Smoked cocaine self-administration is decreased by modafinil.

Division on Substance Abuse, New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Neuropsychopharmacology (Impact Factor: 7.83). 04/2008; 33(4):761-8. DOI: 10.1038/sj.npp.1301472
Source: PubMed

ABSTRACT Modafinil has been reported to reduce cocaine use in a clinical sample of infrequent users (2 days/week), but the effects of modafinil on cocaine self-administration in the laboratory have not been studied. The present study investigated the effects of modafinil maintenance on cocaine self-administration by frequent users (4 days/week) under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of modafinil maintenance (0, 200, and 400 mg/day) on response to smoked cocaine (0, 12, 25, and 50 mg) were examined in nontreatment-seeking cocaine-dependent individuals (n=8). Cocaine significantly increased self-administration, subjective-effect ratings, and cardiovascular measures; modafinil at both doses (200 and 400 mg/day) markedly attenuated these effects. These findings agree with data from previous human laboratory and clinical investigations of modafinil as a potential cocaine abuse treatment medication. Thus, our data support the potential of modafinil as a pharmacotherapy for cocaine dependence.

1 Bookmark
  • Source
    European Psychiatry 04/2008; 23:S307-S308. DOI:10.1016/j.eurpsy.2008.01.1056 · 3.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment of stimulant-use disorders remains a formidable challenge, and the dopamine transporter (DAT) remains a potential target for antagonist or agonist-like substitution therapies. This review focuses on DAT ligands, such as benztropine, GBR 12909, modafinil, and DAT substrates derived from phenethylamine or cathinone that have atypical DAT-inhibitor effects, either in vitro or in vivo. The compounds are described from a molecular mechanistic, behavioral, and medicinal-chemical perspective. Possible mechanisms for atypicality at the molecular level can be deduced from the conformational cycle for substrate translocation. For each conformation, a crystal structure of a bacterial homolog is available, with a possible role of cholesterol, which is also present in the crystal of Drosophila DAT. Although there is a direct relationship between behavioral potencies of most DAT inhibitors and their DAT affinities, a number of compounds bind to the DAT and inhibit dopamine uptake but do not share cocaine-like effects. Such atypical behavior, depending on the compound, may be related to slow DAT association, combined sigma-receptor actions, or bias for cytosol-facing DAT. Some structures are sterically small enough to serve as DAT substrates but large enough to also inhibit transport. Such compounds may display partial DA releasing effects, and may be combined with release or uptake inhibition at other monoamine transporters. Mechanisms of atypical DAT inhibitors may serve as targets for the development of treatments for stimulant abuse. These mechanisms are novel and their further exploration may produce compounds with unique therapeutic potential as treatments for stimulant abuse. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Drug and Alcohol Dependence 12/2014; 147. DOI:10.1016/j.drugalcdep.2014.12.005 · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Deficits in behavioural inhibitory control are attracting increasing attention as a factor behind the development and maintenance of substance dependence. However, evidence for such a deficit is varied in the literature. Here, we synthesised published results to determine whether inhibitory ability is reliably impaired in substance users compared to controls.
    Drug and Alcohol Dependence 08/2014; DOI:10.1016/j.drugalcdep.2014.08.009 · 3.28 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014