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Official websites use. Share sensitive information only on official, secure websites. Correspondence concerning the paper should be addressed to Krista Lisdahl Medina, Ph. Phone: x Fax: Email: klmedina ucsd. However, recent studies have found that the relationship between ecstasy use and psychological symptoms was no longer significant after controlling for marijuana use e. The goal of the present study was to examine the relationship between ecstasy exposure and self-reported executive functioning and psychological symptoms after controlling for gender, ethnicity, and other drug use. Data were collected from 65 men and women with a wide range of ecstasy use including 17 marijuana-using controls. No gender differences or interactions were observed. These results revealed that, although ecstasy users demonstrate elevated levels of psychological symptoms and executive dysfunction, these symptoms are not statistically associated with their ecstasy consumption. Instead, other drug use alcohol, marijuana, opioids, and inhalants significantly predict psychological symptoms in this sample of polydrug users. Keywords: methylenedioxymethamphetamine, MDMA, polydrug use, adverse effects, drug effects, depression, anxiety, disinhibition, apathy, frontal behavioral syndromes, gender differences. Ecstasy MDMA binds to brain serotonin transporters, which prevents serotonin reuptake and increases serotonin receptor activation, although MDMA can also affect dopamine, noradrenaline, acetylcholine and histamine Parrott, ; Reneman, Booij, et al. Further, there is evidence to suggest that ecstasy may be a selective serotonin neurotoxin in humans as well McCann et al. Serotonin is involved in the regulation of several behavioral domains, including mood, behavioral control, and vigilance Brown et al. Indeed, a growing body of evidence supports the hypothesis that ecstasy users have elevated levels of both semi-acute Curran and Travill, ; Curran et al. More specifically, several studies have demonstrated elevated levels of depression de Win et al. Studies examining executive function among ecstasy users have typically used laboratory-based neuropsychological measures, with conflicting results. Some have found working memory, fluency, and abstract reasoning deficits among ecstasy users, especially among male users Montgomery et al. In addition to this inconsistency in the literature about the presence or absence of executive dysfunction in ecstasy users, little attention has been paid to the possible behavioral deficits that interfere with everyday function, most commonly caused by prefrontal system damage. These behaviors include impulsivity, disinhibition, apathy, inattentiveness, indecision, emotional lability, and poor mental flexibility e. Many of these behaviors are difficult to measure during traditional neuropsychological evaluation, as they are more likely to occur within unstructured or ambiguous contexts. Existing research that has examined behavioral symptoms of executive dysfunction in ecstasy users have found, with few exceptions McCann et al. One consistent critique of the current studies is that the observed effects may be due to comorbid polydrug use, which is the norm among ecstasy users e. Indeed, it is difficult to determine whether reported psychological symptoms are due to ecstasy use, or rather to other drugs of abuse such as alcohol, marijuana, and cocaine. In support of the latter hypothesis, recent research has found that the relationship between ecstasy and psychological problems was no longer significant after taking into account other drug use, especially marijuana use Daumann et al. A related finding is that Lieb and colleagues found that ecstasy use is often initiated after the development of an Axis I mood or anxiety disorder. This pattern highlights the need to exclude individuals with independent mood or anxiety disorders that predate their substance use. Finally, most of the research on the psychological effects of ecstasy abuse is based on comparisons between an ecstasy group, which typically includes individuals with wide variations in usage patterns, and controls. Most studies have not examined exposure effects, although there is preliminary evidence that a positive relationship between extent of ecstasy use and increased psychological symptoms exists, in that heavy users demonstrate more impairment compared to light users Parrott et al. Therefore, the goal of the present study was to examine the relationship between ecstasy exposure from none to heavy use and self-reported executive functioning, anxiety, and depressive symptoms after controlling for frequency of other drug use, gender, and ethnic identification among ecstasy and marijuana users without independent DSM-IV mood or anxiety disorders. It was hypothesized that heavier ecstasy use would be significantly associated with increased levels of psychological symptoms after controlling for other drug use. We also examined gender differences; it was hypothesized that female ecstasy users would demonstrate greater depressive and anxiety symptoms while males would demonstrate increased behavioral symptoms of executive dysfunction. Data were collected in conjunction with a study that focused on the neuropsychological consequences of ecstasy use; see Medina and colleagues for more detailed methodology information. Individuals were recruited through advertisements in a free metropolitan newspaper and screened by phone to determine eligibility. Participants were required to be fluent English speakers, 18 years of age or older, and had to fall within one of the predetermined stratified bins of ecstasy exposure detailed below. Exclusion criteria included mental retardation, major medical or neurologic illnesses including traumatic brain injury, preexisting independent of substance use psychiatric conditions, or use of prescribed psychiatric medications. Individuals who met current diagnostic criteria independent of their substance use for any psychotic disorder, bipolar disorder, major depressive disorder, or anxiety disorder generalized anxiety disorder, panic disorder, and post traumatic stress disorder were excluded from the study. Once deemed eligible, participants were screened with regard to their lifetime ecstasy use. In order to ensure that there were adequate participants across the expected range of ecstasy use, we utilized a proportional quota sampling technique, stratified by lifetime ecstasy use. The estimated range of ecstasy use was split into four bins prior to data collection in order to collect data from approximately equal numbers of participants across the full range of ecstasy use, balanced for gender. Further, because polydrug use is the norm among ecstasy users and marijuana use is particularly prevalent in this population, marijuana users were recruited to fill the first bin. This resulted in the following distribution: bin 1 8 male, 9 female marijuana users with no ecstasy use ; bin 2 9 male, 10 female ecstasy users who used 1—60 lifetime tablets ; bin 3 8 male, 6 female ecstasy users who used 61— tablets ; and bin 4 9 male, 6 female ecstasy users who used over tablets. It is important to again emphasize that these bins reflect a sampling strategy only and do not represent separate groups in the multiple regression analysis; rather, the data from all bins were combined to create a continuous variable reflecting lifetime ecstasy exposure from 0— tablets. Participants were required to remain abstinent from ecstasy and other drugs of abuse for one week. Prior to beginning the study, informed consent was obtained. They also completed a comprehensive neuropsychological evaluation, the results of which have been reported previously Medina et al. A total of 34 men and 31 women were enrolled in the study. Additionally, a semi-structured interview was administered to measure lifetime drug use. For each substance of use, participants were asked their average weekly use each year that they used. Memory cues appropriate to adolescents and young adults, such as developmental milestones, school grades, and relationship changes, were utilized. The following drug categories were assessed: ecstasy, marijuana, alcohol, sedatives e. Norm-based T-scores were utilized for this study. Raw scores were utilized for this study. The scale was designed to elicit ratings of behavior both before and after an acute illness or injury. Individuals rate their own behavior on a scale of 1—5 almost never to almost always. Example items include Speaks only when spoken to , Laughs or cries too easily , Swears , Is unable to plan ahead. Elevations on the Apathy subscale indicate possible problems with initiation, psychomotor speed, drive, blunted affect, or anhedonia. Elevations on the Disinhibition scale may indicate impulsivity, hyperactivity, social inappropriateness, or antisocial behavior. Scores elevated on the Executive Dysfunction scale may indicate poor complex attention, mental rigidity, poor problem solving, planning deficits, or lack of self-monitoring. Norm-based T-scores were utilized for each scale, on which higher scores denote greater executive dysfunction. Although the relationship between ecstasy use and psychological functioning was examined with a continuous variable reflecting lifetime or past year ecstasy consumption, for descriptive purposes a non-parametric statistical analysis Mann-Whitney U and chi-square tests was run to test whether the ecstasy and marijuana-users differed demographically. In addition, in order to provide normative data for the groups, the percentage of ecstasy and marijuana-users who demonstrated impairment on the psychological tests were compared and reported Table 2. Following bivariate analysis, the primary analyses included two series of multiple regressions that tested whether 1 past year or 2 lifetime ecstasy exposure was significantly associated with psychological functioning after controlling for gender, ethnicity which differed between the ecstasy and marijuana-users; see below , and frequency of other drug use besides ecstasy. Further, interactions between ecstasy use and gender were explored. Ordinary least squares OLS multiple regressions were utilized in order to examine the unique variance accounted for by ecstasy use above and beyond the other variables included. This analytic strategy also allowed for examination of the dose-dependent relationship between other drug use e. More specifically, the two series included six separate regressions each for each dependent variable. In the first series, past year ecstasy use was the primary independent variable IV of interest. In the second series, lifetime ecstasy use was primary IV. Independent variables were entered first as a block standard entry : ecstasy use, gender, ethnicity, and comorbid drug use that may affect psychological functioning including alcohol, marijuana, sedatives, opioids, stimulants, hallucinogens, and inhalants; frequency of past year use in the first series, and lifetime use in the second series. Interactions between ecstasy use and gender were then entered as a second block. If the interaction term did not significantly add to the regression model, only results from the first block were reported. On average, participants were 23 years old range 18—35 with an average of 13 years of education range 9— Therefore, ethnicity was statistically controlled for in all the regressions. For the majority of participants, marijuana was used more recently than the other aforementioned drugs. As expected, frequency of ecstasy use was significantly different between the ecstasy and marijuana-users. Further, although marijuana and alcohol use did not differ significantly, in general, the ecstasy-users used significantly more drugs at higher frequencies compared to the marijuana-users. See Table 1 for a detailed description of the type and frequency of past year drug use. As stated previously, frequency of drug use of all the aforementioned drug use categories were included in all the regression models. For additional demographic information, including frequency of lifetime drug use, see Medina and colleagues Mean frequencies were calculated only for participants who reported using the specified drug at least one time during the past year; participants can appear in multiple rows of the tables. The ecstasy and marijuana-users did not differ significantly on any of the self-report measures of anxiety, depression, or executive function. However, as described in detail below, many of the ecstasy and marijuana-users reported clinically elevated levels of state and trait anxiety, depressive symptoms, and apathy, disinhibition, executive dysfunction planning, organizing, working memory compared to published norms. Frequency of ecstasy use, age, education, gender, or length of drug abstinence did not correlate significantly with any of the psychological variables. Higher levels of alcohol, marijuana, and opioids were related to increased psychological symptoms. Further, an interaction between gender and ecstasy use was examined. We found that past year or lifetime ecstasy use was not significantly associated with any of the anxiety, depression, or executive functioning measures after controlling gender, ethnic identification, and frequency of other drug use. Further, no significant relationships were found between ethnicity, gender, or interactions between gender and ecstasy use, and psychological functioning in this sample. Presented below are the significant multivariate predictors. After controlling for ethnicity and gender, no past year or lifetime drug use variables were significantly associated with state anxiety. Trait Anxiety. These results revealed that, although many of the ecstasy-users demonstrated clinically elevated levels of anxiety, depressive, and executive dysfunction symptoms compared to published norms, no dose-dependent relationships were observed between ecstasy use and psychological functioning. Rather, higher levels of alcohol, opioids, marijuana, and inhalants were associated with more psychological symptoms in this sample of ecstasy and marijuana polydrug users. Therefore, polydrug use continues to be an important confound in the examination of psychological consequences of ecstasy use and should be thoroughly examined in all ecstasy studies. However, extent of self-reported trait anxiety was predicted by increased marijuana use, as well as opioid and inhalant use. This is consistent with more recent research indicating that anxiety symptoms observed in ecstasy polydrug users is likely due to comorbid marijuana use Daumann et al. Although relatively understudied, previous research has also found elevated anxiety symptoms among individuals with opioid dependence Ahmadi et al. However, it should be noted that it remains possible that the simultaneous use of marijuana or other substances and ecstasy are necessary for the development of clinically significant psychological symptoms in ecstasy users Sala and Braida, ; Young et al. Although a quarter of the ecstasy users demonstrated mild-to-severe levels of depressive symptoms, after controlling for ethnicity and other drug use, depressive symptoms were best predicted by extent of past year marijuana use and lifetime opioid use. This is consistent with Morgan and colleagues , who found that depressive symptoms among ecstasy polydrug users were best predicted by extent of recent marijuana use. In addition, although de Win and colleagues demonstrated a significant bivariate correlation between lifetime ecstasy consumption and depressive symptoms, these symptoms did not correlate with serotonin transporter density. Therefore, it is not yet clear that the observed depressive symptoms were the direct result of ecstasy-induced alterations in the serotonergic system. Inhalant use has also been previously associated with increased risk for depression Rienour, ; Sakai et al. The current finding that increased hallucinogen use was unexpectedly associated with decreased depressive symptoms is consistent with previous research that has demonstrated low risk for depression among individuals with hallucinogen abuse or dependence Grant, Approximately one quarter of the ecstasy-users demonstrated clinical elevations on both the FrSBe Disinhibition and Executive Dysfunction subscales. This finding is consistent with previous research showing that ecstasy users demonstrate impulsivity and poor abstract reasoning, working memory, and fluency Gerra et al. However, as a group, the ecstasy users did not differ from marijuana users. Further, higher frequency of alcohol and opioid use, but not ecstasy use, was a significant predictor of greater self-reported executive dysfunction and disinhibition. These findings are consistent with previous literature demonstrating significant executive dysfunction associated with alcohol and opioid use e. Frequency of inhalant and sedative use was significantly associated with these symptoms, which is consistent with previous research demonstrating symptoms of apathy following solvent abuse Fukui et al. Less is known regarding the long-term impact of sedative use on symptoms of apathy. Therefore, the increased risk of apathy symptoms associated with sedative use should be interpreted with caution, as it may be a result of a complex multivariate relationship in this sample. We did not find any gender differences in psychological functioning, which is consistent with the report of Fingeret and colleagues One potential reason for these discrepant findings is that the current study excluded participants with pre-existing, independent psychological disorders, which occur more frequently in adolescent girls Garber, Keiley, and Martin, and women Kessler et al. Thus, previous findings that were based on samples that did not exclude individuals who had independent mood disorders may find increased depressive symptoms among female users due to higher population base-rates e. Further, the men in this sample demonstrated heavier alcohol, marijuana, and opioid use, which were each significantly associated with depression, anxiety, and executive dysfunction in this sample. Therefore, it is possible that interactions exist between gender and other drug use among ecstasy users, which was not examined in the current sample. Future studies are necessary to determine whether previously reported gender differences are due to ecstasy use, increased comorbid polydrug use, or preexisting, independent mood disorders. As with any study, there are methodological limitations that need to be considered. One potential weakness of this study is that we did not utilize urinalysis or hair analysis when assessing length of abstinence. Still, attempts were made to maximize the reliability of self-reported drug use, such as guaranteeing confidentiality and privacy by not requiring a signature on the informed consent document. Another potential weakness is that the ecstasy users were not compared to a non-drug using control group. Thus, the relationship between ecstasy exposure and psychological functioning may have been underestimated in this sample. It should, therefore, be emphasized again that, compared to normative controls, a large percentage of ecstasy users did demonstrate significant psychological impairment, including increased depressive, anxiety, and behavioral symptoms of executive dysfunction. It should also be noted that results cannot necessarily be generalized to other samples with different lengths of abstinence or different duration of ecstasy use. It is possible that samples with substantially different patterns of ecstasy use would yield different psychological symptoms. For example, the ecstasy users in this study were abstinent from ecstasy for approximately five months; therefore, more sub-acute Monday blues or short-term psychological effects caused by ecstasy may not have been detected. Further, it is possible that psychological symptoms due to ecstasy use resolve within a few months of abstinence, which has not been sufficiently investigated. Therefore, longitudinal research is necessary to assess how continued ecstasy use or abstinence affects behavioral symptoms of executive dysfunction, anxiety, and depressive symptoms. Further, because individuals with Axis I mood or anxiety disorders that existed independent of substance use were excluded from the study, other samples of ecstasy users may demonstrate higher levels depressive or anxiety symptoms, although these symptoms may predate their drug use Lieb et al. Still, due to potential serotonin neurotoxicity, ecstasy use may exacerbate these preexisting psychiatric conditions. Further, other moderator variables may put certain subgroups at elevated risk for ecstasy-induced psychological symptoms. For example, individuals with certain genetic polymorphisms in the serotonin transporter gene may be at higher risk for deleterious psychological effects of ecstasy exposure Roiser et al. In conclusion, these results are consistent with previous research indicating that comorbid substance use is predictive of elevated psychological symptoms among ecstasy polydrug users Daumann et al. This study added to the current literature by demonstrating significant dose-dependent relationships between marijuana, alcohol, opioid, and inhalant use and psychological symptoms among ecstasy users. We would like to sincerely thank Kevin Cummins, University of California, San Diego, and Jeffrey Welge, University of Cincinnati, for their helpful comments regarding the statistical analysis and interpretation. Portions of this paper were presented at the meeting of the American Psychological Association in Washington, DC. When discrepant reports were given, the shortest length of abstinence was used and re-confirmed later in the interview. Two participants were excluded from the study due to consuming drugs within the past week. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. As a library, NLM provides access to scientific literature. Drug Alcohol Depend. Published in final edited form as: Drug Alcohol Depend. Find articles by Krista Lisdahl Medina. Find articles by Paula K Shear. Issue date Mar PMC Copyright notice. The publisher's version of this article is available at Drug Alcohol Depend. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. 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