A Double-Blind, Placebo-Controlled Trial of Modafinil for Cocaine Dependence

University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Neuropsychopharmacology (Impact Factor: 7.05). 01/2005; 30(1):205-11. DOI: 10.1038/sj.npp.1300600
Source: PubMed


Despite years of active research, there are still no approved medications for the treatment of cocaine dependence. Modafinil is a glutamate-enhancing agent that blunts cocaine euphoria under controlled conditions, and the current study assessed whether modafinil would improve clinical outcome in cocaine-dependent patients receiving standardized psychosocial treatment. This was a randomized, double-blind, placebo-controlled trial conducted at a university outpatient center (from 2002 to 2003) on a consecutive sample of 62 (predominantly African American) cocaine-dependent patients (aged 25-63) free of significant medical and psychiatric conditions. After screening, eligible patients were randomized to a single morning dose of modafinil (400 mg), or matching placebo tablets, for 8 weeks while receiving manual-guided, twice-weekly cognitive behavioral therapy. The primary efficacy measure was cocaine abstinence based on urine benzoylecgonine levels. Secondary measures were craving, cocaine withdrawal, retention, and adverse events. Modafinil-treated patients provided significantly more BE-negative urine samples (p=0.03) over the 8-week trial when compared to placebos, and were more likely to achieve a protracted period (> or =3 weeks) of cocaine abstinence (p=0.05). There were no serious adverse events, and none of the patients failed to complete the study as a result of adverse events. This study provides preliminary evidence, which should be confirmed by a larger study, that modafinil improves clinical outcome when combined with psychosocial treatment for cocaine dependence.

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    • "for the treatment of cocaine or amphetamine-type stimulant use disorders [5] [6] [7] [8] [9] [10] [11]. "

    Full-text · Article · Jan 2015
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    • "Different studies showed that modafinil cognitive-enhancing properties improved outcome in the treatment of pathologic gamblers (Zack and Poulos, 2009), alcoholics (Schmaal et al., 2013), and patients suffering from other neuropsychiatric conditions (Scoriels et al., 2013). The use of modafinil as a treatment for cocaine and METH dependence remains inconclusive, with studies showing positive outcomes (Dackis et al., 2005; McGaugh et al., 2009) and studies showing promising but yet non-significant results in reducing drug use (Dackis et al., 2012; Shearer et al., 2009; Heinzerling et al., 2010). For both cocaine and METH users, modafinil was efficacious in improving several domains of cognitive and executive functions (Kalechstein et al., 2013; Ghahremani et al., 2011; Kalechstein et al., 2010; Hester et al., 2010; Finke et al., 2010). "
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    ABSTRACT: Chronic use of methamphetamine (METH) leads to long-lasting cognitive dysfunction in humans and in animal models. Modafinil is a wake-promoting compound approved for the treatment of sleeping disorders. It is also prescribed off label to treat METH dependence. In the present study, we investigated whether modafinil could improve cognitive deficits induced by sub-chronic METH treatment in mice by measuring visual retention in a Novel Object Recognition (NOR) task. After sub-chronic METH treatment (1 mg/Kg, once a day for 7 days), mice performed the NOR task, which consisted of habituation to the object recognition arena (5 min a day, 3 consecutive days), training session (2 equal objects, 10 min, day 4), and a retention session (1 novel object, 5 min, day 5). One hour before the training session, mice were given a single dose of modafinil (30 or 90 mg/Kg). METH-treated mice showed impairments in visual memory retention, evidenced by equal preference of familiar and novel objects during the retention session. The lower dose of modafinil (30 mg/Kg) had no effect on visual retention scores in METH-treated mice, while the higher dose (90 mg/Kg) rescued visual memory retention to control values. We also measured ERK phosphorylation in medial prefrontal cortex (mPFC), hippocampus, and nucleus accumbens (NAc) of METH- and vehicle-treated mice that received modafinil 1 hr before exposure to novel objects in the training session, compared to mice placed in the arena without objects. Elevated Extracellular signal-regulated kinase (ERK) phosphorylation was found in the mPFC of vehicle-treated mice, but not in METH-treated mice, exposed to objects (p<0.05). The lower dose of modafinil had no effect on ERK phosphorylation in METH-treated mice, while 90 mg/Kg modafinil treatment restored the ERK phosphorylation induced by novelty in METH-treated mice to values comparable to controls (p<0.05). We found neither a novelty nor treatment effect on ERK phosphorylation in hippocampus or nucleus accumbens (NAc) of vehicle- and METH-treated mice receiving acute 90 mg/Kg modafinil treatment. Our results showed a palliative role of modafinil against METH-induced visual cognitive impairments, possibly by normalizing ERK signaling pathways in mPFC. Modafinil may be a valuable pharmacological tool for the treatment of cognitive deficits observed in human METH abusers as well as in other neuropsychiatric conditions.
    Full-text · Article · Feb 2014 · Neuropharmacology
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    • "Our sample size was based on a previous reported trial with modafinil for cocaine dependence (Dackis et al., 2005). Initially, we attempted to collect 100 participants, which would allow us to Figure 1 Overview of the course and assessments of the clinical trial. "
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    ABSTRACT: Poor impulse control plays an important role in the development, course and relapse of substance use disorders. Therefore, improving impulse control may represent a promising approach in the treatment of alcohol dependence. This study aimed to test the effect of modafinil on impulse control and alcohol use in alcohol dependent patients (ADP) in a randomized, double-blind, placebo-controlled trial. Eighty-three abstinent ADP were randomized to 10 weeks modafinil (300mg/d) or placebo. Alcohol use was quantified using the timeline follow-back method and was assessed until 6 months after treatment discontinuation. Impulsivity was assessed using self-report questionnaires (Barratt Impulsiveness Scale; State Impulsivity questionnaire) and neurocognitive tasks (Stop Signal Task; Delay Discounting Task) administered before, during and after treatment. Modafinil significantly improved self-report measures of state impulsivity, but had no effect on percentage of abstinent days or percentage of heavy drinking days, nor on the behavioral measures of impulsivity. However, subgroup analysis revealed that modafinil prolonged the time to relapse (p=.022) and tended to increase the percentage of abstinent days (p=.066) in ADP with poor response inhibition at baseline, whereas modafinil increased the percentage of heavy drinking days (p=.003) and reduced the percentage of abstinent days (p=.002) in patients with better baseline response inhibition. Overall results do not favor the use of modafinil in order to reduce relapse or relapse severity in ADP, and caution is required in prescribing modafinil to a non-selected sample of ADP. Further research on the effect of modafinil in ADP with poor baseline response inhibition is warranted.
    Full-text · Article · Nov 2012 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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