These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function. These findings are compatible with neurotoxicity of ecstasy as shown in animals.

Administration of amphetamine leads to stimulated action monitoring, reflected in increased ERN amplitudes. This result provides evidence for dopaminergic involvement in action monitoring and is in line with differences in ERN amplitude found in neuropsychiatric disorders also suggesting dopaminergic involvement. The different effects for lorazepam and mirtazapine are probably caused by the neurobiological characteristics of these two types of sedation. Action monitoring is suppressed after administration of lorazepam, because the GABAergic pathways directly inhibit ACC functioning, whereas the histaminergic pathways of mirtazapine do not innervate the ACC directly.

The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of c-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.

MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.

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This review of the literature aims to identify the acute effects of MDMA (ecstasy) in healthy volunteers. The wide range of relevant but methodologically diverse tests was .rst grouped into clusters to allow an evaluation of tests that would otherwise have been excluded due to their low frequency of utilization. The following three types of tests were evaluated: (1) functional tests quantifying executive, attention, visual, motor, visuomotor and auditory functions, (2) phenomenological tests assessing personal, subjective experiences, and (3) physiological measures reflecting neurophysiological, endocrine and physiological parameters. MDMA showed robust effects on most of the phenomenological and physiological tests. Functional tests were scarce, preventing any meaningful conclusions to be drawn from their evaluation other than that these tests should be incorporated into future acute-effect studies. A striking doseñresponse relationship appeared for cardiovascular effects. At doses below 1.0 mg/kg MDMA no change was observed relative to placebo while above this dose all studies reported significant increases. Furthermore, pupil size, plasma cortisol and plasma prolactin levels proved responsive to MDMA administration. The reported subjective effects of MDMA matched the entactogenic profile. Although interest in the action of MDMA is considerable, the existing knowledge about the cognitive effects of MDMA in humans is still rather limited and further research into the drug's effects is recommended, also in view of potential therapeutic uses of the drug.

Indirect genomic (allopregnanolone) and non-genomic (allopregnanolone and DHEA) mechanisms are involved in the neurosteroidogenic pathophysiology of depression. Clinical studies in homogeneous groups of non-pharmacologically treated depressed patients are required to elucidate this relationship further.