Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence

Heinzerling, Keith G.; Swanson, Aimee Noelle; Kim, Soeun; Cederblom, Lisa; Moe, Ardis; Ling, Walter; Shoptaw, Steven

doi:10.1016/j.drugalcdep.2009.11.023

Cited by 87 publications

(84 citation statements)

References 51 publications

(50 reference statements)

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“…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: 95%

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

Ghahremani

Tabibnia

Monterosso

et al. 2011

Neuropsychopharmacol

106

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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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Section: Introductionmentioning

confidence: 95%

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

Ghahremani

Tabibnia

Monterosso

et al. 2011

Neuropsychopharmacol

106

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“…Inhaled use of methamphetamine is more common than other routes of administration in habitual and dependent users (Das-Douglas et al, 2008;Heinzerling et al, 2010;Wood et al, 2008). Furthermore, the SAMHSA/TEDS treatment admission database for 2012 shows 4.7% of treatment seekers in the United States were admitted for smoked cocaine vs 2.2% for other routes of cocaine administration as the primary reason for treatment (http://wwwdasis.samhsa.gov/webt/new mapv1.htm).…”

Section: Introductionmentioning

confidence: 99%

Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology

Nguyen

Aarde

Cole

et al. 2016

Neuropsychopharmacol

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Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine.

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“…Results from these trials have sometimes shown a positive effect of modafi nil on stimulant abstinence, but the results have been variable (see Anderson et al, 2009;Heinzerling et al, 2010;McGaugh et al, 2009;Shearer et al, 2009). In particular, moderator variables may play a role in the success of treatment.…”

mentioning

confidence: 99%

“…In particular, moderator variables may play a role in the success of treatment. For example, one study showed that modafi nil (400 mg daily) did not improve the treatment outcomes for MA-dependent participants as a group; however, those with a high frequency of baseline MA use showed trends for improved abstinence and study retention during modafi nil treatment relative to those with a low baseline frequency of MA use (Heinzerling et al, 2010). The therapeutic effect of modafi nil may therefore depend on the frequency of baseline MA use.…”

mentioning

confidence: 99%

Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans

Dean¹,

Sevak²,

Monterosso³

et al. 2011

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine, and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder. Therefore, a medication that improves cognition, such as modafi nil (Provigil), may serve as a useful adjunct to behavioral treatments for methamphetamine dependence. Although cognitive-enhancing effects of modafi nil have been reported in several populations, little is known about the effects of modafi nil in methamphetamine-dependent individuals. We thus sought to evaluate the effects of modafi nil on the cognitive performance of methamphetamine-dependent and healthy individuals. Method: Seventeen healthy subjects and 24 methamphetamine-dependent subjects participated in this randomized, double-blind, placebo-controlled, crossover study. Effects of modafi nil (200 mg, single oral dose) were assessed on participants' performance on tests of inhibitory control, working memory, and processing speed/attention. Results: Across subjects, modafi nil improved performance on a test of sustained attention, with no signifi cant improvement on any other cognitive tests. However, within the methamphetamine-dependent group only, participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafi nil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine. Conclusions: Although modafi nil produced limited effects across all participants, methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated signifi cant cognitive improvement on modafi nil relative to those with low baseline methamphetamine use. These results add to the fi ndings from a clinical trial that suggested that modafi nil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently. (J. Stud. Alcohol Drugs, 72, 943-953, 2011)

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Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence

Cited by 87 publications

References 51 publications

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

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

Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology

Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans

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