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Dopaminergic system dysfunction in recreational dexamphetamine users.

ABSTRACT: Dexamphetamine (dAMPH) is a stimulant drug that is widely used recreationally as well as for the treatment of attention-deficit hyperactivity disorder (ADHD). Although animal studies have shown neurotoxic effects of dAMPH on the dopaminergic system, little is known about such effects on the human brain. Here, we studied the dopaminergic system at multiple physiological levels in recreational dAMPH users and age, gender, and IQ-matched dAMPH-naïve healthy controls. We assessed baseline D2/3 receptor availability, in addition to changes in dopamine (DA) release using single-photon emission computed tomography and DA functionality using pharmacological magnetic resonance imaging, following a dAMPH challenge. Also, the subjective responses to the challenge were determined. dAMPH users displayed significantly lower striatal DA D2/3 receptor binding compared with healthy controls. In dAMPH users, we further observed a blunted DA release and DA functionality to an acute dAMPH challenge, as well as a blunted subjective response. Finally, the lower D2/3 availability, the more pleasant the dAMPH administration was experienced by control subjects, but not by dAMPH users. Thus, in agreement with preclinical studies, we show that the recreational use of dAMPH in human subjects is associated with dopaminergic system dysfunction. These findings warrant further (longitudinal) investigations and call for caution when using this drug recreationally and for ADHD.

SUBMITTER: Schrantee A

PROVIDER: S-EPMC4367461 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Project description:Chronic cocaine use has been associated with impairments in social cognition, self-serving and antisocial behavior, and socially relevant personality disorders (PD). Despite the apparent relationship between Machiavellianism and stimulant use, no study has explicitly examined this personality concept in cocaine users so far. In the frame of the longitudinal Zurich Cocaine Cognition Study, the Machiavellianism Questionnaire (MACH-IV) was assessed in 68 recreational and 30 dependent cocaine users as well as in 68 psychostimulant-naïve controls at baseline. Additionally, three closely related personality dimensions from the Temperament and Character Inventory (TCI)-cooperativeness, (social) reward dependence, and self-directedness-and the screening questionnaire of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) were acquired. At the one-year follow-up, 57 cocaine users and 48 controls were reassessed with the MACH-IV. Finally, MACH-IV scores were correlated with measures of social cognition and interaction (cognitive/emotional empathy, Theory-of-Mind, prosocial behavior) and with SCID-II PD scores assessed at baseline. Both recreational and dependent cocaine users showed significantly higher Machiavellianism than controls, while dependent cocaine users additionally displayed significantly lower levels of TCI cooperativeness and self-directedness. During the one-year interval, MACH-IV scores showed high test-retest reliability and also the significant gap between cocaine users and controls remained. Moreover, in cocaine users, higher Machiavellianism correlated significantly with lower levels of cooperativeness and self-directedness, with less prosocial behavior, and with higher cluster B PD scores. However, Machiavellianism was not correlated with measures of cocaine use severity (r<-.15). Both recreational and dependent cocaine users display pronounced and stable Machiavellian personality traits. The lack of correlations with severity of cocaine use and its temporal stability indicates that a Machiavellian personality trait might represent a predisposition for cocaine use that potentially serves as a predictor for stimulant addiction.

Project description:BackgroundWith the legalization of cannabis in Canada, young adults, who are already at risk of automobile crashes, may increase their use of cannabis, which may further increase the risk of crashes. We examined the effects of inhaled cannabis on driving-related performance in healthy 18- to 24-year-old recreational cannabis users.MethodsIn this within-subject randomized study, participants completed tests in the no-cannabis state and at 1, 3 and 5 hours after inhalation of a standard 100-mg dose of cannabis. We then measured performance (in useful-field-of-view and driving-simulation tests) and self-reported perceptions (driving ability and safety, cannabis effects). Repeated-measures analysis of variance (for cannabis effects on continuous performance measures), Cochran Q tests (for performance-related crash risk and binary complex simulator task scores) and correlational analyses (for self-reported perceptions relative to performance) were employed.ResultsForty-five participants completed all 180 testing sessions. Significant effects of cannabis (relative to no cannabis) were noted on complex useful-field-of-view tasks at 3 hours (complex divided-attention task: 70 ± 24 ms v. 37 ± 12 ms, 95% confidence intervals [CIs] 28-114 ms v. 29-45 ms, t = -2.98, df = 41, p = 0.005; complex selective-attention task: 102 ± 66 ms v. 64 ± 18 ms, 95% CIs 60-144 ms v. 53-75 ms, t = -2.42, df = 41, p = 0.02) and 5 hours (complex selective-attention task: 82 ± 29 ms v. 61 ± 19 ms, 95% CIs 62-100 ms v. 48-75 ms, t = -2.32, df = 41, p = 0.03) after cannabis use when the tasks were novel (performed in a cannabis state at the first session). Participants were significantly more likely to be classified as having a high crash risk (on the basis of simulator tasks) after cannabis use (χ 2 = 13.23, df = 1, p < 0.001, odds ratio 4.31, 95% CI 0.41-45.2) and reported significantly lower perceived driving ability and safety after cannabis use relative to non-use.InterpretationAmong young recreational cannabis users, a 100-mg dose of cannabis by inhalation had no effect on simple driving-related tasks, but there was significant impairment on complex tasks, especially when these were novel. These effects, along with lower self-perceived driving ability and safety, lasted up to 5 hours after use.Trial registrationThe trial was registered with Health Canada (NOL [No Objection Letter] no. 215101).

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Dopaminergic system dysfunction in recreational dexamphetamine users.

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