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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. MDMA exerts its main effects via the serotonergic system and the serotonin transporter. The gene coding for this transporter determines the expression rate of the transporter. Mood was assessed by means of the Profile of Mood States. Findings showed that MDMA induced —independent of sex- a positive mood state, and as a side effect also increased two negative affect states, anxiety and confusion. Anxiety ratings were higher in the l -group and independent of treatment or sex. Depression ratings were lowered by MDMA in the female l -group. Findings indicate that the MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l -allele showing this beneficial effect. It exerts its main effects on the monoamines with most pronounced effects on the central nervous serotonin 5-HT system 1. MDMA has been shown to induce effects on mood, increasing in general positive e. Studies have demonstrated a role for the serotonin transporter in these effects since MDMA effects on mood and consciousness were counteracted by blocking of the 5-HTT 6. The serotonin transporter gene SLC6A4 encodes the serotonin transporter. The s-allele is associated with lower 5-HTT expression and function and higher levels of anxiety and negative mood in healthy individuals as well as smaller amygdala volumes and increased amygdala reactivity which has been shown to be inversely related to the amygdala volume 9 , 10 , 11 , During the last decade, the interest in using MDMA as an adjunct to psychotherapy in the treatment of psychiatric conditions such as post-traumatic stress disorder has grown. Preliminary data have also shown the efficacy of this treatment 13 , Of importance for these patient studies is that MDMA induces, next to elevated positive affect, also an increase in negative affect such as anxiety and confusion, in healthy volunteers 4. Since it previously has been shown that carriers of the s-allele show heightened fear and anxiety 15 it is of interest to investigate how s-allele carriers respond emotionally to a dose of MDMA compared to l-homozygotes. This knowledge could feed into potential tailored MDMA-assisted therapy, based on genetics. The aim of the present study was to investigate whether the MDMA-induced mood effects differ between ecstasy users who are s-carriers and those who are homozygous for the l-allele. It is hypothesized that ecstasy users carrying the slow working variants of the SERT genotype will acutely release less 5-HT via the SERT and consequently experience less pronounced mood effects immediately after use compared to homozygous l-allele carriers who are known to have a greater efficacy in transporting serotonin Since typical sample sizes of placebo-controlled MDMA studies, large enough to detect behavioral effects, are too small to detect effects at the genotype level, data from 4 placebo-controlled studies were pooled 5 , 17 , 18 , GLM analysis revealed a main effect of Treatment on all the positive mood scales. There were no effects of Sex, Genotype, or their interaction with Treatment on the positive mood scales. GLM analysis revealed a main effect of Treatment on 2 negative affect scales, i. Anxiety, showing that anxiety ratings were higher in the L-group compared with the S-group. The response pattern in males in both genotype groups was the complete opposite of that of females in both genotype groups. Findings seem to indicate that MDMA reduces the higher depression ratings in the female L-group compared to the S-group while the opposite though not statistically significant was observed in males Fig. The other scales were not statistically significant correlated with MDMA concentrations in blood Table 1. The aim of the present study was to investigate the role of the serotonin transporter gene in MDMA-induced mood effects. Findings showed that MDMA, in line with previous findings, induced a positive mood state and elevated feelings of anxiety and confusion. One main effect of genotype was revealed, i. In general, genotype did not seem to influence the MDMA effects, except for one affective state, i. The latter findings on l -genotype groups and negative affect seem counterintuitive since most studies have shown that s -carriers have higher levels of anxiety and are more at risk for developing depression compared to homozygous l -individuals 11 , Previously, it was shown by another study that there was a slight tendency for a higher frequency of homozygous s -individuals in an ecstasy user group, although the differences were not statistically significant and samples were in the Hardy—Weinberg equilibrium However, this is speculative and needs further investigation. Interestingly, the literature on the 5-HTTLPR is not that consistent as it seems and since a few years it has been acknowledged that the level of methylation of the transporter may also be a source of diverging outcomes 25 , Associations between 5-HTTLPR polymorphisms and psychological problems are significantly altered by environmentally induced methylation patterns of the transporter MDMA can be seen as a biological stressor, causing a substantial increase in cortisol concentrations 17 and therefore potentially affecting methylation. Yubero et al. However, since there was no genotype by sex interaction effect in the methylation study, confirmation for this suggestion is pending. Another study showed that women had statistically significant more pronounced physiological effects after MDMA administration compared to males and high functionality 5-HTTLPR individuals demonstrated increased cardiovascular effects Partly in line with these findings, i. In the present study, anxiety levels correlated positively to MDMA blood concentrations which is consistent with a previous study showing anxiety to be present when the dose of MDMA was higher The other mood states were unrelated to MDMA blood concentrations indicating that a single fixed dose induces the same mood effect in users. However, since only one dose of MDMA was used in the present study, variation in MDMA concentrations is suggestible lower than when multiple doses are included. Current findings therefore do not allow the exclusion of the possibility that MDMA concentrations and mood states, other than anxiety, are associated. In the present study, a bi-allelic determination of the 5-HTTLPR was done while a tri-allelic determination is also possible and might provide more information. The effects of this are therefore suggested to be minimal, though it would be advisable that future MDMA studies include the tri-allelic determination in larger samples consisting of both sexes. Findings indicate that the MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l -allele of the 5-HTTLPR showing this beneficial effect although this effect was small. This suggests that there is no need to take genotype or sex into account when treating patients with MDMA since these groups demonstrated the same emotional response to MDMA. Replication in larger samples sizes is recommended. Four placebo-controlled within-subject studies investigating the effect of MDMA on mood were included in the present pooled data analysis. The studies were all individually approved by the Medical Ethics Committee of the Academic Hospital of Maastricht and Maastricht University 5 , 17 , 18 , 19 and conducted in accordance with the Declaration of Helsinki. Participants provided written informed consent to participate in the studies and were paid. When participants in the separate studies met the criteria and were physically and mentally healthy as determined by questionnaires and a medical examination, the experimenter assigned a participant number which was linked to a treatment sequence. The treatments were randomized using a Latin Square. Both the participant and the experimenter were blind to the treatment order. The pooled sample size included 72 polydrug ecstasy users. They were all mentally and physically sound as determined by questionnaires and a medical examination. Additional demographic information of the final sample is given per study in Table 2. After study inclusion and before actual test days, participants were familiarized with the study procedure and questionnaire on a training day. They were requested to abstain from any drug use 1 week before the medical examination until the last test day. Prior to experimental sessions at 9 AM participants were screened for drugs of abuse THC, opiates, cocaine, amphetamines, methamphetamines , and had to pass a breathalyzer ethanol test. Women were given a pregnancy test. When tests were negative, participants had breakfast, and a blood sample was taken to determine the 5-HTTLPR genotype afterwards. This was followed by administration of the study treatment. Test days were minimally separated by a 7-day wash-out period. A permit for obtaining, storing, and administering MDMA was obtained from the Dutch drug enforcement administration. Two extra scales are derived, i. Due to the distribution of the genotypes among participants, alleles were grouped in two main clusters, i. MDMA was determined by gas-chromatography coupled to mass spectrometry using a method previously described by Pizarro and colleagues Battaglia, G. Pharmacologic profile of MDMA 3,4-methylenedioxymethamphetamine at various brain recognition sites. European journal of pharmacology , — Cole, J. The pre-clinical behavioural pharmacology of 3,4-methylenedioxymethamphetamine MDMA. Murphy, D. Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Molecular interventions 4 , — Article Google Scholar. Memory and mood during MDMA intoxication, with and without memantine pretreatment. Liechti, M. Neuropsychopharmacology official publication of the American College of Neuropsychopharmacology 22 , — Heils, A. Allelic variation of human serotonin transporter gene expression. Journal of neurochemistry 66 , — The human serotonin transporter gene polymorphism—basic research and clinical implications. Lesch, K. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science New York, N. Hariri, A. Canli, T. Long story short: the serotonin transporter in emotion regulation and social cognition. Kobiella, A. How the serotonin transporter 5-HTTLPR polymorphism influences amygdala function: the roles of in vivo serotonin transporter expression and amygdala structure. Mithoefer, M. Journal of Psychopharmacology 25 , — Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenediozymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology 27 , 28—39 Genetics of emotional regulation: the role of the serotonin transporter in neural function. Article PubMed Google Scholar. Glenn, A. The other allele: exploring the long allele of the serotonin transporter gene as a potential risk factor for psychopathy: a review of the parallels in findings. Kuypers, K. Inhibition of MDMA-induced increase in cortisol does not prevent acute impairment of verbal memory. British Journal of Pharmacology , — No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation. Martin-Santos, R. Roiser, J. Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in ecstasy users. American journal of psychiatry , — Brummett, B. Laucht, M. Interaction between the 5-HTTLPR serotonin transporter polymorphism and environmental adversity for mood and anxiety psychopathology: evidence from a high-risk community sample of young adults. PloS one 11 , e Alexander, N. Palma-Gudiel, H. An integrative review of methylation at the serotonin transporter gene and its dialogue with environmental risk factors, psychopathology and 5-HTTLPR. Yubero-Lahoz, S. Pardo-Lozano, R. Oakly, A. A genetic deletion of the serotonin transporter greatly enhances the reinforcing properties of MDMA in rats. Multifaceted empathy of healthy volunteers after single doses of MDMA: a pooled sample of placebo-controlled studies. Vizeli, P. Safety pharmacology of acute MDMA administration in healthy subjects. Nakamura, M. Molecular Psychiatry 5 , 32—38 Haberstick, B. Population frequencies of the triallelic 5httlpr in six ethnicially diverse samples from north america, southeast asia, and africa. Cami, J. Journal of clinical psychopharmacology 20 , — Transient memory impairment after acute dose of 75 mg 3,4-Methylenedioxymethamphetamine. Journal of Psychopharmacology 19 , — Acute administration of d-amphetamine decreases impulsivity in healthy volunteers. Neuropsychopharmacology official publication of the American College of Neuropsychopharmacology 27 , — Fagundo, A. Pizarro, N. Determination of MDMAand its metabolitesin blood and urine by gas chromatography-mass spectrometry and analysis of enantiomersby capillary electrophoresis. Journal of analytical toxicology 26 , — Richardson, J. Eta squared and partial eta squared as measures of effect size in educational research. Download references. The authors would like to thank Cees van Leeuwen for the medical supervision and all the interns who have worked on these projects and helped out with data collection. Kuypers, E. Universitat Autonoma de Barcelona, Barcelona, Spain. You can also search for this author in PubMed Google Scholar. Correspondence to K. Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and permissions. Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users homozygous for the l-allele of the serotonin transporter. Sci Rep 8 , Download citation. Received : 06 June Accepted : 05 January Published : 18 January Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Skip to main content Thank you for visiting nature. Download PDF. Subjects Behavioural genetics Social behaviour. Abstract MDMA exerts its main effects via the serotonergic system and the serotonin transporter. Improvement in OCD symptoms associated with serotoninergic psychedelics: a retrospective online survey Article Open access 17 August Sexual health and serotonin 4 receptor brain binding in unmedicated patients with depression—a NeuroPharm study Article Open access 06 July Serotonin-releasing agents with reduced off-target effects Article Open access 09 November Figure 1. Full size image. Figure 2. Figure 3. Full size table. Discussion The aim of the present study was to investigate the role of the serotonin transporter gene in MDMA-induced mood effects. Methods Participants Four placebo-controlled within-subject studies investigating the effect of MDMA on mood were included in the present pooled data analysis. References Battaglia, G. Article Google Scholar Download references. Acknowledgements The authors would like to thank Cees van Leeuwen for the medical supervision and all the interns who have worked on these projects and helped out with data collection. Kuypers View author publications. View author publications. Additional information Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. About this article. Cite this article Kuypers, K. Copy to clipboard. Publish with us For authors Language editing services Submit manuscript. Search Search articles by subject, keyword or author. Show results from All journals This journal. Advanced search. Close banner Close. Email address Sign up. Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing.

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Background: The objectives of the study were to determine the prevalence of alcohol and drug use before or during sex among men who have sex with men MSM in Catalonia during , and to identify factors associated with variables of intensive alcohol and drug use. Methods: Cross-sectional study using self-administered questionnaires. Men were recruited in saunas, sex shops, bars and a public park and by mail to all the members of the Catalonia Gay Federation. Results: The multivariate analysis showed an association between having suffered discrimination and frequent alcohol and multidrug use. Being human immunodeficiency virus HIV -positive was associated with frequent use of drugs and multidrug use. Associations between substance use and sexual risk behaviour also emerged. A previous study carried out in Catalonia in revealed drug use before or during sex as one of the factors associated with unprotected anal intercourse among MSM. Prior research has put forward several potential explanations for this association. First, certain drugs are used to enhance sex among MSM, and their use during sex may increase the risk of engaging in unprotected sex due to pharmacological effects such as social disinhibition and prolonged intercourse. There is evidence that drug consumption is a risk factor for HIV infection. This risk increased to 2. Contrary to other countries, e. USA, where a high prevalence of alcohol and recreational drug use among MSM has been widely reported, 11 , 14 , 18 , 19 less data are available in Europe and most are secondary findings with little detail about the type of drug, drug combination or context of use. The lack of studies on drugs and MSM in Europe, and particularly in Spain, reinforces the need for a more in-depth analysis of drug and alcohol use in this group, since identifying the factors that determine the use of these substances will help us design specific strategies for the reduction of the risks and damage associated with their use. In this context, the objectives of our study were to determine the prevalence of alcohol and drug use before or during sex among MSM in Catalonia during and to identify the sociodemographic, psychosocial and behavioural factors associated with three specific variables of intensive alcohol and drug use. In the most recent , a convenience sample of MSM was recruited at saunas, sex shops, bars and a public park frequented by gay men. These sites were selected from a larger list of gay venues screened prior to the survey. Venues were chosen to represent a wide cross-section of MSM in Barcelona. All men present in the venue during a specific period were invited to participate. Of the men approached, The questionnaires were anonymous, self-administered and accompanied by a self-addressed stamped envelope that was to be sent to a post-office box; therefore, it was impossible to ascertain whether anyone had answered more than once. The distributed questionnaires were marked in order to identify the origin of the returned questionnaires. The return rate was The questionnaire used was adapted from a questionnaire developed and validated by the Lausanne University Institute of Social and Preventive, which investigated behavioural patterns over the last 12 months. The degree of internalized homophobia, that is the men ' s own negative attitude towards their homosexuality or bisexuality, was investigated using seven items on acceptance of homosexuality with responses ranging from 1 totally agree to 4 totally disagree. The questionnaire also collected variables on sex practices in the last 12 months with stable and casual partners and on the use of condoms, number of partners, self-reported HIV status and previous history of STI. A stable partner was defined as any person with whom the respondent had sexual relations and felt closer and more committed. Unprotected anal intercourse was defined as inconsistent use of a condom with a sexual partner during the last 12 months. The participant was asked about alcohol and drug use cannabis, heroin, cocaine, crack, ecstasy, amphetamines, poppers, LSD, Viagra, ketamine and methamphetamine before or during sex over the last 12 months and about the frequency of use for each substance always, frequently, occasionally or never. This information was used to construct the specific response variables for the intensive use of alcohol and drugs: i Frequent alcohol use , that is, the use of alcohol always or frequently before or during sex over the last 12 months; ii Frequent drug use , that is, the use of at least one drug always or frequently before or during sex over the last 12 months; iii Multidrug use , that is, the use of three or more different drugs before or during sex over the last 12 months. These variables were not mutually exclusive. The prevalence of drug or alcohol use during sex over the last 12 months was calculated for the descriptive analysis. Logistic regression was used to evaluate the sociodemographic, psychosocial and sexual behaviour variables associated with each of the specific response variables for the intensive use of alcohol and drugs. The calibrations of the models were assessed by the Hosmer—Lemeshow goodness-of-fit statistic. Statistical significance was set at 0. Of the men included in the study, These were the participants included in the analysis. Mean age was 41 years SD 9. Immigrants accounted for Most of the men identified themselves as homosexual As for sexual behaviour during the last 12 months, The self-reported prevalence of HIV was Sociodemographic, psychosocial and sexual behavior characteristics of a sample of MSM in Catalonia, Spain, More than half the participants said they had used alcohol and drugs at some time before or during sex Prevalence of alcohol and drug use before or during sex in a sample of MSM in Catalonia, Spain, last 12 months. Related the variables for the intensive use of alcohol or drugs before or during sex, The results of univariate and multivariate regression models are presented in tables 3 and 4 , respectively. Univariate analysis of the variables of intensive alcohol and drug use before or during sex last 12 months. Multivariate analysis of the variables of intensive alcohol and drug use before or during sex last 12 months a. In the final multivariate regression model adjusted for the recruitment site, men aged 25 years of less OR 1. Having a stable partner proved to be a protective factor against frequent alcohol use OR 0. Finally, men who said they had had unprotected sex with casual partners had a 1. Both variables of sexual risk behaviour were significantly associated with the variable frequent drug use before or during sex in the final multivariate model. Thus, men who said they had had more than 20 partners OR 1. According to the multivariate analysis, the younger responders OR 1. Furthermore, the number of partners OR 2. The results of this study reveal a high prevalence of alcohol and drug use before or during sex among MSM recruited in Catalonia, since more than half of those interviewed said that they had used alcohol and drugs during the last year. The prevalence of drug use by MSM is higher than in the general population, whereas that of alcohol use is similar. If we consider the prevalence of the more intensive use of these substances before or during sex, The multivariate analysis of factors related to intensive alcohol and drug use before or during sex showed an association between age and frequent alcohol and multidrug use. This result corroborates those of other studies that show a greater prevalence of use of these substances among young MSM. As in other studies undertaken in the USA and the UK, 8,12,19,27 a clear association was observed between being HIV-positive and frequent use of drugs and multidrug use. Some authors state that many HIV-infected men use these substances to handle the stress brought about by their illness or homophobia or societal prejudice. In this sense, working against the stigma and discrimination that these individuals face will benefit prevention programs. Of the three psychosocial variables analyzed, only having suffered discrimination due to sexual orientation showed a significant association, not only with frequent alcohol use, but also with multidrug use. This association has been observed elsewhere. Finally, and consistent with the results of other studies, 7 , 8 , 10 , 11 , 26 unprotected sex with casual partners was significantly associated with both frequent use of alcohol and drugs and with multidrug use. Furthermore, having a greater number of partners was associated with alcohol and drug use. This is consistent with the results of other studies 7 , 10 , 12 and confirms the use of substances such as poppers, ecstasy, and methamphetamine as aphrodisiacs. The present study has important limitations. First, the respondents were recruited from multiple venues and not from a probability sample; therefore, caution should be exercised in generalizing the findings to all MSM in Catalonia. However, we did try to diversify as much as possible the places, days, and times of our approach to participants in order to minimize this bias. Young people in general are underrepresented in samples recruited from gay venues. For instance, the mean age of MSM surveyed on-line in Spain in was Furthermore, we do not know the characteristics of the men who refused to participate in the study. Secondly, the return rate of the questionnaires was not high, but it was similar to previous surveys and higher than in other studies that used similar methods. Thirdly, we cannot exclude biases of memory and under-reporting of certain risk practices or of the self-reported results of HIV infection. However, the fact that the questionnaire was anonymous and self-administered may have helped reduce this type of risk. The present study is the first to analyse in depth the intensive use of alcohol and drug use before or during sex among MSM in our setting; therefore, our results can help to guide prevention programs in Catalonia. Finally, in order to be efficient, these programs must try to cover MSM-specific psychosocial aspects, tackle discrimination and include prevention and support groups for HIV-positive men. The results of this study reveal a high prevalence of alcohol and drug use before or during sex among MSM recruited in Catalonia. The multivariate analysis showed an association between variables of intensive alcohol and drug use and having suffered discrimination, being HIV-positive and sexual risk behaviour. Google Scholar. Google Preview. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Advertisement intended for healthcare professionals. Sign in through your institution. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Journal Article. Correlates of intensive alcohol and drug use in men who have sex with men in Catalonia, Spain. Cinta Folch , Cinta Folch. Oxford Academic. Anna Esteve. Kati Zaragoza. Jordi Casabona. Select Format Select format. Permissions Icon Permissions. Abstract Background: The objectives of the study were to determine the prevalence of alcohol and drug use before or during sex among men who have sex with men MSM in Catalonia during , and to identify factors associated with variables of intensive alcohol and drug use. Table 1 Open in new tab. UAI, unprotected anal intercourse. Table 2 Open in new tab. Alcohol use sometimes Table 3 Open in new tab. Frequent alcohol use. Frequent drug use. Multidrug use. Table 4 Open in new tab. Frequent alcohol use b. Frequent drug use c. Multidrug use d. Key points. Technical document; Google Scholar Crossref. Search ADS. Factors associated with unprotected sexual intercourse with steady male, casual male, and female partners among men who have sex with men in Barcelona, Spain. Substance use, substance choice, and unprotected anal intercourse among young Asian American and Pacific Islander men who have sex with men. Unprotected anal intercourse and substance use among men who have sex with men with recent HIV infection. Substance use and sexual behaviours of Japanese men who have sex with men: a nationwide internet survey conducted in Japan. Prevalence and correlates of substance use among young Asian Pacific Islander men who have sex with men. Alcohol use, drug use and alcohol-related problems among men who have sex with men: the Urban Men's Health Study. Intertwining epidemics: A review of research on substance use among men who have sex with men and its connection to the AIDS epidemic. The relationship of substance use with sex to the use of condoms among young adults in two urban areas of Scotland. Google Scholar PubMed. No connection between alcohol use and unsafe sex among gay and bisexual men. Regional patterns and correlates of substance use among young men who have sex with men in 7 US urban areas. Factors associated with HIV seroconversion in gay men in England at the start of the 21st century. Recreational drug use and sexual risk practice among men who have sex with men in the United Kingdom. Correlates of internalized homophobia in a community sample of lesbian and gay men. Longitudinal patterns of methamphetamine, popper amyl nitrite , and cocaine use and high-risk sexual behavior among a cohort of San Francisco men who have sex with men. Sexual risk behavior among HIV-positive men who have sex with men: A literature review. Crystal methamphetamine, its analogues, and HIV infection: medical and psychiatric aspects of a new epidemic. Crystal methamphetamine use predicts incident STD infection among men who have sex with men recruited online: A nested case-control Study. Predictors of substance use over time among gay, lesbian, and bisexual youths: An examination of three hypotheses. All rights reserved. Issue Section:. Download all slides. Comments 0. Add comment Close comment form modal. I agree to the terms and conditions. You must accept the terms and conditions. Add comment Cancel. Submit a comment. Comment title. You have entered an invalid code. Submit Cancel. Thank you for submitting a comment on this article. Your comment will be reviewed and published at the journal's discretion. Please check for further notifications by email. Views More metrics information. Total Views Email alerts Article activity alert. Advance article alerts. New issue alert. Receive exclusive offers and updates from Oxford Academic. 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