Evaluation of the Abuse Liability of Modafinil and Other Drugs for Excessive Daytime Sleepiness Associated with Narcolepsy

Jasinski, Donald R.; Kovačević-Ristanović, Ružica

doi:10.1097/00002826-200005000-00004

Cited by 283 publications

(66 citation statements)

References 36 publications

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“…Studies in healthy volunteers, cocaine users and ADHD patients have found fewer side effects than placebo and little evidence of dependence [106]. Use by injection or smoking is limited by the relative insolubility of modafinil and its instability at high temperatures [107]. Consistent with biochemical data, human laboratory studies comparing discriminative stimuli, subject-rated effects and cardiovascular effects concluded that modafinil did not produce cocaine-like responses in subjects with cocaine use histories [107,108].…”

Section: Modafinil and Glutamate Agonismmentioning

confidence: 99%

The principles of agonist pharmacotherapy for psychostimulant dependence

Shearer

2008

Drug and Alcohol Review

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Issues. Psychostimulant dependence is a chronic, relapsing condition which is highly treatment refractory. No medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Agonist strategies have attracted limited attention. Approach. Successful examples of agonist pharmacotherapy in the treatment of heroin and nicotine dependence are first considered. Agonist pharmacological approaches to the treatment of psychostimulant dependence are then examined, based on the dopamine receptor agonist and indirect dopamine agonist strategies. Finally, the potential extension of the concept of agonist pharmacotherapy to include the novel non-amphetamine-type stimulant, modafinil, is discussed. Conclusions. Agonist approaches appear to be viable with risks outweighed by benefits in carefully selected, monitored and motivated patients. On the other hand, the effectiveness of indirect agonists such as dexamphetamine and methylphenidate are not established. Further research is required to determine optimal treatment models (whether maintenance or withdrawal), effective safe dosages and duration (short or long term). [Shearer J. The principles of agonist pharmacotherapy for psychostimulant dependence. Drug Alcohol Rev 2008;27:301-308]

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Section: Modafinil and Glutamate Agonismmentioning

confidence: 99%

The principles of agonist pharmacotherapy for psychostimulant dependence

Shearer

2008

Drug and Alcohol Review

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“…Recently, ( ± )-MOD has been clinically investigated for the treatment of cocaine and methamphetamine addiction. As ( ± )-MOD is a mild psychostimulant and a dopamine transporter (DAT) inhibitor, but with no reported abuse liability (Jasinski and Kovacevic-Ristanovic, 2000;Myrick et al, 2004), it has been suggested as useful for the treatment of psychostimulant dependence. Camacho and Stein (2002) first reported that ( ± )-MOD was effective in treatment of amphetamine dependence in a patient with comorbid social phobia.…”

Section: Introductionmentioning

confidence: 99%

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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“…In addition, it has recently been reported that patients with baseline cocaine withdrawal (Sofuoglu et al, 2003), and abstinence-related depression and irritability (Newton et al, 2003), report enhanced euphoria after cocaine administration under controlled conditions, suggesting that the reversal of cocaine withdrawal might be clinically advantageous. Modafinil is a reasonable medication for cocaine-dependent individuals because it has low abuse potential (Jasinski, 2000;Jasinski and Kovacevic-Ristanovic, 2000;Rush et al, 2002a, b), neurochemical effects that differ markedly from those of psychostimulants (Lin et al, 1996;Ferraro et al, 1997), and good tolerability (Becker et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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

Dackis

Kampman

Lynch

et al. 2004

Neuropsychopharmacol

341

193

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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 ¼ 0.03) over the 8-week trial when compared to placebos, and were more likely to achieve a protracted period (X3 weeks) of cocaine abstinence (p ¼ 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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Evaluation of the Abuse Liability of Modafinil and Other Drugs for Excessive Daytime Sleepiness Associated with Narcolepsy

Cited by 283 publications

References 36 publications

The principles of agonist pharmacotherapy for psychostimulant dependence

The principles of agonist pharmacotherapy for psychostimulant dependence

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

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

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