Purpose: Psychological; to investigate the acute and sub-acute effects of ecstasy, with specific interest in possible gender differences in acute or sub-acute effects. Specific hypotheses tested - 1) That female ecstasy users would report more residual (post use) depressed mood than male users and 2) that men would report more post-use aggressiveness than female users.

Design: Non-experimental (retrospective) 2(gender) x 2(drug use) x 2(time since use) between subjects/within-subjects design, with gender (male or female) and drug use (ecstasy use on Day 0 versus no ecstasy use on Day 0) serving as between-subjects factors and time since use (Day 0 versus Day 4) serving as a within-subjects factor. All participants completed measures of mood and aggression, and pulse rate was measured on half of all participants on Day 0. Subjects: 40 ecstasy users (on the evening of Day 0) and 40 non-ecstasy users probably residing in the London (England) area, with all participants recruited via snowball technique at successive parties occurring on Friday or Saturday nights over a 5-month period. Matching - Drug-use groups matched on gender and approximately matched on age and use of some other drugs (alcohol, cannabis).

Criteria for Inclusion - Ecstasy Users - Self-reported using ecstasy at least 20 times in year previous to study and having taken ecstasy on the evening of Day 0. Non-ecstasy users - Little or no lifetime use of ecstasy, not having taken ecstasy on Day 0; use of drugs other than ecstasy permitted. All Groups - Apparently self-reported absence of past or present major medical or psychiatric illness, not being pregnant, and lack of opiate or alcohol dependence.

Drug Use Parameters, Ecstasy Use - Ecstasy users reported having used 784.42 +/- 938.85 ecstasy tablets over a lifetime (calculated as dose x year x frequency by authors), with average dose per use reported as 2.92 +/- 1.66 tablets per session. (Men reported using 3.55 +/- 1.99 tablets per session; women reported using 2.26 +/- 0.87 tablets per session). Average frequency of ecstasy use was 4.32 +/- 2.98 times per month. 8 / 40 non-ecstasy users (3 men, 5 women) reported having used ecstasy at least once in the previous six months, but none reported having used ecstasy more than once a month. None had taken ecstasy 21 days prior to study. (Men took ecstasy 4.63 +/- 3.58 times a month, women took ecstasy 4 +/- 2.29 times per month). Duration of use, in months, was reported at 52.2 +/- 35.76 months. Time since last use, in days, was 0 days on Day 0 (measure of acute effects) and 3 days prior to Day 4 on Day 4, with time since last use verified via self-report only. Amount of ecstasy reportedly used on Day 0 (in tablets); women reported taking 1.8 ecstasy tablets and men reported taking 2.1 tablets. Other Drugs, Lifetime Use - Alcohol was used by all participants in both drug use groups. Tobacco was used by 34 ecstasy users and 28 non-ecstasy users. Cannabis had been used by 36 ecstasy users and by 34 non-ecstasy users. Amphetamine had been used by 10 ecstasy users and by 2 non-ecstasy users. Cocaine had been used by 26 ecstasy users, and by 8 non-ecstasy users. Ketamine had been used by 12 ecstasy users, but none of the non-ecstasy group had used it. LSD had been used by 7 ecstasy users, and 2 non-ecstasy users. GHB was not used by ecstasy users or non-ecstasy users. Benzodiazepines had been used by 1 ecstasy user, but not by any of the non-ecstasy users. Other Drugs, Day 0 use - Alcohol was used by 38 ecstasy users (19 men, 19 women) and 38 non-ecstasy users (17 men, 21 women). On Day 0, ecstasy users reportedly drank 4.5 units of alcohol (men = 5.3 units, women = 3.7 units), and non-ecstasy users reportedly drank 5.2 units (men = 5 units, women = 5.4 units). Cannabis was used by 15 ecstasy users (9 men, 6 women) and 22 non-ecstasy users (13 men, 9 women). Amphetamines were used by 1 female ecstasy user only. Cocaine was used by 5 male ecstasy users and 1 female non-ecstasy user. Ketamine was used by 4 ecstasy users (3 men, 1 women) and none of the non-ecstasy users. LSD was not used by any member of either of the two drug use groups on Day 0. GHB was not used by any member of either drug use group on Day 0. Benzodiazepines were used by 1 male ecstasy user on Day 0.

Group Demographics and Matched Variables - The authors matched ecstasy users and non-users by gender, and groups were approximately matched by age and use of other drugs. However, male ecstasy users were significantly older than female ecstasy users, male non-ecstasy users, and female non-ecstasy users. Male ecstasy users had higher lifetime use of ecstasy than female ecstasy users, and they also used more alcohol and tobacco. A greater number of ecstasy users reported using drugs other than ecstasy compared with non-ecstasy users, and they used greater amounts of alcohol and tobacco than non-ecstasy users. Gender, as M/F ratio - Ecstasy users, 21/19, non-ecstasy users, 19/21. Age - Average age of ecstasy users = 22.3 +/- 3.41 years (men = 23.43 +/- 4.2, women = 21.05 +/- 1.54). Average age of non-ecstasy users = 20.45 +/- 1.85 years (men = 20.26 +/- 1.56, women = 20.62 +/- 2.11). Education - No information is provided concerning educational level attained by members of either drug use group.

Measures: Mood - Mood state assessed on Day 0 and Day 4 via modified BDI (responses refer to day of study rather than the last 3 days), and 4 visual analog scales; the Mood Rating Scale (MRS), the Aggression Rating Scale (ARS), the Impulsivity Self-Rating scale (ISRS), and the Bodily Symptoms Scale (BSS (measure of somatic symptoms associated with ecstasy / MDMA). On day 4 only, Trait depression and anxiety were assessed via Hospital Anxiety and Depression scale (HADS), and trait aggression was assessed via Aggression Questionnaire (AQ).

Physiological Measure - Pulse rate was assessed in approximately half the participants, with assessment occurring on Day 0 and Day 4. (One researcher failed to assess pulse rate).

Analyses: Mood - Changes in mood score were examined via repeated measures analysis of covariance (ANCOVA), with gender (male or female) and drug use (presence versus absence of ecstasy use on Day 0) serving as between-groups factors, day of study (Day 0 or Day 4) as a within-subjects repeated measure, and age as a covariate, with p set at 0.05. Trait mood scales (administered on Day 4 only) presumably analyzed via 2(gender) x 2(drug use) ANCOVA, with age serving as covariate. P. value not stated but apparently set at 0.01.

Physiological Measure - Differences in pulse rate were examined via a repeated-measures ANOVA, with gender and drug use serving as between-subjects variables, and with day of measurement serving as a within-subjects variable. P was set at 0.05. Drug Use Parameters and Mood - Relationships between ecstasy or other drug use parameters and mood scores were assessed via correlation (Pearson's product-moment correlation).

Results - Significant Differences: Mood - Increase in modified BDI score from Day 0 to Day 4 was greater in female ecstasy users than in male ecstasy users. Increase in MRS-discontentment in female ecstasy users on Day 4 was higher than increase in discontentment for male ecstasy users. Both male and female ecstasy users had lower state depression scores on Day 0 than non-ecstasy users, and higher depression scores on Day 4 than non-ecstasy users. Ecstasy users had lower cognitive depression scores on Day 0 than non-ecstasy users, but on Day 4, ecstasy users had higher cognitive depression scores. Women had lower MRS-calmness scores than men in both drug use groups, and both women and men in both drug use groups reported being more alert on Day 4 compared with Day 0. Aggression - Non-ecstasy users had higher aggression scores on Day 0 than ecstasy users, but on Day 4, ecstasy users had higher aggression scores than non-ecstasy users. Impulsivity - Ecstasy users had higher impulsivity scores on both study days, compared with non-ecstasy users on both days 0 and 4. Ecstasy users reported more acute side effects on Day 0 than on Day 4 (palpitations, loss of appetite, muscle tension and visual sensitivity), with no difference between groups on Day 4. On other BSS subscales, ecstasy users had lower anxiety and depression on Day 0 than non-ecstasy users, and higher anxiety and depression on Day 4. Women in both ecstasy user and non-user groups had lower BSS depression scores than men on Day 0, and higher depression scores on Day 4. Ecstasy users had higher self-reported memory loss scores, and reported poorer concentration when compared with non-ecstasy users.

Pulse rate - The difference between pulse rate on Day 0 and pulse rate on Day 4 was greater for ecstasy users than for non-ecstasy users, with elevated pulse rate recorded for ecstasy users on Day 0 only.

Drug use parameters and mood - Amount of ecstasy taken on Day 0 was positively associated with changes in modified BDI score over time, with higher ecstasy dose on Day 0 associated with decreased depressed mood on Day 0 and/or increased depressed mood on Day 4. Separate analyses for men and women indicated that amount of ecstasy used on Day 0 was associated with Day 4 depression score for women only. Amount of ecstasy tablets taken on Day 0 was positively associated with degree of change in aggression scores over time, with higher doses of ecstasy associated with lower aggression on Day 0 and higher aggression on Day 4. However, when separate analyses were conducted for each gender, the positive relationship between ecstasy dose on Day 0 and change in aggression score was only significant for male ecstasy users. There was a negative association between amount of alcohol consumed on Day 0 and change in modified BDI score over time in male, but not female, ecstasy users, with higher doses of alcohol on Day 0 associated with less difference between depression rating on Day 0 and Day 4.

Results - No Significant Differences Found: Mood - Female non-ecstasy users only had a slight difference in modified BDI score between Day 0 and Day 4. Male and female ecstasy users did not differ on the somatic scale of the modified BDI. Non-ecstasy users did not show any change in MRS-discontentment score over time. Ecstasy users did not differ from non-ecstasy users on most MRS calmness or alertness scores on either day or over time. Both male and female ecstasy users did not significantly differ on trait depression or anxiety scores when compared with male or female non-ecstasy users (as measured on Day 4). Aggression - Male ecstasy users did not have significantly different aggression scores from female ecstasy users across both days, and there were no significant differences in the trait aggression scores of male and female non-users Ecstasy users and non-ecstasy users did not significantly differ on trait aggression scores. Impulsivity - Men and women (across groups) did not have significantly different impulsivity scores. There were no 3-way (gender x drug use x day) interactions for BSS scores, indicating that female ecstasy users did not report significantly different ecstasy side effects than male ecstasy users on Day 0 or Day 4, and there was a similar lack of gender difference in non-ecstasy users.

Drug Use Parameters and Mood - The relationship between amount of ecstasy used on Day 0 and change in aggression score over time was weak for women, and the relationship between ecstasy dose on Day one and change in modified BDI score was weak over time for men. Lifetime ecstasy use, average dose per use, and duration of ecstasy use were not associated with changes in aggression scores at either point in time, and for either men or women. There were no associations between lifetime ecstasy use, average dose per use, or duration of use and changes in depressed mood (measured via modified BDI) from Day 0 to Day 4.

Overall Effects: Both men and women in a sample of 40 predominantly young ecstasy users recruited at parties reported being acutely less depressed and less aggressive immediately after ecstasy use when compared with a sample of 40 individuals recruited from the same environment who had not used ecstasy. Both men and women also reported experiencing common side effects associated with ecstasy use, including palpitations, loss of appetite, visual sensitivity and muscle tension. Pulse rate (measured in approximately half the participants) was more elevated in ecstasy users on Day 0 than non-ecstasy users. Taking larger amounts of ecstasy seemed to produce greater differences in aggression measured acutely after drug and again 4 days after taking ecstasy, whereas changes in self-reported depressed mood were only related to amount of ecstasy used on Day 0 in women, and not men. However, while women reported greater depressed mood 4 days after taking ecstasy, as compared with women not using ecstasy, both men and women who had taken ecstasy had significantly higher aggression scores 4 days later. Self-reported impulsivity was elevated in ecstasy users, as compared with non-ecstasy users, with the difference apparent both on Day 0 and Day 4. Ecstasy users did not have significantly higher trait aggression or depression scores than non-ecstasy users. Self-reported memory loss and difficulty concentrating were reported by both male and female ecstasy users. Extent of cumulative exposure (lifetime ecstasy use), average dose per use and duration of use were unrelated to changes in mood, aggression or impulsivity. The authors' hypotheses were partially confirmed. As predicted, women had higher depressed mood scores than men 4 days after ecstasy use. However, while there was a relationship between amount of ecstasy used on Day 0 and self-reported aggressiveness on Day 4 for men, men who used ecstasy were not more likely than women to have higher aggression scores 4 days after ecstasy use. Instead, self-rated aggression was higher in men and women who used ecstasy 4 days after ecstasy use. It should also be noted that women in this sample were no more likely to report more acute or sub-acute side effects than were men.

Comments: This is the second of two reports examining the sub-acute effects of ecstasy via retrospective study design (see Curran & Travill 1998). Sample sizes are larger in this study, and the authors examined mood, and not cognitive function, in this study. A comparison by gender of a sample of people taking part in a clinical trial of MDMA also found that women reported more sub-acute side effects than men. However, the same study also found that women and men differed in reporting of acute side effects, with women reporting more side effects than men. It is noteworthy that ecstasy use, and not gender, was associated with aggression score on Day 4. While the authors hypothesize that temporary depletion of central serotonin stores are a probable cause of the sub-acute effects of ecstasy reported here, studies in non-human animals suggest that serotonin levels should have been restored at 4 days post-drug. Changes in serotonin receptors, might also be involved in producing these greater depressed mood in women and greater aggressiveness in both male and female ecstasy users. While the sample in this study is large, ecstasy users are not well matched with non-ecstasy users in their use of other drugs. Prospective studies and clinical trials provide a better means to test hypotheses concerning the effects of ecstasy or MDMA on mood than retrospective studies. Use of ecstasy or other drugs should have been verified through detection methods rather than relying on self-report alone, and increased pulse rate cannot be used as an indicator of ecstsay use, as stimulants and other drugs also increase pulse.