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Gerra G, Zaimovic A, Ampollini R, Giusti F, Delsignore R, Raggi MA, Laviola G, Macchia T, Brambilla F. 
“Experimentally induced aggressive behavior in subjects with 3,4- methylenedioxy-methamphetamine ('Ecstasy') use history: psychobiological correlat”. 
Journal of Substance Abuse. 2001;13(4):471-491.

PURPOSE: Objective measures of experimentally induced aggressiveness were evaluated in 12 male 3,4-methylenedioxy-methamphetamine (MDMA, 'Ecstasy') users, in comparison with 20 healthy male subjects.

METHODS: All the subjects were preliminarily submitted to DSM-IV interviews and Buss-Durkee Hostility Inventory (BDHI). During a laboratory task, the Point Subtraction Aggression Paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money that was attributed to a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). Escape responses were also possible protecting the counter from monetary subtractions.

RESULTS: Money-earning responses were not different in Ecstasy users and controls; aggressive responses were significantly higher in Ecstasy users in comparison with control subjects (F=20.74, P<.001). Baseline adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels were higher in Ecstasy users than in controls. No difference was found in norepinephrine (NE) and epinephrine (EPI) basal levels of the two groups. During the experimentally induced aggressiveness, plasma ACTH concentrations increased significantly less and NE and EPI levels, together with heart rate (HR), increased significantly more in Ecstasy users than in healthy subjects. Despite ACTH-blunted responses, CORT did not increase differently from controls in Ecstasy users. PSAP aggressive responses positively correlated with catecholamines and CORT changes, BDHI Direct Aggression and Irritability scores, both in Ecstasy users and controls. A significant correlation was found between Ecstasy exposure extent and aggressive responses (r=.78, P<.001). IMPLICATIONS: Our findings suggest that Ecstasy users have higher outward-directed aggressiveness than healthy subjects. Aggressiveness in MDMA subjects seems to be associated more with MDMA pharmacological effects than with personality traits: Nevertheless, a premorbid psychobiological proneness to aggressive behavior cannot be excluded. Increased catecholamines reactivity, basal hypothalamus-pituitary- adrenal (HPA) axis hyperactivity, and blunted ACTH responses could be due to MDMA action on monoaminergic pathways and adrenal function
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