No medications are currently approved specifically to treat cocaine addiction. Researchers are studying the use of medications approved for other conditions to treat cocaine addiction. The medications showing the most promise are psychostimulants, modafinil, bupropion, topiramate and disulfiram. However, due to small study size and inconsistent results, there is no strong support for any individual drug at this time.
Cocaine addiction affects the way the user processes information and handles interpersonal relationships. It can also lead to such severe eating and sleeping disorders that the user can no longer carry out the normal activities of daily life.
Habitual Cocaine Use Will Eventually Lead To Addiction
Addictive social media use will look much like any other substance use disorder and may include mood modification (i.e., engagement in social media leads to a favorable change in emotional states), salience (i.e., behavioral, cognitive, and emotional preoccupation with social media), tolerance (i.e., ever-increasing use of social media over time), withdrawal symptoms (i.e., experiencing unpleasant physical and emotional symptoms when social media use is restricted or stopped), conflict (i.e., interpersonal problems ensue because of social media usage), and relapse (i.e., addicted individuals quickly revert back to their excessive social media usage after an abstinence period).
Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented (defined as Substance Dependence by the Diagnostic and Statistical Manual of Mental Disorders [DSM] of the American Psychiatric Association; Koob and Le Moal, 1997; Table 1). The occasional but limited use of an abusable drug is clinically distinct from escalated drug use, loss of control over limiting drug intake, and the emergence of chronic compulsive drug-seeking that characterizes addiction. The critical nature of the distinction between drug use, abuse, and dependence has been illuminated by data showing that approximately 15.6% (29 million) of the US adult population will go on to engage in nonmedical or illicit drug use at some time in their lives, with approximately 2.9% (5.4 million) going on to substance dependence on illicit drugs (Grant and Dawson, 1998; Grant et al, 2004). For alcohol, 51% (120 million) of people over the age of 12 were current users, and of these current users, 7.7% (18 million) met the criteria for Substance Abuse or Dependence on Alcohol. For nicotine, in 2007, approximately 28.6% (70.9 million) Americans aged 12 or older were current (past month) users of a tobacco product, and of these current users, 24.2% (60.1 million) were current cigarette smokers; 5.4% (13.3 million) smoked cigars; 3.2% (8.1 million) used smokeless tobacco; and 0.8% (2.0 million) smoked tobacco in pipes (Substance Abuse and Mental Health Services Administration, 2008).
Within-system neuroadaptations to chronic drug exposure include decreases in function of the neurotransmitter systems in the neurocircuits implicated in the acute reinforcing effects of drug of abuse. One prominent hypothesis is that dopamine systems are compromised in crucial phases of the addiction cycle, such as withdrawal, and lead to decreased motivation for nondrug-related stimuli and increased sensitivity to the abused drug (Melis et al, 2005; see brain imaging studies below). Psychostimulant withdrawal in humans is associated with fatigue, decreased mood and psychomotor retardation, and in animals is associated with decreased motivation to work for natural rewards (Barr and Phillips, 1999) and decreased locomotor activity (Pulvirenti and Koob, 1993), behavioral effects that may involve decreased dopaminergic function. Animals during amphetamine withdrawal show decreased responding on a progressive-ratio schedule for a sweet solution, and this decreased responding was reversed by the dopamine partial agonist terguride (Orsini et al, 2001), suggesting that low dopamine tone contributes to the motivational deficits associated with psychostimulant withdrawal. Decreases in activity of the mesolimbic dopamine system and decreases in serotonergic neurotransmission in the nucleus accumbens occur during acute drug withdrawal from all major drugs of abuse in animal studies (Rossetti et al, 1992; Weiss et al, 1992, 1996).
Human subjects with cocaine addiction show impaired performance in tasks involving attention, cognitive flexibility, and delayed reward discounting that are mediated by the medial and orbital prefrontal cortices, as well as spatial, verbal, and recognition memory impairments that are mediated by the hippocampus, and these deficits can predict poor treatment outcomes (Aharonovich et al, 2006; Bolla et al, 2003). Parallel animal studies of the orbitofrontal, prefrontal cortex, and hippocampus in addiction using animal models have begun to show some of the deficits reflected in human studies. Experimenter-administered cocaine produced impairments in reversal learning (an orbital frontal task) in rats and monkeys (Jentsch et al, 2002; Schoenbaum et al, 2004; Calu et al, 2007). Perhaps even more compelling, animals allowed extended access, but not limited access, to cocaine showed deficits in working memory (a prefrontal-cortex-dependent task), sustained attention task (a prefrontal-cortex-dependent task), and an object recognition task (a hippocampus-dependent task; Briand et al, 2008a, 2008b; George et al, 2008). In one study (Briand et al, 2008a), these deficits were associated with a significant decrease in dopamine D2 receptor mRNA in the medial and orbital prefrontal cortices, an observation also consistent with human imaging studies. Thus, animal studies using models of compulsive stimulant administration are beginning to show deficits associated with human cocaine addiction (see Human studies: imaging and neuropsychopharmacology).
As noted above, evidence from preclinical and clinical studies suggests that addiction represents sequential neuroadaptations. As a result, an initial impulsive action turns compulsive and becomes (eventually) chronic and relapsing. Work from imaging studies has provided evidence that this transition involves reprogramming of neuronal circuits that process (1) reward and motivation; (2) memory, conditioning, and habituation; (3) executive function and inhibitory control; (4) interoception and self-awareness; and (5) stress reactivity. This transition is heavily influenced by genetic, developmental, and environmental factors and their dynamic interactions, which will determine the course and severity of the addiction.
Schematic drawing describing the sequential and cumulative effects of neuroadaptive changes hypothesized to contribute to the neuroplasticity that promotes compulsive drug-seeking. An early neuroadaptation, common to all drugs of abuse and observed after a single injection of cocaine, is increased excitability of the mesolimbic dopamine system reflected in long-term potentiation dependent on changes in glutamate activity. Subsequently, the activation of dopamine contributes to increased excitability of the ventral striatum with decreased glutamatergic activity during withdrawal and increased glutamatergic activity during drug-primed and cue-induced drug-seeking. The engagement of ventral striatal-pallidal-thalamic loops is hypothesized to translate to the dorsal striatum to contribute to engagement of habits and automaticity that resemble compulsive-like behavior. As compulsivity evolves into full-blown addiction, loss of function occurs in the frontal cortex systems that control executive function, contributing to poor decision-making and gain of function in the brain stress systems but contributing to incentive salience for drugs over natural reinforcers.
One major hypothesis guiding the neuroplasticity associated with addiction is focused on the mesolimbic dopamine system. The hypothesis is that drugs of abuse, particularly cocaine and amphetamine, increase dopamine release in a more prolonged and unregulated manner than natural stimuli, resulting in changes in synaptic plasticity both within the dopamine system and in dopamine-receptive neurons (Wolf, 2002). These changes ultimately usurp normal learning mechanisms to shift neurocircuitry to associations or a form of habit-learning that persists in the face of significant adverse consequences (a component of compulsivity; Everitt and Wolf, 2002; Hyman et al, 2006).
Another plasticity associated with behavioral sensitization is a persistent potentiation of nucleus accumbens excitatory synapses that is observed after repeated drug exposure followed by an extended drug-free period (Kourrich et al, 2007). Repeated cocaine administration increases glutamate neurotransmission only in rats that showed behavioral sensitization (Pierce et al, 1996). In addition, cocaine-sensitized mice showed an enhancement of LTP in nucleus accumbens slices during withdrawal, presumably reflecting increased activity of glutamatergic activity (Yao et al, 2004). An increased surface-to-intracellular ratio of glutamate-1 receptors (GluR1) has been observed 21 days after the last injection of cocaine, suggesting a slowly developing redistribution of AMPA receptors to the surface of nucleus accumbens neurons, particularly in those lacking GluR2 (Boudreau and Wolf, 2005; Conrad et al, 2008). The increases in cell-surface AMPA receptors depends on activation of dopamine D1 receptors and subsequent protein kinase A signaling (Chao et al, 2002). Functionally, overexpression of GluR1 in the nucleus accumbens facilitated extinction of cocaine-seeking responses (Sutton et al, 2003) and increased brain stimulation reward thresholds, reflecting decreased reward and possibly decreased motivated behavior (Todtenkopf et al, 2006). However, a single reexposure to cocaine during extended withdrawal produced synaptic depression, which may reflect the enhanced glutamate release during cocaine reexposure (Kourrich et al, 2007). Curiously, the increase in AMPA receptor expression observed with cocaine does not occur in amphetamine-sensitized rats, leading to the hypothesis of different functional effects of glutamate projections to the nucleus accumbens during cocaine vs amphetamine withdrawal (Nelson et al, 2009).
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