Memory-related hippocampal dysfunction in poly-drug ecstasy (3,4-methylenedioxymethamphetamine) users

Rationale 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic in animal studies and its use has been associated with cognitive impairments in humans. Objective To study hippocampal activation during the retrieval from episodic memory in polyvalent users of ecstasy. Methods Twelve polyvalent ecstasy users and twelve matched controls were examined by means of functional magnetic resonance imaging (fMRI) while they retrieved face-profession associations from episodic memory. Results Ecstasy users had a normal structural MRI scan without focal brain lesions or anatomical abnormalities. They exhibited equal retrieval accuracy during memory retrieval to that of the matched controls. Yet, their retrieval-related activity was lower and more spatially restricted in the left anterior hippocampus than that of the controls. Conclusions These results provide evidence for abnormal hippocampal functioning in MDMA users even at the presence of normal memory performance. This finding may be linked to MDMA-induced neurotoxicity and suggests that diminished hippocampal activation during memory retrieval might be a more sensitive or earlier index of MDMA-related neurotoxicity than neuropsychological performance.     

Long-term neuropsychological effects of ecstasy in middle-aged ecstasy/polydrug users

Rationale  

Studies reporting ecstasy-induced serotonin-toxicity and (neuro)psychological dysfunctions have been conducted in young adults. Little is known about ecstasy effects later in life, when serotonin levels and cognition decrease as a consequence of normal ageing.     

Hearing loss in amphetamine users

Sensory perceptions are modified by amphetamines. Prolonged and heavy use can lead to neuronal damage, neurotransmitter depletion and receptor supersensitivity. Sensorineural deafness had been reported in chronic users of volatile inhalants, alcohol and heroin. There are no reports of hearing problems with amphetamines. Hearing loss was identified in seven amphetamine-dependent inpatients in the detox unit at Al Amal Hospital, Jeddah. Subjects were men aged 18 and over who met DSM IV criteria for substance dependence. The hearing loss was suspected on clinical grounds during the admission interview, and was quite noticeable. Both ears were similarly affected. The symptom mostly appeared three to eight hours after ingestion of the tablets, and did not develop every time the drug was used. Hearing was apparently recovered in every case within four to ten days of cessation of amphetamine use. During the hearing loss, sounds were perceived as less loud and less sharp compared to normal. These cases suggest that chronic amphetamine use may result in reversible hearing loss. The various mechanisms by which this might occur are discussed. The author concludes that these observations should be replicated with a large group of subjects and recommends further investigations to elucidate the nature and site of the damage.     

Impulsivity, inhibition and negative priming in ecstasy users

A modified Stroop color-word interference paradigm was used to investigate the effects of recreational ecstasy (MDMA) use on central executive inhibitory processes. Ecstasy users who also used cannabis were compared with non-users matched for cannabis consumption and with non-drug users on a Stroop task in which standard color-word interference trials were interspersed with trials in which the target color was the same as the distractor word on the immediately preceding trial. Ecstasy's effects on standard inhibition (conscious suppression of a prepotent response pattern--responsible for Stroop interference) could thus be contrasted with its effect on the short-term, unconscious, inhibitory process responsible for suppression of the preceding distractor word (negative priming). Neither drug group differed from the non-drug users in level of Stroop interference but ecstasy users showed reduced negative priming compared to the cannabis users and non-drug users. The loss of inhibition in the ecstasy users was not related to impulsivity assessed by two standard scales since these were similar in both drug-user groups and raised relative to the non-drug users. It is argued that previous failures to demonstrate loss of inhibition could be partly due to the fact that standard executive function tests, such as the Stroop, are unable to differentiate between sub-types of inhibition, only some of which may be affected by ecstasy use.     

Attention and memory in illicit amphetamine users

The purpose of this study was to assess cognitive functioning in a group of illicit amphetamine users. A neuropsychological test battery (Wechsler Memory Scale-Revised (WMS-R) and the digit symbol, block design and vocabulary subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the National Adult Reading Test (NART)) was administered to 78 amphetamine users (mean age=22.5 years; 46 males, 33 females). Severity of amphetamine dependence was found to be associated with poorer performance on both memory and attention/concentration indices of the WMS-R. The relative contribution of amphetamine dependence, concurrent drug use and other drug related factors to neuropsychological functioning are discussed.     

Cognitive performance and serotonergic function in users of ecstasy

RATIONALE: (+/-) 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to cause long term damage to serotonergic cerebral neurons in animals. The neurotoxic effects in humans are less clear and little is known about the functional consequences, although some studies suggest memory impairment. Given the widespread use of MDMA, our lack of knowledge raises concerns. OBJECTIVE: We investigated, in humans, the relation between past use of ecstasy and cognitive performance as well as serotonergic function. Methods: Two groups of 21 males with moderate and heavy recreational use of MDMA, respectively, and a control group of 20 males without use of MDMA were compared. All were from the same subculture. Reaction time, direct recall, and recognition were assessed. Serotonergic function was measured by the neuro-endocrine response to a placebo-controlled, crossover challenge with dexfenfluramine. RESULTS: Ecstasy users showed a broad pattern of statistically significant, but clinically small, impairment of memory and prolonged reaction times. Heavy users were affected stronger than moderate users. Release of cortisol but not of prolactin after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls. Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy, psychosocial profiles and use of other drugs did not explain the differences found between the groups. CONCLUSIONS: These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function. These findings are compatible with neurotoxicity of ecstasy as shown in animals.     

Coping style and ecstasy use motives as predictors of current mood symptoms in ecstasy users

Background

Elevated depressive and anxiety symptoms during childhood and adolescence have been associated with greater risk of later ecstasy use. Ecstasy users have reported using ecstasy to reduce depression or worry, or to escape. While these findings suggest that some people use ecstasy as a form of self-medication, limited research has been conducted examining the relationship between affective symptoms, coping styles and drug use motives in ecstasy users. This cross-sectional study aimed to determine if coping style and/or ecstasy use motives are associated with current mood symptoms in ecstasy users.

Methods

A community sample (n = 184) of 18–35 year olds who had taken ecstasy at least once in the past 12 months completed self-report measures of depression, anxiety, ecstasy use motives and coping styles. Timeline followback methods were used to collect information on lifetime ecstasy, recent drug use and life stress. Trauma exposure was measured using the Composite International Diagnostic Interview—Trauma List.

Results

Coping motives for ecstasy use and an emotion-focused coping style were significantly associated with current depressive and anxiety symptoms. Emotion-focused coping mediated the relationship between a history of trauma and current anxiety symptoms and moderated the relationship between recent stressful life events and current depressive symptoms.

Conclusions

These findings highlight the importance of interventions targeting motives for ecstasy use, and providing coping skills training for managing stressful life events among people with co-occurring depressive/anxiety symptoms and ecstasy use.     

Substitution therapy for amphetamine users

At the commencement of the third millenium, the illicit use of amphetamines continues to be a growing problem in many countries around the world, yet treatment responses remain in need of further development. This is particularly true with regards to pharmacotherapy for amphetamine dependence. In this Harm Reduction Digest four authors who bring together considerable research and clinical experience in this area describe the nature of amphetamine-related problems and consider the role of amphetamine agonists in substitution therapy for amphetamine dependence. This is a timely paper which should be of interest to clinicians, researchers and regulators.     

Criminal involvement among young male ecstasy users

Ecstasy (MDMA) use increased rapidly in the U.S. between about 1995 and 2001. Most research on the drug focused on its psychopharmacological and public health contexts. Previous research on drugs-crime linkages suggests that there may have been a concommitant rise in ecstasy-related crimes. We explore this dimension here using data from 7794 arrested men, age 16 to 25, in the 2001 Arrestee Drug Abuse Monitoring (ADAM) sample and 9764 male respondents of similar age in the 2001 National Household Survey on Drug Abuse (NHSDA). Our results using a variety of bivariate and regression methods indicate that ecstasy use is less prevalent among young male arrestees than young men in general and that ecstasy use among arrestees is positively associated with various measures of drug market participation but negatively related to violent and property offenses. We recommend further investigation of ecstasy use in drug-oriented data sets and longitudinal studies to evaluate the link between ecstasy use and overall drug marketing.     

Self reported sleep quality and cognitive performance in ecstasy users

OBJECTIVES: Research suggests that ecstasy users exhibit psychobiological changes relative to nonusers such as altered sleep patterns and cognitive deficits. In turn, it has been suggested that sleep quality may be a mediator of such cognitive deficits in ecstasy users. The present study sought to investigate this proposed relationship. METHODS: Aspects of cognitive functioning in 104 ecstasy users and 103 nonusers obtained from our previous studies were reanalysed to explore the extent to which ecstasy-related group differences were attributable to differences in sleep quality. Cognitive function was assessed via the computation span test, consonant updating, paired associate learning, syllogistic reasoning and word fluency. Sleep quality was measured via the Epworth Sleepiness Scale (ESS), and the Karolinska Sleepiness Scale (KSS). RESULTS: Ecstasy users performed worse than nonusers on all cognitive measures. While no differences were observed on the ESS, ecstasy users reported greater tiredness at the beginning of testing than nonusers. When the sleep variables were included as covariates, the effects of ecstasy on all cognitive measures remained significant. CONCLUSIONS: The results of the present study suggest little evidence for the mediating effects of sleep on cognitive function in ecstasy users.     

Alcohol use and risk taking among regular ecstasy users

We examine alcohol use in conjunction with ecstasy use and risk-taking behaviors among regular ecstasy users in every capital city in Australia. Data on drug use and risks were collected in 2004 from a national sample of 852 regular ecstasy users (persons who had used ecstasy at least monthly in the preceding 6 months). Users were grouped according to their typical alcohol use when using ecstasy: no use, consumption of between one and five standard drinks, and consumption of more than five drinks ("binge" alcohol use). The sample was young, well educated, and mainly working or studying. Approximately two thirds (65%) of the regular ecstasy users reported drinking alcohol when taking ecstasy. Of these, 69% reported usually consuming more than five standard drinks. Those who did not drink alcohol were more disadvantaged, with greater levels of unemployment, less education, higher rates of drug user treatment, and prison history. They were also more likely than those who drank alcohol when using ecstasy to be drug injectors and to be hepatitis C positive. Excluding alcohol, drug use patterns were similar between groups, although the no alcohol group used cannabis and methamphetamine more frequently. Binge drinkers were more likely to report having had three or more sexual partners in the past 6 months and were less likely to report having safe sex with casual partners while under the influence of drugs. Despite some evidence that the no alcohol group were more entrenched drug users, those who typically drank alcohol when taking ecstasy were as likely to report risks and problems associated with their drug use. It appears that regular ecstasy users who binge drink are placing themselves at increased sexual risk when under the influence of drugs. Safe sex messages should address the sexual risk associated with substance use and should be tailored to reducing alcohol consumption, particularly targeting "heavy" alcohol users. The study's limitations are noted.     

Information processing speed in ecstasy (MDMA) users

Previous research draws parallels between ecstasy-related and age-related deficits in cognitive functioning. Age-related impairments in working memory have been attributed to a slow down in information processing speed. The present study compared 29 current ecstasy users, 10 previous users and 46 non-users on two tests measuring information processing speed and a computation span task measuring working memory. Results showed that ecstasy users performed worse than non-ecstasy users in the letter comparison task although the overall difference was not significant (p=0.089). Results from the pattern recognition task showed that current ecstasy users produced significantly more errors than the other two groups (p<0.01). When results were combined for both the letter and pattern tasks, once again current ecstasy users produced significantly more errors than non-ecstasy users (p<0.01). Working memory deficits obtained were statistically significant with both ecstasy using groups performing significantly worse than non-users on the computation span measure (p<0.01). Moreover, ANCOVA with measures of processing speed as covariates failed to eliminate the group difference in computation span (p<0.01). Therefore, it is likely the mechanism responsible for impairments in the computation span measure is not the same as that in elderly adults where processing speed generally removes most of the age-related variance. Also of relevance is the fact that the ecstasy users reported here had used a range of other drugs making it difficult to unambiguously attribute the results obtained to ecstasy use.     

Reasoning deficits in ecstasy (MDMA) polydrug users

RATIONALE/OBJECTIVES: Previous research has shown that ecstasy users are impaired in thinking and reasoning. The present study sought to explore the possibility that syllogistic reasoning errors in ecstasy users were due to an inability to construct a model of the premises due to working memory limitations. METHODS: Twenty-nine ecstasy users and 25 nonecstasy user controls completed abstract syllogistic reasoning problems varying in difficulty. Pairs of premises were provided, and participants were required to generate conclusions that followed necessarily from them. RESULTS: On the easier problems, both groups performed at well above chance although nonusers achieved significantly more correct responses. Consistent with existing research, on the more difficult problems, errors by nonusers were characterised by incorrect conclusions suggesting that while nonusers have the working memory capacity to construct a single model of the premises, this is not an exhaustive representation and usually results in an erroneous conclusion. On the other hand, for all problem types, ecstasy users, rather than produce incorrect responses, were more likely to fail to generate a conclusion. CONCLUSIONS: The present results are consistent with the possibility that ecstasy users with their reduced working memory capacity may experience difficulty in constructing even a single model of the premises. While this might be attributable to the effects of 3,4-methlylenedioxymethamphetamine neurotoxicity, many of the ecstasy users in the present study were polydrug users. Thus, the possibility that other drugs including cannabis and cocaine might contribute to the present results cannot be excluded.     

Sexual and injecting risk behaviours among regular ecstasy users

Substance users may be at a heightened risk for the transmission of HIV and other blood-borne viral infections (BBVI) through injecting drug use or risky sexual behaviours. The current study aimed to investigate the engagement in BBVI-risk behaviours among a sentinel group of regular ecstasy users in Australia, with a particular focus on sexual practices and describe the occurrence of BBVI testing among this group. Participants were regular ecstasy users recruited across Australia in 2007 who were administered a structured interview that contained questions regarding substance use, sexual behaviours and occurrence of BBVI testing. Results indicate high levels of unprotected sex in the past 6 months (77% reported inconsistent condom use with a regular partner; 54% with a casual partner). Half the sample reported never having an HIV test. Unprotected sex was associated with being heterosexual; despite this, heterosexuals were also less likely to report HIV testing status. These data suggest that targeted health promotion messages may be needed for this group of predominantly young, heterosexual substance users who may fall out of the reach of traditional messages.     

Harm reduction and decision making among recreational ecstasy users

Recent research indicates that 3,4-methylene-dioxymethamphetamine (MDMA), also known as ‘ecstasy’, is becoming increasingly popular as an illicit drug among young people. This study investigated risk and harm reduction practices among recreational ecstasy users. A semi-structured interview with 40 participants was designed to investigate how ecstasy users identify and manage the harms associated with their drug use, and the underlying decision-making process. Overall, the participants identified both positive and negative effects. The reported positive effects predominantly centred around enhanced psychological, physiological and social experiences. However, there were a number of factors that contributed to regulating ecstasy use. These included specific in-group and out-group practices executed within the peer group, preventative harm-reducing practices, shared decision making, and shared responsibility for harm prevention. Recommendations for promoting harm reduction strategies and suggestions for future research are discussed.     

Disrupted 'reflection' impulsivity in cannabis users but not current or former ecstasy users

Evidence for serotonin involvement in impulsivity has generated interest in the measurement of impulsivity in regular ecstasy users, who are thought to display serotonergic dysfunction. However, current findings are inconsistent. Here, we used a recently developed Information Sampling Test to measure 'reflection' impulsivity in 46 current ecstasy users, 14 subjects who used ecstasy in the past, 15 current cannabis users and 19 drug-na?ve controls. Despite elevated scores on the Impulsivity subscale of the Eysenck Impulsiveness-Venturesomeness-Empathy questionnaire, the current and previous ecstasy users did not differ significantly from the drug-naive controls on the Information Sampling Test. In contrast, the cannabis users sampled significantly less information on the task, and tolerated a lower level of certainty in their decision-making, in comparison to the drug-naive controls. The effect in cannabis users extends our earlier observations in amphetamine- and opiate-dependent individuals (Clark, et al., 2006, Biological Psychiatry 60: 515-522), and suggests that reduced reflection may be a common cognitive style across regular users of a variety of substances. However, the lack of effects in the two ecstasy groups suggests that the relationship between serotonin function, ecstasy use and impulsivity is more complex.