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Objective: The use of prescription stimulants for cognitive enhancement by healthy university students, identified as the largest cohort of cognitive enhancer (CE) users, is of growing interest. The purpose of this study was to look at the understanding, perception, experience, and level of access of CEs among healthy university students in the United Arab Emirates (UAE)., Methods: The study was conducted in six highly competitive university programmes. Semi-structured interviews were conducted with 18 university students to discuss their own experiences and those of their friends and peers regarding the use of prescription stimulants. In addition, semi-structured interviews were conducted with seven teaching faculty staff members (registered pharmacists and medical doctors) to explore their views on the use of CEs in their university., Results: Data were analysed thematically for the identification of themes and subthemes within the data using coding. It was found that, 'Adderall' was the most common prescribed CE drug and caffeine super strength pills were the most common non-prescribed CE drug, both reported to enhance concentration, motivation, and meet academic deadlines., Conclusions: It is expected that the findings of this study will be of interest to a wide range of services in UAE universities. This will enable them to raise awareness about the use of CEs among students., (© 2023 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons Ltd.)

Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an "atypical" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders., (Copyright © 2024. Published by Elsevier Inc.)

The so-called neurorights are emerging human rights, or rather reconfigurations of already existing human rights, seeking to address the impact of the possible misuse of neurotechnologies, which have the potential to become more invasive and harmful in the future if not regulated. The aim of specifying neurorights is to protect the dignity and autonomy of the individual in the face of neurotechnological advances. Recently, Chile proposed a Constitutional reform inspired by the neurorights, opening a debate. One of the proposed neurorights is fair and equitable access to cognitive enhancement, which will be the specific object of this perspective article. Starting from the legal proposal, we analyse and discuss some perspectives on cognitive enhancement, or "neuroenhancement", which could be considered as part of enhancement neurotechnologies, pointing out that pharmacological enhancers, or "smart drugs", might be considered as part of these enhancers. We present a classification of the different types of cognitive enhancements as it has been proposed in the literature, into which pharmacological cognitive enhancement can be included, concluding that there is currently no agreement amongst scholars and lawyers about the ethical consideration of pharmacological cognitive enhancement. We therefore argue that it is necessary for the legislator to explicitly address the issue in the proposed regulations, in order to take a clear position on the topic, as it has been done in the United Kingdom, where the pharmacological neuroenhancers have been explicitly excluded from the regulation. If pharmacological neuroenhancers are going to be considered neurotechnologies, then new law proposals should seek harmonization with the already existing legislation regulating pharmacological health and consumer rights (both globally, taking into account international drug laws, and locally, according to each country's internal regulations) and of course, with the whole system of fundamental rights. Finally, we briefly discuss the ethical problem of equitable access to this new type of neurotechnologies (as part of the neurorights) and leave the debate open for new insights from the scientific community on the possible consequences of including (or not) pharmacological neuroenhancers as neurotechnologies for cognitive enhancement in the framework of the ethical and legal debate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cornejo-Plaza and Saracini.)

Plant-based nootropics are a diverse group of natural drugs that can improve cognitive abilities through various physiological mechanisms, especially in cases where these functions are weakened or impaired. In many cases, the nootropics enhance erythrocyte plasticity and inhibit aggregation, which improves the blood's rheological properties and increases its flow to the brain. Many of these formulations possess antioxidant activity that protects brain tissue from neurotoxicity and improves the brain's oxygen supply. They can induce the synthesis of neuronal proteins, nucleic acids, and phospholipids for constructing and repairing neurohormonal membranes. These natural compounds can potentially be present in a great variety of herbs, shrubs, and even some trees and vines. The plant species reviewed here were selected based on the availability of verifiable experimental data and clinical trials investigating potential nootropic effects. Original research articles, relevant animal studies, meta-analyses, systematic reviews, and clinical trials were included in this review. Selected representatives of this heterogeneous group included Bacopa monnieri (L.) Wettst., Centella asiatica (L.) Urban, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., Ginkgo biloba L., Lepidium meyenii Walp., Panax ginseng C.A. Meyer, Paullinia cupana Kunth, Rhodiola rosea L., Schisandra chinensis (Turcz.) Baill., and Withania somnifera (L.) Dunal. The species are depicted and described, together with their active components and nootropic effects, and evidence of their efficacy is presented. The study provides brief descriptions of the representative species, their occurrence, history, and the chemical composition of the principle medicinal compounds, with uses, indications, experimental treatments, dosages, possible side effects, and contraindications. Most plant nootropics must be taken at optimal doses for extended periods before measurable improvement occurs, but they are generally very well tolerated. Their psychoactive properties are not produced by a single molecule but by a synergistic combination of several compounds. The available data suggest that including extracts from these plants in medicinal products to treat cognitive disorders can have substantial potential therapeutic benefits.

Nootropics, also known as "smart drugs" are a diverse group of medicinal substances whose action improves human thinking, learning, and memory, especially in cases where these functions are impaired. This review provides an up-to-date overview of the potential effectiveness and importance of nootropics. Based on their nature and their effects, this heterogeneous group of drugs has been divided into four subgroups: classical nootropic compounds, substances increasing brain metabolism, cholinergic, and plants and their extracts with nootropic effects. Each subgroup of nootropics contains several main representatives, and for each one, its uses, indications, experimental treatments, dosage, and possible side effects and contraindications are discussed. For the nootropic plant extracts, there is also a brief description of each plant representative, its occurrence, history, and chemical composition of the medicinal part. Lastly, specific recommendations regarding the use of nootropics by both ill and healthy individuals are summarized.

In recent years, people in the United States and other countries have been using smart drugs, called nootropic or cognitive enhancers, to improve concentration and memory learning skills. However, these drugs were originally prescribed for attention-deficit hyperactivity disorder and dementia, and their efficacy in healthy people has not yet been established. We focused on acetylcholine in the hippocampus, which is responsible for memory learning, and elucidate the long-term effects of smart drugs on the neural circuits. Smart drugs were administered orally in normal young mice for seven weeks. The hippocampus was sectioned and compared histologically by hematoxylin and eosin (HE) staining, immunohistochemistry for acetylcholine, and immunoelectron microscopy. There were no significant changes in acetylcholinesterase staining. However, in HE, we found perivascular edema, and choline acetyltransferase staining showed increased staining throughout the hippocampus and new signal induction in the perivascular area in the CA3, especially in the aniracetam and α-glyceryl phosphoryl choline group. Additionally, new muscarinic acetylcholine receptor signals were observed in the CA1 due to smart drug intake, suggesting that vasodilation might cause neuronal activation by increasing the influx of nutrients and oxygen. Moreover, these results suggest a possible new mechanism of acetylcholine-mediated neural circuit activation by smart drug intake.

In an effort for better memory, greater motivation, and concentration, otherwise healthy individuals use pharmaceutical cognitive enhancers (PCEs), medicines for the treatment of cognitive deficits of patients with various disorders and health problems, to achieve greater productivity, efficiency, and performance. We examined the use of PCEs among 289 students at the Slovenian Faculty of Electrical Engineering and Computer Science in the behavioral and psychosocial context (students' attitudes towards study, parents, health, leisure time, and work). Furthermore, we also addressed the immediate reasons, or the hypothesized connections of behavioral and psychosocial aspects, related to PCE misuse. The study consisted of a structured questionnaire, and chi-squared tests were used. An analysis of student statements revealed differences in students' and parents' attitudes toward good academic grades. In addition, students chose among 17 values related to relationships with parents, friends, partners, careers, study obligations, leisure, hobbies, material goods, appearance, and the future, and assessed their importance. Regardless of the group they belonged to, young people cited the same values among the most important. Good grades and parental opinions have proven to be key factors in the context of PCE abuse. This research was the first study to examine the relation between PCE misuse and the role of different behavioral and psychosocial factors.

Zornia latifolia is a plant suspected to possess psychoactive properties and marketed as a marijuana substitute under the name ' maconha brava '. In this study, the effects of fractions obtained from a 2-propanol extract of aerial portions of the plant were determined by multielectrode array (MEA) analyses on cultured networks of rat cortical neurons. Lipophilic (ZL_lipo, mainly containing flavonoid aglycones), and hydrophilic (ZL_hydro, mainly containing flavonoid glycosides) fractions were initially obtained from the raw extract. ZL_lipo significantly inhibited mean firing rate (MFR) and mean bursting rate (MBR) of MEA recordings, while ZL_hydro induced no inhibition. Column chromatography separation of ZL_lipo yielded five fractions (ZL1-ZL5), among which ZL1 induced the strongest MFR and MBR inhibition. NMR and HPLC-MS analyses of ZL1 revealed the prevalence of the common flavonoids genistein ( 1 ) and apigenin ( 2 ) (in about a 1:1 ratio), and the presence of the rare flavone syzalterin (6,8-dimethylapigenin) ( 3 ) as a minor compound. Exposures of MEA to apigenin and genistein standards did not induce the MFR and MBR inhibition observed with ZL1, whereas exposure to syzalterin standard or to a 1:9 mixture syzalterin-genistein induced effects similar to ZL1. These inhibitory effects were comparable to that observed with high-THC hashish, possibly accounting for the plant psychoactive properties. Data indicate that Z. latifolia , currently marketed as a free herbal product, should be subjected to measures of control. In addition, syzalterin showed distinctive pharmacological properties, opening the way to its possible exploitation as a neuroactive drug.

Introduction : Smart drugs are among the most common drugs used by students. It is estimated that they are second in incidence after cannabis. Although they are usually used for diseases such as attention deficit hyperactivity disorder (ADHD) and dementia, in most cases the use of smart drugs is illegal and without a prescription. Methodological issues : A systematic review was conducted according to PRISMA guidelines. SCOPUS, Medline (using PubMed as a search engine), Embase, Web of Sciences, and Google Scholar were used as search engines from January 1, 1980 to June 1, 2021 to evaluate the association between smart drugs and neuro-enhancement. A total of 4715 articles were collected. Of these, 295 duplicates were removed. A total of 4380 articles did not meet the inclusion criteria. In conclusion, 48 articles were included in the present systematic review. Results : Most of the studies were survey studies, 1 was a prospective longitudinal study, 1 was a cross-over study, and 1 was an experimental study in an animal model (rats). The largest group of consumers was school or university students. The most frequent reasons for using smart drugs were: better concentration, neuro enhancement, stress reduction, time optimization, increased wake time, increased free time, and curiosity. There are conflicting opinions, in fact, regarding their actual functioning and benefit, it is not known whether the benefits reported by consumers are due to the drugs, the placebo effect or a combination of these. The real prevalence is underestimated: it is important that the scientific community focus on this issue with further studies on animal models to validate their efficacy., (© 2021 The Author(s). Published by BRI.)

Metal-organic frameworks (MOFs) hold great promise for biomedical applications owing to their unique properties. The porous structures make MOFs excellent candidates for the delivery of different drugs; the flexibility in choosing metal ions and organic ligands makes it feasible to prepare MOFs with intrinsic antitumor activities and further devise MOF-drug synergistic systems; many other types of antitumor agents could also be developed using MOFs as the precursors/templates. Thus, the past two decades have witnessed the great development of MOF-based drugs, especially in the antitumor field. This Minireview mainly focuses on the design and applications of MOF-based antitumor agents. Four aspects covering the whole field are introduced: MOFs as carriers, MOFs as antitumor agents, MOF-drug synergistic systems, and MOF-derived antitumor agents. The challenges and opportunities of MOFs for clinical antitumor applications are also discussed., (© 2021 Wiley-VCH GmbH.)

Introduction: Cognitive enhancers (CEs), also known as "smart drugs", "study aids" or "nootropics" are a cause of concern. Recent research studies investigated the use of CEs being taken as study aids by university students. This manuscript provides an overview of popular CEs, focusing on a range of drugs/substances (e.g., prescription CEs including amphetamine salt mixtures, methylphenidate, modafinil and piracetam; and non-prescription CEs including caffeine, cobalamin (vitamin B12), guarana, pyridoxine (vitamin B6) and vinpocetine) that have emerged as being misused. The diverted non-prescription use of these molecules and the related potential for dependence and/or addiction is being reported. It has been demonstrated that healthy students (i.e., those without any diagnosed mental disorders) are increasingly using drugs such as methylphenidate, a mixture of dextroamphetamine/amphetamine, and modafinil, for the purpose of increasing their alertness, concentration or memory., Aim: To investigate the level of knowledge, perception and impact of the use of a range of CEs within Higher Education Institutions., Methodology: A systematic review was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Whilst 1400 studies were identified within this study through a variety of electronic databases (e.g., 520 through PubMed, 490 through Science Direct and 390 through Scopus), 48 papers were deemed relevant and were included in this review., Results: The most popular molecules identified here included the stimulant CEs, e.g., methylphenidate, modafinil, amphetamine salt mixtures and caffeine-related compounds; stimulant CEs' intake was more prevalent among males than females; drugs were largely obtained from friends and family, as well as via the Internet. It is therefore suggested that CEs are increasingly being used among healthy individuals, mainly students without any diagnosed cognitive disorders, to increase their alertness, concentration, or memory, in the belief that these CEs will improve their performance during examinations or when studying. The impact of stimulant CEs may include tolerance, dependence and/or somatic (e.g., cardiovascular; neurological) complications., Discussion: The availability of CEs for non-medical indications in different countries is influenced by a range of factors including legal, social and ethical factors. Considering the risk factors and motivations that encourage university students to use CE drugs, it is essential to raise awareness about CE-related harms, counteract myths regarding "safe" CE use and address cognitive enhancement in an early stage during education as a preventative public health measure.

Trojan horse technology institutes a potentially promising strategy to bring together a diagnostic or cell-based drug design and a delivery platform. It provides the opportunity to re-engineer a novel multimodal, neurovascular detection probe, or medicine to fuse with blood-brain barrier (BBB) molecular Trojan horse. In Alzheimer's disease (AD) this could allow the targeted delivery of detection or therapeutic probes across the BBB to the sites of plaques and tangles development to image or decrease amyloid load, enhance perivascular Aβ clearance, and improve cerebral blood flow, owing principally to the significantly improved cerebral permeation. A Trojan horse can also be equipped with photosensitizers, nanoparticles, quantum dots, or fluorescent molecules to function as multiple targeting theranostic compounds that could be activated following changes in disease-specific processes of the diseased tissue such as pH and protease activity, or exogenous stimuli such as, light. This concept review theorizes the use of receptor-mediated transport-based platforms to transform such novel ideas to engineer systemic and smart Trojan detection or therapeutic probes to advance the neurodegenerative field.

Cognitive enhancement, a rather broad-ranging principle, can be achieved in various ways: healthy eating and consistent physical exercise can lead to long-term improvements in many cognitive domains; commonplace stimulants such as caffeine, on the other hand, temporarily raise levels of alertness, attentiveness, and concentration; sedative substances are also used as an indirect form of enhancement to relax before an exam or an important meeting. Such approaches raise no ethical issue. Nonetheless, clinical research has led to the off-label use of drugs called nootropics or "smart drugs", which can, under certain conditions, elicit some degree of cognition-improving effects: methylphenidate and modafinil can enhance working memory and concentration in healthy individuals, although the significance and effectiveness of such applications are dubious. Such "cognitive enhancement" methods, however, do raise multiple ethical issues, and their contentious nature has caused bioethical authorities to lay out opinions and recommendations meant to regulate their use. Most notably, the Italian Committee on Bioethics has extensively dealt with the spread of nootropics, which resulted in the Italian Code of Medical Ethics including "cognitive enhancement" drugs and their prescription by doctors as critical points, along with cosmetic surgery (the latest version of the Code, updated in December 2017, deals with the two separately, in Article 76 and 76 BIS). The United States Presidential Commission for the Study of Bioethical Issues broadened the scope of cognitive enhancement techniques so as to include neural modifiers, i.e. mechanisms of brain and nervous system change: a much wider array of interventions, technologies, behaviors, and environmental conditions that may potentially affect several aspects of the human brain and nervous system. The potential of neuroscience to profoundly reshape society is nothing short of mind-blowing., (Copyright © 2020 Ricci.)

Background: Sporting authorities and policy makers have warned of a radical increase in the availability and use of so-called 'smart' drugs, which putatively deliver cognitive enhancements in the form of improved focus, concentration, alertness, and rapid decision-making. Although the potential for health risks is well documented when it comes to performance enhancing drugs in sport, the health implications of cognitive enhancing drugs (CEDs) remain unclear. Objectives : This article aims to provide a foundational understanding about CEDs and their application in sport. It considers what little is known about the types, nature, impact, and implications of their use for athletes and sport policy. Method : A narrative literature review was undertaken to ascertain the emerging role of CEDs beyond their clinical use to treat prescribed disorders, including the limited studies in the sporting domain. This review also considered literature pertinent to the impact of CEDs in sport and the challenges for sport policy. Results : Given the prospects of negative health impacts, policy-makers interested in preventing and controlling the use of CEDs, as well as reducing harm to athletes at all levels of performance, need guidance. This article highlights multi-faceted concerns and shines a spotlight on key issues for sporting bodies to consider regarding the critical impact that widespread use and adoption of these substances might entail. Conclusion : While the World Anti-Doping Agency (WADA) is seemingly awake to the threat posed, actions to circumvent the spread of CEDs throughout sport are nascent and require greater understanding and attention.

Background: There are reports of prescription stimulants being purchased online for use as cognitive enhancers or "smart drugs." Objectives: The aim of this study was to investigate availability of modafinil and methylphenidate from internet suppliers from the perspective of a typical United Kingdom (UK) based customer. Methods: Using European Monitoring Center for Drugs and Drug Addiction (EMCDDA) internet snapshot methodology, we undertook an English language internet snapshot survey in July-August 2018 to gather information on the availability and price of modafinil and methylphenidate from online retailers. Results: A total of 55 modafinil and 14 methylphenidate websites were identified from which the drug could be purchased without a prescription. Minimum purchase quantities ranged from 10 to 90 tablets for modafinil and 1-1,005 tablets for methylphenidate with no apparent upper limit to the number that could be purchased. The price per tablet varied from £0.38-5.31 for modafinil and £0.16-5.70 for methylphenidate. Free shipping was offered if more than a certain amount was spent on 46 (83.6%) modafinil and 7 (50.0%) methylphenidate websites and discounts were offered on 43 (78.2%) modafinil and 4 (28.6%) methylphenidate websites. Conclusions: Modafinil and methylphenidate are widely available to purchase via internet from the UK without a prescription. The pricing on websites encourages users to buy greater quantities to qualify for discounts and free shipping. The quantities available suggest these purchases may be used in greater amounts than would be legitimately prescribed, increasing the risk of misuse or diversion to other individuals.

The debate about the desirability of using drugs to enhance human skills encompasses cognitive abilities such as memory and attention, and moral capacities such as emotional empathy and a sense of fairness. These two strands of literature in bioethics have grown relatively independent from each other, and an implicit framing assumption has emerged suggesting that apparently morally neutral cognitive capacities and paradigmatically moral capacities are distinct and vary independently of each other. Here, we identify key distinctions between competing accounts of cognitive enhancement and moral enhancement and argue that, despite the polarized nature of the bioethical debate, cognitive and moral capacities are intertwined. For example, moral behavior can be improved by enhancing "morally neutral" abilities such as attention span; and cognitive skills can be honed by means of socio-moral interaction. Further, cognitive skill is frequently assigned the abstract status of virtue and treated in the same way as more paradigmatically "moral" traits. We argue that the distinction between moral and cognitive enhancement is more apparent than real, since despite being nominally treated as distinct, cognitive and moral skills are frequently interdependent. As such we present evidence to support the claim that the enhancement of these two kinds of capacities cannot be clearly disaggregated from each other in the way that the theoretical poles of the debate in the literature suggest. We synthesize relevant scientific and bioethical literature and combine it with a line of analysis derived from Peter Hacker to show more clearly the terms of what can be said intelligibly about cognitive and moral skills and their enhancement. As a result of this analysis, we conclude that ethical questions in human bioenhancement are only fully intelligible at the level of persons imbued with feelings, thoughts, intentions, desires, values, and abilities, embedded within a particular social context, rather than at the level of pharmacological modulation of particular cognitive or affective capacities which, though conceptually distinguishable, in the embodied context of moral agency are profoundly intertwined.

Aims: To assess the prevalence and factors associated with stimulant and depressant pharmacological cognitive enhancement (PCE) drug use among Norwegian students., Design: In the first wave (T1), 28,553 students were invited to participate, of whom 9370 (32.8%) responded and completed the survey (mean age = 24.9 years, 63.5% female). One year later (T2) those who had responded to some items at T1 were invited to participate in a follow-up survey, where 4783 (47.2%) responded and completed the survey (mean age = 24.8 years, 64.8% female)., Results: Lifetime prevalence of stimulant PCE drug use was 2.1% at T1 and 3.6% at T2. The lifetime prevalence of depressant PCE drug use was 1.5% at T1 and 3.3% at T2. Stimulant PCE drug use at T2 was predicted by low scores on agreeableness and anxiety, high scores on intellect/openness, and alcohol use, and stimulant and depressant PCE drug use at T1; while depressant PCE drug use at T2 was predicted by low scores on extroversion, high scores on conscientiousness, intellect/openness, and anxiety, and stimulant and depressant PCE drug use at T1., Conclusions: The rates of stimulant and depressant PCE drug use increased from T1 to T2. Pharmacological cognitive enhancement drug use may be explained by a combination of a motivation for improving academic achievements and a general inclination towards substance use. The current results may suggest that stimulant PCE drug users are more antisocial and indifferent to rules, while depressant PCE drug users are more motivated by coping with stress., Competing Interests: Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2018.)

Dried herbal preparations, based on "Zornia latifolia," are commonly sold on web, mainly for their supposed hallucinogenic properties. In this work, we demonstrate that these commercial products contain a different Fabacea, i.e., Stylosanthes guianensis, a cheaper plant, widely cultivated in tropical regions as a fodder legume. We were provided with plant samples of true Zornia latifolia from Brazil, and carried out a thorough comparison of the two species. The assignment of commercial samples was performed by means of micro-morphological analysis, DNA barcoding, and partial phytochemical investigation. We observed that Z. latifolia contains large amounts of flavonoid di-glycosides derived from luteolin, apigenin, and genistein, while in S. guianensis lesser amounts of flavonoids, mainly derived from quercetin, were found. It is likely that the spasmolytic and anxiolytic properties of Z. latifolia, as reported in traditional medicine, derive from its contents in apigenin and/or genistein.

Since two decades, neuroenhancement is a major topic in neuroethics and still receives much attention in the scholarly literature as well as in public media. In contrast to high hopes at the beginning of the "Decade of the Brain" in the United States and Europe that we subsume under the "pharmacological optimism hypothesis," recent evidence from clinical neuroscience suggests that developing drugs that make healthy people smarter is even more difficult than finding new treatments for patients with mental disorders. However, cognitive enhancing drugs even for patients with impaired intellectual performance have not been successfully developed yet and new drugs that might have a disruptive impact on this field are unlikely to be developed in the near future. Additionally, we discuss theoretical, empirical, and historical evidence to assess whether cognitive enhancement of the healthy is common or even epidemic and if its application will further increase in the near future, as suggested by the "neuroenhancement prevalence hypothesis." Reports, surveys, and reviews from the 1930s until today indicate that psychopharmacological neuroenhancement is a fact but less common than often stated, particularly in the public media. Non-medical use of psychostimulants for the purpose of cognitive enhancement exists since at least 80 years and it might actually have been more common in the past than today. Therefore, we conclude that the pharmacological optimism hypothesis and neuroenhancement prevalence hypotheses have to be rejected and argue that the neuroenhancement debate should take the available evidence more into account.

Actualmente las enfermedades cardiovasculares representan la principal causa de morbimortalidad en el mundo; la aplicación de la nanotecnología es una gran promesa en su prevención y tratamiento. Se están desarrollando nanodispositivos para la liberación dirigida y controlada de medicamentos en sitios específicos en el organismo, por ejemplo, en células, tejidos, vasos sanguíneos y el corazón, así como para el diagnóstico, detección temprana de enfermedades cardiovasculares y tratamiento individualizado de pacientes. Otra posible aplicación de los nanodispositivos es la liberación de fármacos para corregir el mal acoplamiento de proteínas defectuosas. Con potentes superefectos, las nanopartículas deberán ser capaces de provocar efectos terapéuticos a bajas dosis en periodos prolongados. La fabricación de nanodispositivos y nanoacarreadores deberá llevarse a cabo con un enfoque integral que tome en cuenta las propiedades generales, con la finalidad de evaluar la biocompatibilidad y, en consecuencia, evitar efectos adversos y tóxicos. La investigación intensificada en este campo ayudará a reducir significativamente la morbimortalidad provocada por las enfermedades cardiovasculares., Currently, cardiovascular disease represents the main cause of morbidity and mortality worldwide; the application of nanotechnology holds great promise for its prevention and treatment. Nanodevices (“smart drugs”) are currently being developed for directed and controlled delivery of drugs to specific sites in the body, such as cells, tissues, blood vessels and the heart, as well as for diagnosis and early detection of cardiovascular conditions and patient-individualized treatment. Another application of nanodevices is the delivery of drugs to correct defective protein bad coupling or binding. With potent super-effects, nanoparticles should be able to elicit therapeutic effects at lower doses and prolonged periods. The manufacture of nanodevices and nanocarriers should be with a comprehensive approach that takes general properties into account in order to assess for biocompatibility and, therefore, avoid adverse and toxic effects. Intensified research in this field will help to significantly reduce morbidity and mortality caused by cardiovascular disease., (Copyright: © 2018 SecretarÍa de Salud.)

2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil) is commonly prescribed for the treatment of narcolepsy. Increasing popularity and off-label use as a cognitive enhancer has resulted in a reputation as an intelligence boosting 'wonder drug'. Common alternatives available from online shops and other retail outlets include 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide (adrafinil), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}acetamide (CRL-40,940), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}-N-hydroxyacetamide (CRL-40,941), and N-methyl-4,4-difluoro-modafinil (modafiendz), respectively. Gas chromatography-mass spectrometry (GC-MS) is a common tool used in forensic and clinical analysis but there is a potential for inducing analysis-related ambiguities. This study reports on the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940, and CRL-40,941 due to exposure to the heated GC injection port dissolved in a variety of solvents. Key degradation products common to modafinil, modafinic acid, and adrafinil analysis included diphenylmethanol and 1,1,2,2-tetraphenylethane (TPE), the latter of which was verified by its synthesis and characterization by x-ray crystallography. The investigated compounds were also characterized by 1 H and 13 C NMR. Diphenylmethane and thiobenzophenone were also identified in some instances. TPE formation was suggested to involve the generation of a benzhydrylium ion and its reaction with the sulfoxide oxygen of the parent compound to give an oxysulfonium intermediate. Correspondingly, the fluorinated TPE analogue was formed during heat-induced degradation of modafiendz, CRL-40,940 and CRL-40,941, respectively. When a mixture of modafinil (non-fluorinated) and modafiendz (fluorinated) were subjected to GC analysis, 4,4'-(2,2-diphenylethane-1,1-diyl)bis(fluorobenzene) was detected as a third cross reaction product in addition to the two expected TPE analogues. These observations served as a reminder that the seemingly straightforward implementation of GC-MS analysis can lead to challenges during routine analysis., (Copyright © 2016 John Wiley & Sons, Ltd.)

Six collected phenidates, i.e., 4-methylmethylphenidate, 3,4-dichloromethylphenidate, ethylphenidate, 3,4-dichloroethylphenidate, ethylnaphthidate, and N-benzyl-ethylphenidate were fully characterized by means of X-ray, nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), electrospray ionization-tandem mass spectrometry (ESI-MS/MS), attenuated total reflectance Fourier transform infrared (ATR-FTIR) and GC solid-state IR analysis. Crystallography revealed the exclusive presence of the threo-configuration. Steric crowding induced by N-benzyl substitution at the piperidine moiety prompted an adoption of an unexpected axial positioning of substituents on the piperidine moiety in the crystal state as opposed to the exclusive equatorial positioning encountered in N-unsubstituted phenidate analogues. Gas phase computations of the relative lowest energy conformers confirm that the axial positioning appears to be favoured over the equatorial positioning; in solution, however, equatorial positioning is predominant according to nuclear Overhauser effect experiments. All samples, mainly originating from China, had a good to very good degree of purity indicative of their professional chemical synthesis. Routine analysis of these drugs by GC-MS revealed thermal decomposition of phenidate analogues in the injection port and/or on column to 2-aryl-ethyl-acetates and 2,3,4,5-tetrahydropyridines. The decomposition pathway was suggested to proceed via a 6-membered transition state which was supported by density functional theory (DFT) computations. Fragmentation pathways of decomposition products as well as the corresponding electron ionization (EI) mass spectra are provided. The thermal instability might thus render smoking or 'vaping' of these drugs a less effective route of administration. The analytical fingerprints of six structurally diverse phenidate analogues provide a helpful reference to forensic chemists in charge of identifying new psychoactive substances. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Few empirical studies in the UK have examined the complex social patterns and values behind quantitative estimates of the prevalence of pharmacological cognitive enhancement (PCE). We conducted a qualitative investigation of the social dynamics and moral attitudes that shape PCE practices among university students in two major metropolitan areas in the UK. Our thematic analysis of eight focus groups ( n  = 66) suggests a moral ecology that operates within the social infrastructure of the university. We find that PCE resilience among UK university students is mediated by normative and cultural judgments disfavoring competitiveness and prescription drug taking. PCE risk can be augmented by social factors such as soft peer pressure and normalization of enhancement within social and institutional networks. We suggest that moral ecological dynamics should be viewed as key mechanisms of PCE risk and resilience in universities. Effective PCE governance within universities should therefore attend to developing further understanding of the moral ecologies of PCE.

The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, while achieving unprecedented precision in treatment. By using small molecules, photopharmacology provides a viable alternative to optogenetics. We present here a critical overview of the different pharmacological targets in various organs and a survey of organ systems in the human body that can be addressed in a non-invasive manner. We discuss the prospects for the selective delivery of light to these organs and the specific requirements for light-activatable drugs. We also aim to illustrate the druggability of medicinal targets with recent findings and emphasize where conceptually new approaches have to be explored to provide photopharmacology with future opportunities to bring "smart" molecular design ultimately to the realm of clinical use., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In addition to causing distress and disability to the individual, neuropsychiatric disorders are also extremely expensive to society and governments. These disorders are both common and debilitating and impact on cognition, functionality and wellbeing. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used to treat cognitive dysfunction in Alzheimer's disease and attention deficit hyperactivity disorder, respectively. Other cognitive enhancers include specific computerized cognitive training and devices. An example of a novel form of cognitive enhancement using the technological advancement of a game on an iPad that also acts to increase motivation is presented. Cognitive enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition, but also improves 'hot' cognition, such as emotion recognition and task-related motivation. The lifestyle use of 'smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups (e.g. military, doctors) under what conditions (e.g. war, shift work) and by what methods we would wish to improve and flourish.

Background: Pharmacological cognitive enhancement, using chemicals to change cellular processes in the brain in order to enhance one's cognitive capacities, is an often discussed phenomenon. The prevalence among Dutch university students is unknown., Methods: The study set out to achieve the following goals: (1) give an overview of different methods in order to assess the prevalence of use of prescription, illicit and lifestyle drugs for cognitive enhancement (2) investigate whether polydrug use and stress have a relationship with cognitive enhancement substance use (3) assessing opinions about cognitive enhancement prescription drug use. A nationwide survey was conducted among 1572 student respondents of all government supported Dutch universities., Results: The most detailed level of analysis-use of specific substances without a prescription and with the intention of cognitive enhancement-shows that prescription drugs, illicit drugs and lifestyle drugs are respectively used by 1.7, 1.3, and 45.6% of the sample. The use of prescription drugs and illicit drugs is low compared to other countries. We have found evidence of polydrug use in relation to cognitive enhancement. A relation between stress and the use of lifestyle drugs for cognitive enhancement was observed. We report the findings of several operationalizations of cognitive enhancement drug use to enable comparison with a wider variety of previous and upcoming research., Conclusions: RESULTS of this first study among university students in the Netherlands revealed a low prevalence of cognitive enhancement drug use compared to other countries. Multiple explanations, such as a difference in awareness of pharmacological cognitive enhancement among students, accessibility of drugs in the student population and inclusion criteria of enhancement substances are discussed. We urge enhancement researchers to take the different operationalizations and their effects on the prevalence numbers into account.

Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine-like dissociatives, piperazines, GABA-A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in routine drug screenings. This paper aims at providing psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of these substances. Indeed, these drugs act on a range of neurotransmitter pathways/receptors whose imbalance has been associated with psychopathological conditions, including dopamine, cannabinoid CB1, GABA-A/B, 5-HT2A, glutamate, and k opioid receptors. An overall approach in terms of clinical management is briefly discussed., (© 2015 World Psychiatric Association.)

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined.

A primary means for the augmentation of cognitive brain functions is "pharmacological cognitive enhancement" (PCE). The term usually refers to the off-label use of medical substances to improve mental performance in healthy individuals. With the final aim to advance the normative debate taking place on that topic, several empirical studies have been conducted to assess the attitudes toward PCE in the public, i.e., in groups outside of the academic debate. In this review, we provide an overview of the 40 empirical studies published so far, reporting both their methodology and results. Overall, we find that several concerns about the use of PCE are prevalent in the public. These concerns largely match those discussed in the normative academic debate. We present our findings structured around the three most common concerns: medical safety, coercion, and fairness. Fairness is divided into three subthemes: equality of opportunity, honesty, and authenticity. Attitudes regarding some concerns are coherent across studies (e.g., coercion), whereas for others we find mixed results (e.g., authenticity). Moreover, we find differences in how specific groups-such as users, nonusers, students, parents, and health care providers-perceive PCE: a coherent finding is that nonusers display more concerns regarding medical safety and fairness than users. We discuss potential psychological explanations for these differences.

The current analytical technology for the determination of New Psychoactive Substances in biological samples is still largely inadequate, because the immunoassays are unsuitable for the detection of most of these compounds and the use of traditional gas chromatography-mass spectrometry techniques is hampered by the lack of chromatographic standards and mass fragmentation patterns. Taking advantage of the molecular recognition capability of high-resolution mass spectrometry, the present work aimed to apply liquid chromatography-quadrupole-time of flight mass spectrometry for the rapid identification of New Psychoactive Substances in the hair, a peculiar tissue which "keeps memory" of the recent history of drug intake of the subject. All the samples were screened for the presence of 50 different New Psychoactive Substances (synthetic cannabinoids, cathinones and phenethylamines), substances that had been reported officially by the National Early Warning System in the period 2009-2011. Among the 435 samples analyzed, 8 were found "positive" for the following compounds: JWH-018, JWH-073, JWH-081, JWH-250, JWH-122, in a broad range of concentrations (0.010-1.28 ng/mg). Results strongly support the use of hair analysis to monitor the diffusion of new psychoactive drugs in the community.