We present some ideas on logical process descriptions, using relations from the DIO (Drug Interaction Ontology) as examples and explaining how these relations can be naturally decomposed in terms of more basic structured logical process descriptions using terms from linear logic. In our view, the process descriptions are able to clarify the usual relational descriptions of DIO. In particular, we discuss the use of logical process descriptions in proving linear logical theorems. Among the types of reasoning supported by (...) DIO one can distinguish both (1) basic reasoning about general structures in reality and (2) the domain-specific reasoning of experts. We here propose a clarification of this important distinction between (realist) reasoning on the basis of an ontology and rule-based inferences on the basis of an expert’s view. (shrink)

Drive en Mille Sons (Drifting in a Thousand Sounds)is a musical work that uses mobile media technology to artistically examine the relationship between music and the listener. Contemporary media technologies, be they at work, home or in your pocket, emphasize playback. These devices are designed to facilitate the storage and retrieval of pre-made media assets. This work leverages the processing capabilities that rest dormant within these technologies. Drawing from the writings of Guy Debord and the situationist/surrealist practice of the (...) drive, drifting becomes a metaphor for instrumental performance in which the openness and emergence of interactivity is articulated through sound, as music. (shrink)

Ventricular Fibrillation is responsible for a majority of sudden cardiac death, but little is known about how ventricular tachycardia (VT) degenerates into ventricular fibrillation. Several clinical studies focused only on preventing VT with a class III antiarrhythmic drug resulted in many deaths. Our simulations investigate the interactions between an antiarrhythmic drug likely to suppress a VT and a Figure 8 reentry. A parameter AAR is introduced to increase the action potential duration and therefore simulate various Class III drugs. (...) Simulations are ran under several conditions (phases of the reentry, values of AAR, durations). They show that a VT can be suppressed whatever the phase of the reentry but it strongly depends on the duration of the effect. It confirms that a drug which can suppress a reentry can also worsen it. It also shows a great variety of activation patterns and thus the complexity of antiarrhythmic drugs effects. Simulations also demonstrate that suppressing VT is an increasing function of AAR. (shrink)

Signaling complexes and networks are being intensely studied in an attempt to discover pathways that are amenable to therapeutic intervention. A challenge in this search is to understand the effect that the modulation of a target will have on the overall function of a cell and its surrounding neighbors. Protein‐interaction mapping reveals relationships between proteins and their impact on cellular processes and is being used more widely in our understanding of disease mechanisms and their treatment. The review discusses challenges (...) and breakthroughs in this new and evolving area and its impact on medicine. BioEssays 27:958–969, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

A general framework by which dynamic interactions within a protein will promote the necessary series of structural changes, or “conformational cycle,” required for function is proposed. It is suggested that the free‐energy landscape of a protein is biased toward this conformational cycle. Fluctuations into higher energy, although thermally accessible, conformations drive the conformational cycle forward. The amino acid interaction network is defined as those intraprotein interactions that contribute most to the free‐energy landscape. Some network connections are consistent in (...) every structural state, while others periodically change their interaction strength according to the conformational cycle. It is reviewed here that structural transitions change these periodic network connections, which then predisposes the protein toward the next set of network changes, and hence the next structural change. These concepts are illustrated by recent work on tryptophan synthase. Disruption of these dynamic connections may lead to aberrant protein function and disease states. (shrink)

Use of medication for treatment of ADHD (or its historical precursors) has been debated for more than forty years. Reasons for the ongoing differences of opinion are analyzed by exploring some of the arguments for and against considering ADHD a mental disorder. Relative to two important DSM criteria — that a mental disorder causes some sort of harm to the individual and that a mental disorder is the manifestation of a dysfunction in the individual — ADHD’s classification as a mental (...) disorder is found to be contentiously value-laden. The disagreements spill over to reasoning regarding appropriate management, because justification for a drug prescription is in part predicated on the idea that the drugs manage mental disorders. These debates do not appear to be nearing resolution, so individuals offering advice, or trying to decide whether ADHD drugs are appropriate for themselves or their children, may find it helpful to compare the values underlying various perspectives with their own. (shrink)

BackgroundLow-stakes crimes related to alcohol and/or drugs are common around the world, but research is lacking on police–suspect interactions of such crimes. A large proportion of these suspects are intoxicated during interrogations, and many may have substance use disorder, making them potentially vulnerable to interrogative pressure.MethodsTo address this lack of knowledge, the taxonomy of interrogation methods framework and a common classification of question types were applied in the coding of written police interrogations. Two archival studies, one pilot and one main (...) study analyzed police interrogations with suspects of alcohol- and drug-related crimes in Sweden.ResultsFor both Study 1 and 2, suspects showed signs of alcohol and/or drug intoxication, hangover or withdrawal in more than 50% of all interrogations. In Study 2, additional coding indicated that suspects displayed signs of substance use disorder in 57% of the interrogations. The main results from both studies revealed a large number of direct questions asked by the police across all interrogations, and relatively little use of the strategic interrogation techniques from the taxonomy of interrogation methods framework. In fact, when it came to interrogation techniques, law enforcement used more confrontational techniques in their interactions with intoxicated suspects compared to sober suspects. Furthermore, suspects displaying signs of substance use disorder were significantly more cooperative and prone to confess than suspects without indicators of substance use disorder.ConclusionAs the first novel study on low-stakes crime interrogations related to alcohol and/or drugs, the present study provides useful information about current Swedish interrogation practices and areas for improvement. The study results indicate that suspects displaying signs of intoxication or substance use disorder may be more vulnerable during police interrogations. This may in turn have the potential to inform the development of new interrogation policies. Due to the novelty of this research, more studies are needed, both on a national and international level, to examine interrogations in low-stakes crimes further. (shrink)

When behaviors assemble into combinations, then synergies have a central role in the discovery of productive patterns of behavior. In our view—what we call the Synergy Emergence Principle (SEP)—synergies are dynamic attractors, drawing interactions toward greater returns as they happen, in the moment. This Principle offers an alternative to the two conventionally acknowledged routes to discovery: directed problem solving, involving forethought and planning; and the complete randomness of trial and error. Natural selection has a role in the process, in humans (...) favoring the maintenance and improvement of certain key underlying capabilities, such as prosocial helping and episodic foresight, but selection is not required for discovery by synergy (which occurs too rapidly for selection anyway). Here we discuss the consequences of the SEP for the evolution in humans of key synergies such as tool usage and interactions that reward cooperation, show how discovery by synergy and the selection of synergy-supporting abilities formed a positive feedback loop, and show how synergies can combine, forming clusters and packages that are the core of institutions and cultures. Finally, clusters and packages represent an intermediate level of organization above the individual and below whole society, with consequences for our understanding of the major transitions in evolution. (shrink)

Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a “necessary” prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of “drug instrumentalization.” Psychoactive drugs are consumed for their effects on mental states. Humans (...) are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific “instrumentalization goals” and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future. (shrink)

Nietzsche offers us an account of how different drives interact with one another; it is rich but also appears to risk the homunculus fallacy. Competing attempts to deflect this charge on his behalf share an implicit consensus about the ‘epistemic ends’ of the account: they assume Nietzsche is trying to provide true explanations of psychological phenomena. I argue against this consensus. I claim that Nietzsche's characterisations of drive interaction are to be taken as fictive and are not intended (...) to have explanatory value. They nevertheless facilitate genuine epistemic achievement. Drawing on Catherine Elgin's account of the epistemic role of idealised models in science, I argue that Nietzsche's account of drive interaction is a ‘model of the mind’ that, despite relying on falsehoods, can exemplify features of our psychology that aid us in making novel predictions. We then see that Nietzsche neatly sidesteps the homunculus fallacy; we can further understand more fully what Nietzsche hopes his drive psychology will teach us. We can now resolve, for example, outstanding interpretative puzzles about the relationship between psychic integration and Nietzsche’s distinctive notion of spiritual health. (shrink)

Part II of Fichte’s System of Ethics is titled “Deduction of the Reality and Applicability of the Moral Law.” In this chapter, I argue that what motivates Fichte’s new deduction is a concern to avoid what he calls “empty formula philosophy,” that is, a philosophy which fails to explain how willing an object is possible. Fichte sets out to avoid this shortcoming by offering a complex theory of the drives, focusing first on what he calls our “lower capacity of desire.” (...) I argue that the key to understanding this section of the System of Ethics lies in Fichte's attempt to derive the character of our “natural drive” (Naturtrieb) from how we represent the system of “nature“ (Natur) as a whole. At the centre of this derivation we find Fichte drawing upon an organicist model of nature, according to which all the parts of natural systems reciprocally interact for the sake of the whole, and vice versa. While largely overlooked by scholars, I contend that this organicist model gives Fichte the resources to present an original theory of desire as an activity of “forming and being formed” by natural objects, in a way that foreshadows what he later calls our “ethical drive” (sittlicher Trieb) to unite with others, both cooperatively and reciprocally, in rational community. (shrink)

The literature on self-driving cars and ethics continues to grow. Yet much of it focuses on ethical complexities emerging from an individual vehicle. That is an important but insufficient step towards determining how the technology will impact human lives and society more generally. What must complement ongoing discussions is a broader, system level of analysis that engages with the interactions and effects that these cars will have on one another and on the socio-technical systems in which they are embedded. To (...) bring the conversation of self-driving cars to the system level, we make use of two traffic scenarios which highlight some of the complexities that designers, policymakers, and others should consider related to the technology. We then describe three approaches that could be used to address such complexities and their associated shortcomings. We conclude by bringing attention to the “Moral Responsibility for Computing Artifacts: The Rules”, a framework that can provide insight into how to approach ethical issues related to self-driving cars. (shrink)

The problem of the biology of money is twofold: It subsumes both the identification of behavioral mechanisms that account for the power of money as an incentive, and the elucidation of the phylogeny of such mechanisms. The drugs–tool distinction, as articulated by Lea & Webley (L&W) in their fascinating synthesis, is a welcome step toward their solution. Compared to the direct invocation of instinctual drives, however, conditioning processes provide a conceptually and empirically clearer road from evolution to money. (Published Online (...) April 5 2006). (shrink)

Advocates of moral enhancement through pharmacological, genetic, or other direct interventions sometimes explicitly argue, or assume without argument, that traditional moral education and development is insufficient to bring about moral enhancement. Traditional moral education grounded in a Kohlbergian theory of moral development is indeed unsuitable for that task; however, the psychology of moral development and education has come a long way since then. Recent studies support the view that moral cognition is a higher-order process, unified at a functional level, and (...) that a specific moral faculty does not exist. It is more likely that moral cognition involves a number of different mechanisms, each connected to other cognitive and affective processes. Taking this evidence into account, we propose a novel, empirically informed approach to moral development and education, in children and adults, which is based on a cognitive-affective approach to moral dispositions. This is an interpretative approach that derives from the cognitive-affective personality system (Mischel and Shoda, 1995). This conception individuates moral dispositions by reference to the cognitive and affective processes that realise them. Conceived of in this way, moral dispositions influence an agent's behaviour when they interact with situational factors, such as mood or social context. Understanding moral dispositions in this way lays the groundwork for proposing a range of indirect methods of moral enhancement, techniques that promise similar results as direct interventions whilst posing fewer risks. (shrink)

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary (...) dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed. (shrink)

Social media advertisement is a growing phenomenon designed to reach and engage customers. However, despite their continued adoption, less remains known regarding the effectiveness of social media ads to co-create brand value. In response to this gap, this study aims to deepen the theoretical understanding of consumer value co-creation through social media advertising value. The data were collected using purposive sampling from 286 experienced social-media users, and the model was tested using partial least square -based structural equation modeling. The results (...) indicate that entertainment, aesthetic appeal, interactivity, and trendiness significantly affect the adverting value of social media ads. In turn, ad value affects consumers’ intention for value co-creation. Consequently, our findings suggest the importance of social media advertising value where marketers may enhance consumer-brand engagement by incorporating interesting content, which may encourage the customer’s interaction with the social media ads and strengthen value co-creation behavior. The results further contribute to nascent marketing literature by demonstrating that value co-creation acts as an antecedent to generating positive electronic word-of-mouth on social media platforms to drive consumers’ online brand purchase intention. (shrink)

Based on their framework, Müller & Schumann (M&S) propose a staged drug policy that matches well the neoliberal governance scheme. To mend the sad loss of the sociocultural dimension in their model, I propose three such considerations: first, sociocultural interactions with the brain; second, sociocultural context and justice of drug use; and third, sociocultural preparedness for implementing their drug policy.

_Clinical Interaction and the Analysis of Meaning_ evinces a therapeutic vitality all too rare in works of theory. Rather than fleeing from the insights of other disciplines, Dorpat and Miller discover in recent research confirmation of the possibilities of psychoanalytic treatment. In Section I, "Critique of Classical Theory," Dorpat proposes a radical revision of the notion of primary process consonant with contemporary cognitive science. Such a revised conception not only enlarges our understanding of the analytic process; it also provides (...) analysis with a conceptual language that can articulate meaningful connections with a growing body of empirical research about the development and nature of human cognition. In Section II, "Interactional Theory," Miller reverses the direction of inquiry. He begins with the literature on cognitive development and functioning, and proceeds to mine it for concepts relevant to the clinical process. He shows how a revised understanding of the operation of cognition and affect can impart new meaning to basic clinical concepts such as resistance, transference, and level of psychopathology. In Section III, "Applications and Exemplifications," Dorpat concludes this exemplary collaboration by exploring select topics from the standpoint of his and Miller's new psychoanalytic theory. At the heart of the authors' endeavor it "meaning analysis," a concept that integrates an up-to-date model of human information processing with the traditional goals of psychoanalysis. The patient approaches the clinical encounter, they argue, with cognitive-affective schemas that are the accumulatice product of his life experience to date; the manifold meanings ascribed to the clinical interaction must be understood as the product of these schemas rather than as distortions deriving from unconscious, drive-related fantasies. The therapist's goal is to make the patient's meaning-making conscious and thus available for introspection. (shrink)

This research is part of the last study Drugs and School IX developed in the Basque Country (Spain) by the Instituto Deusto de Drogodependencias (Deusto Institute of Drug Addiction) of the University of Deusto and the data gathered by means of cluster sampling in two stages. The sample is made up of N= 6.007 girls and boys ranging from 12 to 22 years of age in Secondary Education and the aim is to answer the following new research questions based (...) on those parameters: (1) describe the reality of drug consumption and some psychosocial variables in this sample, as well as analyse several relations between variables; (2) analysing the role of school well-being, self-esteem and self-concept regarding consumption; (3) taking a close look at the moderating role of age and gender on the relationship of school well-being, self-concept and self-esteem with consumption; and (4) understand the existing interaction between all these variables, studying the moderating role of self-esteem and self-concept in the influence of school well-being on consumption. Using a correlation, hierarchical regression and mediation analysis with SPSS (v. 26) and Amos (v. 26) applications, three main conclusions were reached. Firstly, that educational and academic well-being, academic self-concept and self-esteem seem to play the role of protecting factors in adolescence, while assertiveness is linked to a higher consumption level. Secondly, that academic self-concept has a mediating effect between well-being and consumption. Some of these relations are moderated by the variables of gender and age. Thirdly, that age and gender are very relevant sociodemographic variables that must be taken into account in order to understand this phenomenon. Age has shown its covariant effect, which is especially relevant in the influence of academic well-being measured as being held back years. It has also proved to be important in order to understand its experiential or experimental and transitory character. Moreover, significant differences in consumptions have been found based on gender. (shrink)

For the purposes of conservation or suppression of species, gene drive technology has significant potential. Theoretically speaking, with the release of even relatively few animals with gene drive systems in an ecosystem, beneficial or harmful genes could be introduced into the entire wild-type population of that species. Given the profound impact that gene drives could have on species and ecosystems, their use is a highly contentious issue. Communities and groups have differing beliefs about nature and its conservation or (...) preservation, as well as concerns about the ecological safety of the eradication, replacement or enhancement of particular species of animals by means of genetic engineering. For all those reasons, the rigorous regulation of insects and other animals with gene drive systems is crucial. In this paper, we consider the question of whether the United States Food and Drug Administration is prepared to effectively regulate insects and other animals with gene drives. (shrink)

From antiquity, Galenic physicians extensively discussed the active powers of simple and compound drugs. In their views, simple drugs, that is, single ingredients, acted according to their material qualities and the properties of their substance. As for compound drugs, their efficacy resulted from the mutual interaction of their ingredients and their modes of preparation. In the late Renaissance, Galenic physicians and naturalists, such as Leonhart Fuchs and Pietro Andrea Mattioli, attempted to explain these pharmacological properties or “faculties” at the (...) intersection of medicine, botany, and natural philosophy. This chapter examines the case of the Italian physician and botanist Andrea Cesalpino. His pharmacological treatise De medicamentorum facultatibus [On the Faculties of Drugs, 1593] was particularly significant for its reception of ancient and medieval texts on drug properties, materia medica, and the role of the senses in the knowledge of bodies. (shrink)

In this article we examine gender differences in nonverbal expressiveness, with a particular focus on crying and smiling. We show that women cry and smile more as well as show more facial expressiveness in general, but that the size of this gender difference varies with the social and emotional context. We interpret this variation within a contextual framework (see also Brody & Hall, 2008; Deaux & Major, 1987; LaFrance, Hecht, & Paluck, 2003). More specifically, we distinguish three factors that predict (...) the size of gender differences in emotional expressiveness: gender-specific norms, social role and situational constraints, and emotional intensity. These factors interact in different ways for smiling and crying. (shrink)

Street vendors are prominent on public streets and in traditional markets in most developing countries. They raise significant problems for public authorities, residents, pedestrians, and formal retailers. Their informal business is problematic, leading to conflicts and sometimes violence. Moreover, unlicensed street vendors employ children and women and are accused of counterfeiting and drug trading. However, they participate in reducing poverty and unemployment. The current data article aims to formulate a public perception on the problematic issue of street vending pervasiveness (...) by describing a survey dataset on street vending and its main driving factors. Street vending has traditionally be examined by linking it with one or more determinants; thus, the dataset covers poverty, lack of education, immigration, unemployment, urban culture, low-income consumption, resistance, and lack of microfinance as latent constructs. Five measurable variables are introduced that reflect each construct. All variables are measured via seven-point Likert scales. Using a Google Form, 425 responses were collected that reflect the attitudes of the general public in Baghdad, Iraq. This dataset is useful for research on socio-economic problems; more specifically, it introduces reliable measurement models for street vending and the eight factors driving it. (shrink)

The instrumental model offered by Müller & Schumann (M&S) is broadened to apply not only to drugs, but also to other methods of self-control, including the use of mental constructs to produce adaptive changes in behavior with the possibility of synergistic interactions between various instruments.

Pharmacoresistant schizophrenia is a significant impediment to the successful management of the disease. The expression and function of P‐glycoprotein (P‐gp) has recently been implicated in this phenomenon. P‐gp is a multidrug efflux transporter that prevents drug substrates from crossing the blood–brain barrier (BBB). Although the direct interaction between individual antipsychotic agents and P‐gp has been demonstrated, the effect of antipsychotic drug combinations used in disease management on P‐gp transport function remains to be elucidated. This could have important (...) clinical implications in some individuals as dosage adjustments based on plasma drug concentration changes may not always be appropriate if drug–drug interactions and the resulting changes in drug concentration in the brain are not considered. This paper introduces the potential impact that combination antipsychotic therapy may have on P‐gp function at the BBB and discusses the consequences of this in the prevention and circumvention of unfavourable therapeutic response in schizophrenic disorders. BioEssays 30:183–188, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Most new drugs are protected by pharmaceutical patents, which give the patent holder exclusive control over that drug’s supply for 20 years. When the patent term expires, the drug becomes available for generic production by any company. The resulting competition typically leads to dramatic reductions in price. In Brazil, generic drugs are on average 40% cheaper than reference or brand-name drugs. In the United States, the Federal Drug Administration reports up to 85% price differences. Consumers in India (...) have witnessed more than 100-fold price reduction for antiretroviral drugs due to generic production. Generics thus play a key role in broadening access to health care, mostly by driving costs down, both in the developing and developed world. (shrink)

The understanding of decision-making systems has come together in recent years to form a unified theory of decision-making in the mammalian brain as arising from multiple, interacting systems (a planning system, a habit system, and a situation-recognition system). This unified decision-making system has multiple potential access points through which it can be driven to make maladaptive choices, particularly choices that entail seeking of certain drugs or behaviors. We identify 10 key vulnerabilities in the system: (1) moving away from homeostasis, (2) (...) changing allostatic set points, (3) euphorigenic signals, (4) overvaluation in the planning system, (5) incorrect search of situation-action-outcome relationships, (6) misclassification of situations, (7) overvaluation in the habit system, (8) a mismatch in the balance of the two decision systems, (9) over-fast discounting processes, and (10) changed learning rates. These vulnerabilities provide a taxonomy of potential problems with decision-making systems. Although each vulnerability can drive an agent to return to the addictive choice, each vulnerability also implies a characteristic symptomology. Different drugs, different behaviors, and different individuals are likely to access different vulnerabilities. This has implications for an individual's susceptibility to addiction and the transition to addiction, for the potential for relapse, and for the potential for treatment. (shrink)

Addiction: A Philosophical Approach CHAPTER ABSTRACTS “Introduction: Dismantling the Catchphrase” by Candice Shelby Shelby dismantles the catchphrase “disease of addiction.” The characterization of addiction as a disease permeates both research and treatment, but that understanding fails to get at the complexity involved in human addiction. Shelby introduces another way of thinking about addiction, one that implies that is properly understood neither as a disease nor merely as a choice, or set of choices. Addiction is a phenomenon emergent from a complex (...) dynamic system that is at once physical, psychological, social, and more. “A Philosophical Analysis of Addiction” by Candice Shelby Shelby brings much-needed clarity to the discourse surrounding the topic of addiction. Arguing that addiction can neither properly be understood as a disease nor as merely a set of choices, Shelby exposes the weaknesses of both approaches. She shows that addicted persons do not exhibit the elements characteristic of compulsion, nor does an account of addiction in terms of weakness of will, or irrational choosing, provide a satisfying explanation. Instead, by replacing traditional substance ontology with process ontology, and accepting the reality of emergent entities, a coherent account of persons, minds, and addiction can be provided. A fundamental philosophical shift is necessary to see that bodies, minds, values, and addictions are all part of the natural world. “Addiction at the Individual Level” by Candice Shelby Shelby discusses the most influential accounts of addiction as it is understood at the purely individual level. From hedonic theories to incentive sensitization, to habit theories of addiction, to behavioral theories and the ego depletion theory, Shelby considers a variety of approaches to understanding addiction in individuals, as framed in both psychological and in neuroscientific terms. She notes some important caveats that should be considered before accepting the research regarding addiction at the individual level, namely that the scanning studies that are so popularly used to characterize addiction in neurobiological terms are ambiguous, and rely on numerous assumptions that may be false, and that certainly mislead. Shelby provides much-needed critique of both disease and choices models as they characterize addiction at the individual level. “Addiction and the Local Environment” by Candice Shelby Shelby argues that human addiction cannot be understood without serious consideration of the individual’s local environment, her home and family. From the gestational environment to interactions with caregivers during post-natal development to the adult environment in which people become addicted, Shelby shows that no one becomes an addict in a vacuum. Stress is a major influence in the environment throughout life, and has serious consequences for addictive vulnerability. Genetic influences as well are important to addictive vulnerability, but genes always express in interaction with their environment. Social acceptance or rejection is another particularly important factor in the local environment with respect to both coming to be addicted and transitioning out of it. “The Relation Between Addiction and Culture” by Candice Shelby Shelby provides a groundbreaking analysis of the relation between addicts and the cultures that breed them. In this cultural critique, Shelby shows that addictions to certain substances have historically been both the solution to the problem of how to grow economies and control people, and a problem for economic productivity and controlling citizens. Not all cultures have even the concept of addiction, while others, such as the contemporary Western world, and the U.S. in particular, seem to foster it. Shelby shows that addiction is both a cultural construct and, from another way of thinking about it, the result of conditions created by particular cultures. Social inequities, alienation, driving capitalism, and in particular the power of pharmaceutical companies, all contribute to the spiraling endemic of addiction. “Addiction and Meaning” by Candice Shelby Shelby provides a unique argument that understanding how meanings work is essential to a complete analysis of addiction. Individuals experiencing addiction and those who care about and for them often utterly fail to communicate. This is because their respective systems of meanings come to be significantly different. Meanings are not, Shelby argues, best understood in the symbolic terms that characterized the theory of language in the 20th century, but are better apprehended as emotion-rich prototypes carved from repeated interaction with the world. Becoming addicted essentially changes one’s entire system of meanings. Requisite to transitioning out of addiction is a Gestalt-type shift in one’s system of meanings. This holistic way of understanding meanings also provides one level of explanation of what happens when an addict relapses. “The Phenomenology of Addiction and its Implications” by Candice Shelby One way of judging theories of addiction is by how well they capture the phenomenal descriptions that addicts give of their own experiences. Shelby considers variations on 5 basic patterns of addictive experience through the eyes of particular individuals who lived through addictive periods, and shows how even the most influential theories of addiction fail to capture all of them. She argues that an important implication of taking the details of individuals’ addictive stories seriously is that addiction must be understood as a personal phenomenon emergent from a particular complex dynamic system. As her theory of addiction would lead one to expect, no two addicts are the same, and no single-focus theory can explain why not. “Possibilities for Transitioning Out of Addiction” by Candice Shelby Shelby provides numerous strategies for transitioning out of addiction. Given that the vast majority of addiction treatment programs currently available are 12-step based and only successful about 5-8% of the time, it is essential that other approaches be undertaken. Shelby canvasses a variety of options for helping addicted individuals to make the transition out of their troubled pattern of thinking and behaving. From direct brain interventions to drugs to trauma therapy to exercise and nutrition to habit reformation to use of narrative and changing one’s social context as ways of redefining the self, Shelby shows that the possibilities for transitioning out of addiction are legion. Perhaps the best approach is to understand addiction treatment in terms of providing physical, psychological, and social tool kits. “Addiction Emerges from a Complex Dynamic System” by Candice Shelby Shelby considers whether there truly exists such a thing as “an addict” or “addictive thinking” in the universal sense. She concludes that within the context of disruptive substance use or repetitive engagement in certain activities, ordinary human cognitive biases and behavior patterns are categorized as addictive. Addiction, she argues, is best understood as an irreducible human reality, emergent from a sufficiently complex dynamic system (an organism with self-awareness, within a particular cultural milieu) that is both shaped by and contributes to the shaping of its environment. Attempts to simplify addiction into one or a few dimensions may create a solvable problem, but by doing so they fail to solve the real one. (shrink)

The understanding of decision-making systems has come together in recent years to form a unified theory of decision-making in the mammalian brain as arising from multiple, interacting systems (a planning system, a habit system, and a situation-recognition system). This unified decision-making system has multiple potential access points through which it can be driven to make maladaptive choices, particularly choices that entail seeking of certain drugs or behaviors. We identify 10 key vulnerabilities in the system: (1) moving away from homeostasis, (2) (...) changing allostatic set points, (3) euphorigenic signals, (4) overvaluation in the planning system, (5) incorrect search of situation-action-outcome relationships, (6) misclassification of situations, (7) overvaluation in the habit system, (8) a mismatch in the balance of the two decision systems, (9) over-fast discounting processes, and (10) changed learning rates. These vulnerabilities provide a taxonomy of potential problems with decision-making systems. Although each vulnerability can drive an agent to return to the addictive choice, each vulnerability also implies a characteristic symptomology. Different drugs, different behaviors, and different individuals are likely to access different vulnerabilities. This has implications for an individual's susceptibility to addiction and the transition to addiction, for the potential for relapse, and for the potential for treatment. (shrink)

Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro‐environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin (...) complex 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. (shrink)

I welcome with great enthusiasm Meling and Scheidegger’s (2023; henceforth “M&S”) timely contribution to advance an enactive approach to psychedelic therapy, especially to the complex causality involved. Their two main research questions concerned:(i) the causal interaction between the psychedelic molecule and brain activity; and (ii) the causal interaction between brain activity and the psychedelic experience. While I largely agree with and celebrate much of what is proposed by M&S, especially their employment of key enactive concepts to advance our (...) understanding of the first research question, in the following, I will present some worries regarding their answers to the second. Although I agree that there is probably a two-way reciprocal relationship between neural activity and experience, I have several points of contention regarding M&S’s proposal. My hope is to stimulate discussion on M&S’s important contribution, and to help advance a much-needed enactive science of psychedelics. (shrink)

Rational drug design is a method for developing new pharmaceuticals that typically involves the elucidation of fundamental physiological mechanisms. It thus combines the quest for a scientific understanding of natural phenomena with the design of useful technology and hence integrates epistemic and practical aims of research and development. Case studies of the rational design of the cardiovascular drugs propranolol, captopril and losartan provide insights into characteristics and conditions of this integration. Rational drug design became possible in the 1950s (...) when theoretical knowledge of drug-target interaction and experimental drug testing could interlock in cycles of mutual advancement. The integration does not, however, diminish the importance of basic research for pharmaceutical development. Rather, it can be shown that still in the 1990s, linear processes of innovation and the close combination of practical and epistemic work were interdependent. (shrink)