Overview of MDMA-related Literature for January 2002
One clinical study, eight retrospective studies comparing ecstasy users with non-users, four studies of ecstasy user demographics, three studies of ecstasy user characteristics, seven review papers, three studies of MDMA neurotoxicity in non-human animals and two in vitro studies were located in January 2002.
MDMA and Ethanol in Humans
Findings from the first study of the combined effects of MDMA and ethanol in a placebo-controlled clinical trial were reported by a Spanish team that researched the immunological effects of this combination in earlier publications (e.g. Pacifici et al. 2000; 2001). Though the subjective effects of MDMA predominate when MDMA is combined with ethanol, impairment of reaction time and psychomotor performance (as assessed via digit-symbol task) is equal to or greater than impairment produced by ethanol alone. Findings from this study suggest that people who have taken ecstasy with ethanol may overestimate their ability to drive or perform other tasks.
Psychological Problems
Four of eight comparisons of ecstasy users and non-users addressed psychological problems or psychological differences between ecstasy users and non-users (Daumann et al. 2001; Dughiero et al. 2001; Gerra et al. 2001; Parrott et al. 2001). While all three studies that measured self-reported psychological function found that ecstasy users were subject to a greater number of psychological problems than non-users, these studies also found that use of cannabis or other drugs appears to be more strongly related to reported problems than does ecstasy use (Daumann et al. 2001; Parrott et al. 2001b). One report found that cannabis use, and not ecstasy use, was related to increased self-reported aggression (Daumann et al. 2001), whereas another study employing a behavioral measure found that male ecstasy users exhibited more aggression (retaliation against an opponent) than did male non-users (Gerra et al. 2001). Not surprisingly, ecstasy users had higher novelty seeking scores than non-users, and "experimenters" had higher harm-avoidance scores than "abusers" in an Italian community sample (Dughiero et al. 2001). Findings from these papers and from other recently published studies (e.g. Morgan et al. 2002) suggest that the relationship between ecstasy use and psychological function is complex.
Cognitive Function and Memory
Four more studies examined cognitive function, and memory in particular, in ecstasy users and non-users (Fox et al. 2001a; 2001b: Heffernan 2001; Rodgers et al. 2001). As has been shown in previous studies, ecstasy users in one study had lower scores on a list-based measure of verbal recall (RAVLT) than non-users when compared with controls (Fox 2001a), and that long-term users (duration = 8 years or more) fared worse than short-term users. In another study conducted by the same research team, ecstasy users, especially those with the highest self-reported lifetime usage, did less well on a visual memory task, but performed similarly to non-users on the WCST (assesses executive function) and on a different measure of verbal recall (Fox et al. 2001b). This study also found that ecstasy users who reported having "problems" resulting from ecstasy use performed no differently on these same measures of recall and executive function than did ecstasy users who did not report having any ecstasy-related problems. In other studies, self-reported failure in prospective memory (remembering to perform an act in the future, planning action) and retrospective memory (recall) was compared in ecstasy users and non-users in two studies (Heffernan 2001, Studies 1 and 3; Rodgers et al. 2001), one in an on-line study (Rodgers et al. 2001). Ecstasy users reported more difficulties with prospective memory than with retrospective memory, but differences in sub-scale scores were not always consistent. Heffernan and colleagues also found impairment in executive function in ecstasy users (Heffernan et al. 2001, Study 2), but they did not correlate or regress executive function performance on prospective memory scores. Hence it is not clear what relationship, if any, self-reported impairment in prospective memory has to executive function and memory, and this is especially true considering findings in other reports suggesting a dissociation between self-reported problems and measurable differences in neurocognitive function (Croft et al. 2001; Fox et al. 2001a).
Demographics
Studies considered the demographics and features of ecstasy use in a community sample of adolescents (Cottler 2001), a sample of gay and bisexual men attending circuit parties (Colfax et al. 2001) and in Irish drug users who smoked heroin (Gervin et al. 2001). Another report used data culled from the nationwide Monitoring the Future study to estimate past and current use of ecstasy and other drugs (Golub 2001). One of these studies sought to test the reliability of DSM substance abuse and dependence criteria in adolescents and to develop measures of abuse and dependence on ecstasy (Cottler et al. 2001). The authors used already existing items to generate an assessment of abuse and dependence, and were apparently could reliably measure abuse and dependence in a sample of regular ecstasy users.
Pregnant Ecstasy Users
A comparison of pregnant women who did and did not report ecstasy use found that ecstasy users were younger, were more likely to have an unplanned pregnancy and usually stopped using ecstasy when they learned they were pregnant (Ho et al. 2001).
Qualitative Study of Subjective Effects
Information gathered from participants in the dance event and rave scene in Northern Ireland found that while expected subjective effects of ecstasy (closeness to others, euphoria) are often reported, feelings of aggression and feelings of fatigue or cynicism in relation to ecstasy-induced sociability are also reported (McElrath and McEvoy 2001).
Psychological Problems-Analysis of Case Reports
An examination of medical case studies reporting various psychiatric problems after ecstasy use found that personal or family history of prior psychological problems, higher (versus lower) doses of ecstasy and use of other drugs all increased risk of psychiatric problems after ecstasy use (Soar et al. 2001).
Rats: Changes in Anxiety
Two studies using the same measures of anxiety, but in different rat strains and different doses of MDMA reached conflicting conclusions, with one study finding increased anxiety in the plus maze and open field (Morley et al. 2002), and one found decreased anxiety in these same tests (Mechan et al. 2002). Findings of reduced anxiety were reported in Dark Agouti rats given 12.5 mg/kg MDMA on the last of three trials in the plus maze and open fields, but not trials 8 or 29 days after MDMA. Increased anxiety was seen in Wistar rats tested in the plus maze and open field 12 weeks (84 days) after receiving four doses of 5 mg/kg MDMA every four hours for two days, though rats given a lower dose of MDMA only differed from saline treated animals, and not rats given a high dose of amphetamine. Interactions with familiar objects was impaired in the high MDMA dose group, suggesting decreased recall for them, and fewer social interactions were observed in both MDMA groups, particularly in those given higher doses. These findings suggest either that the long-term effects of MDMA differ across rat strains or that the effects of different dose regimens could be significant.
Mouse Neurotoxicity
A knockout mouse study (Fornai et al. 2001) finding a role for MAO-B in attenuating serotonergic neurotoxicity after 50 mg/kg MDMA may have limited generalizability to humans (since mice experience dopaminergic, and not serotonergic, neurotoxicity).
Rat Brain: Neurotoxicity, AVP Release
An in vitro study using rat neurons presents strong evidence that MDMA-induced changes or reductions in serotonin function are due to damage to serotonin axons, and not downregulation of the serotonin system. Anterograde transport of tritiated proline in rostral raphe was impaired in rats either given MDMA, fenfluramine or the known serotonin neurotoxin 5,7-DHT (Callahan et al. 2001). Another study using rat brain slices found that when MDMA and various MDMA metabolites (MDA, HMMA) were directly applied to hypothalamic tissue in concentrations intended to simulate those found in human ecstasy users, they induced AVP release and oxytocin (Forsling et al. 2002). Study findings suggest that increased risk for hyponatremia after ecstasy use may be due to the combination of AVP release produced by MDMA (leading to increased water retention) and increased water consumption, usually undertaken as a means to stave off dehydration or hyperthermia associated with MDMA.