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As marijuana use becomes legal in some states, the dominant public opinion is that marijuana is a harmless source of mood alteration. Although the harms associated with marijuana use have not been well studied, enough information is available to cause concern. In light of the rapidly shifting landscape regarding the legalization of marijuana for medical and recreational purposes, patients may be more likely to ask physicians about its potential adverse and beneficial effects on health. The popular notion seems to be that marijuana is a harmless pleasure, access to which should not be regulated or considered illegal. Currently, marijuana is the most commonly used “illicit” drug in the United States, with about 12% of people 12 years of age or older reporting use in the past year and particularly high rates of use among young people. 1 The most common route of . . .

The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and non-cognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD.

Smoking is the leading cause of preventable illness in the world today. Prenatal cigarette smoke exposure (PCSE) is a particularly insidious form because so many of its associated health effects befall the unborn child and produce behavioural outcomes that manifest themselves only years later. Among these are the associations between PCSE and conduct disorders, which have been mostly ascribed to the deleterious effects of nicotine on the fetal brain. Here we hypothesize that inhibition of brain monoamine oxidase (MAO) during fetal brain development, secondary to maternal cigarette smoking and in addition to nicotine, is a likely contributor to this association. MAOs play a central role in monoaminergic balance in the brain, and their inhibition during fetal development — but not during adult life — is known to result in an aggressive phenotype in laboratory animals. This paper provides theoretical and experimental support for the notion that cigarette smoke–induced inhibition of MAO in the fetal brain, particularly when it occurs in combination with polymorphisms in the MAOA gene that lead to lower enzyme concentration in the brain, may result in brain morphologic and functional changes that enhance the risk of irritability, poor self-control and aggression in the offspring. It also encourages research to evaluate whether the interaction of smoking exposure during fetal development and MAOA genotype increases the risk for conduct disorder over that incurred by mere fetal exposure to tobacco smoke.

Does chronic drug abuse cause brain abnormalities, or do they develop before the onset of dependence? The traffic light turns from green to yellow. With just one car between you and the intersection, your brain sprints into action, calculating distances and relative velocities; checking for hurried pedestrians; simulating the mental processes of the driver in front of you; and readying every muscle in preparation for a split-second decision that could literally change your life: Which pedal? So many of our mental processes, at any given moment, rely upon this constant, “high stakes” computation involving powerful impulses on one hand and inhibitory control on the other. This balancing act of neuronal signals is at the core of complex human behaviors and thus, its malfunction could have a range of adverse medical and social consequences. On page 601 of this issue, Ersche et al. ( 1 ) identify common abnormalities in fronto-striatal brain systems associated with poorer self-control in both drug-dependent individuals and their nonaddicted siblings.

Thus, the intensity and quality of behavioral output are strongly influenced by both dopaminergic and glutamatergic input to the nucleus accumbens. It is of consequence that increased activity at accumbal synapses has been reported to produce dramatic morphological changes in the dendrites of nucleus accumbens spiny cells, because it suggests that the early phases of addiction are associated with aberrant neuroplasticity in these critical cellular mechanisms of synaptic organization.

Addiction is characterized by compulsion to seek and take a given drug; loss of control in limiting intake; and emergence of a negative emotional state when the drug is unavailable or access to it is prevented. Physical dependence results in withdrawal symptoms, when drugs, such as alcohol and heroin, are discontinued, and can be a normal physiological response to any drug. The adaptations that are responsible for these effects are different from those that underlie addiction. These adaptations are described in detail in this chapter. The chapter is based on DSM‐IV definitions whenever dealing with prevalence rates. Selective deletion of the genes for the expression of different dopamine receptor subtypes and the dopamine transporter (DAT) has revealed significant effects to challenges with psychomotor stimulants.

Key Points The motivation to eat, like the motivation to take addictive drugs, activates the forebrain dopamine systems. Excessive activation of this system strengthens the specific habits that precede the activation, sensitizing the animal's responsiveness to the specific conditions that elicit those habits. At the same time, overactivation of the dopamine system downregulates the dopamine receptors, leaving the subject less interested in other activities. The repeated intake of high-impact foods or addictive drugs thus makes food consumption or drug taking more habitual and decreases the importance of stimuli calling for alternatives. Repeated drug use erodes the function of brain networks necessary for self-regulation, thereby facilitating impulsive, inflexible and compulsive actions. The dopamine motive system, which integrates reinforcement and motivation, is influenced by obesogenic foods and addictive drugs. In this Review, Volkow and colleagues highlight how these stimuli sensitize the subject's motivation towards them while desensitizing the subject's motivation towards alternative reinforcers. Behaviours such as eating, copulating, defending oneself or taking addictive drugs begin with a motivation to initiate the behaviour. Both this motivational drive and the behaviours that follow are influenced by past and present experience with the reinforcing stimuli (such as drugs or energy-rich foods) that increase the likelihood and/or strength of the behavioural response (such as drug taking or overeating). At a cellular and circuit level, motivational drive is dependent on the concentration of extrasynaptic dopamine present in specific brain areas such as the striatum. Cues that predict a reinforcing stimulus also modulate extrasynaptic dopamine concentrations, energizing motivation. Repeated administration of the reinforcer (drugs, energy-rich foods) generates conditioned associations between the reinforcer and the predicting cues, which is accompanied by downregulated dopaminergic response to other incentives and downregulated capacity for top-down self-regulation, facilitating the emergence of impulsive and compulsive responses to food or drug cues. Thus, dopamine contributes to addiction and obesity through its differentiated roles in reinforcement, motivation and self-regulation, referred to here as the 'dopamine motive system', which, if compromised, can result in increased, habitual and inflexible responding. Thus, interventions to rebalance the dopamine motive system might have therapeutic potential for obesity and addiction.

Receptor heteromers constitute a new area of research that is reshaping our thinking about biochemistry, cell biology, pharmacology and drug discovery. In this commentary, we recommend clear definitions that should facilitate both information exchange and research on this growing class of transmembrane signal transduction units and their complex properties. We also consider research questions underlying the proposed nomenclature, with recommendations for receptor heteromer identification in native tissues and their use as targets for drug development.