The limited impact that cocaine use patterns have on neurocognitive functioning in individuals with cocaine use disorder.

It is well-documented in the literature that cocaine use is associated with neurocognitive impairment. The manner in which patterns of cocaine use, such as years of use, recent use over the past month, and daily amount of cocaine use, moderate neurocognition has been studied in a relatively piecemeal manner. Hence, the purpose of the study was to evaluate whether cocaine use patterns modulate neurocognition in individuals with cocaine use disorder. Cocaine users who were cocaine-negative ( n=125) were divided into tertiles based on cocaine use patterns and the performances of the highest and lowest groups were compared on the following cognitive measures: Continuous Performance Task-II, n-back, and Hopkins Verbal Learning Task-Revised. Participants with cocaine use disorder who used for more years (25.2±0.6 versus 10.1±0.6 years; mean±standard error of the mean) and who had more recent cocaine use over the past month (26.3±0.5 versus 6.0±0.6 days) did not differ significantly on any of the neurocognitive variables when compared to those with use patterns of shorter duration and less frequency (all p's >0.05). Lastly, participants reporting the greatest amount daily cocaine use (1.8±0.0 g) demonstrated better performance on an auditory working memory task when compared to those with the lowest daily use (0.7±0.0 g; p=0.04). While one might expect that individuals who used greater amounts of cocaine over longer periods of time would demonstrate relatively poorer performance on measures of neurocognition, particularly in the initial phase of abstinence, our findings did not confirm this. While speculative, a potential explanation for these findings is that after an individual uses cocaine for a certain number of years, or uses a specific amount over time, then the deleterious effects of cocaine on neurocognition stabilizes, and increased duration of cocaine use does not further exacerbate those impairments.

The relationship between premorbid IQ and neurocognitive functioning in individuals with cocaine use disorders.

OBJECTIVE: To determine whether premorbid IQ mediates performance on neurocognitive tests in individuals diagnosed with cocaine use disorder (CUD). METHOD: Recently abstinent cocaine users (N = 113) completed measures sensitive to the effects of cocaine on cognition: Conners' Continuous Performance Task-II (CPT-II), n-back working memory test, and Hopkins Verbal Learning Task-Revised (HVLT-R). Premorbid IQ was calculated using the Oklahoma Premorbid Intelligence Estimate, which integrates scores from the Wechsler Adult Intelligence Scale-III and demographic variables. Participants were grouped according to their premorbid IQ using commonly accepted classifications of ability level (above average [>110], average [90-109], and below average [<90]) and comparisons in neurocognitive performance were performed using one-way analysis of variance. RESULTS: Significant differences were detected between groups on the HVLT-R including Trial 1 (p = .002), total word recall across the 3 list-learning trials (p < .001), and recall following a delay (p < .001). Significant differences were also detected on the N-back, including auditory and visual accuracy (p = .022 and p < .001, respectively) and mean and maximum block length (p < .001). Although significant differences were observed between the above average and average groups (mean effect size = .418 [Cohen's d]), the magnitude of group differences was greatest between the average and below average groups (mean effect size = .716). CONCLUSIONS: These results raise questions as to whether the neurocognitive impairment observed in individuals diagnosed with CUD predated the onset of cocaine use or whether the impairments were caused by cocaine use. Because these impairments are potential risk factors for poor treatment outcomes, it is important to consider the need to modify treatment programs to account for lower premorbid IQ. (PsycINFO Database Record

Short-term, low-dose varenicline administration enhances information processing speed in methamphetamine-dependent users.

UNLABELLED: Long-term, high-dose methamphetamine (METH) use is associated with decrements in neurocognition and, given the association between impaired neurocognition and poorer treatment outcomes in individuals dependent on alcohol and drugs, it is considered to be a neglected area of critical concern. The objective of this study was to determine whether varenicline, a partial agonist at α4ß2- and a full agonist at α7-nicotinic acetylcholine receptors, enhances attention/information processing speed, episodic memory, and working memory in non-treatment seeking METH-dependent participants. Twenty-six participants were randomly assigned to receive oral placebo or oral varenicline (titrated up to 1 mg) over 5 days during three separate inpatient phases, and 17 completed each inpatient phase. Participants were predominately male (71%) and Caucasian (71%). Varenicline significantly improved reaction time on the n-back for visual stimuli (F(1,47)=5.369, p=0.025, η2=0.103), and a trend was observed for improvement in reaction time for auditory stimuli (F(1,47)=3.141, p=0.083, η2=0.063). For those study participants whose reaction time was in the lower half of the distribution at baseline, the effect was even more pronounced for auditory (F(1,22)=5.287, p=0.031, η2=0.194) and visual (F(1,22)=11.981, p=0.002, η2=0.353) stimuli relative to placebo. In contrast, varenicline did not modulate mean or maximum span of working memory or performance on tests of episodic memory or attention (p's>0.05). Given the potential importance of this finding, it should be replicated in a larger sample over a longer treatment period with a higher dose of varenicline (2 mg). TRIAL REGISTRATION: clinicalTrials.gov Identifier NCT01571167.

Preliminary findings of the effects of rivastigmine, an acetylcholinesterase inhibitor, on working memory in cocaine-dependent volunteers.

Long-term cocaine use is a risk factor for the onset of neurocognitive impairment. This study sought to determine whether the cholinesterase inhibitor rivastigmine could improve neurocognitive performance in cocaine-dependent individuals. Cocaine-dependent individuals who were not seeking treatment at the time of enrollment in the study were randomly assigned to receive placebo (n=16), rivastigmine 3mg (n=13), or rivastigmine 6mg (n=12). The baseline neurocognitive assessment, which included measures of attention/information processing (as measured by the Continuous Performance Task-II (CPT-II)), verbal learning/episodic memory (as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R)), and working memory (as measured by the Dual N-Back Task), was conducted prior to the administration of study medication (Day 0). The follow-up assessment was conducted on Day 8 after the participants had received rivastigmine or placebo for 7days (Day 2-8). Rivastigmine administration significantly improved performance on one measure of working memory span (mean n-back span). This study provides additional data showing that cocaine-associated neurocognitive impairment, specifically working memory deficits, can be remediated, at least to some degree.

Acute modafinil exposure reduces daytime sleepiness in abstinent methamphetamine-dependent volunteers.

The purpose of this study was to evaluate the effects of acute, oral modafinil (200 mg) exposure on daytime sleepiness in methamphetamine (Meth)-dependent individuals. Eighteen Meth-dependent subjects were enrolled in a 7-d inpatient study and were administered placebo or modafinil on day 6 and the counter-condition on day 7 (randomized) of the protocol. Subjects completed several subjective daily assessments (such as the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Beck Depression Inventory and visual analogue scale) throughout the protocol as well as objective assessments on days 5-7, when the Multiple Sleep Latency Test was performed. The results of the current study suggest that short-term abstinence from Meth is associated with increased daytime sleepiness and that a single dose of 200 mg modafinil reduces daytime somnolence in this population. In addition, a positive correlation was found between subjective reporting of the likelihood of taking a nap and craving and desire for Meth, as well as the likelihood of using Meth and whether Meth would make the participant feel better. The results of this study should be considered when investigating candidate medications for Meth-dependence, especially in those individuals who attribute their Meth use to overcoming deficits resulting from sleep abnormalities.

Low dose, short-term rivastigmine administration does not affect neurocognition in methamphetamine dependent individuals.

Neurocognitive impairment is a well-documented consequence of methamphetamine addiction. Not surprising, methamphetamine-associated neurocognitive impairment has been identified as an important target of treatment. Thus, this study sought to determine whether rivastigmine, an acetylcholinesterase inhibitor and cognition enhancing agent, could improve neurocognitive performance in a sample of long-term, high-dose methamphetamine addicts who were not seeking treatment at the time of enrollment in the study. This double-blind, placebo-controlled study evaluated whether a daily dose 0, 3, or 6 mg of rivastigmine, administered over six consecutive days, would enhance performance on measures of attention/information processing speed, episodic memory, and executive/frontal lobe functioning relative to test performance at baseline. The results revealed that rivastigmine did not alter neurocognition in this cohort. There are a number of factors that may have mitigated the effects of rivastigmine in this particular study, including especially the short-term, low-dose treatment regimen utilized. The negative findings notwithstanding, the study serves as a springboard for future investigations that will examine whether other medications can alter neurocognition in methamphetamine dependent study participants.

The relationship between impulsivity and craving in cocaine- and methamphetamine-dependent volunteers.

Impulsivity and craving have been independently hypothesized to contribute to sustained drug use and relapse in addiction. The primary focus of this project was to determine the relationship between impulsivity and craving in 85 cocaine-dependent and 73 methamphetamine-dependent, non-treatment-seeking volunteers. Drug use was assessed with a 14-item, self-report drug and alcohol use questionnaire. Self report instruments utilized included the Barratt Impulsivity Scale (BIS) and the Visual Analog Scale (VAS), which probed "just before your last use of cocaine (for cocaine-dependent participants) or methamphetamine (for methamphetamine-dependent participants), how much craving did you experience?" The groups were similar with respect to recent use of cocaine or methamphetamine, alcohol, nicotine, and marijuana. Analysis of variance (ANOVA) did not reveal significant differences between cocaine and methamphetamine groups for total impulsivity or total craving. Simple linear regression revealed correlations between total impulsivity and total craving in cocaine (r(2)=0.05, p≤0.03) and methamphetamine users (r(2)=0.09, p≤0.008). Participants were separated into high impulsivity (HIBIS) or low impulsivity (LOBIS) subgroups using a median split. ANOVA revealed significantly higher craving in the HIBIS group versus the LOBIS group in methamphetamine users (p≤0.02), but not in cocaine users. For both cocaine and methamphetamine groups, level of impulsivity and craving were found to be related to some drug use variables including years of alcohol use, severity of withdrawal, and craving level following drug use. Taken together, this study shows a marginal relationship between impulsivity and craving, which may further the understanding of motivational factors contributing to ongoing drug use and addiction in psychostimulant users.

Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline.

Abstinent methamphetamine (Meth) dependent individuals demonstrate poorer performance on tests sensitive to attention/information processing speed, learning and memory, and working memory when compared to non-Meth dependent individuals. The poorer performance on these tests may contribute to the morbidity associated with Meth-dependence. In light of this, we sought to determine the effects of acute, low-dose Meth administration on attention, working memory, and verbal learning and memory in 19 non-treatment seeking, Meth-dependent individuals. Participants were predominantly male (89%), Caucasian (63%), and cigarette smokers (63%). Following a four day, drug-free washout period, participants were given a single-blind intravenous infusion of saline, followed the next day by 30 mg of Meth. A battery of neurocognitive tasks was administered before and after each infusion, and performance on measures of accuracy and reaction time were compared between conditions. While acute Meth exposure did not affect test performance for the entire sample, participants who demonstrated relatively poor performance on these tests at baseline, identified using a median split on each test, showed significant improvement on measures of attention/information processing speed and working memory when administered Meth. Improved performance was seen on the following measures of working memory: choice reaction time task (p≤0.04), a 1-back task (p≤0.01), and a 2-back task (p≤0.04). In addition, those participants demonstrating high neurocognitive performance at baseline experienced similar or decreased performance following Meth exposure. These findings suggest that acute administration of Meth may temporarily improve Meth-associated neurocognitive performance in those individuals experiencing lower cognitive performance at baseline. As a result, stimulants may serve as a successful treatment for improving cognitive functioning in those Meth-dependent individuals experiencing neurocognitive impairment.

Relationship between gender and psychotic symptoms in cocaine-dependent and methamphetamine-dependent participants.

BACKGROUND: It has been well documented that cocaine and methamphetamine use can lead to the onset of psychotic symptoms similar to schizophrenia. However, the research and literature on gender differences and stimulant-induced psychosis have been mixed. OBJECTIVE: The primary aim of this study was to investigate gender differences in the reporting of psychotic symptoms in cocaine- versus methamphetamine-dependent individuals. METHODS: Participants were recruited from the Los Angeles, California, community via radio and newspaper advertisements. All met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for cocaine or methamphetamine dependence, and all reported either methamphetamine or cocaine as their primary drug of abuse. During a screening interview, participants answered questions from the Psychotic Symptom Assessment Scale, which characterizes various types of psychotic symptoms during drug use ("while high") or during periods of nonuse ("while abstinent"). RESULTS: Participants included 42 cocaine-dependent individuals (27 men, 15 women) and 43 methamphetamine-dependent individuals (25 men, 18 women). Among cocaine users, there were no significant differences between men and women with regard to ethnicity, years of use, route of administration, and amount used in the past week, though they differed significantly with regard to age (P = 0.029). In the "while abstinent" condition, women were significantly more likely than men to report experiencing auditory hallucinations (13% vs 0%, respectively; P = 0.050) and tactile hallucinations (20% vs 0%; P = 0.016), whereas men were more likely to report delusions of grandeur (48% vs 6%; P = 0.006). During the "while high" condition, women were significantly more likely than men to report delusions of grandeur (13% vs 0%, respectively; P = 0.050), tactile hallucinations (33% vs 0%; P = 0.001), and olfactory hallucinations (13% vs 0%; P = 0.050). Among methamphetamine users, there were no significant differences between men and women with regard to age, ethnicity, years of use, route of administration, or amount used in the past week. In the "while abstinent" condition, women were significantly more likely than men to report feeling that something was wrong with the way a part of their body looked (72% vs 32%, respectively; P = 0.009), olfactory hallucinations (39% vs 8%; P = 0.010) and dressing inappropriately (22% vs 0%; P = 0.010). During the "while high" condition, women were more likely than men to report delusions of grandeur (33% vs 16%, respectively; P = 0.030), paranoia (50% vs 16%; P = 0.017), and tactile hallucinations (61% vs 32%; P = 0.050). CONCLUSIONS: The findings of the present study revealed that cocaine- and methamphetamine-dependent women were more likely than their male counterparts to report experiencing various psychotic symptoms. This information may be useful for clinicians and mental health professionals, who should take these symptoms into account as potential barriers that may impede effective treatment.

Modafinil administration improves working memory in methamphetamine-dependent individuals who demonstrate baseline impairment.

Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects. This double-blind, placebo-controlled study evaluated whether a daily dose of 400 mg of modafinil, administered over three consecutive days, would enhance performance on a measure of working memory relative to test performance at baseline and following 3 days of placebo administration in 11 methamphetamine addicted, nontreatment-seeking volunteers. The results revealed that participants demonstrating relatively poor performance on the third day of a 3-day washout period (ie, at baseline), showed significant improvement on measures of working memory, but not on measures of episodic memory or information processing speed. In contrast, for participants demonstrating relatively high performance at baseline, modafinil administration did not affect test scores. The findings provide an initial indication that modafinil can reverse methamphetamine-associated impairments in working memory.

Influence of verbal recall of a recent stress experience on anxiety and desire for cocaine in non-treatment seeking, cocaine-addicted volunteers.

It has long been postulated that stress increases the risk of drug abuse and relapse. The principal goal of this project was to evaluate the effects of verbal recall of a recent stress experience (specifically meaningful to each individual) on physiological and subjective measures in cocaine-addicted participants. Subjects described a recent stressful non-drug-related experience and a neutral non-stressful experience, and then completed mood and drug effect questionnaires, while heart rate and blood pressure were recorded. Participants (N = 25) were predominantly African American and male. As a group, participants used cocaine for more than 15 years and approximately 18 of the last 30 days, and a majority reported use of nicotine and/or alcohol. All participants were evaluated during a time in which they tested positive for cocaine metabolite. On a scale of 1-10, participants reported their verbal recall of a recent stress event as highly stressful and their verbal recall of a recent neutral event as non-stressful (p < 0.0001). The self-reported vividness of this recall was high (>8 out of 10) for both the stress and neutral events. Heart rate and systolic and diastolic blood pressure did not differ after verbal recall of either stress or neutral events. Similarly, self-reported subjective effects (including ratings of anxiety and craving for cocaine) did not differ after verbal recall of either stress or neutral events. In summary, despite the fact that participants recounted highly stressful and vivid memories, this experience did not elicit significant changes in cardiovascular or subjective effects. These data suggest that simply recalling a stressful event may not be a sufficient enough stimulus to contribute to craving or relapse in cocaine-addicted individuals.

Quantitative EEG abnormalities are associated with memory impairment in recently abstinent methamphetamine-dependent individuals.

This study examined the association between brain electrical activity, measured using quantitative electroencephalography (QEEG), and performance on measures of episodic memory in a sample of nine methamphetamine-dependent individuals who were evaluated after 4 days of monitored abstinence and 10 non-drug-using comparison subjects. In methamphetamine users, but not in comparison subjects, increased theta power was correlated with poorer performance on the delayed recall subtests of the Rey Auditory Verbal Learning Test and the Rey-Osterrieth Complex Figure Test (p<0.05). There was no association between alpha, beta, and delta power and performance on the memory tests. These results complement previous findings by demonstrating that the electrophysiological abnormalities associated with methamphetamine dependence are likely to affect behavior in an observable and important manner (i.e., memory deficits) when users are not intoxicated.

Predicting adherence to treatment for methamphetamine dependence from neuropsychological and drug use variables.

Although some individuals who abuse methamphetamine have considerable cognitive deficits, no prior studies have examined whether neurocognitive functioning is associated with outcome of treatment for methamphetamine dependence. In an outpatient clinical trial of bupropion combined with cognitive behavioral therapy and contingency management (Shoptaw, S., Heinzerling, K.G., Rotheram-Fuller, E., Steward, T., Wang, J., Swanson, A.N., De La Garza, R., Newton, T., Ling, W., 2008. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence. Drug Alcohol Depend 96, 222-232.), 60 methamphetamine-dependent adults completed three tests of reaction time and working memory at baseline. Other variables that were collected at baseline included measures of drug use, mood/psychiatric functioning, employment, social context, legal status, and medical status. We evaluated the relative predictive value of all baseline measures for treatment outcome using Classification and Regression Trees (CART; Breiman, L., Friedman, J.H., Olshen, R.A., Stone, C.J., 1984. Classification and Regression Trees. Wadsworth, Belmont, CA.), a nonparametric statistical technique that produces easily interpretable decision rules for classifying subjects that are particularly useful in clinical settings. Outcome measures were whether or not a participant completed the trial and whether or not most urine tests showed abstinence from methamphetamine abuse. Urine-verified methamphetamine abuse at the beginning of the study was the strongest predictor of treatment outcome; two psychosocial measures (e.g., nicotine dependence and Global Assessment of Functioning) also offered some predictive value. A few reaction time and working memory variables were related to treatment outcome, but these cognitive measures did not significantly aid prediction after adjusting for methamphetamine usage at the beginning of the study. On the basis of these findings, we recommend that research groups seeking to identify new predictors of treatment outcome compare the predictors to methamphetamine usage variables to assure that unique predictive power is attained.

Theories of addiction: methamphetamine users' explanations for continuing drug use and relapse.

A variety of preclinical models have been constructed to emphasize unique aspects of addiction-like behavior. These include Negative Reinforcement ("Pain Avoidance"), Positive Reinforcement ("Pleasure Seeking"), Incentive Salience ("Craving"), Stimulus Response Learning ("Habits"), and Inhibitory Control Dysfunction ("Impulsivity"). We used a survey to better understand why methamphetamine-dependent research volunteers (N = 73) continue to use methamphetamine, or relapse to methamphetamine use after a period of cessation of use. All participants met DSM-IV criteria for methamphetamine abuse or dependence, and did not meet criteria for other current Axis I psychiatric disorders or dependence on other drugs of abuse, other than nicotine. The questionnaire consisted of a series of face-valid questions regarding drug use, which in this case referred to methamphetamine use. Examples of questions include: "Do you use drugs mostly to make bad feelings like boredom, loneliness, or apathy go away?", "Do you use drugs mostly because you want to get high?", "Do you use drugs mostly because of cravings?", "Do you find yourself getting ready to take drugs without thinking about it?", and "Do you impulsively take drugs?". The scale was anchored at 1 (not at all) and 7 (very much). For each question, the numbers of participants rating each question negatively (1 or 2), neither negatively or affirmatively (3-5), and affirmatively (6 or 7) were tabulated. The greatest number of respondents (56%) affirmed that they used drugs due to "pleasure seeking." The next highest categories selected were "impulsivity" (27%) and "habits"(25%). Surprisingly, many participants reported that "pain avoidance" (30%) and "craving" (30%) were not important for their drug use. Results from this study support the contention that methamphetamine users (and probably other drug users as well) are more heterogeneous than is often appreciated, and imply that treatment development might be more successful if treatments targeted subtypes of patients, though a range of limitations to the approach used are acknowledged.

Presence and persistence of psychotic symptoms in cocaine- versus methamphetamine-dependent participants.

The primary objective of this study was to compare and contrast psychotic symptoms reported by cocaine- and methamphetamine-dependent individuals. Participants included 27 cocaine-dependent and 25 methamphetamine-dependent males, as well as 15 cocaine-dependent and 18 methamphetamine-dependent females. After screening, participants were excluded if they met criteria for any Axis I diagnosis other than nicotine dependence, or methamphetamine or cocaine dependence (ie, participants had to use either methamphetamine or cocaine but were excluded if they met dependence criteria for both). The participants were administered the newly developed Psychotic Symptom Assessment Scale (PSAS), which assesses psychotic symptoms. A high proportion of both cocaine- and methamphetamine-dependent men and women reported delusions of paranoia and auditory hallucinations. However, during the abstinent and intoxicated conditions, methamphetamine-dependent men and women were more likely than cocaine-dependent men and women to report psychotic symptoms. Future studies will compare psychotic symptoms reported by non-dependent recreational stimulant users to stimulant-dependent individuals.

Pathological gamblers demonstrate frontal lobe impairment consistent with that of methamphetamine-dependent individuals.

Using tests that are frequently administered by neuropsychologists, the authors investigated whether pathological gambling is associated with frontal lobe abnormalities. The sample comprised 10 pathological gamblers, 25 methamphetamine-dependent subjects, and 19 matched comparison subjects. The pathological gamblers and methamphetamine-dependent subjects performed significantly less well than comparison subjects, and the gamblers' test scores were comparable to those of the methamphetamine-dependent participants. The overall magnitude of the effect size was large. These findings demonstrate that the severity of frontal lobe dysfunction in pathological gambling is similar to that observed in methamphetamine-dependent individuals on frequently used clinical measures.

A qualitative and quantitative review of cocaine-induced craving: the phenomenon of priming.

UNLABELLED: Drug-induced craving is thought to play an important role in relapse occasioned by a "slip", or an isolated use of a previously abused drug after a period of abstinence. Clinical experience suggests that acute exposure to cocaine elicits craving (hereafter referred to as "priming"); however, this has received surprisingly little attention in the clinical literature. AIMS: The intentions of this review are to provide a qualitative review of the literature as well as a more stringent quantitative review of the existence and presence of cocaine-induced priming effects. METHODS: In order to determine whether priming effects occur following cocaine administration, we conducted qualitative and quantitative reviews of studies in which participants received cocaine under experimentally controlled conditions in the laboratory. RESULTS: The results of the qualitative review were equivocal, while the quantitative review revealed that cocaine administration was associated with a significant increase in craving for cocaine, and the effect size of this relationship was large. CONCLUSION: A review of the individual studies revealed marked variability, suggesting that priming effects did not occur consistently and that there may be factors that mediate or moderate the intensity of the priming effects induced by cocaine. The implications of these findings are discussed.

MDMA use and neurocognition: a meta-analytic review.

RATIONALE: To determine the association between MDMA misuse and neurocognition using meta-analysis. OBJECTIVE: Separate analyses were conducted based on two sets of inclusion/exclusion criteria. A relatively stringent set required that the subjects be matched on important moderator variables, whereas the other did not. The study participants' performance in the following neurocognitive domains was reviewed: attention/concentration, verbal and nonverbal learning and memory, psychomotor speed and executive systems functioning. RESULTS: In the 11 studies meeting the relatively stringent inclusion/exclusion criteria for this review, MDMA use was associated with neurocognitive deficits in each domain. Similarly, in the 23 studies meeting the relatively lenient inclusion/exclusion criteria for this review, MDMA use was associated with neurocognitive deficits in each domain. Small to medium effect sizes were generally observed. A comparison of the effect sizes across the two sets of analyses did not reveal significant differences. CONCLUSIONS: The findings from this review reveal that MDMA use is associated with neurocognitive deficits. The implications of these findings are discussed.

Apathy predicts hedonic but not craving response to cocaine.

Cocaine-induced craving has been implicated in the maintenance of ongoing cocaine use and is presumed to be mediated by enhanced synaptic availability of monoamines, including dopamine. Apathy is a neuropsychiatric syndrome that is associated with hypodopaminergic functioning and is neurobiologically distinct from depression. Apathy has been observed to be prevalent during the initial phases of abstinence in cocaine-dependent individuals. In the current report, we sought to investigate the relationship between apathy, depression, and craving in response to an acute intravenous administration of cocaine. To this end, sixteen non-treatment seeking volunteers were evaluated. Following acute administration of cocaine (40 mg, IV), patients with low apathy scores exhibited increased craving, whereas patients with high apathy scores exhibited decreased craving. In addition, patients with high apathy scores exhibited increased ratings of the subjective measure of "High", suggesting that high apathy predicts a greater hedonic response in dependence. Self-reported ratings of depression did not account for the observed differences. The data reveal that cocaine-induced craving is not ubiquitous, and may not play a critical role in the maintenance of cocaine dependence. Overall, the findings suggest that apathy predicts hedonic but not craving response to cocaine.