Dataset Information

Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects.

ABSTRACT: No pharmacotherapies are approved for the treatment of cocaine use disorders (CUD). Behavioral treatments for CUD are efficacious for some individuals, but recovery rates from CUD remain low. Cognitive impairments in CUD have been linked with poorer clinical outcomes. Cognitive enhancing pharmacotherapies have been proposed as promising treatments for CUD. Atomoxetine, a norepinephrine transporter inhibitor, shows potential as a treatment for CUD based on its efficacy as a cognitive enhancer in other clinical populations and impact on addictive processes in preclinical and human laboratory studies. In this randomized, double-blind, crossover study, abstinent individuals with CUD (N=39) received placebo, 40 and 80mg atomoxetine, over three sessions. Measures of attention, response inhibition and working memory; subjective medication effects and mood; and cardiovascular effects were collected. Analyses assessed acute, dose-dependent effects of atomoxetine. In addition, preliminary analyses investigating the modulation of atomoxetine dose effects by sex were performed. Atomoxetine increased heart rate and blood pressure, was rated as having positive and negative subjective drug effects, and had only modest effects on mood and cognitive enhancement.

SUBMITTER: DeVito EE

PROVIDER: S-EPMC5573182 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects.

DeVito Elise E EE Herman Aryeh I AI Konkus Noah S NS Zhang Huiping H Sofuoglu Mehmet M

Pharmacology, biochemistry, and behavior 20170714

No pharmacotherapies are approved for the treatment of cocaine use disorders (CUD). Behavioral treatments for CUD are efficacious for some individuals, but recovery rates from CUD remain low. Cognitive impairments in CUD have been linked with poorer clinical outcomes. Cognitive enhancing pharmacotherapies have been proposed as promising treatments for CUD. Atomoxetine, a norepinephrine transporter inhibitor, shows potential as a treatment for CUD based on its efficacy as a cognitive enhancer in ...[more]

PMID: 28716656

Similar Datasets

Project description:OBJECTIVES:Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine and also whether cognitive function was affected by atomoxetine during short-term administration. METHODS:In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in sequential daily sessions. RESULTS:Preinfusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Preinfusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80- and 100-mg atomoxetine doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS) scores for "bad effect" in the atomoxetine group were significantly higher at baseline, then declined, and for "likely to use" declined with atomoxetine treatment. On the Addiction Research Center Inventory, the atomoxetine group scored significantly lower on amphetamine, euphoria, and energy subscales (P < 0.0001). Other VAS descriptors, Brief Substance Craving Scale, Profile of Moods State, and Brief Psychiatric Rating Scale showed no differences. Atomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. CONCLUSIONS:Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine.

Project description:Background: Psychopathy and substance use disorders (SUDs) are both characterized by neurocognitive impairments reflecting higher levels of impulsivity such as reward-driven decision-making and deficient inhibitory control. Previous studies suggest that psychopathy may exacerbate decision-making deficits, but it may be unrelated to other neurocognitive impairments among substance dependent individuals (SDIs). The aim of the present study was to examine the role of psychopathy and its interpersonal-affective and impulsive-antisocial dimensions in moderating the relationships between dependence on different classes of drugs and neurocognitive domains of impulsivity. Method: We tested 693 participants (112 heroin mono-dependent individuals, 71 heroin polysubstance dependent individuals, 115 amphetamine mono-dependent individuals, 76 amphetamine polysubstance dependent individuals, and 319 non-substance dependent control individuals). Participants were administered the Psychopathy Checklist: Screening Version (PCL:SV) and seven neurocognitive tasks measuring impulsive choice/decision-making (Iowa Gambling Task; Cambridge Gambling Task; Kirby Delay Discounting Task; Balloon Analog Risk Task), and impulsive action/response inhibition (Go/No-Go Task, Immediate Memory Task, and Stop Signal Task). Results: A series of hierarchical multiple regressions revealed that the interpersonal-affective dimension of psychopathy moderated the association between decision-making, response inhibition and both amphetamine and heroin dependence, albeit differently. For amphetamine users, low levels of interpersonal-affective traits predicted poor decision-making on the Iowa Gambling Task and better response inhibition on the Stop Signal task. In contrast, in heroin users high interpersonal-affective psychopathy traits predicted lower risk taking on the Cambridge Gambling Task and better response inhibition on the Go/No-Go task. The impulsive-antisocial dimension of psychopathy predicted poor response inhibition in both amphetamine and heroin users. Conclusions: Our findings reveal that psychopathy and its dimensions had both common and unique effects on neurocognitive function in heroin and amphetamine dependent individuals. Our results suggest that the specific interactions between psychopathy dimensions and dependence on different classes of drugs may lead to either deficient or superior decision-making and response inhibition performance in SDIs, suggesting that psychopathy may paradoxically play a protective role for some neurocognitive functions in specific subtypes of substance users.

Dataset Information

Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects.

Publications

Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets