ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

Everyday and prospective memory deficits in ecstasy/polydrug users

The impact of ecstasy/polydrug use on real-world memory (i.e. everyday memory, cognitive failures and prospective memory [PM]) was investigated in a sample of 42 ecstasy/polydrug users and 31 non-ecstasy users. Laboratory-based PM tasks were administered along with self-reported measures of PM to test whether any ecstasy/polydrug-related impairment on the different aspects of PM was present. Self-reported measures of everyday memory and cognitive failures were also administered. Ecstasy/polydrug associated deficits were observed on both laboratory and self-reported measures of PM and everyday memory. The present study extends previous research by demonstrating that deficits in PM are real and cannot be simply attributed to self-misperceptions. The deficits observed reflect some general capacity underpinning both time- and event-based PM contexts and are not task specific. Among this group of ecstasy/polydrug users recreational use of cocaine was also prominently associated with PM deficits. Further research might explore the differential effects of individual illicit drugs on real-world memory

Reasoning deficits among illicit drug users are associated with aspects of cannabis use

Background. Deficits in deductive reasoning have been observed among ecstasy/polydrug users. The present study seeks to investigate dose-related effects of specific drugs and whether these vary with the cognitive demands of the task. Methods. One hundred and five participants (mean age 21.33, S.D. 3.14; 77 females, 28 males) attempted to generate solutions for eight one-model syllogisms and one syllogism for which there was no valid conclusion (NVC). All of the one model syllogisms generated at least one valid conclusion and six generated two valid conclusions. In these six cases one of the conclusions was classified as common and the other as non-common. Results. The number of valid common inferences was negatively associated with aspects of short term cannabis use and with measures of IQ. The outcomes observed were more than simple post intoxication effects since cannabis use in the 10 days immediately before testing was unrelated to reasoning performance. Following adjustment for multiple comparisons, the number of non-common valid inferences was not significantly associated with any of the drug use measures. Conclusions. Recent cannabis use appears to impair the processes associated with generating valid common inferences while not affecting the production of non-common inferences. It is possible, therefore, that the two types of inference may recruit different executive resources which may differ in their susceptibility to cannabis-related effects

Effects of ecstasy/polydrug use on memory for associative information

Rationale Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. Objectives A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. Methods After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. Results Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. Conclusions Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value

EFFECTS OF ACUTE AND CHRONIC TREATMENT WITH 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) AND THE CANNABINOID RECEPTOR AGONIST WIN55,212-2 ON BEHAVIOUR AND COGNITION IN RATS

MDMA (3,4-methylenedioxymetamphethamine, ecstasy ) is one of the most popular illicit recreational drugs among young adults. However, the underlying neurobiological mechanisms responsible for the physiological, behavioural and psychological effects, as well as the influence on cognitive functions such as memory and decision making are still not fully examined. Furthermore, if and to what extend this drug has neurotoxic properties is debated. Most ecstasy users are polydrug users, and the majority concomitantly consumes cannabis. Cannabis is the most frequently consumed illegal psychoactive drug world wide. While cannabis products are generally perceived as soft drugs and their potential medical usefulness is progressing, cognitive impairments and long-term alterations in the brain, especially following prolonged and heavy use in adolescence, are observed. This thesis investigates the influence of MDMA and the synthetic cannabinoid receptor agonist, WIN55,212-2 (WIN), on different forms of decision making, memory function, locomotor activity and physiological parameters such as body temperature and food intake. Within both an acute as well as chronic systemic administration schedule, effects of each substance alone as well as their combination is tested in order to mimic co-consumption of these drugs. Within chronic treatment, adult as well as pubertal rats and their respective brain myelination levels are examined to determine vulnerable periods of drug consumption or age-related differences

Effects of alcohol on subjective ratings of prospective and everyday memory deficits

Background: Research has shown that heavy alcohol use has a detrimental effect on retrospective memory. Less is known about the effect of alcohol on everyday memory. Methods: This study examined self-ratings of two aspects of memory performance: prospective memory (for example, forgetting to pass on a message) and everyday memory (measured by cognitive failures, such as telling someone a joke that you have told them before). To ensure anonymity and expand on the numbers of participants used in previous studies, data were collected by using the Internet. Data from 763 participants remained after data screening. Results: After controlling for other drug and strategy use, there was clear evidence that differential use of alcohol was associated with impairments in the long-term aspect of prospective memory and with an increased number of cognitive failures. Conclusions: These results support and extend the findings of previous research: our findings are consistent with the idea that heavy use of alcohol does have a significant and negative effect on everyday cognitive performance. Possible causes of these impairments are discussed

MDMA and brain activity during neurocognitive performance: An overview of neuroimaging studies with abstinent 'Ecstasy' users.

MDMA/Ecstasy has had a resurgence in popularity, with recent supplies comprising higher strength MDMA, potentially leading to increased drug-related harm. Neurocognitive problems have been widely reported in ecstasy users, equally some studies report null findings, and it remains unclear which factors underlie the development of neurocognitive impairments. This review covers the empirical research into brain activity during neurocognitive performance, using fMRI, fNIRS, and EEG. Our main conclusion is that chronic repeated use of recreational ecstasy can result in haemodynamic and electrophysiological changes that reflect recruitment of additional resources to perform cognitive tasks. Findings are consistent with serotonergic system changes, although whether this reflects neurotoxicity or neuroadaptation, cannot be answered from these data. There is a degree of heterogeneity in the methodologies and findings, limiting the strengths of current conclusions. Future research with functional neuroimaging paired with molecular imaging, genetics or pharmacological challenges of the serotonin system may help to decipher the link between serotonergic and cognitive changes in ecstasy users

Cortical oxygenation suggests increased effort during cognitive inhibition in ecstasy polydrug users

Background: It is understood that 3,4-methylenedioxymethamphetamine (ecstasy) causes serotonin dysfunction and deficits in executive functioning. When investigating executive function, functional neuroimaging allows the physiological changes underlying these deficits to be investigated. The present study investigated behavioural and brain indices of inhibition in ecstasy-polydrug users. Methods: Twenty ecstasy-polydrug users and 20 drug-naïve participants completed an inhibitory control task (Random Letter Generation (RLG)) while prefrontal haemodynamic response was assessed using functional near infrared spectroscopy (fNIRS). Results: There were no group differences on background measures including sleep quality and mood state. There were also no behavioural differences between the two groups. However, ecstasy-polydrug users displayed significant increases in oxygenated haemoglobin (oxy-Hb) from baseline compared to controls at several voxels relating to areas of the inferior right medial prefrontal cortex, as well the right and left dorsolateral prefrontal cortex. Regression analysis revealed that recency of ecstasy use was a significant predictor of oxy-Hb increase at two voxels over the right hemisphere after controlling for alcohol and cannabis use indices. Conclusion: Ecstasy-polydrug users show increased neuronal activation in the prefrontal cortex compared to non-users. This is taken to be compensatory activation/recruitment of additional resources to attain similar performance levels on the task, which may be reversible with prolonged abstinence

fNIRS suggests increased effort during executive access in ecstasy polydrug users

BACKGROUND: Ecstasy use is associated with cognitive impairment, believed to result from damage to 5-HT axons. Neuroimaging techniques to investigate executive dysfunction in ecstasy users provide a more sensitive measure of cognitive impairment than behavioural indicators. The present study assessed executive access to semantic memory in ecstasy polydrug users and non-users. METHODS: Twenty ecstasy polydrug users and 20 non-user controls completed an oral variant of the Chicago Word Fluency Test (CWFT), whilst the haemodynamic response to the task was measured using functional near-infrared spectroscopy (fNIRS). RESULTS: There were no between-group differences in many background measures including measures of sleep and mood state (anxiety, arousal, hedonic tone). No behavioural differences were observed on the CWFT. However, there were significant differences in oxy-Hb level change at several voxels relating to the left dorsolateral prefrontal cortex (DLPFC) and right medial prefrontal cortex (PFC) during the CWFT, indicating increased cognitive effort in ecstasy users relative to controls. Regression analyses showed that frequency of ecstasy use, total lifetime dose and amount used in the last 30 days was significant predictors of oxy-Hb increase at several voxels after controlling for alcohol and cannabis use indices. CONCLUSION: The results suggest that ecstasy users show increased activation in the PFC as a compensatory mechanism, to achieve equivalent performance to non-users. These findings are in agreement with much of the literature in the area which suggests that ecstasy may be a selective serotonin neurotoxin in humans

Recent Changes in Drug Abuse Scenario: The Novel Psychoactive Substances (NPS) Phenomenon

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