Response to commentary. We are grateful to Crockett and Craigie for their interesting remarks on our paper. We accept Crockett’s claim that there is a need for caution in drawing inferences about patient groups from work on healthy volunteers in the laboratory. However, we believe that the evidence we cited established a strong presumption that many of the patients who are routinely taking a medication, including many people properly prescribed the medication for a medical condition, have morally significant aspects of (...) their cognition and behavior modified in a way that is unintended and may sometimes be unwelcome. Crockett notes that in some cases the effects of long-term drug use may differ, sometimes markedly, from the effects of short-term use. However, if acute use of a drug affects a neural system involved in mediating moral cognition or behavior, this nevertheless provides some evidence that chronic use of the drug may affect that same system and thus have morally significant effects. It is also plausible, in some cases, that an acute moral effect would give rise to a chronic moral effect via cognitive mechanisms. ... (shrink)

Die Posttraumatische Belastungsstörung (PTBS) ist ein schwerwiegendes psychisches Krankheitsbild, das Betroffene nach dem Erleben traumatisierender Situationen entwickeln. Im Zusammenhang mit den Auslandseinsätzen der Bundeswehr ist die PTBS bei Soldaten in den letzten Jahren verstärkt in den Fokus der deutschen Öffentlichkeit gerückt. Auch zivile Traumata bergen ein großes PTBS-Risiko. Seit einigen Jahren werden Methoden zur medikamentösen Prävention der PTBS erforscht. Die beiden wichtigsten Ansätze, die Prävention mit zentralnervös wirkenden Betablockern und Glukokortikoiden, basieren auf der Idee, durch den Eingriff in neuroendokrine Stressachsen (...) Einfluss auf die Art und Weise zu nehmen, in der die Erinnerung im Gedächtnis konsolidiert wird. Durch eine Entemotionalisierung und Abschwächung entsprechender Gedächtnisspuren soll das spätere Auftreten einer PTBS verhindert werden. Beide Ansätze zeigen in Pilotstudien vielversprechende Ergebnisse. Angesichts der herausragenden Bedeutung des Gedächtnisses für Individuum und Gesellschaft sollten Ansätze zur medikamentösen Gedächtnismodifikation (MGM) unter neuroethischen Gesichtspunkten diskutiert und bewertet werden. Der Text beleuchtet die MGM zur PTBS-Prävention entlang von fünf Problemachsen: 1) der Einflussnahme von MGM auf den Prozess der normalen psychischen Verarbeitung traumatischer Erlebnisse, 2) der Gefahr einer Entkopplung von Erinnerung und Realität, 3) der Bedeutung von emotionaler Erinnerung für die Moral, 4) der sozialen, juristischen und historischen Relevanz einer wahrhaftigen Erinnerungskultur und 5) der potenziellen Förderung eines gesellschaftlichen Medikalisierungsprozesses. Trotz ernsthaft zu diskutierender ethischer Bedenken ist – vor dem Hintergrund der Schwere des Krankheitsbilds – aus unserer Sicht eine MGM zur PTBS-Prävention grundsätzlich begrüßenswert, sollte jedoch derzeit nur im Rahmen klinischer Studien erfolgen. Hierfür stellen wir acht forschungsethische Aspekte zur Diskussion, die bei solchen Studien zu berücksichtigen sind. (shrink)

Sixteenth century pharmacology was still very much under the influence of a distinction going back to ancient medicine: the distinction between effects of medicaments that were taken to be explainable by the elementary qualities, their mutual modification in mixture, and the combination of these modified elementary qualities on the one hand, and the effects of medicaments that were taken not to be explicable in this manner.1 Galen coined the expression that a medicament of the latter kind possesses the capacity (...) of acting "by its whole substance,"2 and the question of how actions of the whole substance could be explicated gave rise to heated controversies in early modern pharmacology. Did Galen just... (shrink)

The possibility of enhancing human abilities often raises public concern about equality and social impact. This chapter aims at one particular group of technologies, cognitive enhancement, and one particular fear, that enhancement will create social divisions and possibly expanding inequalities. The chapter argues that cognitive enhancements could offer significant social and economic benefits. The basic forms of internal cognitive enhancement technologies foreseen today are pharmacological modifications, genetic interventions, transcranial magnetic stimulation, and neural implants. Cognitive enhancements can influence the economy (...) through reduction of losses, individual economic benefits, and society‐wide benefits. The strongest objection to the introduction of any enhancement technology is that it will create inequality, injustice, and unfairness. While there are clear economic and social benefits to cognitive enhancement, there exist anumber of obstacles to its development and use. One obstacle is the present system for licensing drugs and medical treatments. (shrink)

These lectures outline the project of a general organology, which is to say an account of life when it is no longer just biological but technical, or when it involves not just organic matter but organized inorganic matter. This organology is also shown to require a modified Simondonian account of the shift from vital individuation to a three-stranded process of psychic, collective and technical individuation. Furthermore, such an approach involves extending the Derridean reading of Socrates's discussion of writing as a (...) pharmakon, so that it becomes a more general account of the pharmacological character of retention and protention. By going back to Leroi-Gourhan, we can recognize that this also means pursuing the history of retentional modifications unfolding in the course of the history of what, with Lotka, can also be called exosomatization. It is thus a question of how exteriorization can, today, in an epoch when it becomes digital, and in an epoch that produces vast amounts of entropy at the thermodynamic, biological and noetic levels, still possibly produce new forms of interiorization, that is, new forms of thought, care and desire, amounting to so many chances to struggle against the planetary-scale pharmacological crisis with which we are currently afflicted. (shrink)

Memory blunting is a pharmacological intervention that decreases the emotional salience of memories. The technique promises a brighter future for those suffering from memory-related disorders such as PTSD, but it also raises normative questions about the limits of its permissibility. So far, neuroethicists have staked out two primary camps in response to these questions. In this paper, I argue both are problematic. I then argue for an alternative approach to memory blunting, one that can accommodate the considerations that motivate (...) rival approaches even while avoiding the problems these rivals face. In addition to arguing for this primary thesis, the paper also aims to suggest something about neuroethics generally: despite what some neuroethicists claim, new discoveries in neuroscience may not typically upend traditional views of morality. Rather, discoveries in neuroscience often provide us with new occasions to reflect on enduring questions about what it means to be human. (shrink)

Healthcare workers are at a high risk of psychological morbidity in the face of the COVID-19 pandemic. However, there is significant variability in the impact of this crisis on individual healthcare workers, which can be best explained through an appreciation of the construct of resilience. Broadly speaking, resilience refers to the ability to successfully adapt to stressful or traumatic events, and thus plays a key role in determining mental health outcomes following exposure to such events. A proper understanding of resilience (...) is vital in enabling a shift from a reactive to a proactive approach for protecting and promoting the mental well-being of healthcare workers. Research in the past decade has identified six areas that provide promising leads in understanding the biological basis of individual variations in resilience. These are: the key role played by the monoamines noradrenaline and serotonin, the centrality of the hypothalamic-pituitary-adrenal axis in influencing stress vulnerability and resilience, the intimate links between the immune system and stress sensitivity, the role of epigenetic modulation of gene expression in influencing the stress response, the role played by certain neuropeptides as a natural “brake” mechanism in the face of stress, and the neurobiological mechanisms by which environmental factors, such as exercise, diet, and social support, influence resilience to subsequent life events. Though much of this research is still in its early stages, it has already provided valuable information on which strategies – including dietary changes, lifestyle modification, environmental modification, psychosocial interventions, and even pharmacological treatments – may prove to be useful in fostering resilience in individuals and groups. This paper examines the above evidence more closely, with a specific focus on the challenges faced by healthcare workers during the COVID-19 pandemic, and provides suggestions regarding how it may be translated into real-world interventions, as well as how the more tentative hypotheses advanced in this field may be tested during this critical period. (shrink)

Corporeality, Medical Technologies and Contemporary Culture engages the confusions and contradictions in current attitudes to, and practices of, the body. On the one hand, the body is where we turn for the certainties of nature; yet, on the other, it is the locus of a desire for permanent transformation and for constant reinvention. The body is at the same time worshipped and despised: so that now it has come to constitute not just an object of desire, but an object of (...) design. Addressing practices of corporeal ascesis- such as bodybuilding and dietetics - medical technologies - such as plastic surgery, prosthetics, and pharmacological interventions - and radical anatomical modifications- such as voluntary amputations, Francisco Ortega analyses how the body has become a screen for the projection of our ideas and imaginings about ourselves; and has also been turned into an object of suspicion, fear, anxiety, insecurity and discomfort. From the disembodied ideal of the digital purity of models - in which every little piece of fat is digitally eliminated - through the disembodiment implicit in social constructivist rejections of materiality, to the various projects of virtual reality, artificial intelligence, and posthumanism, Corporeality, Medical Technologies and Contemporary Culture documents the ambiguous legacy of a western theoretical tradition that has always despised the body. (shrink)

One of the immediate eukaryotic cellular responses to DNA breakage is the covalent post‐translational modification of nuclear proteins with poly(ADP‐ribose) from NAD+ as precursor, mostly catalysed by poly(ADP‐ribose) polymerase‐1 (PARP‐1). Recently several other polypeptides have been shown to catalyse poly(ADP‐ribose) formation. Poly(ADP‐ribosyl)ation is involved in a variety of physiological and pathophysiological phenomena. Physiological functions include its participation in DNA‐base excision repair, DNA‐damage signalling, regulation of genomic stability, and regulation of transcription and proteasomal function, supporting the previously observed correlation of (...) cellular poly(ADP‐ribosyl)ation capacity with mammalian life. The pathophysiology effects are mediated through PARP‐1 overactivity, which can cause cell suicide by NAD+ depletion. It is apparent that the latter effect underlies the pathogenesis of a wide range of disease states including type‐1 diabetes, ischaemic infarcts in various organs, and septic or haemorrhagic shock. Therefore pharmacological modulation of poly(ADP‐ribosyl)ation may prove to be an exciting option for various highly prevalent, disabling and even lethal diseases. BioEssays 23:795–806, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Moonlighting – the performance of more than one function by a single protein – is becoming recognized as a common phenomenon with important implications for systems biology and human health. The different functions of a moonlighting protein may use different regions of the protein structure, or alternative structures that occur due to post-translational modifications and/or differences in binding partners. Often the different functions of moonlighting proteins are used at different times or in different places. The existence of moonlighting functions complicates (...) efforts to under- stand metabolic and regulatory networks, as well as physiological and pathological processes in organisms. Because moonlighting functions can play important roles in disease processes, an improved understanding of moonlighting proteins will provide new opportunities for pharmacological manipulations that specifically target a function involved in pathology while sparing physiologically important functions. (shrink)

IntroductionTranscranial magnetic stimulation is a consolidated procedure for the treatment of depression, with several meta-analyses demonstrating its efficacy. Theta-burst stimulation is a modification of TMS with similar efficacy and shorter session duration. The geriatric population has many comorbidities and a high prevalence of depression, but few clinical trials are conducted specifically for this age group. TBS could be an option in this population, offering the advantages of few side effects and no pharmacological interactions. Therefore, our aim is to (...) investigate the efficacy of TBS in geriatric depression.Clinical trial registration[https://clinicaltrials.gov/ct2/], identifier [NCT04842929]. (shrink)

During the last congress of the International Association of Bioethics in Beijing, there was a special session on human enhancement. John Harris, pioneer in the discussions on the ethics of enhancement,1 summarised this session, describing the focus of different panelists.2 This session included: Biopsychological enhancements The possibility of regulating emotions through pharmacological means Biases that may affect our judgments against human enhancement Health care inequalities that will follow from the adoption of genetic technology Social impact and costs of adopting (...) the new technology A discussion on women enhancing their physical strength as men through genetic modification .The Beijing panel did not address women’s involvement in the enhancement scenario. Of course, not every aspect of a topic can be covered in one session of a congress and some aspects may remain unaddressed; mainly, because these sessions draw from the research interests of the presenters. However, neither John Harris nor Julian Savulescu has yet addressed women’s crucial involvement in the enhancement scenario. It is the aim of this paper to draw attention to the invisibility of the ‘vessel’ in these discussions. Enhancement may be justified; but clearly, it will also affect women. In this scenario, will women be worse off?LATE ONSET DISEASES AND ENHANCEMENTFirstly, I would like to point out that I believe that enhancement may be a necessary step in the future of human evolution. As I have explained elsewhere,3 health care systems in the developed world are near to collapse under the pressure of late onset chronic diseases. Largely successful in preventing early deaths in the last century, health care systems have prompted a new plague, recognised lately by the World Health Organization as a new pandemic …. (shrink)

Poly(ADP‐ribosyl)ation is an immediate DNA‐damage‐dependent post‐translational modification of histones and other nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP‐ribose) polymerases (PARPs) now constitute a large family of 18 proteins, encoded by different genes and displaying a conserved catalytic domain in which PARP‐1 (113 kDa), the founding member, and PARP‐2 (62 kDa) are so far the sole enzymes whose catalytic activity has been shown to be immediately stimulated by DNA strand breaks. A large repertoire of sequences (...) encoding novel PARPs now extends considerably the field of poly(ADP‐ribosyl)ation reactions to various aspects of the cell biology including cell proliferation and cell death. Some of these new members interact with each other, share common partners and common subcellular localizations suggesting possible fine tuning in the regulation of this post‐translational modification of proteins. This review summarizes our present knowledge of this emerging superfamily, which might ultimately improve pharmacological strategies to enhance both antitumor efficacy and the treatment of a number of inflammatory and neurodegenerative disorders. A provisional nomenclature is proposed. BioEssays 26:882–893, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The aim of the paper is to investigate paths along which a transformation of the doctrine of natural signs was developed in works by Paracelsians, forming one of the main religious and philosophic currents of Late Renaissance. The modifications of the doctrine are discussed in a context of intensive speculations on the essence of the primordial language of humankind and on the possibility of its restoration, which can describe the intellectual life of that epoch. It is argued that within “chemical (...) philosophy” the possibility of restoration of the Adamic language directly depends on mastering the art of interpreting natural signs, which can give a key to correct understanding of nature. And shifts in the conceptualization of such signatures involved transformations in formulating and solving of the Adamistic problems, which did not exclude reverse causation. It is also ascertained that the most orthodox followers of Paracelsus usually appealed to the Adamistic narrative in order to reinforce legitimacy of the symbolic hermeneutics of nature, developed with chiefly medico-pharmacological purposes. Meanwhile, relatively more independent Paracelsians often paid more attention to linguo-philosophic issues. Realizing the deficiency of the doctrine of signatures for reconstruction of the primordial language, they postulated the necessity of one of the following premises: supplementing the doctrine with a mystical illumination; acceptance of a weaker version, according to which natural signs are just sparse reference points slightly simplifying empirical study of nature; abandonment of search for the Ursprache and constructing its artificial substitute, a universal semiotic system. (shrink)

This chapter addresses the problem of ranking available drugs in guideline development to support clinicians in their work. Based on a pragmatic approach to the notion of evidence and a hierarchical view on different kinds of evidence this chapter introduces a decision aid, HiDAD, which draws on the multi criteria decision making literature. This decision aid implements the wide-spread intuition that there are different kinds of evidence with varying degrees of importance by relying on a strict ordinal ordering of kinds (...) of evidence. In order to construct a ranking every pair of drugs is first compared separately on all kinds of evidence. Next, these quantitative comparisons are then aggregated into an overall comparison between drugs based on all the available evidence in a way which avoids that evidence of less importance is trumped by evidence of the higher levels. Finally, these overall comparisons are used to determine the final ranking of drugs which then informs the process of guideline writing. Properties, modifications and applicability of the decision aid HiDAD are discussed and assessed. (shrink)

The latest advances in quantum computing forced the National Institute of Standards and Technology (NIST) to launch an initiative for selecting quantum-resistant cryptographic algorithms. One of the best-known proposals is NewHope, an algorithm that was initially designed as a key exchange algorithm. In its original design, NewHope presented a reconciliation mechanism that is complex and represents an entry barrier for potential implementers. This contribution presents equivalent schemes in one, two and three dimensions, which allow anyone to make the transition to (...) the 4D NewHope algorithm easier to undertake. In addition to that, the effect of modifying some of the parameters associated to NewHope’s reconciliation mechanism is studied, which has allowed us to propose different sets of parameters that could increase the security of NewHope implementations. (shrink)

There are numerous ways people can improve their cognitive capacities: good nutrition and regular exercise can produce long-term improvements across many cognitive domains, whilst commonplace stimulants such as coffee temporarily boost levels of alertness and concentration. Effects like these have been well-documented in the medical literature and they raise few ethical issues. More recently, however, clinical research has shown that the off-label use of some pharmaceuticals can, under certain conditions, have modest cognition-improving effects. Substances such as methylphenidate and modafinil can (...) improve capacities such as working memory and concentration in some healthy individuals. Unlike their more mundane predecessors, these methods of “cognitive enhancement” are thought to raise a multitude of ethical issues. This paper presents the six principal ethical issues raised in relation to pharmacological cognitive enhancers —issues such as whether: the medical safety-profile of PCEs justifies restricting or permitting their elective or required use; the enhanced mind can be an “authentic” mind; individuals might be coerced into using PCEs;, there is a meaningful distinction to be made between the treatment vs. enhancement effect of the same PCE; unequal access to PCEs would have implications for distributive justice; and PCE use constitutes cheating in competitive contexts. In reviewing the six principal issues, the paper discusses how neuroscientific research might help advance the ethical debate. In particular, the paper presents new arguments about the contribution neuroscience could make to debates about justice, fairness, and cheating, ultimately concluding that neuroscientific research into “personalized enhancement” will be essential if policy is to be truly informed and ethical. We propose an “ethical agenda” for neuroscientific research into PCEs. (shrink)

In psychiatry, pharmacological research has played a crucial role in the formulation, revision, and refinement of neurobiological theories of psychopathology. Besides being utilized as potential treatments for various mental disorders, pharmacological drugs play an important epistemic role as experimental instruments that help scientists uncover the neurobiological underpinnings of mental disorders (Tsou, 2012). Interventions with psychiatric patients using pharmacological drugs provide researchers with information about the neurobiological causes of mental disorders that cannot be obtained in other ways. This (...) important source of evidence for the biological causes of mental disorder is often overlooked in philosophical analyses of psychiatry, especially in skeptical analyses that debase the biological aspects of psychopathology (e.g., Szasz, 1960; Scheff, 1963; Laing, 1967). In discussing pharmacological interventions as a form of evidence for the physical basis of mental disorders, this paper aims to clarify the nature, reliability, and limitations of this evidence. In addition, it illustrates the central role that pharmacological findings in applied clinical contexts play in the acquisition of neurobiological knowledge in research contexts. (shrink)

The potential of memory modification techniques (MMTs) has raised concerns and sparked a debate in neuroethics, particularly in the context of identity and authenticity. This paper addresses the question whether and how MMTs influence authenticity. I proceed by drawing two distinctions within the received views on authenticity. From this, I conclude that an analysis of MMTs based on a dual-basis, process view of authenticity is warranted, which implies that the influence of MMTs on authenticity crucially depends on the specifics (...) of how memory modification would eventually work. Therefore, I continue with a systematic analysis of possible properties of MMTs in which I distinguish between the dimensions of memories and the kinds of experiences that can be modified as well as the properties of the process of memory modification. The impact of MMTs on authenticity is analyzed regarding the possible properties of MMTs and based on a narrative approach to authenticity which fulfills the requirements of a dual-basis, process view of authenticity. Lastly, I explore the potential of MMTs to shift the balance between self-discovery and self-creation within authenticity and thereby alter the concept itself as well as the value of authenticity. (shrink)

Recent studies have shown that pharmacological treatment may have an impact on aggressive and impulsive behavior. Assuming that these results are correct, would it be morally acceptable to instigate violent criminals to accept pharmacological rehabilitation by offering this treatment in return for early release from prison? This paper examines three different reasons for being skeptical with regard to this sort of practice. The first reason concerns the acceptability of the treatment itself. The second reason concerns the ethical legitimacy (...) of making offers under coercive conditions. The third relates to the acceptability of the fact that those criminals who accepted the treatment would be exempted from the punishment they rightly deserved. It is argued that none of these reasons succeeds in rejecting this sort of offer. (shrink)

Pharmacological cognitive enhancements nontherapeutically improve cognitive functioning, though recent critics have challenged their use by claiming that cognitive success, aided by the use of cognitive enhancement, is less valuable than otherwise. We criticize two recent responses to this objection, due to Carter and Pritchard and Wang, and propose a different response on behalf of proponents of cognitive enhancement that is shown to be more promising.

A good part of the explanation for differences in happiness has to do with genetics. This chapter reviews the scientific data relevant to a heritable component to happiness, and the prospects for using current and future technologies to alter those who have not won the genetic lottery. The chapter looks at the concept of heritability, and then at the heritability of happiness. The notion of heritability is typically seen as a composite of two factors: genetics and the environment. Three promising (...) technologies could be used to change the biological basis of happiness: pre‐implantation genetic diagnosis (PGD), genetic engineering, and advanced pharmacology. Unfortunately, on enhancing the moods of healthy individuals, there is limited research. The fact that two thirds of these “normal and healthy” volunteers felt “better than well” sounds like good news for happy‐people‐pills. The chapter touches upon the paucity of studies of the effects of antidepressants on healthy individuals. (shrink)

BackgroundSocial cognitive impairments adversely affect social functioning in patients with schizophrenia. Although pharmacological interventions have been suggested to provide some benefits on social cognition, little information is available on the comparative efficacy of pharmacotherapy. Thus, the aim of this planned systematic review and network meta-analysis is to perform a quantitative comparison of the effects of various psychotropic drugs, including supplements, on social cognition disturbances of schizophrenia.MethodsThe literature search will be carried out using the PubMed, Embase, Cochrane Central Register of (...) Controlled Trials, PsycINFO, ClinicalTrials.gov, and International Clinical Trials Registry Platform databases from inception onward. Randomized controlled trials that examined the efficacy of drugs in social cognitive disturbances will be included, based on the most recent studies and the broader literature than previously searched. This protocol defines a priori the methods that will be used for study selection, data collection, quality assessment, and statistical syntheses.DiscussionThe findings this work are expected to help promote the development of better therapeutics of social cognitive impairments in schizophrenia and related psychiatric conditions.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42021293224]. (shrink)

By drawing on the philosophy of Bernard Stiegler, the phenomena of mechanical (a.k.a. artificial, digital, or electronic) intelligence is explored in terms of its real significance as an ever-repeating threat of the reemergence of stupidity (as cowardice), which can be transformed into knowledge (pharmacological analysis of poisons and remedies) by practices of care, through the outlook of what researchers describe equivocally as “artificial stupidity”, which has been identified as a new direction in the future of computer science and machine (...) problem solving as well as a new difficulty to be overcome. I weave together of web of “artificial stupidity”, which denotes the mechanic (1), the human (2), or the global (3). With regards to machine intelligence, artificial stupidity refers to: 1a) Weak A.I. or a rhetorical inversion of designating contemporary practices of narrow task-based procedures by algorithms in opposition to “True A.I.”; 1b) the restriction or employment of constraints that weaken the effectiveness of A.I., which is to say a “dumbing-down” of A.I. by intentionally introducing mistakes by programmers for safety concerns and human interaction purposes; 1c) the failure of machines to perform designated tasks; 1d) a lack of a noetic capacity, which is a lack of moral and ethical discretion; 1e) a lack of causal reasoning (true intelligence) as opposed to statistical associative “curve fitting”; or 2) the phenomenon of increasing human “stupidity” or drive-based behaviors, which is considered as the degradation of human intelligence and/or “intelligent human behavior” through technics; and finally, 3) the global phenomenon of increasing entropy due to a black-box economy of closed systems and/or industry consolidation. (shrink)

This is a commentary piece on Marco Pavanini's article ' ‘Multistability and Derrida’s Différance: Investigating the Relations Between Postphenomenology and Stiegler’s General Organology' in which I critically extend upon his comparative analysis of postphenomenology''s notion of multistability and Stiegler's conception of organology, focusing in particular on the pharmacological nature of Stiegler's organology and the latter's most recent re-interpretation of it in terms of entropy and negentropy. Among other things I show, and both are more intended as additions than criticisms (...) with respect to Pavanini’s very helpful comparison, that the most important concern for Stiegler in theorizing technology is the fact that the transductive relations between the three organ systems distinguished in his pharmaco-organology of technology open up affective or libidinal circuits between these systems, i.e., circuits either of desire or drive depending on the way the pharmakon is adopted or not, and that these circuits are fundamentally noetic circuits vulnerable to denoetization; and that these libidinal-noetic circuits as conditioned by technology should be interpreted in terms of entropy and negentropy. Both insights are lacking in postphenomenology, which generally fails to consider the irreducibly destitutive character of all technology, rightfully emphasized by Pavanini, since it lacks a genuine pharmacological awareness. (shrink)

Clinical Pharmacology is a specialty with many attributes and our association with the subject has allowed us to acquire, apply and disseminate myriad aspects of research and practice. Though clinical pharmacologists are conspicuous by virtue of their small number, recent years have shown a growing need for the course. In the review below we navigate through several aspects of the subject as we encountered them from time to time. From critical appraisal of literature, to application of knowledge of drugs, to (...) clinical practice; moving on to clinical and basic research, to drug development process, to policy making - these are but a few of the many fields which constitute the scope of clinical pharmacology. The importance of the subject lies in allowing a trainee to develop a broad overview of the entire process, from drug generation to drug distribution to drug utilization, a process meant for the greater common goal of better health for all. We foresee a bright future for the subject though with a slight skepticism thrown in. In the present article, we make use of personal experiences and reference from literature to help you get a broad view of what clinical pharmacology means to us. (shrink)

Recent discussions of cognitive enhancement often note that drugs and technologies that improve cognitive performance may do so at the risk of “cheapening” our resulting cognitive achievements Arguing about bioethics, Routledge, London, 2012; Harris in Bioethics 25:102–111, 2011). While there are several possible responses to this worry, we will highlight what we take to be one of the most promising—one which draws on a recent strand of thinking in social and virtue epistemology to construct an integrationist defence of cognitive enhancement.. (...) According to such a line, there is—despite initial appearances to the contrary—no genuine tension between using enhancements to attain our goals and achieving these goals in a valuable way provided the relevant enhancement is appropriately integrated into the agent’s cognitive architecture. In this paper, however, we show that the kind of integration recommended by such views will likely come at a high cost. More specifically, we highlight a dilemma for users of pharmacological cognitive enhancement: they can meet the conditions for cognitive integration at the significant risk of dangerous dependency, or remain free of such dependency while foregoing integration and the valuable achievements that such integration enables. After motivating and clarifying the import of this dilemma, we offer recommendations for how future cognitive enhancement research may offer potential routes for navigating past it. (shrink)

The pharmacological literature on negative dream experiences is reviewed with respect to Revonsuo's threat rehearsal theory of dreaming. Moderate support for the theory is found, although much more work is needed. Significant questions that remain include the precise role of acetylcholine in the generation of negative dream experiences and dissociations between the pharmacology of waking fear and anxiety and threatening dreams. [Revonsuo].

Apathy and depression are frequently observed as behavioral and psychological symptoms of dementia, respectively, and are important for ensuring adequate care. This study aims to explore effective non-pharmacological interventions for apathy and depression with mild cognitive impairment and dementia. Five search engines including PubMed, Scopus, CINAHL, PsycInfo, and Web of Science were used to extract relevant studies. Inclusion criteria were studies that involved participants who were diagnosed with MCI or dementia, included quantitative assessments of each symptom, and employed randomized (...) controlled trials. Twenty studies were extracted, with interventions have been conducted in care facilities, the community, and hospitals. Participants in many studies had MCI or mild-to-moderate dementia but were not diagnosed with the subtypes of dementia. Few studies had set apathy and depression as the primary outcomes of non-pharmacological interventions. The findings suggested that emotional and stimulation-oriented approaches to apathy and depression would be useful for people with MCI or mild-to-moderate dementia. It would be helpful for therapists to assess the clinical features of the target symptoms for selecting suitable interventions. Additionally, increasing the number of randomized controlled trials focusing on apathy or depression as primary outcomes would offer a more definite conclusion for future systematic reviews. (shrink)

It is a commonplace of the critical innovation literature that experiment has replaced mass production as the driving force of accumulation. But while many theorists have explored the politics and dynamics of such economies of experiment under the rubric of ‘immaterial’, cognitive or affective labour, few have examined the intersection of labour, experiment and the speculative in the clinic. Taking the clinic as representative of contemporary transformations in the commodity-form, labour and innovation, this article will look at recent attempts to (...) reform the clinical trial, arguing that these developments represent a far-reaching shift in our understanding of medicine. First, I investigate recent efforts (associated with the discourse of ‘translational medicine’) to rethink the interface between experimental lab-based science and the clinic. I also look at closely associated efforts to reintroduce an element of experimental surprise into the clinical trial process itself, through the adoption of novel trial designs. If the randomized controlled trial was conceived essentially along the lines of a product testing procedure, recent efforts have attempted to reintroduce surprise into the testing process itself – in other words, to invent a trial process capable of producing unexpected events as leads for further innovation. I then move from the experimental clinic to what I call the distributed experiment. Here I focus on efforts to outsource pharmacological innovation to a distributed public of patients through the use of social networking software. These platforms allow drug developers to escape the limits of the conventional clinical trial by tracking the experimental practices taking place in the distributed clinic of unregulated drug consumption. (shrink)

This article offers the first edition and translation of two heretofore unpublished pharmacological treatises by Abū Bakr al-Rāzī, namely Fī ittikhādh māʾ al-jubn and Fī manāfiʿ māʾ al-jubn, which seem to have formed part of a lost volume on dairy products. As it demonstrates, al-Rāzī’s examination of whey is connected to his philosophical interest in the complex nature of simple substances such as milk. The article also highlights how these two treatises built on the Greek pharmacological tradition by (...) incorporating ingredients from Persia and India. (shrink)

Digital technologies induce organised immaturity by generating toxic sociotechnical conditions that lead us to delegate autonomous, individual, and responsible thoughts and actions to external technological systems. Aiming to move beyond a diagnostic critical reading of the toxicity of digitalisation, we bring Bernard Stiegler’s pharmacological analysis of technology into dialogue with the ethics of care to speculatively explore how the socially engaged arts—a type of artistic practice emphasising audience co-production and processual collective responses to social challenges—play a care-giving role that (...) helps counter technology-induced organised immaturity. We outline and illustrate two modes by which the socially engaged arts play this role: 1) disorganising immaturity through artivism, most notably anti-surveillance art, that imparts savoir vivre, that is, shared knowledge and meaning to counter the toxic side of technologies while enabling the imagination of alternative worlds in which humans coexist harmoniously with digital technologies, and 2) organising maturity through arts-based hacking that imparts savoir faire, that is, hands-on knowledge for experimental creation and practical enactment of better technological worlds. (shrink)

Beginning with a review of Michael Pollan's latest book about the renaissance of research into the use of psychedelics to treat addiction, depression, and end-of-life anxiety, this essay considers wisdom and insight that might be gained by examining the psychedelic practices of primitive people. Pollan finds that almost all who begin using psychedelics to treat the ill eventually come to the conclusion that they should be made available for the broader purpose of 'the betterment of well people'. By considering both (...) scientific and spiritual perspectives on these compounds, the book offers insight into the toxicity not only of our mental environment, but at the same time our relationship to fellow humanity and Mother Nature. However, Pollan does not consider what is perhaps the greatest source of wisdom regarding the pharmacological potential of psychedelics: primitive societies who have long incorporated these compounds into their ways of being. By casting anthropological accounts of primitive psychedelic practices against those of contemporary research, this essay seeks to deepen enquiry into the pathologies of modern personhood as they bear upon the ecological crisis, together with the potential value of entheogens for understanding and responding to these problems. (shrink)

Objectives To understand the ethical principles guiding college students’ abstention from pharmacological cognitive enhancement, and to determine the correlates associated with endorsing different principles. Design One-stage cluster sampling was used to implement a paper-based survey among undergraduate students attending one university in the U.S. Thematic analysis was used to explore the ethical principles guiding PCE abstention. Multivariate logistic regression analyses were used to examine sociodemographic correlates associated with endorsed ethical principles. Participants Of the 499 eligible students who completed the (...) survey, 259 students had a negative attitude towards PCE, did not engage in PCE, and provided reasons for abstention. Results The thematic analysis resulted in the identification of eight themes, with respondents often endorsing more than one theme per response. The three themes most endorsed were non-malfeasance, disapproval of drugs and dosage beneficence. The sociodemographic correlates associated with endorsing each theme varied across themes. Conclusions Students abstain from PCE for a multitude of reasons, many of which are guided by ethical principles. These findings may be incorporated into future prevention programming messages. (shrink)

ObjectivesTo understand the ethical principles guiding college students’ abstention from pharmacological cognitive enhancement, and to determine the correlates associated with endorsing different principles.DesignOne-stage cluster sampling was used to implement a paper-based survey among undergraduate students attending one university in the U.S. Thematic analysis was used to explore the ethical principles guiding PCE abstention. Multivariate logistic regression analyses were used to examine sociodemographic correlates associated with endorsed ethical principles.ParticipantsOf the 499 eligible students who completed the survey, 259 students had a (...) negative attitude towards PCE, did not engage in PCE, and provided reasons for abstention.ResultsThe thematic analysis resulted in the identification of eight themes, with respondents often endorsing more than one theme per response. The three themes most endorsed were non-malfeasance, disapproval of drugs and dosage beneficence. The sociodemographic correlates associated with endorsing each theme varied across themes.ConclusionsStudents abstain from PCE for a multitude of reasons, many of which are guided by ethical principles. These findings may be incorporated into future prevention programming messages. (shrink)

Much recent discussion has focused on the nature of artifacts, particularly on whether they have essences. While it is often held that artifacts are intention-dependent and necessarily have functions, it is equally commonly held, though far less discussed, that artifacts are the result of physical modification of some material objects. This paper argues that the physical modification condition on artifacts is false. First, it formulates the physical modification condition perspicuously for the first time. Second, it offers counterexamples (...) to this condition, both concrete and abstract. Third, it considers, and rejects, two responses to these counterexamples, one which appeals to the distinction between being a K and being used as a K and another which argues that the counterexamples are merely of functional, not artifactual, kinds. Finally, it considers, and rejects, a more general objection that appropriation makes artifact creation too easy. As a consequence, artifacts can be created by appropriating pre-existing objects and it sketches some success conditions for such appropriation. (shrink)

An engagement with Derrida's "Plato's Pharmacy." The paper addresses: where wordless things exist , Derrida's presentation of what he calls true morality , the son's replacement of the father in writing, , and "pharmacological therapeia ." The paper ends with an account of "sensible awareness" and the ways in which the functions of cultural sensibility both confirm and show limits in Derrida's pharmacological practices. The paper throughout addresses issues basic to how people live in the context of a (...) pharmacological disposition. (shrink)

Adverbial modification is probably one of the least understood areas of linguistics. The essays in this volume all address the problem of how to give an analysis of adverbial modifiers within truth-conditional semantics. Chapters I-VI provide analyses of particular modifiers within a possible worlds framework, and were written between 1974 and 1981. Original publication details of these chapters may be found on p. vi. Of these, all but Chapter I make essential use of the idea that the time reference (...) involved in tensed sentences should be a time interval rather than a single instant. The final chapter (Chapter VII) was written especially for this volume and investigates the question of how the 'situation semantics' recently devised by Jon Barwise and John Perry, as a rival to possible-worlds semantics, might deal with adverbs. In addition I have included an appendix to Chapter III and an introduction which links all the chapters together. (shrink)

Bernard Stiegler’s theoretical and practical Internation Project called for a refoundation of theoretical computer science that would also put the fact of exchange back at the centre of the conceptualization and organization of the economy. This can be interpreted as a call to critique a form of capitalism that has arisen over the past 70 years through an ideology via which ‘information’ conjoins computation and economics into what becomes an absolute market. But another history of exchange unfolds contemporaneously with this (...) ideology: that pursued in responses to Marcel Mauss’s anthropology of the gift, by Claude Lévi-Strauss, Georges Bataille and Maurice Godelier, among others. Stiegler’s ‘neganthropology’ equally responds to and is informed by this other history of the fact of exchange but, by looking at these works more closely, it may be possible to pursue Stiegler’s project in fields such as kinship and sexuality, which were not his direct concern. (shrink)

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. (shrink)

The complexity of the Hedgehog (Hh) signaling cascade has increased over the course of evolution; however, it does not suffice to accommodate the dynamic yet robust requirements of differential Hh signaling activity needed for embryonic development and adult homeostatic maintenance. One solution to solve this dilemma is to apply multiple forms of post‐translational modifications (PTMs) to the core Hh signaling components, modulating their abundance, localization, and signaling activity. This review summarizes various forms of protein modifications utilized to regulate Hh signaling, (...) with a special emphasis on crosstalk between different forms of PTMs and their feedback regulation by Hh signaling. (shrink)

A modified subformula property for the modal logic KD with the additionalaxiom □ ◊ ⊃ □ ◊ A ∨ □ ◊B is shown. A new modification of the notion of subformula is proposed for this purpose. This modification forms a natural extension of our former one on which modified subformula property for the modal logics K5, K5D and S4.2 has been shown. The finite model property as well as decidability for the logic follows from this.

For nearly two decades, ethicists have expressed concerns that the further development and use of memory modification technologies (MMTs)—techniques allowing to intentionally and selectively alter memories—may threaten the very foundations of who we are, our personal identity, and thus pose a threat to our well-being, or even undermine our “humaneness.” This paper examines the potential ramifications of memory-modifying interventions such as changing the valence of targeted memories and selective deactivation of a particular memory as these interventions appear to be (...) at the same time potentially both most promising clinically as well as menacing to identity. However, unlike previous works discussing the potential consequences of MMTs, this article analyzes them in the context of the narrative relational approach to personal identity and potential issues related to autonomy. I argue that such a perspective brings to light the ethical aspects and moral issues arising from the use of MMTs that have been hidden from previously adopted approaches. In particular, this perspective demonstrates how important the social context in which an individual lives is for the ethical evaluation of a given memory-modifying intervention. I conclude by suggesting that undertaking memory modifications without taking into account the social dimension of a person’s life creates the risk that she will not be able to meet one of the basic human needs—the autonomous construction and maintenance of personal identity. Based on this conclusion, I offer some reflections on the permissibility and advisability of MMTs and what these considerations suggest for the future. (shrink)