Pharmacological cognitive enhancement (PCE) refers to the use of pharmaceuticals to improve cognitive function when that use is not intended to prevent or treat disease. Those who favour a liberal approach to PCE trust users to make informed decisions about whether enhancing is in their best interest. The author argues that making informed decisions about PCE requires a nuanced risk-benefit analysis that is not accessible to many users. Presently, the PCE use of prescription medications such as methylphenidate and modafinil is widespread but most commonly happens without medical supervision. Direct and indirect barriers generate a situation where the risks and benefits of PCE are inequitably distributed; as a result, PCE is sometimes not in the user’s best interest. This is likely to also be the case for future pharmaceuticals. As a result, even if PCE pharmaceuticals were equitably distributed, its associated risks and benefits would not be. The article concludes with a discussion of the prospects of the clinical consultation on one hand, and e-health solutions on the other, in ameliorating the situation, arguing for cautious optimism.

Antipsychotics are the cornerstone of schizophrenia management but they are not adequate in treating the negative and cognitive symptoms of the illness. The Cochrane review discussed in this commentary examines the safety and effectiveness of the wakefulness-promoting agent, modafinil, as an adjunct to standard care in the mitigation of negative and cognitive symptoms of schizophrenia. Add-on modafinil, compared to add-on placebo and standard treatment, did not result in a clear benefit. Due to the heterogenous body of evidence, the quality of which ranged from very low to moderate, the review's conclusions are equivocal.

Modafinil is a mild psychostimulant-like drug enhancing wakefulness, improving attention and developing performance in various cognitive tasks, but its mechanism of action is not completely understood. This is the first combination of amperometry, electrochemical cytometry and mass spectrometry to interrogate the mechanism of action of a drug, here modafinil, at cellular and sub-cellular level. We employed single-cell amperometry (SCA) and intracellular vesicle impact electrochemical cytometry (IVIEC) to investigate the alterations in exocytotic release and vesicular catecholamine storage following modafinil treatment. The SCA results reveal that modafinil slows down the exocytosis process so that, the number of catecholamines released per exocytotic event is enhanced in the modafinil-treated cells. Also, IVIEC results offer an upregulation effect of modafinil on the vesicular catecholamine storage. Mass spectrometry imaging by time-of-flight secondary ion mass spectrometry (ToF-SIMS) illustrates that treatment with modafinil reduces the cylindrical-shaped phosphatidylcholine at the cellular membrane, while the high curvature lipids with conical structures such as phosphatidylethanolamine and phosphatidylinositol are elevated after modafinil treatment. Combining the results obtained by SCA, IVIEC and ToF-SIMS suggests that modafinil-treated cells release a larger portion of their vesicular content at least in part by changing the lipid composition of the cell membrane, suggesting regulation of cognition.

Modafinil is a new psychotropic compound with central α1, adrenergic-stimulant activity in animals. In the present study, its pharmacological activity in man was evaluated in the sleep-deprivation induced psychomotor and cognitive impairment paradigm. This was a double-blind placebo-controlled study involving 12 healthy volunteers. Standard psychomotor and memory tasks were used, including critical flicker fusion frequency determination (CFF), choice reaction time and short- and long-term memory evaluation. Results revealed a clear antagonism by modafinil of the psychomotor and cognitive impairment induced by sleep-deprivation in most tasks 6 h after drug administration, and marginal effects 18 h after. These results therefore support a psychostimulant activity of modafinil in man.

The subjective, behavioral and physiological effects of modafinil (300 mg PO) a new central adrenergic stimulant, were compared with those of dextroamphetamine (15 mg PO), caffeine (300 mg PO) and placebo in a randomized double-blind cross-over study. Sixteen healthy volunteers participated in the study y: 8 males and 8 females with no history of drug abuse and moderate use of caffeine. Subjective and behavioral effects were studied using the Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS) and Visual Analog Scales before and 1, 2, 4 and 8 h post single oral dosing. Results showed that subjective effects of modafinil (300 mg) differed markedly from those of dextroamphetamine (15 mg). They were close to those produced by caffeine (300 mg). These results indicate that modafinil (300 mg) does not possess amphetamine-like subjective effects in a healthy population. If subjective feelings are related to drug abuse liability, it could be assumed that modafinil, at the dose used in therapeutics, does not possess any abuse liability comparable to amphetamine.

We report on two areas in which UK law and ethics seem out of step with each other. 2013 saw the passing of the Human Transplantation (Wales) Bill, which will introduce an opt-out system of organ donation in Wales from 2015. In the first section, we discuss the convoluted evolution of the Bill and some potential problems that we consider may prevent it from achieving its intended goal of increasing the number of organs transplanted. The prospect of being able to enhance human cognition through cognitive-enhancing drugs (“smart drugs”) also presents a nexus of questions associated with future ambitions, hopes, and concerns as a society. How these drugs might affect the future of work and employment is beginning to generate wide public engagement in the UK and forms the focus of the second section.

Although not all individuals who work outside of standard daytime hours develop physical and psychiatric issues, there is a substantial portion of shift workers who develop shift work disorder. Shift work disorder is due to a misalignment between an individual's endogenous circadian rhythms and environmental stimuli, and can have potentially serious consequences to an individual's health and quality of life. This article reviews the neurobiological and genetic underpinnings of shift work disorder, and describes how desynchronization of the molecular clock may lead to both physical and psychiatric illnesses. Diagnostic tools and treatment guidelines to address the circadian misalignment, excessive sleepiness, and insomnia experienced by patients with shift work disorder are also discussed.

ABSTRACT

There has been continuous progress in neurotherapeutics and neuropsychopharmacology in the past year. Notable are the reports of successful preliminary disease-modifying trials in Niemann-Pick disease and Friedreich's ataxia. Progress also has been made in treatment of migraine, stroke, epilepsy, multiple sclerosis, traumatic brain injury, and pain. Biomarkers are increasingly used to establish proof of pharmacology including measures of cerebrospinal fluid constituents and brain changes on magnetic resonance imaging. There is an increasing diversity of patient populations participating in clinical trials, including pediatric migraine and traumatic brain injury.

ABSTRACT

Background: Although historically neglected in clinical research, negative symptoms of schizophrenia are now considered distinct targets of pharmacotherapy. While second-generation antipsychotic treatments were heralded as having a greater therapeutic impact on negative symptoms than their conventional antipsychotic counterparts, the size of this effect is modest. Adjunctive medications such as antidepressants offer limited efficacy, while stimulants have a poor risk–benefit profile. More recently, promising results have been demonstrated with pro-glutamatergic agents such as glycine or D-cycloserine, although a larger trial found no advantage with either agent compared with placebo. Modafinil, a novel wakefulness-promoting agent, is an intriguing candidate for adjunctive pharmacotherapy to treat negative symptoms in schizophrenia. We explored this therapeutic potential through a placebo-controlled trial of patients with prominent negative symptoms. Methods: We randomly assigned patients with schizophrenia or schizoaffective disorder to treatment with either modafinil or placebo for 8 weeks. Double-blind assessments of clinical symptoms and neurocognition were administered at baseline and every 2 weeks thereafter. Results: Twenty subjects were enrolled (N = 10 modafinil, N = 10 placebo). There were no significant differences between modafinil and placebo for changes in negative symptom ratings, the primary study endpoint. However, modafinil treatment was associated with a greater rate and degree of global improvement at study endpoint compared with placebo. No significant worsening of psychopathology was observed and modafinil was well-tolerated. Interpretation: Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms. These findings support additional research into a potential role for modafinil in the treatment of negative symptoms in schizophrenia.