Aim: To explore the role of cannabis use for the availability of ecstasy as a potential pathway to subsequent first ecstasy use. Methods: Baseline and 4-year follow-up data from a prospective-longitudinal community study of originally 3021 adolescents and young adults aged 14–24 years at baseline were assessed using the standardized M-CIDI and DSM-IV criteria. Results: Baseline cannabis users reported at follow-up more frequent access to ecstasy than cannabis non-users. Higher cannabis use frequencies were associated with increased ecstasy availability reports. Logistic regression analyses revealed that cannabis use and availability of ecstasy at baseline are predictors for incident ecstasy use during the follow-up period. Testing simultaneously the impact of prior cannabis use and ecstasy availability including potential confounders, the association with cannabis use and later ecstasy use was confirmed (OR = 6.3; 95% CI = 3.6–10.9). However, the association with ecstasy availability was no longer significant (OR = 1.2; 95% CI = 0.3–3.9). Conclusions: Results suggest that cannabis use is a powerful risk factor for subsequent first onset of ecstasy use and this relation cannot be sufficiently explained by availability of ecstasy in the observation period.

Background: Post-traumatic stress disorder (PTSD) and substance use disorders (SUDs) often co-occur in adolescent patients. Previous research has shown that these patients differ from SUD patients without PTSD in terms of their substance use patterns. In this study, we aimed to test whether substance use in this population is related to an attempt to self-medicate PTSD-related symptoms. - Methods: German adolescent patients (aged 13–18 years) at an outpatient clinic for SUD treatment, n = 111 (43% female), completed a self-designed questionnaire on use motives, a measure of PTSD-related experiences, and underwent a standardized psychiatric interview including structured substance use questions. Participants were subsequently classified as ‘no traumatic experiences (‘noTEs’ but SUD), ‘traumatic experiences but no current PTSD diagnosis’ (‘TEs’ with SUD), and ‘PTSD’ with SUD. After establishing a self-designed motive measurement through exploratory and confirmatory factor analyses, we calculated non-parametric group differences and a mediation analysis in a linear regression framework. - Results: The past-year frequency of MDMA use was highest in the PTSD group and lowest in the noTE group (H (2) = 7.2, p = .027, η² = .058), but no differences were found for frequencies of tobacco, alcohol, cannabis, or stimulant use (all H ≤ 4.9, p ≥ .085, η² ≤ .033). While controlling for sex, the three groups showed a similar pattern (highest in the PTSD group and lowest in the noTE group) for coping scores (F (103) = 5.77, p = .004, η² = .101). Finally, mediation analyses revealed an indirect effect of coping score (b = 0.61, 95% CI [0.29, 1.58], p = .145) on the association between group membership and MDMA use frequency. - Conclusions: In adolescent SUD patients, we found an association of current PTSD and lifetime traumatic experiences with higher MDMA use that could be partially explained by substance use being motivated by an attempt to cope with mental health symptoms. This indicates a coping process involved specifically in MDMA use compared to the use of other psychoactive substances, possibly due to unique psychoactive effects of MDMA.

Objectives: Both substance use, on the one hand, and the first signs of psychosis, on the other, commonly begin in adolescence. Adolescents with substance use disorder (SUD) frequently show recreational use of cannabis and 3,4-methylenedioxymethamphetamine (MDMA). When attenuated psychotic symptoms (APS) occur during the course of SUD, they are commonly attributed to the cannabis use, neglecting the role of other substances abused, such as MDMA in the risk of psychosis. Methods: We analyzed retrospective self-reports on APS (Prodromal Questionnaire, PQ-16) and amount of cannabis and MDMA use in n = 46 adolescent psychiatry outpatients with SUD. N = 17 (35%) individuals reported MDMA consume additional to cannabis. Furthermore, we examined the associations of APS with cannabis and MDMA use in stepwise hierarchical regressions while controlling for trauma history, birth complications and gender. Results: APS were not related to cannabis (B = 0.04, p = 0.842), but to MDMA use (B = 4.88, p = 0.001) and trauma history (B = 0.72, p = 0.001). Gender (B = −0.22, p = 0.767) and birth complications (B = −0.68, p = 0.178) were not associated with APS. Discussion: Our results indicate that MDMA use additional to cannabis use is associated with APS among adolescent SUD patients. Contrary to our expectations, we did not see an association of cannabis use and APS. We speculate that cannabis increases the risk for psychosis after a longer period of use and in combination with other risk factors, such as trauma history. Clinicians should screen for APS among SUD patients using MDMA and cannabis in order to adapt treatment plans of SUDs. Future research should validate these findings in longitudinal studies including polysubstance use and trauma history.

A 3,4-metilenodioximetanfetamina (MDMA, ecstasy), derivada da anfetamina, é uma droga largamente utilizada para fins recreacionais devido à sensação de euforia, energia e desejo de socialização. Apesar de ter a reputação de ser uma droga segura, um número crescente de relatos clínicos e estudos experimentais indica que a MDMA pode produzir toxicidade no SNC, rim, fígado e coração. Embora esteja contida nos comprimidos de ecstasy como racemato (uma mistura de 50% de seus enantiômeros), sua biotransformação é enantioseletiva; em ratos, o enantiômero R é biotransformado mais rapidamente que o S. Como a biotransformação de MDMA é capaz de produzir metabólitos reativos, muito provavelmente, a forma R tenha um maior potencial para gerar ERO/ERN e dano oxidativo nos tecidos do que a forma S. Nos seres humanos ocorre o inverso. Portanto, o presente trabalho teve como objetivo avaliar a contribuição individual de cada enantiômero da MDMA isoladamente, tendo como referência a mistura racêmica, no estresse oxidativo hepático renal e estriatal de ratos. Ratos Wistar machos adultos (180-220g) foram divididos em quatro grupos: controle (salina), MDMA racêmico, R-MDMA e S-MDMA. (2 doses consecutivas de 10 mg/kg no intervalo de 24h, gavage). Parâmetros de estresse oxidativo serão utilizados como a medida da formação de malonaldeído, a determinação de níveis de glutationa reduzida e a atividade da glutationa-S-transferase. Os enantiômeros da MDMA racêmica foram separados por meio da cromatografia em fase líquida de alta eficiência em fase estacionária quiral. Os enantiômeros obtidos mostraram um alto grau de pureza e um bom rendimento. Nossos resultados mostraram que o conteúdo hepático de glutationa total dos ratos do grupo R,S-MDMA e do grupo R-MDMA, foi significativamente menor do que os do controle e os do S-MDMA, revelando que é o enantiômero R que contribui para a depleção de glutationa hepática induzida pela mistura racêmica. A alta reatividade do enantiômero R no fígado também pode ser constatada nos animais tratados apenas com R-MMDA, uma vez que houve uma produção significativamente aumentada de MDA, comparativamente aos outros grupos tratados e o controle. O conteúdo renal de glutationa total foi significantemente menor para todos os grupos tratados quando comparados com o controle. Com relação ao estriado, apenas os animais tratados com o isômero S isoladamente mostraram uma queda significativa da atividade da GST em comparação aos demais grupos tratados e controle. Tomando todos esses dados em conjunto, esse trabalho mostrou que os enantiômeros isolados da MDMA podem atuar de formas distintas no que se refere ao estado redox, principalmente no fígado, uma vez que o isômero R foi o que mais contribuiu para um dano oxidativo. / MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine derivate that is largely used for recreational purpose due to its feeling of euphoria, energy and the desire to socialize. Although MDMA has the reputation of being safe, a growing number of clinical reports and experimental studies indicate that MDMA can produce toxicity in the CNS, kidney, liver and heart.Although MDMA is present in ecstasy tablets as a racemate (a 50% mixture of its enantiomer) it has an enantioselective metabolism; in rats, the S-enantiomer is metabolized faster than the R-enantiomer and it is the more active pharmacological form. As the MDMA biotransformation can produce reactive metabolites, probably the R form has a greater potential to generate ROS / ERN and oxidative damage in tissues than the S. In humans, the opposite occurs. Therefore, this aim of the present study was to evaluate the individual contribution of single MDMA enantiomers, compared to racemic mixture in liver, kidney and striatal rats oxidative stress. Adult male Wistar rats (180- 220g) will be divided into four groups: control treatment (saline), racemic MDMA, R-MDMA and S-MDMA (two consecutive doses 24h apart with 10mg/kg, gavage). Oxidative stress status parameters will be used to measure malondialdehyde formation, the reduced glutathione levels determination and the glutathione-S-transferase activity. The enantiomers of racemic MDMA were separated by liquid chromatography high-efficiency chiral stationary phase. The enantiomers showed a high degree of purity and a good recovery. Our results showed that the total glutathione content in liver of rats in R,S-MDMA and R-MDMA group was significantly lower than the control and S-MDMA, revealing that the R-enantiomer that contributes to hepatic glutathione depletion induced by the racemic mixture. The high reactivity of the R enantiomer in the liver can also be observed in animals treated with R-MMDA, since there was a significantly increased production of MDA, compared with other treated and control groups. The total glutathione content in kidney was significantly lower for all treated groups compared with control. With respect to the striatum, only animals treated with the S isomer alone showed a significant decrease in GST activity compared to other treatment and control groups. Taking all these data together, this study shows that the isolated enantiomers of MDMA can act differently with regard to the redox state, mainly in the liver, since the R isomer was the largest contributor to oxidative damage.

Em todo o mundo é crescente o uso drogas de abuso sintéticas conhecidas com designer drugs. Os principais representantes desta classe são o Ecstasy ou 3,4-metilenodioximetanfetamina (MDMA) e o Eve ou 3,4-metilenodioxietilanfetamina (MDEA), substâncias com efeitos estimulantes e alucinógenos. No Brasil é crescente sua divulgação pela mídia e o uso recreacional tem sido constatado em vários pacientes que buscam tratamento nas clínicas para dependentes. O presente trabalho constitui validação de metodologia analítica para o diagnóstico laboratorial do uso de MDMA, MDEA e seu produto de biotransformação, o 3,4-metilenodioxianfetamina (MDA), em sangue total e urina, por cromatografia líquida de alta eficiência com detecção por fluorescência. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão, rendimento e capacidade de detectar os analitos mesmos quando presentes em baixas concentrações, o que permite sua aplicação na verificação da intoxicação aguda quanto no uso recreacional destas drogas de abuso. / There is a worldwide increase in the use of the synthetic drugs of abuse known as designer drugs. The main representatives of this class are Ecstasy or 3,4-methylenodioxymethamphetamine (MDMA) and Eve or 3,4- methylenodioxyethylamphetamine (MDEA), substances with stimulant and hallucinogenic effects. In Brazil media coverage of them is on the increase and their recreational is in evidence by the growing numbers of patients who seek treatment at drug treatment centers. This paper validates the analytical methodology for the laboratory diagnosis of the use of MDMA, MDEA and their product of biotransformation, 3,4-methylenodioxyamphetamine (MDA), in whole blood and urine by high performance liquid chromatography with fluorescence. The developed methods showed good linearity, precision, accuracy, yield and capacity to detect analytes even when present in low concentrations, which enables its application in cases high intoxication as well as in cases of the recreational use of these drugs of abuse.

Em todo o mundo é crescente o uso drogas de abuso sintéticas conhecidas com designer drugs. Os principais representantes desta classe são o Ecstasy ou 3,4-metilenodioximetanfetamina (MDMA) e o Eve ou 3,4-metilenodioxietilanfetamina (MDEA), substâncias com efeitos estimulantes e alucinógenos. No Brasil é crescente sua divulgação pela mídia e o uso recreacional tem sido constatado em vários pacientes que buscam tratamento nas clínicas para dependentes. O presente trabalho constitui validação de metodologia analítica para o diagnóstico laboratorial do uso de MDMA, MDEA e seu produto de biotransformação, o 3,4-metilenodioxianfetamina (MDA), em sangue total e urina, por cromatografia líquida de alta eficiência com detecção por fluorescência. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão, rendimento e capacidade de detectar os analitos mesmos quando presentes em baixas concentrações, o que permite sua aplicação na verificação da intoxicação aguda quanto no uso recreacional destas drogas de abuso. / There is a worldwide increase in the use of the synthetic drugs of abuse known as designer drugs. The main representatives of this class are Ecstasy or 3,4-methylenodioxymethamphetamine (MDMA) and Eve or 3,4- methylenodioxyethylamphetamine (MDEA), substances with stimulant and hallucinogenic effects. In Brazil media coverage of them is on the increase and their recreational is in evidence by the growing numbers of patients who seek treatment at drug treatment centers. This paper validates the analytical methodology for the laboratory diagnosis of the use of MDMA, MDEA and their product of biotransformation, 3,4-methylenodioxyamphetamine (MDA), in whole blood and urine by high performance liquid chromatography with fluorescence. The developed methods showed good linearity, precision, accuracy, yield and capacity to detect analytes even when present in low concentrations, which enables its application in cases high intoxication as well as in cases of the recreational use of these drugs of abuse.

A 3,4-metilenodioximetanfetamina (MDMA, ecstasy), derivada da anfetamina, é uma droga largamente utilizada para fins recreacionais devido à sensação de euforia, energia e desejo de socialização. Apesar de ter a reputação de ser uma droga segura, um número crescente de relatos clínicos e estudos experimentais indica que a MDMA pode produzir toxicidade no SNC, rim, fígado e coração. Embora esteja contida nos comprimidos de ecstasy como racemato (uma mistura de 50% de seus enantiômeros), sua biotransformação é enantioseletiva; em ratos, o enantiômero R é biotransformado mais rapidamente que o S. Como a biotransformação de MDMA é capaz de produzir metabólitos reativos, muito provavelmente, a forma R tenha um maior potencial para gerar ERO/ERN e dano oxidativo nos tecidos do que a forma S. Nos seres humanos ocorre o inverso. Portanto, o presente trabalho teve como objetivo avaliar a contribuição individual de cada enantiômero da MDMA isoladamente, tendo como referência a mistura racêmica, no estresse oxidativo hepático renal e estriatal de ratos. Ratos Wistar machos adultos (180-220g) foram divididos em quatro grupos: controle (salina), MDMA racêmico, R-MDMA e S-MDMA. (2 doses consecutivas de 10 mg/kg no intervalo de 24h, gavage). Parâmetros de estresse oxidativo serão utilizados como a medida da formação de malonaldeído, a determinação de níveis de glutationa reduzida e a atividade da glutationa-S-transferase. Os enantiômeros da MDMA racêmica foram separados por meio da cromatografia em fase líquida de alta eficiência em fase estacionária quiral. Os enantiômeros obtidos mostraram um alto grau de pureza e um bom rendimento. Nossos resultados mostraram que o conteúdo hepático de glutationa total dos ratos do grupo R,S-MDMA e do grupo R-MDMA, foi significativamente menor do que os do controle e os do S-MDMA, revelando que é o enantiômero R que contribui para a depleção de glutationa hepática induzida pela mistura racêmica. A alta reatividade do enantiômero R no fígado também pode ser constatada nos animais tratados apenas com R-MMDA, uma vez que houve uma produção significativamente aumentada de MDA, comparativamente aos outros grupos tratados e o controle. O conteúdo renal de glutationa total foi significantemente menor para todos os grupos tratados quando comparados com o controle. Com relação ao estriado, apenas os animais tratados com o isômero S isoladamente mostraram uma queda significativa da atividade da GST em comparação aos demais grupos tratados e controle. Tomando todos esses dados em conjunto, esse trabalho mostrou que os enantiômeros isolados da MDMA podem atuar de formas distintas no que se refere ao estado redox, principalmente no fígado, uma vez que o isômero R foi o que mais contribuiu para um dano oxidativo. / MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine derivate that is largely used for recreational purpose due to its feeling of euphoria, energy and the desire to socialize. Although MDMA has the reputation of being safe, a growing number of clinical reports and experimental studies indicate that MDMA can produce toxicity in the CNS, kidney, liver and heart.Although MDMA is present in ecstasy tablets as a racemate (a 50% mixture of its enantiomer) it has an enantioselective metabolism; in rats, the S-enantiomer is metabolized faster than the R-enantiomer and it is the more active pharmacological form. As the MDMA biotransformation can produce reactive metabolites, probably the R form has a greater potential to generate ROS / ERN and oxidative damage in tissues than the S. In humans, the opposite occurs. Therefore, this aim of the present study was to evaluate the individual contribution of single MDMA enantiomers, compared to racemic mixture in liver, kidney and striatal rats oxidative stress. Adult male Wistar rats (180- 220g) will be divided into four groups: control treatment (saline), racemic MDMA, R-MDMA and S-MDMA (two consecutive doses 24h apart with 10mg/kg, gavage). Oxidative stress status parameters will be used to measure malondialdehyde formation, the reduced glutathione levels determination and the glutathione-S-transferase activity. The enantiomers of racemic MDMA were separated by liquid chromatography high-efficiency chiral stationary phase. The enantiomers showed a high degree of purity and a good recovery. Our results showed that the total glutathione content in liver of rats in R,S-MDMA and R-MDMA group was significantly lower than the control and S-MDMA, revealing that the R-enantiomer that contributes to hepatic glutathione depletion induced by the racemic mixture. The high reactivity of the R enantiomer in the liver can also be observed in animals treated with R-MMDA, since there was a significantly increased production of MDA, compared with other treated and control groups. The total glutathione content in kidney was significantly lower for all treated groups compared with control. With respect to the striatum, only animals treated with the S isomer alone showed a significant decrease in GST activity compared to other treatment and control groups. Taking all these data together, this study shows that the isolated enantiomers of MDMA can act differently with regard to the redox state, mainly in the liver, since the R isomer was the largest contributor to oxidative damage.

Regular use of illegal drugs is suspected to cause cognitive impairments. Two substances have received heightened attention: 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’) and δ-9-tetrahydrocannabinol (THC or ‘cannabis’). Preclinical evidence, as well as human studies examining regular ecstasy consumers, indicated that ecstasy use may have negative effects on learning, verbal memory and complex attentional functions. Cannabis has also been linked to symptoms of inattention and deficits in learning and memory. Most of the published studies in this field of research recruited participants by means of newspaper advertisements or by using word-of-mouth strategies. Because participants were usually aware that their drug use was critical to the research design, this awareness may have caused selection bias or created expectation effects. Focussing on attention and memory, this study aimed to assess cognitive functioning in a community-based representative sample that was derived from a large-scale epidemiological study. Available data concerning drug use history allowed sampling of subjects with varying degrees of lifetime drug experiences. Cognitive functioning was examined in 284 young participants, between 22 and 34 years. In general, their lifetime drug experience was moderate. Participants completed a neuropsychological test battery, including measures for verbal learning, memory and various attentional functions. Linear regression analysis was performed to investigate the relationship between cognitive functioning and lifetime experience of drug use. Ecstasy and cannabis use were significantly related to poorer episodic memory function in a dose-related manner. For attentional measures, decrements of small effect sizes were found. Error measures in tonic and phasic alertness tasks, selective attention task and vigilance showed small but significant effects, suggesting a stronger tendency to experience lapses of attention. No indication for differences in reaction time was found. The results are consistent with decrements of memory and attentional performance described in previous studies. These effects are relatively small; however, it must be kept in mind that this study focussed on assessing young adults with moderate drug use from a population-based study.

Objective: To determine incidence and patterns of natural course of ecstasy/stimulant/hallucinogen (ESH) use and disorders as well as cohort effects in a community sample of adolescents and young adults. Method: Cumulative incidence and patterns of ecstasy use and disorders were examined in a prospective longitudinal design (mean follow-up period=42 months) in a representative sample (N=2446) aged 14–24 years at the outset of the study. Patterns of DSM-IV defined ESH use, abuse and dependence were assessed with the Munich Composite International Diagnostic Interview (M-CIDI). Results: (1) Cumulative lifetime incidence for use of ESH at second follow-up: 9.1%, 1.0% for abuse, 0.6% for dependence; (2) men used and abused ESH more often than women; (3) the younger birth cohort (1977–81) tended to start earlier with substance (ab)use compared to the older birth cohort (1970–77); (4) use of ESH was associated with increasing rates of concomitant use of other licit and illicit drugs; (5) the majority of the lifetime ESH users without disorder had stopped to use these substances and not consumed them during the 12 months preceding the second follow-up; (6) those who had stopped to take ecstasy and related drugs at follow-up also took other illicit drugs less often than those who continued to consume ESH. Conclusions: Use of designer drugs is widespread in our sample, but the probability of developing use disorders is fairly low (1.6%). The majority of the ESH users stopped their use spontaneously in their twenties (80% of the prior users without disorder, 67% of the prior abusers), but 50% of those that once had fulfilled DSM-IV criteria of dependence continued to use these substances.

Regular use of illegal drugs is suspected to cause cognitive impairments. Two substances have received heightened attention: 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’) and δ-9-tetrahydrocannabinol (THC or ‘cannabis’). Preclinical evidence, as well as human studies examining regular ecstasy consumers, indicated that ecstasy use may have negative effects on learning, verbal memory and complex attentional functions. Cannabis has also been linked to symptoms of inattention and deficits in learning and memory. Most of the published studies in this field of research recruited participants by means of newspaper advertisements or by using word-of-mouth strategies. Because participants were usually aware that their drug use was critical to the research design, this awareness may have caused selection bias or created expectation effects. Focussing on attention and memory, this study aimed to assess cognitive functioning in a community-based representative sample that was derived from a large-scale epidemiological study. Available data concerning drug use history allowed sampling of subjects with varying degrees of lifetime drug experiences. Cognitive functioning was examined in 284 young participants, between 22 and 34 years. In general, their lifetime drug experience was moderate. Participants completed a neuropsychological test battery, including measures for verbal learning, memory and various attentional functions. Linear regression analysis was performed to investigate the relationship between cognitive functioning and lifetime experience of drug use. Ecstasy and cannabis use were significantly related to poorer episodic memory function in a dose-related manner. For attentional measures, decrements of small effect sizes were found. Error measures in tonic and phasic alertness tasks, selective attention task and vigilance showed small but significant effects, suggesting a stronger tendency to experience lapses of attention. No indication for differences in reaction time was found. The results are consistent with decrements of memory and attentional performance described in previous studies. These effects are relatively small; however, it must be kept in mind that this study focussed on assessing young adults with moderate drug use from a population-based study.