MDMA Users Research Articles

MDMA-related deaths: About 3 cases

MDMA is currently regaining popularity, especially in festive context. In this context, MDMA is usually consumed [1] with other psychostimulants, including cocaine, to increase level of vigilance, and/or [2] with cannabis and alcohol, in order to prolong the feeling of well-being, and/or with sedatives [3] , especially benzodiazepines, in order to manage side effect [1] . Currently, the degree of purity together with the MDMA content of Ectasy resold on the clandestine market increases [2] . Although fatalities stills considered rare [1] , the authors report three cases of death related to massive MDMA uptake in the south of France during the summer of 2018. Case 1: 29-year-old man found dead in his swimming pool after a party; the initial diagnosis was drowning. Cases 2 and 3: a 17-year-old man (case 2) and his girlfriend (case 3), aged 18, are found dead in their studio by the young man's parents, last contact dated from the night before. Autopsies, performed the day after the discovery in all three cases, showed only diffuse polyvisceral congestion, and no sign of drowning in case 1. For cases 1 and 2, usual toxicological samples, including fluorinated peripheral blood were send to the laboratory (for case 1, a pool water sample was taken). In case 3, analyzes were performed in urine and lung exsudate as no blood sample was available. Screenings (including NPS) were performed using LC-HRMS. Alcohols were analyzed by HS-GC-FID, illicit drugs by GC-MS and LC-MS/MS. For the case 1, strontium was measured in blood and pool water sample using ICP-MS. Analyzes show the following results ( Table 1 ). In all three cases, death was attributed to MDMA (the drowning diagnosis was ruled out in case 1). The blood levels found in MDMA users after usual single oral dose (125 mg) are generally between 20 and 250 μg/L. Concentrations in MDMA-related deaths range from 478 to 53,900 μg/L for MDMA alone and from 40 to 41,000 μg/L in cases of polydrug use [3] . In the context of a recent upsurge in MDMA consumption, three cases confirm that health monitoring stills necessary to promote information, prevention, risk reduction and learning of the effects management for potential users and health professionals.

Correspondence between Oral Fluid Drug Test Results and Self-Reported Illicit Drug Use among Music Festival Attendees

Background: Use of illicit substances is often under-reported. Testing positive in oral fluid provides an objective confirmation of recent intake. Objectives: To examine the agreement between oral fluid test results and self-reported substance use among music festival attendees, and factors associated with reporting past 48 h drug use among users identified by drug testing. Methods: One thousand three hundred nine participants were recruited from six music festivals in Norway (June–August 2016). They completed a questionnaire and provided oral fluid samples analyzed for amphetamines, MDMA, tetrahydrocannabinol (cannabis), and cocaine. Additionally, their blood alcohol levels were measured. Results: Overall, 5.5% reported use of amphetamines, cannabis, cocaine, and/or MDMA during past 48 h in the questionnaire, whereas 10.8% tested positive in oral fluid. Only 16.7% of identified cocaine users and 31.1% of identified MDMA users reported past 48 h cocaine or MDMA use, respectively. Higher proportions of identified cannabis and amphetamine users reported past 48 h use (53.8% and 55.6%, respectively). Multivariable logistic regression analysis showed that among participants who tested positive, those reporting weekly illicit substance use (Adjusted Odds Ratio [AOR] 30.6; 95% Confidence Interval [CI] 6.3–147.9), and using such substances when younger than 18 years (AOR 5.0; 95% CI 1.9–13.4) were more likely to report past 48 h use. Conclusions/Importance: Oral fluid testing appears to be an important tool when studying illicit substance use among music festival attendees, as significant under-reporting was observed. Among those testing positive, regular, and experienced users were more likely to report recent use, compared to less regular and experienced users.

Comparing Mental Health across Distinct Groups of Users of Psychedelics, MDMA, Psychostimulants, and Cannabis

ABSTRACTDifferences in mental health (MH) of users of distinct psychoactive substances have been shown. Both substance use (SU) and MH in users are influenced by stressful life events. This study compared MH parameters in distinct groups of substance users and evaluated the impact of stress factors on these outcomes. Data stem from the longitudinal Swiss Cohort Study on Substance Use Risk Factors (C-SURF) involving 4,475 young adult men. Distinct groups were created for the past 12 months’ use of psychedelics, MDMA, psychostimulants, and cannabis. MH measurements (depressive symptoms, overall MH, perceived stress, life satisfaction) were used as outcome variables, while indicators of past family functioning and stressful life events served as covariates. The MH of psychedelics users was not significantly different from the no-drug-use group, whereas poorer MH was found in the other SU groups. Observed effects were influenced by the tested stress factors. The absence of association between use of psychedelics and worsening of MH deserves further investigation in male and female samples. Stressful life experiences must be considered when assessing the MH of users of illicit substances. These findings suggest that some men practice SU as self-medication to cope with life adversity.

Greater empathy in MDMA users.

3,4-Methylenedioxymethamphetamine (MDMA) is widely known for its positive acute effects on social behaviour, such as increasing empathy, whilst also attenuating the negative impact of social exclusion. However there is a scarcity of research that investigates the long-term impact of recreational MDMA use on these fundamental social processes. Sixty-seven individuals were split into three groups based on their drug-use history: poly-drug MDMA users ( n = 25), poly-drug users who do not use MDMA ( n = 19), alcohol-only users ( n = 23), and were tested in an independent groups design. Participants completed both a self-report measure of emotional and cognitive empathy, along with the Multifaceted Empathy Task - a computerised assessment of empathy - and the Cyberball Game - a social exclusion paradigm. MDMA users had significantly greater subjective emotional empathy, and greater cognitive empathy on the computer task compared with the poly-drug users who do not use MDMA. There were no significant differences in subjective responses to social exclusion between the groups. Indices of MDMA use did not correlate with empathy. Long-term MDMA users in this sample exhibited normal psychosocial functioning in regard to empathy and social pain and had higher subjective emotional empathy. This conflicts with previous suggestions that moderate, long-term MDMA use may cause heightened social distress, and is further evidence of the safety of the drug, which is relevant to considerations of its therapeutic use.

MDMA Abuse in Relation to MicroRNA Variation in Human Brain Ventral Tegmental Area and Nucleus Accumbens.

3,4-methylenedioxymethamphetamine (MDMA) is one of the most widespread illegal drugs, that have been used particularly by young people in the 15-34 age group. MicroRNAs (miRNAs) are endogenously synthesized, non-coding, and small RNAs that post-transcriptionally regulate their target genes’ expression by inhibiting protein translation or degradation. miRNAs are increasingly implicated in drug-related gene expressions and functions. Notably, there are no reports of miRNA variation in the human brain in MDMA abuse. We here present a miRNA profiling study – the first such study, to the best of our knowledge – into the post-mortem human brains of a sample of people with MDMA abuse, along with non-drug dependent controls. The miRNA profiling of nucleus accumbens (NAc) and ventral tegmental areas (VTA) was performed by microarray analysis. Subsequently, two candidate miRNA putative biomarkers were selected according to significant regional differential expression (miR-1202 and miR-7975), using quantitative reverse-transcription PCR (qRT-PCR). We showed that the expression level of miR-7975 was significantly lower in the VTA regions of the 30 MDMA users, as compared with the 30 control samples. Another significantly deregulated miR-1202 was down-regulated in the NAc regions of 30 MDMA samples in comparison to the control samples. Alteration of these miRNAs can potentially serve as novel biomarkers for MDMA abuse, and warrant further research in independent and larger samples of patients.

Substance usage intention does not affect attentional bias: implications from Ecstasy/MDMA users and alcohol drinkers

BackgroundAn attentional bias towards substance-related stimuli has been demonstrated with alcohol drinkers and many other types of substance user. There is evidence to suggest that the strength of an attentional bias may vary as a result of context (or use intention), especially within Ecstasy/MDMA users. ObjectiveOur aim was to empirically investigate attentional biases by observing the affect that use intention plays in recreational MDMA users and compare the findings with that of alcohol users. MethodRegular alcohol drinkers were compared with MDMA users. Performance was assessed for each group separately using two versions of an eye-tracking attentional bias task with pairs of matched neutral, and alcohol or MDMA-related visual stimuli. Dwell time was recorded for alcohol or MDMA. Participants were tested twice, when intending and not intending to use MDMA or alcohol. Note, participants in the alcohol group did not complete any tasks which involved MDMA-related stimuli and vice versa. ResultsSignificant attentional biases were found with both MDMA and alcohol users for respective substance-related stimuli, but not control stimuli. Critically, use intention did not affect attentional biases. Attentional biases were demonstrated with both MDMA users and alcohol drinkers when usage was and was not intended. ConclusionsThese findings demonstrate the robust nature of attentional biases i.e. once an attentional bias has developed, it is not readily affected by intention.

Gene expression analysis indicates reduced memory and cognitive functions in the hippocampus and increase in synaptic reorganization in the frontal cortex 3\xa0weeks after MDMA administration in Dark Agouti rats

Background3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) is a widely used entactogenic drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions frequently described in otherwise healthy MDMA users. Meanwhile, in post-traumatic stress disorder (PTSD) patients seem to benefit from therapeutic application of the drug, where damage in hippocampal cue extinction may play a role. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the consequences of a single dose of MDMA (15 mg/kg) 3 weeks earlier.ResultsThe number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of ‘memory’ and ‘cognition’, ‘dendrite development’ and ‘regulation of synaptic plasticity’ gene sets in the hippocampus, parallel to the downregulation of CaMK II subunits, glutamate-, CB1 cannabinoid- and EphA4, EphA5, EphA6 receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while ‘dendrite development’, ‘regulation of synaptic plasticity’ and ‘positive regulation of synapse assembly’ gene sets were upregulated besides elevated levels of a CaMK II subunit and NMDA2B glutamate receptor. Changes in the dorsal raphe region were mild and in most cases not significant.ConclusionThe present data raise the possibility of new synapse formation / synaptic reorganization in the frontal cortex 3 weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is proposed by downregulations of members in long-term potentiation pathway and synaptic plasticity emphasizing the particular vulnerability of this brain region and proposing a mechanism responsible for cognitive problems in healthy individuals. At the same time, these results underpin benefits of MDMA in PTSD, where the drug may help memory extinction.

MDMA (ecstasy/molly) use among African Americans: The perceived influence of hip-hop/rap music

ABSTRACTOver the past two decades, the demographic profile of MDMA (ecstasy/molly) users has changed. In particular, African American MDMA use has risen in some cities. One explanation of this new trend is the drug’s recent popularity (as molly) in hip-hop/rap (HHR) music. Several top rappers endorse the drug as a way to have fun or get women “loose.” There are currently no studies, however, that investigate the extent to which African American MDMA users listen to HHR music or the influence that these pro-MDMA messages have on their use of the drug. To address this gap, the current study used survey data to (a) identify the extent to which HHR music is listened to by African American MDMA users and (b) assess the perceived influence of HHR music on their decision to begin using. Qualitative interview data are also presented to contextualize the influence of these messages on their use of MDMA. The findings of this study suggest that African American MDMA users are high consumers of HHR music and that pro-MDMA messages in HHR music are influencing their expectations of the drug and their decision to initiate use. These findings add to the limited amount of research on African American MDMA use and have the potential to inform future interventions.

Medical Emergencies Related to Ethanol and Illicit Drugs at an Annual, Nocturnal, Indoor, Electronic Dance Music Event.

Statistical data on the medical problems encountered during two editions of an indoor electronic dance event with around 30,000 attendants were retrieved from the Belgian Red Cross (Mechelen, Belgium) database. Data on drug use were prospectively collected from the patient (or a bystander), the clinical presentation, and/or toxicological screening. In the on-site medical station, 487 patients were treated (265 in 2013 and 222 in 2014). The most frequent reasons were trauma (n=171), headache (n=36), gastro-intestinal problems (n=44), and intoxication (n=160). Sixty-nine patients were transferred to a hospital, including 53 with severe drug-related symptoms. Analysis of blood samples from 106 intoxicated patients detected ethanol in 91.5%, 3,4-methylenedioxymethamphetamine (MDMA) in 34.0%, cannabis in 30.2%, cocaine in 7.5%, amphetamine in 2.8%, and gamma-hydroxybutyric acid (GHB) in 0.9% of patients (alone or in combination). In only six of the MDMA-positive cases, MDMA was the sole substance found. In 2014, the neuroleptic drug clozapine was found in three cases and ketamine in one. Additional analyses for NPS were performed in 20 cases. Only in one agitated patient, the psychedelic phenethylamines 25B-NBOMe and 25C-NBOMe were found. At this particular event, recreational drug abuse necessitated on-site medical treatment in one out of 350 attendants and a hospital transfer in one out of 1,000. Ethanol remains the most frequently abused (legal) drug, yet classical illicit recreational drugs are also frequently (co-) ingested. The most worrying observation was high-risk poly-drug use, especially among MDMA users. Regarding NPS, the number of cases was low and the clinical presentations were rather mild. It should be stressed that these observations only apply to this particular event and cannot be generalized to other EDM events. Calle P , Sundahl N , Maudens K , Wille SMR , Van Sassenbroeck D , De Graeve K , Gogaert S , De Paepe P , Devriese D , Arno G , Blanckaert P . Medical emergencies related to ethanol and illicit drugs at an annual, nocturnal, indoor, electronic dance music event. Prehosp Disaster Med. 2018;33(1):71-76.

Nonmedical prescription drug use among African Americans who use MDMA (ecstasy/molly): Implications for risk reduction

Recent data suggest that both nonmedical prescription drug and MDMA (ecstasy/molly) use have risen among African Americans. However, studies investigating these two forms of drug use among African Americans are rare. As a result, very little is known about African-American MDMA users and their nonmedical use of prescription medications. The primary goal of this study, therefore, was to describe patterns of nonmedical prescription drug use among African Americans who use MDMA. We also assessed alcohol and illicit drug use among the sample. Surveys (n=100) and in-depth interviews (n=15) were conducted with African-American young adults in Southwest Florida between August 2014 and November 2015. Survey results show that a significant proportion of the sample used MDMA in conjunction with prescription medications (benzodiazepines=59%; opioids=35%; stimulants=13%). Qualitative findings suggest that benzodiazepine medications were used to alleviate MDMA comedown symptoms, opioids were used to achieve a different quality high, and stimulants were used to provide added energy throughout the night. These results suggest that treatment practitioners and harm reduction professionals should pay particular attention to informing users of the potential hazards of combining MDMA with prescription medications. Although additional research is clearly needed, these findings are an important first step towards understanding both nonmedical prescription drug and MDMA use among African Americans, and could be used to tailor treatment and risk reduction interventions to this population.

MDMA (Ecstasy/Molly) Use Among African Americans: Patterns of Initiation

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy/molly) use among African Americans has increased over the last two decades, yet there has been little examination into how African Americans initiate their use of the drug. This study aimed to fill this knowledge gap by exploring the initiation experiences of African Americans and their narrative accounts of the circumstances surrounding their MDMA onset. Audiotapes of in-depth interviews were transcribed, coded, and thematically analyzed. Analyses revealed the presence of initiation patterns that contrast somewhat with those found in other groups of MDMA users. This study adds to the limited research on African American MDMA use and sheds light on why some African Americans decide to start using the drug. The findings provide insights to prevention specialists, harm reduction workers, and treatment providers who work with African American drug users.

From ecstasy to MDMA: Recreational drug use, symbolic boundaries, and drug trends

BackgroundEcstasy pills with MDMA as the main ingredient were introduced in many European countries in the 1980s, and were often linked to the rave and club scenes. However, use gradually levelled off, in part as a response to increased concerns about possible mental health consequences and fatalities. Extensive use of MDMA now seems to be re-emerging in many countries. In this study, we investigated the cultural and social meaning associated with MDMA use in Oslo, Norway, with an emphasis on how users distinguish MDMA crystals and powder from “old ecstasy pills”. MethodsQualitative in-depth interviews (n=31, 61,3% males) were conducted with young adult party-goers and recreational MDMA/ecstasy users (20–34 years old, mean age 26.2 years). ResultsResearch participants emphasised three important perceived differences between the MDMA crystals and ecstasy pills: (i) The effects of MDMA were described as better than ecstasy; (ii) MDMA was regarded as a safer drug; (iii) Users of MDMA crystals were described as more distinct from and less anchored in out-of-fashion rave culture than those using ecstasy. These differences were an important part of the symbolic boundary work MDMA users engaged in when justifying their drug use. ConclusionMDMA has re-emerged as an important psychoactive substance in Oslo’s club scene. One important reason for this re-emergence seems to be its perceived differentiation from ecstasy pills, even though the active ingredient in both drugs is MDMA. This perceived distinction between MDMA and ecstasy reveals the importance of social and symbolic meanings in relation to psychoactive substance use. Insights from this study can be important in terms of understanding how trends in drug use develop and how certain drugs gain or lose popularity.

Discrete memory impairments in largely pure chronic users of MDMA

Chronic use of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulant-naïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (dprimary=.90, dpolydrug=1.21), followed by working memory (dprimary=.52, dpolydrug=.96), executive functions (dprimary=.46, dpolydrug=.86), and attention (dprimary=.23, dpolydrug=.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use.

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor.

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol), which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg), combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg). Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS) 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations). Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.

Additive Effects of Former Methylenedioxymethamphetamine and Cannabis Use on Subclinical Psychotic Symptoms.

Methylenedioxymethamphetamine (MDMA) is an amphetamine-derived psychostimulant, usually known as "ecstasy." The long-term neuropsychological effects of MDMA are examined in several studies with conflicting results. The most common findings reported are depression, anxiety, and memory and attention deficits. In addition to acute psychotic reactions observed after MDMA use, serotonergic and dopaminergic toxicities may increase the psychosis risk in the long-term. Cannabis usage among MDMA users is very high. The aim of this study was, therefore, to examine the additive effects of cannabis and MDMA on subclinical psychotic symptoms (SPS). Here, 131 healthy controls (hC), 54 former cannabis and MDMA users (C&M), and 46 former cannabis users (C) were evaluated for SPS. The definition of former user was based on the Munich Composite International Diagnostic Interview. The SPS scores were assessed by using the Schizotypal Personality Questionnaire (SPQ). The relationship between substance-free periods and total MDMA exposure with SPS was also examined. The C&M group had higher levels of SPS than both C and hC groups. This is true not only for the total SPQ scores but both positive and negative schizotypy scores as well as cognitive-perceptual, disorganized, and interpersonal schizotypy scores aligned hierarchically in the 3 study groups (C&M>C>hC). The total MDMA exposure was positively correlated and MDMA-free period was negatively correlated with the SPS score. We found that the former use of cannabis and MDMA is associated with marked elevation in SPS. Moreover, the exposure amount of MDMA and MDMA-free periods are important determinants of SPS. The longer the cannabis and ecstasy free periods, the larger is the waning of SPS.

Psychomotor Tremor and Proprioceptive Control Problems in Current and Former Stimulant Drug Users: An Accelerometer Study of Heavy Users of Amphetamine, MDMA, and Other Recreational Stimulants.

The recreational use of various stimulant drugs has been implicated in the development of movement disorders through dysregulation of the dopaminergic and serotoninergic neurotransmitter systems. The present study investigated psychomotor differences in current and former recreational stimulant drug users compared with nonusing controls. Sixty participants comprised 3 groups: 20 current stimulant drug users (CSUs; 11 men, aged 31.4 ± 9.1 years), 20 former stimulant drug users (FSUs; 5 men, aged 39.1 ± 8.5 years), and 20 nonuser controls (NUCs; 5 men, aged 35.7 ± 6.4 years). Psychomotor arm steadiness for each participant was assessed with a wrist-attached accelerometer during 5 arm positions with eyes open and then eyes closed. Arm-drop of arm position was indicated by the arm longitudinal rotation axis (ALoRA), and tremor was indicated by the overall vector of dynamic body acceleration (VeDBA). Overall, CSUs performed the most poorly on ALoRA (P < .05) and VeDBA indices (P < .05), and FSUs perform almost as poorly on VeDBA indices (P < .05) compared with NUCs. It was concluded that stimulant drug use, primarily MDMA and amphetamines, may result in acute stimulant-induced tremor as well as long-term proprioceptive deficits in terms of arm-droop.

Motivations for Using MDMA (Ecstasy/Molly) among African Americans: Implications for Prevention and Harm-Reduction Programs

ABSTRACTDespite the growing popularity of MDMA (ecstasy/molly) among African Americans, their motives for using the drug are still largely unknown. The purpose of this study was to identify and describe the most salient motivations for using MDMA among this understudied population. In-depth interviews (n = 15) were conducted with a sample of African American young adults in Southwest Florida between August 2014 and November 2015. The primary motivations for using MDMA included: (1) altering the effects of marijuana and alcohol; (2) lasting longer sexually; (3) enhancing sexual pleasure; and (4) facilitating “freaky” sexual experiences. This is the first study to directly examine MDMA motivations specifically among African American drug users, and findings shed light on why some African Americans use MDMA. A better understanding of why African Americans use this drug should help to inform prevention and harm-reduction efforts. Study findings show the need for health messages that include the potential consequences of mixing MDMA with other drugs, and engaging in high-risk sexual behaviors after taking MDMA. These data contrast with motivations (e.g., introspection, self-enlightenment, getting into the music) commonly reported among groups of largely White MDMA users, suggesting that interventions tailored specifically for African American users are needed.

Decision-making in chronic ecstasy users: a systematic review.

Different cognitive impairments have been reported as a result of long-term MDMA/ecstasy use. Increased impulsivity and altered decision-making have been shown to be associated with the development and maintenance of addictive disorders pointing toward the necessity to understand a potential impairment of decision-making due to MDMA use. Thus, assessing the long-term effects of MDMA is crucial in order to evaluate its controversially discussed therapeutic use. The aim of this systematic review was to summarize the scientific literature on potential effects of chronic MDMA use on higher order decision-making processes in humans. Therefore, a systematic search for controlled trials relevant to the topic has been performed. Only studies using specific tasks on decision-making were included that involved subjects in the drug-free interval with drug-naïve, and/or polydrug control groups. A total of 12 studies could be identified that met the inclusion criteria, all of which were cross-sectional studies. The findings on decision-making disturbances in MDMA users were heterogeneous. Seven studies reported increased risky decisions, whereas five studies did not find MDMA-specific influences on decision-making. Increased impulsivity was observed both in MDMA groups and in (poly)drug control groups in almost all studies. Thus, the current state of research does not allow for the conclusion that long-term use of MDMA affects decision-making behavior in general. More detailed specifications as well as further investigations of the relevant processes are needed. Significant tendencies toward risky decision-making among long-term MDMA use have been observed, but need to be confirmed by studies using a longitudinal design.

Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration.

Animal models of drug self-administration are currently the gold standard for making predictions regarding the relative likelihood that a recreational drug substance will lead to continued use and addiction. Such models have been found to have high predictive accuracy and discriminative validity for a number of drug classes including ethanol, nicotine, opioids, and psychostimulants such as cocaine and methamphetamine. Members of the entactogen class of psychostimulants (drugs that produce an "open mind state" including feelings of interpersonal closeness, intimacy and empathy) have been less frequently studied in self-administration models. The prototypical entactogen 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") supports self-administration but not with the same consistency nor with the same efficacy as structurally related drugs amphetamine or methamphetamine. Consistent with these observations, MDMA use is more episodic in the majority of those who use it frequently. Nevertheless, substantial numbers of MDMA users will meet the criteria for substance dependence at some point in their use history. This review examines the currently available evidence from rodent self-administration studies of MDMA and two of the new and emerging psychoactive substances (NPS) that produce entactogen type neuropharmacological responses - mephedrone (4-methylmethcathinone; 4MMC; "meow meow") and methylone (3,4-methylenedioxymethcathinone). Overall, the current evidence predicts that these NPS entactogens have enhanced abuse liability compared with MDMA.

Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study.

3,4-Methylenedioxymethamphetamine (MDMA) is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six subjects were assessed, at the second follow-up assessment: 31 of these were non-users, 55 moderate-users, and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory, and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns, and subjective well-being were assessed. The Repeated measures analysis of variance (rANOVA) revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, the groups differed in their use of concomitant use of illicit drugs. Therefore, performance differences between the groups cannot completely ascribed to the use of MDMA.