Purpose: Pharmacological, pharmacokinetic; To compare drug concentrations in saliva and urine for MDMA, MDEA and other drugs soon after drug administration and again 3-5 h after attending a nightclub or party.

Design: Uncontrolled, non-blinded within-subjects experimental design with time of measurement (1 h post-drug or "after party" 3-5 h post-drug) serving as one repeated measure, and session (on-drug, no drugs) serving as another repeated measure. Participants instructed to self-administer only 1 ecstasy tablet before first sample, and to self-administer whatever they would normally use at a club or party before the "after party" sample. Urine and saliva samples collected from participants at both times (1 h and after party, using identical or nearly identical time-points in the no-drugs condition) and at both the on-drugs and no-drug sessions. All save two participants submitted a second ecstasy tablet (presumed identical to the one they self-administered) for analysis. (This study was designed to compare on-drug and off-drug performance on a driving simulation).

Subjects: 19 MDMA-experienced participants (5 women and 14 men, ages not provided, perhaps no older than 30) living in or near Groningen (the Netherlands), with no information provided concerning participant recruitment.

Criteria for Inclusion - Having used ecstasy, with minimum number of uses not provided but presumably at least once, abstinence from all psychoactive drugs for an unspecified time (perhaps 2 weeks, and at least 1 day) prior to no-drugs study day, with abstinence verified through urinary analysis, and healthy, with means of confirming health unspecified.

Measures: Urine - Urine samples were collected twice during each session (on-drug and no-drugs), at 1 h post-ecstasy administration (or same time on no-drugs evening), and after attending club or party (approximately 3-6 h post-ecstasy), or same time on no-drugs evening, and urinary content of MDMA was assessed with gas chromatography-mass spectrometry (GC-MS-EI). During the on-drug condition "after party" (multiple drugs) samples were also screened for other drugs, including cannabis, cocaine, amphetamine, LSD, GHB and psilocin (from psilocybin).

Saliva - On-drug salivary samples were collected 1 h post-ecstasy and again "after party" (3-5 h post-ecstasy). No-drugs salivary samples were collected at the same times of day as the 1 h-post-ecstasy and "after party" salivary samples collected during on-drug session, and MDMA or related drug concentrations assessed via reverse phase HPLC-MS.

Tablet analysis - Ecstasy tablets were submitted by 17 of 19 participants. Tablets were analyzed for contents, with analysis not described. MDMA, MDE and amphetamine were assessed in each tablet submitted.

Analyses: No formal analyses were applied to the data collected. However, values collected 1-h post-ecstasy ("MDMA only") were informally compared across subjects and with values recorded after party, 3-6 h post-ecstasy ("multiple drugs"). The complete design was not used in analyses, though contents of samples collected at both times on the no-drugs session were reported in tables, and informal comparisons were made as to presence or absence of urinary and salivary drug values. A correlation between salivary and urinary amphetamines was performed.

Results: Time elapsed between self-administration of ecstasy and first samples was 62 +/- 23 minutes after ingestion. Time elapsed between 1 h post-ecstasy and "after party" sample was 4.7 h excluding two individuals who returned at a much later time (22.1 and 21.5 h respectively). Including these individuals, average time elapsed between 1 h post-ecstasy and "after party" sample was 6.5 h. Most people returned between 4 and 5 hours later. On average, nearly 1 extra ecstasy tablet was taken between 1 h post-ecstasy and "after party" session (0.973 pills), with number of additional pills taken ranging from none in 6 / 19 participants to 4.5 pills in 1/19 participants. Urine - Urinary MDMA values were generally higher "after party" than 1 h post-ecstasy, with 9 / 19 concentrations greater than 2000 ng/ml "after party," whereas only 5/19 had concentrations above 2000 ng/ml at 1 h post-ecstasy. However, only 7 of 9 reported taking more than 0.5 extra tablets before the "after party" sample. It should be noted that 3/19 participants had urinary MDMA concentrations (6689 ng/ml, 2007 ng/ml and 5405 ng/ml) on the no-drugs condition, and 1/19 had a urinary amphetamine concentration of 1274 on the no-drugs condition.

Saliva - Amphetamines (usually MDMA, also MDE or amphetamine) were detectable in saliva 1 h post-ecstasy, and ranged from 15 ng/ml amphetamine to 3533 ng/ml MDMA. An increase in salivary MDMA was found in all 6 participants who did not take any additional ecstasy in the "after party" sample. salivary MDMA concentrations collected "after party" ranged from 19 ng/ml to 7077 ng/ml MDMA, 322 ng/ml to 3320 ng/ml MDE and 129 ng/ml to 753 ng/ml amphetamine. Salivary and Urinary MDMA (amphetamines) - There was a significant relationship between salivary MDMA concentrations and urinary MDMA concentrations, with only two cases of urinary detection without salivary detection. Salivary MDMA in the "no drugs" session was detected in 2/19 participants, and one acknowledged taking ecstasy the previous day.

Tablet Analysis - Average amount of MDMA detected in pills was 57 +/- 20 mg, and MDMA content ranged from 25 mg to 95 mg, with most doses being in the range of 50-80 mg. 1 pill contained amphetamine only, and 2 pills either only contained MDE or an admixture of MDMA and MDE.

Detection of other drugs - In the "after party" urinary sample (taken 3 to 6 hours after first sample), amphetamine, cannabis, cocaine, LSD and psilocin (metabolite of psilocybin) detected. Amphetamine was detected in 7 / 19 participants (6 reported), cannabis was detected in 13 / 19 cases, (16 reported), cocaine was detected in 2 / 19 cases (2 reported), LSD in 1/19 case (1 reported), and psilocin in 2/19 (2 reported). Though 2/19 reported GHB use, none was detected in urine. While cannabis use was reported in 30% of the sample (5 or 6 participants) before the "no drugs" condition, cannabis was detected in urine of 60% (about 11) of 19 participants, but since cannabis can be detected in urine up to weeks after use, it is uncertain as to when those not reporting use had last used cannabis.

Overall Effects: MDMA (and MDE and amphetamine) were detected in saliva and urine 1 h after self-administration of ecstasy tablets with an average dosage of 57 mg (range 25-95 mg). MDMA and other drugs were usually detected in both fluids, though in 2 cases MDMA was detected in urine, but not saliva. People took nearly 1 additional tablet when attending a club or party (range 0-4.5 tablets), and many people also used cannabis. Some used amphetamine, and a few used cocaine, psilocybin-containing mushrooms, LSD or GHB. MDMA or amphetamine was occasionally was detected in urine in the "no drugs" session, indicating recent use despite request for abstention from drugs prior to study day. Coadministration of other drugs did not seem to interfere with detection of MDMA, MDE or amphetamine in samples taken "after party," but no formal analyses were applied that would have tested effects of drug combinations on detectability. The authors conclude that saliva could serve as a non-invasive measure of MDMA concentration (for use in arrests or stops for suspected impaired driving), at least if the cut-off is around 50 ng/ml.

Adverse Effects: None reported in this paper.

Comments: This paper is notable for its examination of MDMA excretion in salivary and urinary MDMA after street administration of ecstasy, both before and after participants attended clubs or parties and took additional ecstasy tablets and other drugs, such as cannabis or amphetamine. This paper is also notable for presenting laboratory analyses of ecstasy tablets identical to or similar to those taken by participants, and the number of tablets participants took subsequent to initial ecstasy self-administration. This could serve as a measure of preferred dosage. Because of its uncontrolled design and the wide variation in amount of MDMA or MDE contained in illicit ecstasy tablets, it is hard to examine inter-subject variability in this study. Perhaps because of the great variability in subsequent ecstasy use, the authors did not attempt to investigate whether co-administration with other drugs (as cannabis) altered drug excretion in any way. MDMA was only slightly easier to detect in urine than it was in saliva. (The authors noted difficulties in collecting salivary samples due to participants reporting dry mouth.) Conclusions are limited by reliance on self-reported use of ecstasy and other drugs after the first "on-drug" sample, and by wide variability in initial dose of MDMA (or MDE), and variability in use of other drugs.