Modafinil: Preclinical, Clinical, and Post-Marketing Surveillance—A Review of Abuse Liability Issues

Myrick, Hugh; Malcolm, Robert; Taylor, Brent R.; LaRowe, Steven D.

doi:10.1080/10401230490453743

Cited by 132 publications

(119 citation statements)

References 38 publications

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“…Unlike data from our previous study with methamphetamine, ratings of 'good drug effect' and participants' reported desire to take the drug again were not significantly altered by modafinil. This is consistent with clinical observations (for a review, see Myrick et al, 2004) and human laboratory data (Rush et al, 2002), indicating that the abuse potential of modafinil is low.…”

Section: Discussionsupporting

confidence: 77%

Modafinil Attenuates Disruptions in Cognitive Performance During Simulated Night-Shift Work

Hart

Haney

Vosburg

et al. 2005

Neuropsychopharmacol

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Common complaints among shift workers are sleep disruptions and increased sleepiness while working, which may contribute to shift workers being more susceptible to diminished performance and work-related accidents. The purpose of this double-blind, withinparticipant study was to examine the effects of the alerting agent modafinil on cognitive/psychomotor performance, mood, and measures of sleep during simulated shift work. In all, 11 participants completed this 23-day residential laboratory study. They received a single oral modafinil dose (0, 200, 400 mg) 1 h after waking for three consecutive days under two shift conditions: day shift and night shift. Shifts alternated three times during the study, and shift conditions were separated by an 'off' day. When participants received placebo, cognitive performance and subjective ratings of mood were disrupted during the night shift, relative to the day shift. Objective and subjective measures of sleep were also disrupted, but to a lesser extent. Modafinil reversed disruptions in cognitive performance and mood during the night shift. While modafinil produced few effects on sleep measures during the night shift, the largest dose produced several sleep alterations during the day shift. These data demonstrate that abrupt shift changes produced cognitive performance impairments and mood disruptions during night shift work. Therapeutic doses of modafinil attenuated night-shift-associated disruptions, but the larger dose produced some sleep impairments when administered during day-shift work.

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Section: Discussionsupporting

confidence: 77%

Modafinil Attenuates Disruptions in Cognitive Performance During Simulated Night-Shift Work

Hart

Haney

Vosburg

et al. 2005

Neuropsychopharmacol

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“…Modafinil was originally developed as a treatment for narcolepsy, and can be used to reduce performance decrements due to sleep loss with apparently small side effects and little risk of dependency (Teitelman 2001;Myrick et al 2004). The drug improved attention and working memory in sleep-deprived physicians (Gill et al 2006) and aviators (Caldwell et al 2000).…”

Section: Drugsmentioning

confidence: 99%

Cognitive Enhancement: Methods, Ethics, Regulatory Challenges

2009

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Cognitive enhancement takes many and diverse forms. Various methods of cognitive enhancement have implications for the near future. At the same time, these technologies raise a range of ethical issues. For example, they interact with notions of authenticity, the good life, and the role of medicine in our lives. Present and anticipated methods for cognitive enhancement also create challenges for public policy and regulation.

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“…In terms of abuse liability, human volunteers selfadminister modafinil more than placebo under certain conditions , but most studies suggest that the medication has low abuse liability even among drug abusers (Jasinski 2000;Rush et al 2002a, b), and post-marketing surveillance indicate modafinil misuse is low (see Myrick et al 2004). The presence of positive mood effects, in fact, is likely a positive feature in that it improves medication compliance.…”

Section: Clinical Datamentioning

confidence: 99%

Controversies in translational research: drug self-administration

2008

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Rationale Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable. Objective The objective of this study was to track how antagonist, agonist, and partial agonist medication approaches influence heroin and cocaine self-administration by rodents, non-human primates, and humans and to compare these results to clinical outcomes. Results Across species, heroin self-administration was decreased by all three medication approaches, paralleling their demonstrated clinical utility. The heroin data emphasize the importance of assessing a medication's abuse liability preclinically to predict medication abuse and compliance and of considering subject characteristics (e.g., opioid dependence) when interpreting medication effects. For cocaine, the effects of ecopipam, modafinil, and aripiprazole were consistent in the laboratory and clinic, provided that the medications were administered repeatedly before self-administration sessions. Modafinil attenuated cocaine's reinforcing effects in the human laboratory and improved treatment outcome, while ecopipam and aripiprazole increased the reinforcing effects of cocaine and do not appear promising in the clinic. Conclusions The self-administration model has reliably identified medications to treat opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence. There have been numerous false positives when subjective effects are the primary outcome measure, but not when self-administration is the outcome. Factors relevant to the predictive validity of self-administration procedures include medication maintenance and the concurrent assessment of a range of behaviors to determine abuse liability and the specificity of effect.Keywords Cocaine . Opioid . Naloxone . Dopamine receptor . Drug abuse . Model . Monkey . Human . Reinforcement Laboratory testing of potential pharmacotherapies for drug abuse is an essential component of medication development. Although well-designed clinical trials are the standard by which the efficacy of a new medication is assessed, clinical trials test the effects of a potential treatment medication on a broad sample of patients, which is both costly and potentially risky. Before exposing a large number of treatment seekers to a medication, there needs to be both a strong scientific rationale for combining the medication with a drug of abuse as well as a demonstration that the co-administration of the medication and the abused drug is safe and selectively modifies the behavior of interest: drug taking.Models of drug self-administration in rodents, nonhuman primates, and humans have been used to evaluate the effects of candidate medications for the treatment of drug dependence. The self-administration model provides Psychopharmacology (2008) meaningful behavioral data on the safety and efficacy of potentia...

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Modafinil: Preclinical, Clinical, and Post-Marketing Surveillance—A Review of Abuse Liability Issues

Cited by 132 publications

References 38 publications

Modafinil Attenuates Disruptions in Cognitive Performance During Simulated Night-Shift Work

Modafinil Attenuates Disruptions in Cognitive Performance During Simulated Night-Shift Work

Cognitive Enhancement: Methods, Ethics, Regulatory Challenges

Controversies in translational research: drug self-administration

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