Current Drug Abuse Reviews - Volume 5, Issue 3, 2012

Issues: By allowing for the efficient delivery of instructional content and the secure collection of self-report data regarding substance use and related problems, the Internet has tremendous potential to improve the effectiveness and accessibility of Substance Use Disorder (SUD) treatment and recovery-oriented services. Approach: This article discusses some of the ways in which Internet and mobile technology can facilitate, complement and support the process of traditional clinician-delivered treatment for individuals with SUDs. Key Findings: Internet applications are being used to support a range of activities including (a) the assessment and feedback process that constitutes a key feature of brief motivational interventions; and (b) the concurrent monitoring of patients who are receiving treatment for SUDs, to support continuing care, and the ongoing recovery of SUD patients who have completed face-to-face treatment. Internet technology is also being used to (c) support efficient delivery of clinical training in evidence-based practices for treating individuals who may have SUDs. Implications: This emerging body of literature suggests that SUD treatment providers and program administrators can enhance the quality of clinician-delivered treatment by incorporating internet applications into existing processes of care and recovery oriented services. Conclusion: Internet applications provide an unparalleled opportunity to engage patients in the treatment process, incorporate real-time data into treatment planning, prevent relapse, and promote evidence-based treatment approaches.

Although dopaminergic system represents the cornerstone in rewarding, other neurotransmitters can modulate both the reward system and the psychomotor effects of addictive drugs. Many hypotheses have been proposed for a better understanding of the reward system and its role in drug addiction. However, after many years of investigation, no single theory can completely explain the neural basis of drug addiction. Recent reports introduce novel neurotransmitters into the game e.g. dynorphins, orexins, histamine, gheralin and galanin. The interacting functions of these neurotransmitters have shown that the reward system and its role in drug dependence, is far more complicated than was thought before. Individual variations exist regarding response to drug exposure, vulnerability for addiction and the effects of different cues on reward systems. Consequently, genetic variations of neurotransmission are thought to influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. However, the individual variations can not be based mainly on genetics; environmental factors seem to play a role too. Here we discuss the current knowledge about the orquestic regulation of different neurotransmitters on reward-seeking behavior and their potential effect on drug addiction.

Background: Attention-deficit hyperactivity disorder (ADHD) is predominantly a diagnosis of childhood and adolescence but has also been recognized in adults. It is associated with high rates of comorbid psychiatric conditions, particularly substance use disorders (SUD). Methods: A review of the literature was conducted with a focus on ADHD, SUD, their comorbidity, and treatment considerations. Results: Literature suggests that the use of methylphenidate (MPH) in children does not increase SUD later in life, and may in fact reduce substance use and abuse in adolescence and adulthood. Concurrent treatment of ADHD-SUD, which may be supported theoretically, has yielded inconsistent data on clinical trials. While MPH use in adults with ADHDSUD may be effective in alleviating ADHD symptoms, the benefits on SUD are not clear and remain controversial. Studies suggest that adults with comorbid ADHD-SUD do not misuse or divert their medication, but MPH does not consistently improve substance use. However, data are lacking for substances other than cocaine and stimulants other than MPH. While the risk of stimulant abuse should not be ignored, it may be minimized by selecting medications that are not readily crushed and solubilized for parenteral administration, or by utilizing non-stimulant medications and/or psychotherapy. Conclusion: While there are a lack of evidence-based guidelines for the concurrent treatment of ADHD and SUD, evidence to date suggests that stimulant medications should not necessarily be avoided for patients with comorbid ADHDSUD and that concurrent treatment may be a successful approach to improve ADHD outcomes without worsening SUD symptoms.

In the nervous system, the interaction of opioids like morphine and its derivatives, with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of analgesic tolerance, as well as physical dependence. Tolerance implies that increasing doses of the drug are required to achieve the same effect, a phenomenon that contributes significantly to the social problems surrounding recreational opioid abuse. In recent years, our understanding of the mechanisms that control MOR function in the nervous system, and that eventually produce opioid tolerance, has increased greatly. Pharmacological studies have identified a number of signaling proteins involved in morphine-induced tolerance, including the N-methyl-D-aspartate acid glutamate receptor (NMDAR), nitric oxide synthase (NOS), protein kinase C (PKC), protein kinase A (PKA), calcium (Ca2+)/calmodulin (CaM)-dependent kinase II (CaMKII), delta-opioid receptor (DOR) and the regulators of G-protein signaling (RGS) proteins. There is general agreement on the critical role of the NMDAR/nNOS/CaMKII pathway in this process, which is supported by the recent demonstration of a physical association between MORs and NMDARs in post-synaptic structures. Indeed, it is feasible that treatments that diminish morphine tolerance may target distinct elements within the same regulatory MOR-NMDAR pathway. Accordingly, we propose a model that incorporates the most relevant signaling components implicated in opioid tolerance in which, certain signals originating from the activated MOR are perceived by the associated NMDAR, which in turn exerts a negative feedback effect on MOR signaling. MOR- and NMDAR-mediated signals work together in a sequential and interconnected manner to ultimately induce MOR desensitization. Future studies of these phenomena should focus on adding further components to this signaling pathway in order to better define the mechanism underlying MOR desensitization in neural cells.

Addiction to methamphetamine (METH) is thought to be mediated by dopaminergic effects in the reward pathway in the brain via the A10 dopaminergic pathway. Herein we describe an overview of the results of the basic preclinical science undertaken to provide mechanistic insights into the action of amphetamines in general and METH in particular. A brief history of amphetamine and METH use and abuse is given, and an overview of the relevant chemical aspects of amphetamine as they relate to neurotransmitters in general is made. A review of the methods used to study the biochemical effects of METH is outlined. Finally, a focused analysis of the kinetic mechanisms of action of the amphetamines in general, and METH in particular, at the transmembrane transporters and at the intracellular vesicular storage sites is made. A description of how catecholaminergic and serotonergic nerve signaling may be altered by METH is proposed. Overall, the emphasis here is on differences in effects observed between the striatal (the A9 substantia nigral dopamine pathway) and nucleus accumbens (the A10, ventral tegmental pathway) areas of the brain following acute as well as repeated dosing and withdrawal.

The relationship between movement disorders and substance abuse, which we previously reviewed, is updated. We examine these relationships bidirectionally with focus on drugs of abuse that are known to cause movement disorders, as well as primary movement disorders that are associated with use and abuse of alcohol and dopaminergic medications. First, we review the movement disorders that may develop from the acute use or withdrawal of frequent drugs of abuse, including alcohol, cocaine, heroin, amphetamine and methcathinone. We then comment on the interaction between alcoholism and alcohol-responsive movement disorders, such as essential tremor and myoclonus-dystonia. Lastly, we discuss the potential for abuse of antiparkinsonian dopaminergic agents in patients with Parkinson’s disease (PD).