Equivalent effects of acute tryptophan depletion on REM sleep in ecstasy users and controls

Introduction  

This study sought to test the association between 3,4-methylenedioxymethamphetamine use, serotonergic function and sleep.     

Patterns of drug use and the influence of gender on self-reports of memory ability in ecstasy users: a web-based study

Research indicates that the use of recreational drugs, including MDMA ('ecstasy') can result in impairments in cognitive functioning. Recent evidence, based on accounts of 'on drug' effects and cortical binding ratios suggests that women may be more susceptible to the effects of MDMA; however, no research has explored whether there are differences in the long-term behavioural sequelae of the drug between men and women. In addition, little is known about the profile of functioning of the 'typical' user. The present investigation accessed a large sample of recreational drug users, using the Internet, to obtain self-reports of memory functioning with a view to exploring any differences in self-reported ability amongst male and female users, and the level of difficulty reported by the 'typical' ecstasy user. A web site (www.drugresearch.org.uk) was developed and used for data collection. Prospective memory ability was assessed using the Prospective Memory Questionnaire. Self-report of day-to-day memory performance was investigated using the Everyday Memory Questionnaire. The UEL Drug Questionnaire assessed the use of other substances. The number of mistakes made while completing the questionnaires was also taken as an objective measure of performance errors. Findings, based on datasets submitted from 763 respondents, indicate no differences in self-reports of functioning between male and female participants. An overall dissociation between the effects of cannabis and ecstasy on self-reported memory functioning and on the likelihood of making an error during the completion of the questionnaire was found. Typical ecstasy users were found to report significantly more difficulties in long-term prospective memory and to make more completion errors than users of other substances and drug naive controls. Whilst taking into account the fact that participants were recruited via the World Wide Web and that a number of stringent exclusion criteria were applied to the data, a number of conclusions can be drawn. Recreational drug users perceive their memory ability to be impaired compared to non-users. The type of memory difficulties reported varies depending upon the drug of choice. These difficulties are exacerbated in ecstasy users. Individuals reporting average levels of use of ecstasy are more likely to report memory problems than non-ecstasy drug users or drug free individuals. The deleterious effects of ecstasy are therefore not restricted to heavy or chronic users. No gender differences were detected, suggesting that there may be a dissociation between cognitive impairment and cortical binding worthy of further exploration.     

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.     

Neuropsychological function in ecstasy users: a study controlling for polydrug use

Rationale

A number of studies have compared ecstasy users to control groups on various measures of neuropsychological function in order to determine whether ecstasy use results in lasting cognitive deficits. However, few of those studies controlled adequately for non-ecstasy illicit drug use.

Objective

The aim of this study was to investigate neuropsychological function in chronic ecstasy users while controlling for polydrug use.

Methods

Neuropsychological function was assessed in four groups—30 current 3,4-methylenedioxymethamphetamine (MDMA) users with a little history of illicit drug use other than ecstasy and cannabis, 30 polydrug controls, 30 drug-naïve controls and 20 ex-MDMA users—using a battery of well-validated, computerized neuropsychological tests. The battery focused on memory, executive function, impulsivity and risk-taking.

Results

Few differences were apparent between the groups, and on no measure were the current MDMA users impaired significantly relative to the polydrug controls. However, within the current MDMA users, questionnaire-measured impulsivity correlated with performance on a number of tests—a relationship that was not apparent in the controls.

Conclusions

These data highlight the complexity in understanding the current ecstasy literature and suggest that some individuals may be particularly vulnerable to cognitive impairment following chronic use. Although no differences were identified between the current MDMA users and the controls, trait impulsiveness was significantly correlated with impairment on a number of neuropsychological outcome measures in the MDMA users, but not in the controls. These data suggest that impulsive individuals may be those most at risk for the development of cognitive impairment following chronic ecstasy use.

     

Cognitive performance in recreational ecstasy polydrug users: a two-year follow-up study

There is important preclinical evidence of long lasting neurotoxic and selective effects of ecstasy MDMA on serotonin systems in non-human primates. In humans long-term recreational use of ecstasy has been mainly associated with learning and memory impairments. The aim of the present study was to investigate the neuropsychological profile associated with ecstasy use within recreational polydrug users, and describe the cognitive changes related to maintained or variable ecstasy use along a two years period. We administered cognitive measures of attention, executive functions, memory and learning to three groups of participants: 37 current polydrug users with regular consumption of ecstasy and cannabis, 23 current cannabis users and 34 non-users free of illicit drugs. Four cognitive assessments were conducted during two years. At baseline, ecstasy polydrug users showed significantly poorer performance than cannabis users and non-drug using controls in a measure of semantic word fluency. When ecstasy users were classified according to lifetime use of ecstasy, the more severe users (more than 100 tablets) showed additional deficits on episodic memory. After two years ecstasy users showed persistent deficits on verbal fluency, working memory and processing speed. These findings should be interpreted with caution, since the possibility of premorbid group differences cannot be entirely excluded. Our findings support that ecstasy use, or ecstasy/cannabis synergic effects, are responsible for the sub-clinical deficits observed in ecstasy polydrug users, and provides additional evidence for long-term cognitive impairment owing to ecstasy consumption in the context of polydrug use.     

Current approaches to HCV infection in current and former injection drug users

Injection drug use (IDU) accounts for 75% of incident cases of hepatitis C virus (HCV) infection in the developed world. Of those infected with HCV, up to 80% will go on to develop chronic disease. Intervention with effective treatment in eligible subjects will limit the impact of the long-term consequences of infection. The use of combination therapy with pegylated interferon and ribavirin may lead to a cure in up to 80% of treated individuals who carry genotype 2 or 3 isolates. Such individuals account for up to 45% of certain cohorts, such as in the inner city of Vancouver. Historically, many IDUs have not received treatment for HCV infection even if it were medically indicated. Recent data (including our own) suggest that, in the right context, response rates similar to those reported in clinical trials of HCV therapy can be achieved in IDUs, even with ongoing drug use. This is all the more important given that prior infection may protect against re-infection even in the presence of ongoing risk behaviors for HCV transmission. The keys to a successful program appear to be appropriate patient selection as well as the delivery of care within an appropriate setting, preferably with a multidisciplinary team in a way that addresses the issue of addiction and other conditions simultaneously. The development of such programs may be quite complex, but the ultimate benefit (for the treated population and for society as a whole) is certainly worth the effort.     

Mood,cognition and serotonin transporter availability in current and former ecstasy (MDMA) users

Rationale. Chronic recreational ecstasy (MDMA) use has often been reported to be associated with psychopathology, memory impairments and serotonergic alterations. However, the findings have not been consistent. Objectives. To attempt to replicate these findings, to investigate whether such alterations would be reversible and whether they could be predicted by parameters of previous drug use. Methods. In a cross-sectional design, 30 current and 31 ex-ecstasy users with ecstasy abstinence of at least 5 months, and 29 polydrug and 30 drug-naive controls were compared on measures of psychopathology, cognitive performance and serotonin transporter availability. Results. The groups did not differ significantly in age, gender distribution, education level and premorbid intelligence. The ecstasy groups did not differ significantly from polydrug controls on most of the relevant parameters of concomitant illegal drug use. Reported drug use was confirmed by hair and urine analyses. All three groups of drug users exhibited significantly elevated psychopathology compared with drug-naive controls. Only ex-ecstasy users were significantly impaired on verbal recall. Current ecstasy users showed significantly reduced distribution volume ratios of serotonin transporter availability in the mesencephalon and caudate nucleus. Regression analyses indicated that psychopathology and serotonergic alterations were best predicted by the number of ecstasy tablets taken on a typical event. Conclusion. The results indicate that verbal memory impairments were possibly aggravated after prolonged ecstasy abstinence while there was tentative evidence of serotonergic recovery. On the other hand, self-reported elevated psychopathology appeared to be associated with polydrug use in general and not specifically with ecstasy use. Electronic Publication     

Contextual profiles of young adult ecstasy users: A multisite study

These analyses assess contextual profiles of 612 young adult ecstasy users, 18-30 years of age, from St. Louis (USA), Miami (USA) and Sydney (Australia). Bivariate analyses revealed different contextual factors influencing ecstasy use. Friends were the most common sources of ecstasy at all sites and most used with friends. St. Louis and Miami use mostly occurred in residences, whereas in Sydney use was mostly at clubs, bars or restaurants. Ecstasy consumption at public places and in cars, trains or ferries was significantly higher in Miami (89% and 77%) than in St. Louis (67% and 65%) and Sydney (67% and 61%). At all sites, simultaneous use of LSD/mushroom and nitrous oxide with ecstasy was common; concurrent amphetamines predominated in Sydney and heroin/opiates in St. Louis Contextual factors influencing ecstasy use among young adults vary by geographic region. Their inclusion may help tailor effective prevention programs to reduce or ameliorate ecstasy use.     

Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: the longitudinal perspective

Although 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a known serotonergic neurotoxin in different animal species, there is to date no conclusive evidence of its neurotoxicity in humans. MDMA use was associated with impairments of psychological well-being, verbal memory and altered serotonergic functioning in a number of cross-sectional studies. Due to inherent methodological limitations, such as the notorious polydrug use of ecstasy users and lack of control of possible pre-existing differences between ecstasy users and control participants, researchers have called for well-controlled, prospective longitudinal studies to shed more light on the issue of MDMA neurotoxicity to the human brain. This longitudinal study investigated whether mood, cognition and central serotonin transporters (SERT) would deteriorate with continued MDMA use and whether or not they would recover over increasing periods of MDMA abstinence. In a repeated-measures design, 11 current and ten ex-ecstasy users, and 11 polydrug (but not MDMA) and 15 drug-naive controls participated three times within approximately two years. Both ecstasy user groups reported a polydrug use pattern besides heavy ecstasy use. Subjective reports of ecstasy use or abstinence were verified by toxicological analyses. On each trial, the participants underwent a cognitive test battery and filled in the Symptom Check List. The availability of central SERT was assessed with positron emission tomography using the McN5652 ligand for all groups at t1, and only for the ecstasy user groups on follow-ups. The factor Group yielded significant results in the SCL-90 scales Global Severity Index, Anxiety, Obsessive/compulsive and Interpersonal sensitivity, with the ex-ecstasy users reporting the highest symptom scores. There were significant Group effects in all measures of verbal memory, with the lowest performance in the group of ex-ecstasy users. The repeated-measures analyses yielded no significant Group x Time interactions in any SCL-90 scales or measures of memory performance, with the exception of AVLT 1 immediate recall. Thus the ex-ecstasy users' psychopathological symptoms and memory performance failed to improve, and the current ecstasy users' failed to deteriorate, over time relative to the other groups. While there was a significant effect of Group in all brain regions examined (except the control region white matter), the current users' SERT availability seems to have recovered in the mesencephalon, as indicated by a significant Group x Time interaction. Reduced SERT availability might be a transient effect of heavy ecstasy use, since it partially recovered as the current users reduced their MDMA use. However, this measure may not necessarily be a valid indicator of the number or integrity of serotonergic neurons. Ex-ecstasy users' verbal memory showed no sign of improvement even after over 2.5 years of abstinence and thus may represent persistent functional consequences of MDMA neurotoxicity. However, alternative causes such as pre-existing group differences cannot be completely ruled out in spite of the longitudinal design.     

Incidence and patterns of polydrug use and craving for ecstasy in regular ecstasy users: an ecological momentary assessment study

BACKGROUND: Previous studies employing retrospective assessments methods found that regular ecstasy users frequently use alcohol, marihuana and other drugs in combination with ecstasy. METHODS: Twenty-two participants (13 males, 9 females) wore a wrist actigraph/data recorder to record real-time drug use and ecstasy craving for 6 weeks. Rates of alcohol and drug use on ecstasy use versus non-use nights, and before, during, and after ecstasy use were analyzed with generalized estimation equations (GEE). Craving was modeled with GEE and linear mixed models. RESULTS: Approximately 70% of ecstasy uses occurred on Friday or Saturday nights. No drug was significantly more likely to be used on ecstasy use nights than comparison Friday and Saturday nights. On nights ecstasy was used, in general across all drugs assessed, use was more likely before and during than after ecstasy intoxication, while alcohol use was also more likely before than during ecstasy intoxication. Though low overall, craving for ecstasy increased over 24 h before use and was higher on Friday nights of weeks ecstasy was used on weekends than weeks it was not used. CONCLUSIONS: Use of ecstasy on a particular night may not be associated with any greater likelihood of using any other intoxicating drug, and use of other drugs on nights involving ecstasy use may simply reflect a "natural history" of drug-use nights that begins with alcohol, progresses to more intoxicating drugs, and ends with little drug use. Confirmation of these findings awaits further advances in the application of ecological momentary assessment methodologies.     

Users' perceptions of the risks and effects of taking ecstasy (MDMA): a questionnaire study

This self-report questionnaire study examined ecstasy users' perceptions of the risks associated with their use of ecstasy, their precautions against such risks, and its perceived effects on their lives. Gender differences in these areas were also explored. The sample comprised 328 ecstasy users (139 female, 187 male, one transsexual) with a mean age of 22.5 years (SD = 4.9 years). Questionnaires were completed either in hard copy or through a website concerned with ecstasy use. The results showed that friends were the most common source of information about ecstasy for the sample overall, although females were more likely to utilize this source than males. None of the five categories of perceived risk (e.g. psychiatric, physical) showed a significant gender difference. Males were more likely to take rest breaks whilst females were more likely to limit consumption as a precaution against harm. Three factors emerged from a principal components analysis concerning perceived personal change since initiation of ecstasy use. Factor 1 (23.8% of the variance) concerned negative experiences (e.g. depression). Factor 2 (22.0% of the variance) concerned positive personal qualities (e.g. caring). Factor 3 (10.5% of the variance) concerned selective aspects of functioning (e.g. alertness). The pattern of Factor 1 and Factor 2 scores over time suggested that 6 years since initiation of ecstasy use might be a time when some long-term users may be open to reassess their use of the drug. Broader implications of the findings for health education initiatives aimed at ecstasy users are discussed.     

Neuroendocrine and subjective responses to pharmacological challenge with citalopram: a controlled study in male and female ecstasy/MDMA users

Despite evidence that +/-3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') causes persistent alterations to the serotonergic system of animals, evidence for long-term neurological effects of ecstasy/MDMA in humans remains equivocal. The current study assessed serotonin functioning of nine male and 11 female recreational ecstasy polydrug users by measuring neuroendocrine (prolactin, cortisol) responses to pharmacological challenge with the selective serotonin reuptake inhibitor citalopram, compared with nine male and five female cannabis polydrug users and 11 male and 11 female non-drug using controls. A single-blind, randomised, placebo-controlled design was used. Subjective responses, other substance use, mood, personality traits and demographic variables were measured to control for potentially confounding variables. There were no significant differences between ecstasy polydrug users, cannabis polydrug users and non-drug using controls in neuroendocrine or subjective responses to serotonergic challenge, and there were no sex by drug group interactions. There was no relationship between extent of ecstasy use and neuroendocrine functioning, alone or in combination with potential confounding variables. Subjective responses to the pharmacological challenge (nausea, tremor, dry mouth), novelty seeking and lifetime dose of alcohol were the only variables that contributed to one or more of the neuroendocrine outcome variables. These data do not support the premise that recreational ecstasy/MDMA use results in measurable impairment of serotonergic control of endocrine activity.     

Transition to and from injecting drug use among regular ecstasy users

There is a scant amount of research investigating injecting drug use among people not selected on the basis of their injecting behaviour, and less attention has been given to stimulant users who may have a different experience with injecting drug use than opioid users who are more commonly studied. The current study aimed to investigate initiation to, and transition from, injecting drug use among a sentinel sample of regular ecstasy users in Australia. Participants were regular ecstasy users recruited across Australia in 2007 who were administered a structured interview that contained questions regarding initiation to injecting, reasons for injecting cessation, and likelihood of future injecting. Among those with a history of injecting drug use, injecting first occurred at a similar age to that of first ecstasy use. The majority did not inject themselves at the first occasion, and two-fifths were under the influence of other drugs at the time. Two-fifths of injectors had not injected in the past 6 months, with many relating this to concerns surrounding stigma. Route of drug administration is clearly not static, and the findings from this study suggest that some who have ceased injecting may still be at risk for future injecting.     

Getting into ecstasy: comparing moderate and heavy young adult users

In this article, the authors examine factors associated with initial and present Ecstasy use among young adults. Face-to-face structured interviews were conducted in Atlanta, Georgia among 261 active Ecstasy users. The median age at which respondents first heard of Ecstasy was 16 years, whereas the median age of first Ecstasy use was 18 years. Initial Ecstasy use frequently involved polydrug use, including alcohol (50.4%). In terms of their current use, 47.5% of respondents were considered heavy Ecstasy users (using on 10 or more separate occasions in the last 90 days). White respondents, those who used more than one pill during their initial use, and those who used again within one month after their initial use were more likely to be current heavy Ecstasy users. Women, those who waited a longer time between initial and subsequent Ecstasy use, and those who considered themselves in the upper SES bracket were less likely to be current heavy Ecstasy users. A better understanding of initial and current Ecstasy use patterns, including polydrug use, is essential for effective prevention and intervention efforts.     

The attitudes of heroin users and matched non-users to drugs and drug users.

Compared with matched controls, heroin users were more tolerant of substance use and perceived themselves as slightly more unemployed, depressed, neat and aggressive. Both groups thought crack cocaine, heroin and alcohol dangerous. Heroin users were most in favour of cannabis, followed by controls who had used cannabis, with only controls who had never used cannabis being against it. It is concluded that the stereotype of a heroin user was not strongly believed by these heroin users or their peers.