A double‐blind, placebo‐controlled trial of modafinil (200 mg/day) for methamphetamine dependence

Shearer, James; Darke, Shane; Rodgers, Craig; Slade, Tim; Beek, Ingrid van; Lewis, John H.; Brady, Donna; McKetin, Rebecca; Mattick, Richard P.; Wodak, A D

doi:10.1111/j.1360-0443.2008.02437.x

Cited by 137 publications

(117 citation statements)

References 43 publications

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“…Camacho and Stein (2002) first reported that ( ± )-MOD was effective in treatment of amphetamine dependence in a patient with comorbid social phobia. This finding was later supported by a number of studies demonstrating that ( ± )-MOD was effective in reducing cocaine and methamphetamine use, subjective euphoric effects, craving, and withdrawal symptoms (Dackis et al, 2005;Dackis et al, 2003;Goudriaan et al, 2013;Hart et al, 2008;Malcolm et al, 2006;McGregor et al, 2008;Shearer et al, 2009). In experimental animals, ( ± )-MOD has been reported to block reinstatement of drug-seeking caused by cocaine, heroin, methamphetamine, or drug-associated environmental cues (Mahler et al, 2014;Reichel and See, 2010;Tahsili-Fahadan et al, 2010).…”

Section: Introductionmentioning

confidence: 80%

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

Wang

et al. 2015

Neuropsychopharmacol

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( ± )-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of ( ± )-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long-Evans rats. As Long-Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long-Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans.

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Section: Introductionmentioning

confidence: 80%

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

Wang

et al. 2015

Neuropsychopharmacol

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“…It has been shown to improve cognitive performance in healthy research volunteers (Randall et al, 2005;Repantis et al, 2010;Turner et al, 2003), with a larger effect in patients with neuropsychiatric disorders such as attention-deficit hyperactivity disorder and schizophrenia (Turner et al, 2004a, b). Cognition-enhancing agents have been suggested as potential treatment medications for stimulant addiction (Sofuoglu, 2010), and some success with such agents has been observed in the treatment of cocaine (Dackis et al, 2005) and MA dependence (Shearer et al, 2009), but few studies have examined the direct effects of these potential pharmacotherapies on behavioral and neural measures of cognition in stimulant-abusing subjects. Modafinil appears to be safe and well-tolerated by MAdependent subjects McGaugh et al, 2009), and some evidence suggests that it enhances the retention of MA-dependent subjects in programs that involve contingency management and cognitive behavioral therapy (Heinzerling et al, 2010), but little is known about the effects of modafinil on cognitive function in MA-dependent individuals (see Kalechstein et al (2010) for an example of working-memory enhancement in this sample).…”

Section: Introductionmentioning

confidence: 99%

Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals

Ghahremani

Tabibnia

Monterosso

et al. 2011

Neuropsychopharmacol

109

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Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function. Therefore, medications that improve cognition in these subjects may improve the success of therapy for their addiction, especially when cognitive behavioral therapies are used. Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers. We therefore conducted a randomized, double-blind, placebo-controlled, cross-over study, using functional magnetic resonance imaging, to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent, MA-dependent, and healthy control participants. Modafinil (200 mg) and placebo were administered orally (one single dose each), in counterbalanced fashion, 2 h before each of two testing sessions. Under placebo conditions, MA-dependent participants showed worse learning performance than control participants. Modafinil boosted learning in MA-dependent participants, bringing them to the same performance level as control subjects; the control group did not show changes in performance with modafinil. After controlling for performance differences, MAdependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants. The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control. These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence. Neuropsychopharmacology (2011) 36, 950-959;

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“…None showed clear efficacy for this indication. However, two of these studies (Shearer et al, 2009;Anderson et al, 2012) indicate through post hoc analyses that patients compliant with the medication do achieve better abstinence than noncompliant patients. Another study (Heinzerling et al, 2010) showed trends toward increased efficacy among users with high baseline methamphetamine use and low attendance in cognitive-behavioral therapy (although neither was statistically significant).…”

mentioning

confidence: 99%

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

et al. 2016

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A double‐blind, placebo‐controlled trial of modafinil (200 mg/day) for methamphetamine dependence

Abstract: Modafinil demonstrated promise in reducing methamphetamine use in selected methamphetamine-dependent patients. The study findings support definitive trials of modafinil in larger multi-site trials.

Cited by 137 publications

References 43 publications

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

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