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Individual predictors of the subjective effects of intravenous cocaine.

ABSTRACT: The subjective and reinforcing effects of addictive substances can vary greatly between individuals. This study compared the relative contributions of baseline drug use, craving, stressful life events, and social factors in determining the subjective effects of cocaine in individual participants. Twelve veterans meeting criteria for cocaine dependence were evaluated in a laboratory setting. Self-report of the subjective effects of intravenous cocaine was recorded following single- and double-blind, placebo-controlled injections. Increased positive subjective effects of cocaine, including drug-induced 'good' effects and the value of intravenous injections, were most strongly correlated with greater family and social dysfunction measured through the Addiction Severity Index (ASI). Social dysfunction was the strongest predictor of cocaine-induced euphoria, accounting for approximately one-half of its variability. Participants who were dissatisfied with their current marital status reported almost no 'bad' effects of cocaine but instead reported increased drug-induced 'high', euphoria, and injection value. Although further research is required to determine the generalizability of this association, our findings are parallel to recent preclinical results showing that social interaction can attenuate psychostimulant reward. Effects of substance abuse treatment that rely on improved social function may be mediated through changes in the brain's reinforcement system that modify the rewarding effects of cocaine.

SUBMITTER: Grasing K

PROVIDER: S-EPMC3747034 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Individual predictors of the subjective effects of intravenous cocaine.

Grasing Kenneth K Mathur Deepan D Newton Thomas F TF Desouza Cherilyn C

Psychiatry research 20130612 3

The subjective and reinforcing effects of addictive substances can vary greatly between individuals. This study compared the relative contributions of baseline drug use, craving, stressful life events, and social factors in determining the subjective effects of cocaine in individual participants. Twelve veterans meeting criteria for cocaine dependence were evaluated in a laboratory setting. Self-report of the subjective effects of intravenous cocaine was recorded following single- and double-bli ...[more]

PMID: 23768613

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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:BackgroundPreclinical research implicates dopaminergic and noradrenergic mechanisms in mediating the reinforcing effects of drugs of abuse, including cocaine. The objective of this study was to evaluate the impact of treatment with the noradrenergic α(1) receptor antagonist doxazosin on the positive subjective effects of cocaine.MethodsThirteen non-treatment seeking, cocaine-dependent volunteers completed this single-site, randomized, placebo-controlled, within-subjects study. In one study phase volunteers received placebo and in the other they received doxazosin, with the order counterbalanced across participants. Study medication was masked by over-encapsulating doxazosin tablets and matched placebo lactose served as the control. Study medication treatment was initiated at 1 mg doxazosin or equivalent number of placebo capsules PO/day and increased every three days by 1 mg. After receiving 4 mg doxazosin or equivalent number of placebo capsules participants received masked doses of 20 and 40 mg cocaine IV in that order with placebo saline randomly interspersed to maintain the blind.ResultsDoxazosin treatment was well tolerated and doxazosin alone produced minimal changes in heart rate and blood pressure. During treatment with placebo, cocaine produced dose-dependent increases in subjective effect ratings of "high", "stimulated", "like cocaine", "desire cocaine", "any drug effect", and "likely to use cocaine if had access" (p<.001). Doxazosin treatment significantly attenuated the effects of 20 mg cocaine on ratings of "stimulated", "like cocaine", and "likely to use cocaine if had access" (p<.05). There were trends for doxazosin to reduce ratings of "stimulated", "desire cocaine", and "likely to use cocaine if had access" (p<.10).ConclusionsMedications that block noradrenergic α₁ receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further.Trial registrationClinicaltrials.gov NCT01062945.

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Individual predictors of the subjective effects of intravenous cocaine.

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Individual predictors of the subjective effects of intravenous cocaine.

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