Plasma drug levels of d-fenfluramine and S-(+)-MDMA, which the authors refer to as d-MDMA, were compared in male rhesus monkeys after the first and seventh dose of an eight-dose regimen. Monkeys in the MDMA condition received 10 mg/kg i.m. S-(+)-MDMA twice daily on 4 consecutive days; monkeys in the d-fenfluramine condition received 5 mg/kg d-fenfluramine, on the same schedule. The researchers measured core body temperature and collected blood samples at 0, 5, 10, 15, 20, 30, 45 min and 1, 2, 3, 4, 5, 6, 7 and 8 h post-drug. Drugs and their metabolites were detected in blood via HPLC. On sacrifice 6 months post-drug, brain serotonin content was assessed in all animals. Peak plasma levels of first-dose S-(+)-MDMA were reached 20 min after drug, and were 9.5 ± 2.53 mcM. Peak values for MDA (enantiomer unspecified, presumably also S-(+)-MDA) were reached 2 to 3 h post-drug, and were 0.92 ± 0.23 mcM. First dose S-(+)-MDMA T1/2 was 2.84 ± 0.37 h, and AUC was 40.96 ± 18.83. T ½ for MDA was not determined directly, but was calculated as 8.3 ± 1 h with the PBPK program. Inter-subject variation in plasma S-(+)-MDMA was great; d-fenfluramine values did not vary as widely. On the seventh dose, peak plasma levels of S-(+)-MDMA were 12.88 ± 4.87 mcM, also peaking 20-40 min post-drug. Seventh-dose S-(+)-MDMA T1/2 was 3.94 ± 1.13 h, and AUC was 75.45 ± 39.06. (Values were not reported for MDA). Apparent distribution of volume was 4.81± 1.68 L/kg. On first dose, body temperature dropped over 8 hours post-drug. Brain serotonin transporter was reduced by 80% after S-(+)-MDMA regimen, with little variability in degree of brain serotonin transporter reduction. A correlational analysis of performance on a learning task conducted during and immediately after MDMA, (described in Frederick et al. 1998) and plasma MDMA levels was conducted. It was found that monkeys with higher plasma MDMA levels took longer to perform the tasks a week after MDMA regimen, though reduced performance was no longer seen a month post-regimen. Peak plasma values, AUCs and T1/2 were reported for d-fenfluramine, but no examinations were made of effects of d-fenfluramine treatment on learning. D-fenfluramine also reduced brain serotonin transporter level. Study findings were examined alongside human plasma MDMA (after 100 mg, about 1.43 mg/kg), and was reported as 1 mcM or less (Mas et al. 1999; Fallon et al. 1999). Peak MDA values in this study were 35-145 mcM, levels similar to those recorded in fatal cases of MDA overdoses (Cimbura 1972). Hence even after the first dose, S-(+)-MDMA levels in this study were ten times those seen in typical doses used recreationally and in clinical or laboratory settings (40-125 mg). The study does not provide information about what dose above the dose producing plasma levels above 1 mcM reduces brain serotonin (e.g. a "threshold dose," and the study used the more active MDMA enantiomer S-(+)-MDMA, even though Ecstasy users take the racemate. Hence it is unclear whether study findings can be directly extrapolated to Ecstasy users or to controlled studies with MDMA, but strongly suggests that MDMA dose regimens used in non-human primates expose animals to far greater levels of plasma MDMA than seen in humans. The surprising findings of a 1.5 to 2 deg. C drop in body temperature is not discussed by the authors; perhaps the temperature rose and then rapidly declined. However, because a threshold dose is not established, it is unclear whether doses matching human exposure would reduce brain serotonin in monkeys.