-NMA) guidelines, and the protocol was registered in PROSPERO (CRD 42017042900). We included 50 RCTs evaluating 12 psychosocial interventions or TAU in 6,942 participants. The strength of evidence ranged from high to very low. Compared to TAU, contingency management (CM) plus community reinforcement approach was the only intervention that increased the number of abstinent patients at the end of treatment (OR 2.84, 95% CI 1.24–6.51, P = 0.013), and also at 12 weeks (OR 7.60, 95% CI 2.03–28.37, P = 0.002) and at longest follow-up (OR 3.08, 95% CI 1.33–7.17, P = 0.008). At the end of treatment, CM plus community reinforcement approach had the highest number of statistically significant results in head-to-head comparisons, being more efficacious than cognitive behavioural therapy (CBT) (OR 2.44, 95% CI 1.02–5.88, P = 0.045), non-contingent rewards (OR 3.31, 95% CI 1.32–8.28, P = 0.010), and 12-step programme plus non-contingent rewards (OR 4.07, 95% CI 1.13–14.69, P = 0.031). CM plus community reinforcement approach was also associated with fewer dropouts than TAU, both at 12 weeks and the end of treatment (OR 3.92, P < 0.001, and 3.63, P < 0.001, respectively). At the longest follow-up, community reinforcement approach was more effective than non-contingent rewards, supportive-expressive psychodynamic therapy, TAU, and 12-step programme (OR ranging between 2.71, P = 0.026, and 4.58, P = 0.001), but the combination of community reinforcement approach with CM was superior also to CBT alone, CM alone, CM plus CBT, and 12-step programme plus non-contingent rewards (ORs between 2.50, P = 0.039, and 5.22, P < 0.001). The main limitations of our study were the quality of included studies and the lack of blinding, which may have increased the risk of performance bias. However, our analyses were based on objective outcomes, which are less likely to be biased.

Conclusions

To our knowledge, this network meta-analysis is the most comprehensive synthesis of data for psychosocial interventions in individuals with cocaine and/or amphetamine addiction. Our findings provide the best evidence base currently available to guide decision-making about psychosocial interventions for individuals with cocaine and/or amphetamine addiction and should inform patients, clinicians, and policy-makers.

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Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis
Ashok, A. H., Mizuno, Y., Volkow, N. D., & Howes, O. D. JAMA psychiatry 74.5 (2017): 511-519.
Importance  Stimulant use disorder is common, affecting between 0.3% and 1.1% of the population, and costs more than $85 billion perRead More...

Importance  Stimulant use disorder is common, affecting between 0.3% and 1.1% of the population, and costs more than $85 billion per year globally. There are no licensed treatments to date. Several lines of evidence implicate the dopamine system in the pathogenesis of substance use disorder. Therefore, understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics.

Objective  To comprehensively review the in vivo imaging evidence for dopaminergic alterations in stimulant (cocaine, amphetamine, or methamphetamine) abuse or dependence.

Data Sources  The entire PubMed, EMBASE, and PsycINFO databases were searched for studies from inception date to May 14, 2016.

Study Selection  Case-control studies were identified that compared dopaminergic measures between stimulant users and healthy controls using positron emission tomography or single-photon emission computed tomography to measure striatal dopamine synthesis or release or to assess dopamine transporter availability or dopamine receptor availability.

Data Extraction and Synthesis  Demographic, clinical, and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted for stimulants combined, as well as for cocaine and for amphetamine and methamphetamine separately if there were sufficient studies.

Main Outcomes and Measures  Differences were measured in dopamine release (assessed using change in the D2/D3 receptor availability after administration of amphetamine or methylphenidate), dopamine transporter availability, and dopamine receptor availability in cocaine users, amphetamine and methamphetamine users, and healthy controls.

Results  A total of 31 studies that compared dopaminergic measures between 519 stimulant users and 512 healthy controls were included in the final analysis. In most of the studies, the duration of abstinence varied from 5 days to 3 weeks. There was a significant decrease in striatal dopamine release in stimulant users compared with healthy controls: the effect size was −0.84 (95% CI, −1.08 to −0.60; P < .001) for stimulants combined and −0.87 (95% CI, −1.15 to −0.60; P < .001) for cocaine. In addition, there was a significant decrease in dopamine transporter availability: the effect size was −0.91 (95% CI, −1.50 to −0.32; P < .01) for stimulants combined and −1.47 (95% CI, −1.83 to −1.10; P < .001) for amphetamine and methamphetamine. There was also a significant decrease in D2/D3 receptor availability: the effect size was −0.76 (95% CI, −0.92 to −0.60; P < .001) for stimulants combined, −0.73 (95% CI, −0.94 to −0.53; P < .001) for cocaine, and −0.81 (95% CI, −1.12 to −0.49; P < .001) for amphetamine and methamphetamine. Consistent alterations were not found in vesicular monoamine transporter, dopamine synthesis, or D1 receptor studies.

Conclusions and Relevance  Data suggest that both presynaptic and postsynaptic aspects of the dopamine system in the striatum are down-regulated in stimulant users. The commonality and differences between these findings and the discrepancies with the preclinical literature and models of drug addiction are discussed, as well as their implications for future drug development.

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Stimulant Medication and Substance Use Outcomes: A Meta-analysis
Humphreys, K. L., Eng, T., & Lee, S. S. JAMA psychiatry 70.7 (2013): 740-749.
Importance  Psychostimulant medication is an efficacious treatment for childhood attention-deficit/hyperactivity disorder, yet controversy remains regarding potential iatrogenic effects of stimulant medication,Read More...

Importance  Psychostimulant medication is an efficacious treatment for childhood attention-deficit/hyperactivity disorder, yet controversy remains regarding potential iatrogenic effects of stimulant medication, particularly with respect to increasing susceptibility to later substance use disorders. However, stimulant treatment was previously reported to reduce the risk of substance problems.

Objective  To meta-analyze the longitudinal association between treatment with stimulant medication during childhood and later substance outcomes (ie, lifetime substance use and substance abuse or dependence).

Data Sources  Studies published between January 1980 and February 2012 were identified using review articles, PubMed, and pertinent listservs.

Study Selection  Studies with longitudinal designs in which medication treatment preceded the measurement of substance outcomes.

Data Extraction and Synthesis  Odds ratios were extracted or provided by the study authors. Odds ratios were obtained for lifetime use (ever used) and abuse or dependence status for alcohol, cocaine, marijuana, nicotine, and nonspecific drugs for 2565 participants from 15 different studies.

Main Outcomes and Measures  Random-effects models estimated the overall association, and potential study moderators were examined.

Results  Separate random-effects analyses were conducted for each substance outcome, with the number of studies ranging from 3 to 11 for each outcome. Results suggested comparable outcomes between children with and without medication treatment history for any substance use and abuse or dependence outcome across all substance types.

Conclusions  These results provide an important update and suggest that treatment of attention-deficit/hyperactivity disorder with stimulant medication neither protects nor increases the risk of later substance use disorders.

Pharmacotherapy, most often with stimulant medication (eg, methylphenidate and mixed amphetamine salts), is a well-established treatment for attention-deficit/hyperactivity disorder (ADHD) and constitutes the first-line ADHD treatment in many clinical settings. However, the use of stimulant medication to treat ADHD remains controversial given concerns about its potential for abuse and possible role in sensitizing patients to later substance problems.Treatment with stimulant medication may be related to substance problems for several reasons. Dopamine neurotransmission is featured prominently in current models of stimulant medication and substance use disorders. Nonhuman animal studies have implicated methylphenidate administration to a later preference for cocaine. In humans, age of methylphenidate treatment initiation was positively associated with nonalcoholic substance use disorders. These results suggest not only an association between stimulants and substance outcomes but also that neural consequences may differ, depending on the age of exposure.

In the only published meta-analysis on the association of treatment for ADHD with stimulant medication and subsequent alcohol or substance disorders, Wilens et al meta-analyzed 6 studies and concluded that children who received stimulant treatment were significantly less likely to develop alcohol and substance use disorders. However, since this review, results from multiple longitudinal studies have not found protective effects of stimulant treatment on substance use outcomes. In a recent qualitative review, Goldenconcluded that inconsistencies in the literature suggest that the predictive validity of stimulant treatment and the development of substance disorders is poorly understood.

Given that 10 years have transpired since the original meta-analysis by Wilens et al and the publication of subsequent multiple studies that failed to replicate the protective effect of stimulant medication treatment for ADHD and substance outcomes, the present meta-analysis included substantially more studies, including several unpublished studies, and investigated both lifetime substance use (ie, ever used) and/or substance abuse or dependence across more substance types (ie, cocaine, marijuana, and nicotine in addition to alcohol and general drug use disorders). Overall, our aim was 2-fold: (1) to meta-analyze the long-term association between medication treatment of children with ADHD (vs children with ADHD not treated with stimulants) and dichotomized measures of lifetime substance use and abuse or dependence across alcohol, cocaine, marijuana, nicotine, and nonspecific drugs (ie, studies that did not provide specific substance type breakdown) and (2) to test theoretically and methodologically relevant moderators if and when significant heterogeneity in effect size was found.

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Khat and synthetic cathinones: a review
Valente, M. J., De Pinho, P. G., de Lourdes Bastos, M., Carvalho, F., & Carvalho, M. Archives of toxicology 88.1 (2014): 15-45.
For centuries, ‘khat sessions’ have played a key role in the social and cultural traditions among several communities around SaudiRead More...

For centuries, ‘khat sessions’ have played a key role in the social and cultural traditions among several communities around Saudi Arabia and most East African countries. The identification of cathinone as the main psychoactive compound of khat leaves, exhibiting amphetamine-like pharmacological properties, resulted in the synthesis of several derivatives structurally similar to this so-called natural amphetamine. Synthetic cathinones were primarily developed for therapeutic purposes, but promptly started being misused and extensively abused for their euphoric effects. In the mid-2000’s, synthetic cathinones emerged in the recreational drug markets as legal alternatives (‘legal highs’) to amphetamine, ‘ecstasyʼ, or cocaine. Currently, they are sold as ‘bath salts’ or ‘plant foodʼ, under ambiguous labels lacking information about their true contents. Cathinone derivatives are conveniently available online or at ‘smartshops’ and are much more affordable than the traditional illicit drugs. Despite the scarcity of scientific data on these ‘legal highs’, synthetic cathinones use became an increasingly popular practice worldwide. Additionally, criminalization of these derivatives is often useless since for each specific substance that gets legally controlled, one or more structurally modified analogs are introduced into the legal market. Chemically, these substances are structurally related to amphetamine. For this reason, cathinone derivatives share with this drug both central nervous system stimulating and sympathomimetic features. Reports of intoxication and deaths related to the use of ‘bath salts’ have been frequently described over the last years, and several attempts to apply a legislative control on synthetic cathinones have been made. However, further research on their pharmacological and toxicological properties is fully required in order to access the actual potential harm of synthetic cathinones to general public health. The present work provides a review on khat and synthetic cathinones, concerning their historical background, prevalence, patterns of use, legal status, chemistry, pharmacokinetics, pharmacodynamics, and their physiological and toxicological effects on animals and humans.

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Methamphetamine use: A comprehensive review of molecular, preclinical and clinical findings
Panenka, W. J., Procyshyn, R. M., Lecomte, T., MacEwan, G.W., Flynn, S. W., Honer, W. G., & Barr, A. M. Drug and alcohol dependence 129.3 (2013): 167-179.
Methamphetamine (MA) is a highly addictive psychostimulant drug that principally affects the monoamine neurotransmitter systems of the brain and results in feelings of alertness, increased energyRead More...

Methamphetamine (MA) is a highly addictive psychostimulant drug that principally affects the monoamine neurotransmitter systems of the brain and results in feelings of alertness, increased energy and euphoria. The drug is particularly popular with young adults, due to its wide availability, relatively low cost, and long duration of psychoactive effects. Extended use of MA is associated with many health problems that are not limited to the central nervous system, and contribute to increased morbidity and mortality in drug users. Numerous studies, using complementary techniques, have provided evidence that chronic MA use is associated with substantial neurotoxicity and cognitive impairment. These pathological effects of the drug, combined with the addictive properties of MA, contribute to a spectrum of psychosocial issues that include medical and legal problems, at-risk behaviors and high societal costs, such as public health consequences, loss of family support and housing instability. Treatment options include pharmacological, psychological or combination therapies. The present review summarizes the key findings in the literature spanning from molecular through to clinical effects.

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Environmental, genetic and epigenetic contributions to cocaine addiction
Pierce, R. C., Fant, B., Swinford-Jackson, S. E., Heller, E. A., Berrettini, W. H., & Wimmer, M. E. Neuropsychopharmacology (2018): 1.
Decades of research on cocaine has produced volumes of data that have answered many important questions about the nature ofRead More...

Decades of research on cocaine has produced volumes of data that have answered many important questions about the nature of this highly addictive drug. Sadly, none of this information has translated into the development of effective therapies for the treatment of cocaine addiction. This review endeavors to assess the current state of cocaine research in an attempt to identify novel pathways for therapeutic development. For example, risk of cocaine addiction is highly heritable but genome-wide analyses comparing cocaine-dependent individuals to controls have not resulted in promising targets for drug development. Is this because the genetics of addiction is too complex or because the existing research methodologies are inadequate? Likewise, animal studies have revealed dozens of enduring changes in gene expression following prolonged exposure to cocaine, none of which have translated into therapeutics either because the resulting compounds were ineffective or produced intolerable side-effects. Recently, attention has focused on epigenetic modifications resulting from repeated cocaine intake, some of which appear to be heritable through changes in the germline. While epigenetic changes represent new vistas for therapeutic development, selective manipulation of epigenetic marks is currently challenging even in animals such that translational potential is a distant prospect. This review will reveal that despite the enormous progress made in understanding the molecular and physiological bases of cocaine addiction, there is much that remains a mystery. Continued advances in genetics and molecular biology hold potential for revealing multiple pathways toward the development of treatments for the continuing scourge of cocaine addiction.

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Nonmedical Use of Prescription Medications Among Adolescents in the United States: A Systematic Review
Young, A. M., Glover, N., & Havens, J. R. Journal of Adolescent Health 51.1 (2012): 6-17.
Purpose The purpose of this review was to systematically summarize research on nonmedical use of prescription medications (NMUPM) among U.S. adolescents, withRead More...

Purpose

The purpose of this review was to systematically summarize research on nonmedical use of prescription medications (NMUPM) among U.S. adolescents, with specific focus on scheduled medications falling into one of the following drug classes: pain relievers, stimulants, sedatives, or tranquilizers.

Methods

Databases were searched for peer-reviewed primary quantitative research published between January 2000 and June 2011 on NMUPM among out-of-treatment U.S. adolescents aged 12–17 years (or age 18 if enrolled in high school).

Results

Thirty publications met inclusion criteria. A total of 25 studies were represented; 15 involved nationally representative samples. The prevalence and correlates of NMUPM varied across studies and by drug class. Nonmedical use of pain relievers was more prevalent than for stimulants, sedatives, and tranquilizers. Female gender was generally associated with pain reliever use and, to a lesser degree, with tranquilizer use. White adolescents also appeared to have a higher prevalence of NMUPM, although there was some evidence to the contrary. Older age, illicit drug use, and delinquency were consistently associated with NMUPM across studies.

Conclusions

This review identified several areas for further research, including that of racially/ethnically diverse samples of adolescents, more focus on sedative and tranquilizer use, and longitudinal research to examine temporal patterns in NMUPM and other illicit drug use, delinquency, and substance abuse and dependence.

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Misuse and Diversion of Stimulants Prescribed for ADHD: A Systematic Review of the Literature
Wilens, T. E., Adler, L. A., Adams, J., Sgambati, S., Rotrosen, J., Sawtelle, R., & Fusillo, S. Journal of the American Academy of Child & Adolescent Psychiatry 47.1 (2008): 21-31.
Objective Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed andRead More...

Objective

Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed and prescribed stimulant medications in adolescent and young adult populations. The purpose of this systematic review of the literature is to evaluate the extent and characteristics of stimulant misuse and diversion in attention-deficit/hyperactivity disorder (ADHD) and non-ADHD individuals.

Method

We conducted a systematic review of the literature of available studies looking at misuse and diversion of prescription ADHD medications using misusediversionstimulantsillicit use, and ADHD medications as key words for the search.

Results

We identified 21 studies representing 113,104 subjects. The studies reported rates of past year nonprescribed stimulant use to range from 5% to 9% in grade school- and high school-age children and 5% to 35% in college-age individuals. Lifetime rates of diversion ranged from 16% to 29% of students with stimulant prescriptions asked to give, sell, or trade their medications. Recent work suggests that whites, members of fraternities and sororities, individuals with lower grade point averages, use of immediate-release compared to extended-release preparations, and individuals who report ADHD symptoms are at highest risk for misusing and diverting stimulants. Reported reasons for use, misuse, and diversion of stimulants include to concentrate, improve alertness, “get high,” or to experiment.

Conclusions

The literature suggests that individuals both with and without ADHD misuse stimulant medications. Recent work has begun to document the context, motivation, and demographic profile of those most at risk for using, misusing, and diverting stimulants. The literature highlights the need to carefully monitor high-risk individuals for the use of nonprescribed stimulants and educate individuals with ADHD as to the pitfalls of the misuse and diversion of the stimulants.

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Cocaine: history, social implications, and toxicity: a review
Goldstein, R. A., DesLauriers, C., Burda, A., & Johnson-Arbor, K. Seminars in diagnostic pathology. Vol. 26. No. 1. WB Saunders, 2009.
The amount of positive cocaine results in an urban emergency department are staggering. The ages of use are becoming moreRead More...

The amount of positive cocaine results in an urban emergency department are staggering. The ages of use are becoming more common in older age groups. Most of these patients have underlying medical conditions, including end-stage renal disease (on hemodialysis) and heart and lung disease. Most of their visits to the emergency department are for cocaine exacerbation of underlying chronic condition, adding exponentially to health care dollars. This article describes the history and pharmacology of illicit cocaine use.

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