Current Drug Abuse Reviews - Volume 1, Issue 3, 2008

Surveys show that “pharming” - the popular term for abuse of prescription drugs - is a widespread problem. For example, a recent SAMHSA survey reports that during the past year over 2.6 million US inhabitants of 12 years and older have used psychoactive medication nonmedical for the first time [1]. This issue of CURRENT DRUG ABUSE REVIEWS features a review by Dr Barrett and colleagues on operational definitions of prescription drug misuse. Dr Barrett warns us that definitions and conceptualization of prescription drug abuse and misuse are diverse and consensus is essential to integrate and interpret future research results on this important topic. Reasons for prescription drug abuse vary greatly from getting high (i.e. painkillers and inhalants), increasing alertness and concentration, or to control weight by reducing appetite (i.e. stimulant drugs). In contrast to street drugs, access to prescription drugs is much easier. Teens can find them unprotected in their own home or steal them from the medicine cabinet in their friends' homes. Parents often do not keep track of the quantity of pills in their medicine cabinet, nor do they destroy unused medication. In addition, prescription drugs can be bought on the streets and it has been reported that even patients have been selling their own drugs to profit from high street prices [2, 3]. Also, the internet plays an important role in selling controlled substances without the normally required prescription. In order to accomplish the wanted “high”, drugs are often used in a different way than prescribed. Slow release tablets are crushed and then swallowed, snorted or dissolved in water and injected to give an immediate effect that's much more intense than when used as prescribed. The pharmacokinetic and pharmacodynamic properties of a drug change dramatically when used in this unintended way. Active compounds manufactured for slow release enter the bloodstream immediately producing much higher blood drug concentrations than intended. Two classes of prescription drugs that are often abused by adolescents and students are stimulants and painkillers. Anxiolytics, sedatives and inhalants are also abused, but to a lesser extend. According to the 2006 National Survey on Drug Use and Health two percent of US adolescents between 12 and 17 years old (about half a million kids) acknowledged abusing prescription stimulants during the past year [1]. The abuse of prescription stimulants is popular among adolescents and young adults (12-26 years old) and twice as high as among adults aged 26 or older. A recent review concluded that prescription stimulants used for the treatment of ADHD are abused by 5-9% of adolescents and 5-35% of students [4]. Ritalin (methylphenidate) is among the most frequently abused prescription stimulants. Ritalin seems safe because this stimulant drug is prescribed also to children who suffer from Attention Deficit Hyperactivity Disorder (ADHD). However, when used as prescribed it comes in tablet form and the dose is adjusted to the individual patient. Moreover, the use of Ritalin and possible side effects are carefully monitored. In contrast, those who abuse Ritalin often do so by crushing and swallowing or snorting the powder. This produces the wanted “high”, but also increases the risk of heart failure, seizures, high body temperature, aggression and confusion. Consequences of prescription stimulant abuse are serious and well documented. The 2006 National Survey on Drug Use and Health reports that 12 to 17 year olds who abuse prescription stimulants are more than twice more likely to be engaged in delinquent behavior [1]. Also, they are about 3 times more likely to develop a major depression episode when compared to youth that does not abuse prescription stimulants (22.8% versus 8.1%). OxyContin (oxycodone) and Vicodin (hydrocodone) are popular prescription painkillers. Each year, about half a million Americans use OxyContin for the first time for recreational purposes. Tablets are chewed or the powder from crushed tablets is snorted to produce a high similar as experienced after taking heroin. Unfortunately, extensive US media attention - enhanced by the increasing number of overdose related deaths and hospitalizations during the past decade - contributed to the popularity and abuse of OxyContin and other painkillers [5]. In 2006, the total number of abusers of prescription painkillers in the USA was about 33 million, of which about 4 million abused OxyContin [1]. Data from the Partnership Attitude and Tracking Study [6] revealed that approximately 18% of US teenagers (4.3 million) use Vicodin to get high and 10% (2.3 million) use OxyContin. Abuse of painkillers seems part of the current teen culture: about 37% of teens report to have friends who use Vicodin and OxyContin [6].

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.

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.

Alcohol dependence is a widespread psychiatric disorder. While relapse prevention therapy in alcoholism was exclusively dominated by social and psychological treatments for many years, in the last decades the benefits of pharmacological agents for the rehabilitation treatment in alcoholism have become increasingly evident. Naltrexone, an opiate receptor antagonist, blocks the pleasant and reinforcing effects of alcohol by preventing the stimulation of opioid receptors and the reduction of dopamine release in the ventral tegmental area (VTA). Clinical evidence about the effectiveness of the substance is not always consistent, but meta-analyses confirm naltrexone's effect on the risk of heavy drinking. Evidence about the abstinence-maintaining effects of the substance comes from a relatively small database and needs further investigation. The evaluation of differential effects of naltrexone depending on biological or psychological profiles, which could further enhance the effectiveness of treatments for alcohol dependence, remains a challenge. Nalmefene, another opioid antagonist, as well as naltrexone depot, a sustained release formulation of naltrexone, are further promising strategies for the treatment of alcohol dependence. The review at hand gives on overview of the current evidence on opioid antagonists for the treatment of alcohol dependence regarding the possible mechanism of action, the substances' safety profiles and their effectiveness. The corresponding evidence is critically reviewed taking into consideration the influence of the study design on the magnitude and consistency of effect sizes as well the impact of patient characteristics on the response to the treatment with opioid antagonists. Future studies on the role of different subtypes of alcoholics according to their genetic or psychological profile to explain or even predict the effects of opioid antagonists in the treatment of alcohol dependence are needed.

Methamphetamine (MA) use is a burgeoning problem worldwide and throughout the United States. Researchers have begun to examine risk behaviors among subgroups of MA users in an attempt to discover strategies to assist MA users in reducing their drug use and preventing transmission of diseases such as HIV and Hepatitis C. Sex risk behaviors have been traditionally difficult to examine and to change through intervention. This is important in light of the fact that MA users report a higher sex drive while on MA. This brief literature review examines recent studies of interest looking at heterosexual risk among MA users in the United States. Over 150 articles were examined from a Medline search, however those that concentrated on men who have sex with men (MSM) and HIV sex risk were eliminated from the review. The findings suggest a dearth of research studies that examine heterosexual sex risk among MA users. This is compelling given the growing problem of MA use nationwide and given the effect that MA has on sex behavior and subsequently HIV risk. This comprises one of the few existing literature reviews focusing solely on sex risk behaviors within in this population, which is vital for moving the field forward and developing successful interventions.

Evidence has emerged in recent years on methadone's cardiac arrhythogenic potential - i.e. QT prolongation and Torsades de Pointes (TdP). Given the potentially fatal consequences of these adverse effects, clinicians need to be alert to avoid this going unrecognised and untreated. In this paper, we briefly discuss normal cardiac conduction and electrocardiogram (ECG) waveforms, and look at theories of methadone - induced QT prolongation and TdP. We then present a summary of the existing evidence base for methadone - associated TdP and offer guidance for the clinician on the need for cardiac screening of patients on methadone treatment.

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.

Recent studies support an association between substance use disorders (SUDs) and cortical excitability. Transcranial magnetic stimulation (TMS) is a non-invasive tool that can be used to assess cortical physiological processes (e.g., inhibition, excitation) and has proven to be a useful diagnostic tool in brain disorders associated with alterations in cortical excitability. In this manuscript, we review studies that employ TMS to evaluate cortical excitability in patients with SUDs. Furthermore, we discuss preliminary studies that examine repetitive TMS (rTMS) as a potential treatment for patients with SUDs. Although the use of TMS to evaluate and to treat those individuals with SUDs is in its early stages, these studies reveal significant alterations in both cortical inhibition and excitation. Specifically, elevated cortical inhibition was reported in both cocaine and nicotine dependent individuals, while one study demonstrated an increase in cortical excitability in those who use 3, 4-methylenedioxymethamphetamine (MDMA). Furthermore, three studies examining rTMS as a potential treatment in cocaine and nicotine addiction report decreases in the level of cravings and in the number of cigarettes smoked following rTMS administration to the dorsal lateral prefrontal cortex. Thus, TMS has provided early interesting findings vis a vis cortical excitability in SUDs. Moreover, preliminary evidence suggests that rTMS is efficacious in the treatment of cocaine and nicotine addiction. Further work is needed to enhance our understanding of the altered neurophysiology in SUDs as well as the ways in which rTMS treatment can be directed to optimize treatment.

Each year, smoking-related illnesses are among the leading causes of preventable death in the U.S. and in many other countries. Although recently there have been substantial developments in pharmaceutical and behavioral smoking cessation treatments, these interventions do not work for all individuals, necessitating development of a wider array of treatments. Despite demonstrated efficacy in several studies, contingency management (CM) is a behavioral intervention that is not widely used as a smoking cessation treatment. This review surveys the current research literature on the efficacy of CM for smoking reduction, and identifies some of the most prominent barriers to wider implementation of CM as a stop-smoking treatment. Suggestions are made for future research to design behavioral smoking cessation programs that may be applied as a treatment for smokers in the community.

Cannabis preparations as recreational drugs are the most widely used illicit drugs in the world. Although cannabis derivatives produce clear subjective motivational responses in humans leading to drug-seeking behavior and in a specific proportion in repeated drug use, the reinforcing/rewarding attributes of these subjective effects are difficult to define in experimental animals. This led to the notion of cannabinoids being considered as “atypical” or “anomalous” drugs of abuse. To this end, our knowledge and understanding of the way cannabis and its main psychoactive constituent, Δ9- tetrahydrocannabinol (Δ9-THC), act in the central nervous system to exert their reinforcing/rewarding effects is far from complete. The aim of the present article is to review from a preclinical perspective the current status of what is known about the behavioral pharmacology of cannabinoids including the recently identified cannabinoid neurotransmission modifiers with a particular emphasis on their motivational/reinforcing and dependence-producing properties. We conclude that cannabinoids exhibit reinforcing/rewarding properties in experimental animals mostly under particular experimental conditions, which is not the case for other drugs of abuse, such as opiates, psychostimulants, alcohol and nicotine. The paper will discuss these findings critically and also point to open questions that should be addressed in the future in order to improve our understanding of these specific actions of cannabinoids that will also impact drug discovery and development efforts of related compounds as therapeutics in the clinic.