Bayne and Carter argue that the mode of consciousness induced by psychedelic drugs does not fit squarely within the traditional account of modes as levels of consciousness, and favor instead a multi-dimensional account according to which modes of consciousness differ along several dimensions—none of which warrants a linear ordering of modes. We discuss the assumption that psychedelic drugs induce a single or paradigmatic mode of consciousness, as well as conceptual issues related to Bayne and Carter’s main argument against the (...) traditional account. Finally, we raise a set of questions about the individuation of dimensions selected to differentiate modes of consciousness that could be addressed in future discussions of the multi-dimensional account. (shrink)

Philosophical and empirical research on bodily awareness has mostly focused so far on bodily disorders – such as anorexia nervosa, somatoparaphrenia, or xenomelia (body integrity dysphoria) – and bodily illusions induced in an experimental setting – such as the rubber hand illusion, or the thermal grid illusion. Studying these conditions can be illuminating to investigate a broad range of issues about the nature, function, and etiology of bodily experience. However, a number of psychoactive compounds can also induce a remarkably (...) wide variety of bodily effects that have received little attention despite their relevance to these issues. Some of these effects are similar to those associated with bodily disorders or experimental bodily illusions, while others appear to be unique. The purpose of this chapter is to provide an overview of these lesser known bodily effects of psychoactive compounds, and outline some ways in which they can bear on recent debates regarding bodily awareness and bodily ownership. (shrink)

In recent years, a debate has emerged on whether bodily sensations are typically accompanied by a sense of body ownership, namely a distinctive experience of one's body or body part as one's own. Realists about the sense of body ownership heavily rely on evidence from experimentally-induced bodily illusions (e.g., the rubber hand illusion) and pathological disownership syndromes (e.g. somatoparaphrenia). In this chapter, I will introduce novel evidence regarding body disownership syndromes induced by psychoactive drugs rather than pathological conditions, (...) and discuss its relevance to the debate on the sense of body ownership. (shrink)

Current computational models predict reward based solely on learning. Real motivation involves that but also more. Brain reward systems can dynamically generate incentive salience, by integrating prior learned values with even novel physiological states (e.g., natural appetites; drug-induced mesolimbic sensitization) to cause intense desires that were themselves never learned. We hope future computational models may capture this too.

It is the central hypothesis of this paper that the mental states commonly referred to as altered states of consciousness are principally due to transient prefrontal cortex deregulation. Supportive evidence from psychological and neuroscientific studies of dreaming, endurance running, meditation, daydreaming, hypnosis, and various drug-induced states is presented and integrated. It is proposed that transient hypofrontality is the unifying feature of all altered states and that the phenomenological uniqueness of each state is the result (...) of the differential viability of various frontal circuits. Using an evolutionary approach, consciousness is conceptualized as hierarchically ordered cognitive function. Higher-order structures perform increasingly integrative functions and thus contribute more sophisticated content. Although this implies a holistic approach to consciousness, such a functional hierarchy localizes the most sophisticated layers of consciousness in the zenithal higher-order structure: the prefrontal cortex. The hallmark of altered states of consciousness is the subtle modification of behavioral and cognitive functions that are typically ascribed to the prefrontal cortex. The theoretical framework presented yields a number of testable hypotheses. (shrink)

Modeling metastasis in animal systems has been an important focus for developing cancer therapeutics. Xenopus laevis is a well‐established model, known for its use in identifying genetic mechanisms underlying diseases and disorders in humans. Prior literature has suggested that the drug, ivermectin, can be used in Xenopus to induce melanocytes to convert into a metastatic melanoma‐like state, and thus could be ideal for testing possible melanoma therapies in vivo. However, there are notable inconsistencies between ivermectin studies in Xenopus and (...) the application of ivermectin in mammalian systems, that are relevant to cancer and melanoma research. In this review, we examine the ivermectin‐induced phenotypes in Xenopus, and we explore the current uses of ivermectin in human research. We conclude that while ivermectin may be a useful drug for many biomedical purposes, it is not ideal to induce a metastatic melanocyte phenotype in Xenopus for testing the effects of potential melanoma therapeutics. (shrink)

Drug effects on consciousness are powerful probes of how physical processes in the body are connected to conscious experience. Drugs that alter consciousness – producing arousal, sedation, sleep, anesthesia, analgesia, euphoria, amnesia, hallucinations, or psychedelic‐like intensification of perceptions, thoughts, and feelings – have been identified as interacting in various ways with cellular and molecular processes within the nervous system. While the focus has thus far been on synaptic connections between neurons, there is likely to be much more going on (...) in the interaction of drugs with living systems that has not yet been identified. Psychedelic drugs, plants, and fungi are associated with perhaps the most interesting and profound of the drug‐induced alterations of consciousness. Contemporary investigations of psychedelics include renewed interest in the transformational therapeutic potential of these substances, and may also lead to new insights into the nature of consciousness. (shrink)

Considerable hope surrounds the use of disease‐specific pluripotent stem cells to generate models of human disease allowing exploration of pathological mechanisms and search for new treatments. Disease‐specific human embryonic stem cells were the first to provide a useful source for studying certain disease states. The recent demonstration that human somatic cells, derived from readily accessible tissue such as skin or blood, can be converted to embryonic‐like induced pluripotent stem cells (hiPSCs) has opened new perspectives for modelling and understanding (...) a larger number of human pathologies. In this review, we examine the opportunities and challenges for the use of disease‐specific pluripotent stem cells in disease modelling and drug screening. Progress in these areas will substantially accelerate effective application of disease‐specific human pluripotent stem cells for drug screening. (shrink)

Sartre's experimentation in February 1935 with the drug mescalin has been well documented by Simone de Beauvoir in her book The Prime of Life. 1 She recalls that Sartre experienced under the influence of the drug not exactly hallucinations, ‘but the objects he looked at changed their appearance in the most horrifying manner:’ [POL 209]. The residual effects of this nightmarish experience left Sartre, not only for several days ‘in a state of deep depression’ [POL 210], but also (...) produced moods that ‘recalled those that had been induced by mescalin.’. (shrink)

Sartre's experimentation in February 1935 with the drug mescalin has been well documented by Simone de Beauvoir in her book The Prime of Life.1 She recalls that Sartre experienced under the influence of the drug not exactly hallucinations, ‘but the objects he looked at changed their appearance in the most horrifying manner:’ [POL 209]. The residual effects of this nightmarish experience left Sartre, not only for several days ‘in a state of deep depression’ [POL 210], but also produced (...) moods that ‘recalled those that had been induced by mescalin.’. (shrink)

Psychedelics have been recognized as model interventions for studying altered states of consciousness. However, few empirical studies of the shamanic state of consciousness, which is anecdotally similar to the psychedelic state, exist. We investigated the neural correlates of shamanic trance using high-density electroencephalography (EEG) in 24 shamanic practitioners and 24 healthy controls during rest, shamanic drumming, and classical music listening, followed by an assessment of altered states of consciousness. EEG data were used to assess changes in absolute power, (...) connectivity, signal diversity, and criticality, which were correlated with assessment measures. We also compared assessment scores to those of individuals in a previous study under the influence of psychedelics. Shamanic practitioners were significantly different from controls in several domains of altered states of consciousness, with scores comparable to or exceeding that of healthy volunteers under the influence of psychedelics. Practitioners also displayed increased gamma power during drumming that positively correlated with elementary visual alterations. Furthermore, shamanic practitioners had decreased low alpha and increased low beta connectivity during drumming and classical music and decreased neural signal diversity in the gamma band during drumming that inversely correlated with insightfulness. Finally, criticality in practitioners was increased during drumming in the low and high beta and gamma bands, with increases in the low beta band correlating with complex imagery and elementary visual alterations. These findings suggest that psychedelic drug-induced and non-pharmacologic alterations in consciousness have overlapping phenomenal traits but are distinct states of consciousness, as reflected by the unique brain-related changes during shamanic trance compared to previous literature investigating the psychedelic state. (shrink)

There is growing evidence that dopamine replacement therapy (DRT) used to treat Parkinson’s Disease can cause compulsive behaviours and impulse control disorders (ICDs), such as pathological gambling, compulsive buying and hypersexuality. Like more familiar drug-based forms of addiction, these iatrogenic disorders can cause significant harm and distress for sufferers and their families. In some cases, people treated with DRT have lost their homes and businesses, or have been prosecuted for criminal sexual behaviours. In this article we first examine the (...) evidence that these disorders are caused by DRT. If it is accepted that DRT cause compulsive or addictive behaviours in a significant minority of individuals, then the following ethical and clinical questions arise: Under what circumstances is it ethical to prescribe a medication that may induce harmful compulsive behaviours? Are individuals treated with DRT morally responsible and hence culpable for harmful or criminal behaviour related to their medication? We conclude with some observations of the relevance of DRT-induced ICDs for our understanding of addiction and identify some promising directions for future research and ethical analysis. (shrink)

Cytochrome P450IIE1 is involved in the metabolic activation of many xenobiotics involved with human toxicity. In particular, cellular concentrations of P450IIE1 are significantly induced by the most widely abused drug in our society today, alcohol. As a result, the synthesis and degradation of this form of P450 has significant health consequences. The regulation of the steady‐state concentration of P450IIE1 is an extremely complex process. The enzyme is regulated by transcriptional activation, mRNA stabilization, increased mRNA translatability and decreased protein (...) degradation. The principal mechanism which controls the induction process depends on the chemical nature of the inducer, the age, and the nutritional and hormonal status of the animal. There also appear to be significant sex differences in the expression of P450IIE1. It is entirely possible that the regulation of the enzyme concentration under any given set of conditions will involve all of the mechanisms to different extents. (shrink)

Two meta-analyses of pharmacological research are presented, demonstrating that psychoactive drugs have consistent effects on EEG and sleep outside of their effects on REM sleep, and demonstrating that drugs other than those affecting sleep neurotransmitter systems and REM sleep can also alter reported nightmare occurrence. These data suggest that the neurobiology data terrain outside activation-synthesis may include sleep and dream electrophysiology, cognitive reports of dreaming, effects of alterations in consciousness on dreaming, immunology and host defense, and clinical therapies for sleep (...) disorders. (shrink)

Studies have shown that both serotonin and glutamate receptor systems play a crucial role in the mechanisms underlying drug-induced synesthesia. The specific nature of these mechanisms, however, continues to remain elusive. Here we propose two distinct hypotheses for how synesthesia triggered by hallucinogens in the serotonin-agonist family may occur. One hypothesis is that the drug-induced destabilization of thalamic projections via GABAergic neuronal circuits from sensory areas leads to a disruption of low-level, spontaneous integration of multisensory stimuli. (...) This sort of integration regularly occurs when spatial and temporal attributes match. Destabilization of feedback loops, however, can result in incongruent experiences or binding of random thalamus activation with sensory input in a particular sensory modality. The second hypothesis builds on embodied cognition, cases in which visual images of external stimuli activate task-related neural regions. On this proposal, binding processes that do not normally generate awareness become accessible to consciousness as a result of decreased attentional discrimination among incoming stimuli. (shrink)

Despite some principal similarities, there is no systematic comparison between the different types of synesthesia . This comprehensive review compares the three principal types of synesthesia and focuses on their phenomenological features and their relation to different etiological models. Implications of this comparison for the validity of the different etiological models are discussed.Comparison of the three forms of synesthesia show many more differences than similarities. This is in contrast to their representation in the literature, where they are discussed in many (...) respects as being virtually similar. Noteworthy is the much broader spectrum and intensity with the typical drug-induced synesthesias compared to genuine and acquired synesthesias. A major implication of the phenomenological comparison in regard to the etiological models is that genuine and acquired synesthesias point to morphological substrates, while drug-induced synesthesia appears to be based on functional changes of brain activity. (shrink)

This article examines the issue of illicit drug control across three broad levels of analysis. On one level, it examines the nature of the response to a ‘global phenomenon’ and its impact on national sovereignty. On a second level, it considers emergent state forms and practices and their relationship to global changes; and, thirdly, it grounds the analysis temporally and empirically in the contemporary European Union. The complex, evolving and essentially fragmented character of state power is placed in the (...) context of the classic state functions of authority and control. This is set against the growing transnational role of expert knowledge in policy‐making, and concludes with an assessment of the political implications that can be drawn from analysis of this complex set of factors. (shrink)

There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the (...) kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other hand, it suggests that ordinary conscious experience might involve a minimal kind of self-awareness rooted in multisensory processing, which is what appears to fade away during DIED. (shrink)

In recent years, the scientific study of meditation and psychedelic drugs has seen remarkable developments. The increased focus on meditation in cognitive neuroscience has led to a cross-cultural classification of standard meditation styles validated by functional and structural neuroanatomical data. Meanwhile, the renaissance of psychedelic research has shed light on the neurophysiology of altered states of consciousness induced by classical psychedelics, such as psilocybin and LSD, whose effects are mainly mediated by agonism of serotonin receptors. Few attempts have (...) been made at bridging these two domains of inquiry, despite intriguing evidence of overlap between the phenomenology and neurophysiology of meditation practice and psychedelic states. In particular, many contemplative traditions explicitly aim at dissolving the sense of self by eliciting altered states of consciousness through meditation, while classical psychedelics are known to produce significant disruptions of self-consciousness, a phenomenon known as drug-induced ego dissolution. In this article, we discuss available evidence regarding convergences and differences between phenomenological and neurophysiological data on meditation practice and psychedelic drug-induced states, with a particular emphasis on alterations of self-experience. While both meditation and psychedelics may disrupt self-consciousness and underlying neural processes, we emphasize that neither meditation nor psychedelic states can be conceived as simple, uniform categories. Moreover, we suggest that there are important phenomenological differences even between conscious states described as experiences of self-loss. As a result, we propose that self-consciousness may be best construed as a multidimensional construct, and that “self-loss,” far from being an unequivocal phenomenon, can take several forms. Indeed, various aspects of self-consciousness, including narrative aspects linked to autobiographical memory, self-related thoughts and mental time travel, and embodied aspects rooted in multisensory processes, may be differently affected by psychedelics and meditation practices. Finally, we consider long-term outcomes of experiences of self-loss induced by meditation and psychedelics on individual traits and prosocial behavior. We call for caution regarding the problematic conflation of temporary states of self-loss with “selflessness” as a behavioral or social trait, although there is preliminary evidence that correlations between short-term experiences of self-loss and long-term trait alterations may exist. (shrink)

ObjectiveThis study aims to investigate anxiety and its influencing factors in patients with drug-induced liver injury (DILI).Materials and MethodsNinety-four patients with DILI were enrolled and evaluated with a self-rating anxiety scale (SAS). According to the anxiety score, they were divided into four groups: the non-anxiety, mild anxiety, moderate anxiety, or severe anxiety groups, and the scores were analyzed based on demographic and biochemical indicators.ResultsOf the 94 patients with DILI, 63 did not have anxiety and 31 had anxiety (32.9%), (...) of which 27 had mild, 3 had moderate, and 1 had severe anxiety. There were no statistically significant differences in gender, age, occupation, and level of education between the groups (F= 1.42,H= 2.361,H= 6.751,H= 1.796, andP> 0.05); anxiety score and degree of anxiety between the types of drugs that led to the liver injury (H= 0.812,H= 1.712, andP> 0.05); anxiety score between the different degrees of liver injury (H= 2.836,H= 4.957,P> 0.05); or length of hospital stay or prognosis between the degrees of anxiety (F= 1.487,H= 0.761,P> 0.05). However, there were statistically significant differences in the degree of anxiety between different degree and types of liver injury (H= 7.981,H= 8.208,P< 0.05).ConclusionPatients with DILI may have anxiety, especially mild anxiety. The occurrence of anxiety in patients with DILI is not related to gender, age, occupation, or level of education but may be related to the degree and type of liver injury. Anxiety has no impact on the length of stay in hospital or the prognosis of the DILI. These findings may contribute to the development of management strategies for patients with DILI. (shrink)

The enjoyment and pleasure derived from sad music has sparked fascination among researchers due to its seemingly paradoxical nature in producing positive affect. Research is yet to develop a comprehensive understanding of this “paradox.” Contradictory findings have resulted in a great variability within the literature, meaning results and interpretations can be difficult to derive. Consequently, this review collated the current literature, seeking to utilize the variability in the findings to propose a model of differential sad states, providing a means (...) for past and future findings to be interpreted. The proposed model is based on theoretical understanding, as such it requires full empirical support. Comparisons to alternative models, theoretical, clinical, and cognitive implications, as well as future directions are discussed. (shrink)

The elimination of subjectivity through brain research and the replacement of so-called ‘folk psychology’ by a neuroscientifically enlightened worldview and self-conception has been both hoped for and feared. But this cultural revolution is still pending. Based on nine months of fieldwork on the revival of hallucinogen research since the ‘Decade of the Brain,’ this paper examines how subjective experience appears as epistemic object and practical problem in a psychopharmacological laboratory. In the quest for neural correlates of (drug-induced altered (...) states of) consciousness, introspective accounts of test subjects play a crucial role in neuroimaging studies. Firsthand knowledge of the drugs’ flamboyant effects provides researchers with a personal knowledge not communicated in scientific publications, but key to the conduct of their experiments. In many cases, the ‘psychedelic experience’ draws scientists into the field and continues to inspire their self-image and way of life. By exploring these domains the paper points to a persistence of the subjective in contemporary neuropsychopharmacology. (shrink)

This paper discusses the post-trial access to drugs for patients who participated in clinical trials in Brazil. The ethical guidance for clinical trials in Brazil is arguably one of the clearest in the world in attributing to research sponsors the responsibility for providing post-trial drugs to patients who participated in their experiments. The Federal Constitution recognizes health as a fundamental right to be fulfilled by the State. Based on the Brazilian constitution and on the National Health Council resolutions, courts have (...) been accepting patients' claims and ordering the State and the pharmaceutical companies to provide these patients with the tested treatment in the quantity and duration they need it. This generous interpretation of the duties of the pharmaceutical companies and the State makes the Brazilian model for post-trial access unique when compared to the experience of other countries and thus should be followed with attention by future research in order to assess its consequences for patients, research sponsors, and the public health system. (shrink)

K L Kahlbaum published in 1874 the first recorded description of catatonia. Akinetic catatonia is now defined as a neuropsychiatric syndrome principally characterised by akinesia, mutism, stupor, and catalepsy. 1 Even if some advances have been made in the recognition of catatonia, in particular by the development of different rating scales, 1 the pathophysiology of this syndrome is not clearly established. A right handed 14 year old girl presented with akinetic catatonia during an episode of depression in the context of (...) a bipolar type I disorder. Her catatonic status was characterised by akinesia with brief episodic spontaneous stereotyped movements, mutism, no spontaneous oral intake, catalepsy, waxy flexibility, and stupor with brief occasional eye contacts. This corresponded to a total score of 19 on the Northoff Catatonia Scale.1 Electroencephalogram performed one day after onset of symptoms showed diffuse theta activity with sporadic diffuse delta activity. Cerebral magnetic resonance imaging was normal. Brain positron emission tomographies (PET) were obtained on a CTI-Siemens HR+ tomograph. A first PET (PET1) using (18F(- fluorodeoxyglucose (FDG) was performed on day 2 in a drug free state. Thereafter, intramuscular injection of 2 mg of lorazepam induced rapid clinical remission of the akinetic phase. Oral lorazepam was then given (3.75 mg/day) during five days. On day 8, a second PET with FDG was performed while the patient was treated by olanzapine (15 mg/day) and presented hyperactivity, logorrhoea, and disinhibition characterised by uncontrolled social interactions and physical contacts. Neuropsychological testing performed some days after remission revealed no apraxia or language disturbances but dysfunction of executive tasks manifested in the revised Wisconsin card sorting, the Tower of London, Stroop, and Trailmaking tests. Voxel based analyses comparing patient’s cerebral glucose metabolism with that of 29 right handed healthy controls (16 women and 13 men, mean age 32) were performed using Statistical Parametric Mapping (SPM99) (Wellcome Department of Cognitive Neurology, London, UK).. (shrink)

This paper discusses the significance for the philosophy of perception and aesthetics of certain productions of the ‘offline brain’. These are experienced in hypnagogic and other trance states, and in disease- or drug-induced hallucination. They bear a similarity to other visual patterns in nature, and reappear in human artistry, especially of the craft type. The reasons behind these resonances are explored, along with the question why we are disposed to find geometrical complexity and ‘supercolouration’ beautiful. The paper (...) concludes with a plea on behalf of neuroaesthetics, but with a caution or two. (shrink)

Schizophrenia is a serious mental illness characterized by a disconnection between brain regions. Transcranial magnetic stimulation is a non-invasive brain intervention technique that can be used as a new and safe treatment option for patients with schizophrenia with drug-refractory symptoms, such as negative symptoms and cognitive impairment. However, the therapeutic effects of transcranial magnetic stimulation remain unclear and would be investigated using non-invasive tools, such as functional connectivity. A longitudinal design was adopted to investigate the alteration in FC dynamics (...) using a dynamic functional connectivity approach in patients with schizophrenia following high-frequency repeated transcranial magnetic stimulation with the target at the left dorsolateral prefrontal cortex. Two groups of schizophrenia inpatients were recruited. One group received a 4-week high-frequency rTMS together with antipsychotic drugs, while the other group only received antipsychotic drugs. Resting-state functional magnetic resonance imaging and psychiatric symptoms were obtained from the patients with schizophrenia twice at baseline and after 4-week treatment. The dynamics was evaluated using voxel- and region-wise FC temporal variability resulting from fMRI data. The pattern classification technique was used to verify the clinical application value of FC temporal variability. For the voxel-wise FC temporary variability, the repeated measures ANCOVA analysis showed significant treatment × time interaction effects on the FC temporary variability between the left DLPFC and several regions, including the thalamus, cerebellum, precuneus, and precentral gyrus, which are mainly located within the cortico-thalamo-cerebellar circuit. For the ROI-wise FC temporary variability, our results found a significant interaction effect on the FC among CTCC. rTMS intervention led to a reduced FC temporary variability. In addition, higher alteration in FC temporal variability between left DLPFC and right posterior parietal thalamus predicted a higher remission ratio of negative symptom scores, indicating that the decrease of FC temporal variability between the brain regions was associated with the remission of schizophrenia severity. The support vector regression results suggested that the baseline pattern of FC temporary variability between the regions in CTCC could predict the efficacy of high-frequency rTMS intervention on negative symptoms in schizophrenia. These findings confirm the potential relationship between the reduction in whole-brain functional dynamics induced by high-frequency rTMS and the improvement in psychiatric scores, suggesting that high-frequency rTMS affects psychiatric symptoms by coordinating the heterogeneity of activity between the brain regions. Future studies would examine the clinical utility of using functional dynamics patterns between specific brain regions as a biomarker to predict the treatment response of high-frequency rTMS. (shrink)

This paper discusses so-called post-trial access to drugs for patients who participated in clinical trials in Brazil. Brazil is currently a relevant country for the pharmaceutical industry due to the dimensions of its actual and potential market. As a consequence, the number of pharmaceutical trials has been rising. It is the largest market for pharmaceutical companies in Latin America, the 8th biggest in the world and second only to China among the so-called BRICS’s emerging countries. The demand for pharmaceutical products (...) in the country has been increasing by double digits over the last few years, reaching 20% in 2008. Not surprisingly, we are also witnessing a steady increase in the number of applications by national and international pharmaceutical companies before ethical research authorities for authorization to perform clinical trials of drugs. (shrink)

Tax avoidance practices by Multinational Enterprises such as Google, Microsoft, Apple, Starbucks and others are increasingly under scrutiny both from a legal and an ethical perspective. In 2013, the OECD launched an ‘Action Plan’ to encourage the G20 countries to address Base Erosion and Profit Shifting through an internationally co-ordinated approach, arguing that tax avoidance represents a risk for tax revenues and tax fairness, potentially “undermining taxpayers voluntary compliance.” The analysis of tax avoidance in the existing business ethics literature suffers (...) from a black-and-white approach, contending either that tax avoidance is unethical or that, being legal, tax avoidance is also ethical. However, we believe that within tax avoidance practices there are important distinctions to be made. In this paper, we analyze the ethics of tax avoidance by identifying three different forms of avoidance practices: state-induced, strategic, and toxic avoidance. We develop a more nuanced approach reviewing both the ethical arguments in defense and the ethical issues associated with each form of tax avoidance. Finally, we propose an ethical framework that could assist executives and policy-makers in their decision-making concerning tax avoidance. (shrink)

It follows from the temporal nature of mind—the main concern of this essay—that mind functions are not localized in brain space.“ Time is extendedness, probably of the mind itself”, concludes Saint Augustine in Book XI of his Confessions (26.33), and, in our days, this extendedness can be made visible through an oscilloscopic “line” or trace of slow potentials. These graded, additive (not all-or-none) autorhythmic and seemingly self-generating potentials are primary events recorded at synapses. Autorhythmic brain structures (Zabara, 1973) appear to (...) be the source of time frames, while a change in time frames (as reflected in the EEG) leads to synchronization and desynchronization of brain structures respectively. Synchronization forms a homogeneous time domain, such as obtained during rhythmic exercises, chanting, listening to music and mental processes that are the hallmark of religious practices (Rogers, 1973). Desynchronization of brain structures on the other hand marks a functional independence of neuronal elements with each element available for separate channels of data processing, for example, during hallucinogenic drug-induced central sympathetic arousal, that is, a waking dream state (Fischer, 1979). (shrink)

Drugs, and the states they induce, play central and interwoven roles in the Dune saga. Spice melange, the most valuable object in the known universe, is a cinnamon‐scented, life‐prolonging, mind‐altering drug found only on the planet of Arrakis. Psychedelics, drugs in the hallucinogen class, share many properties with Arrakeen drugs. It's also intriguing that Imperial denizens refer to the universe's most valuable substance as “spice” and “melange.” Computers, thinking machines, and conscious robots threatened humanity's sovereignty and humanity's unique (...) moral status, particularly from a religious perspective. After years of forced migrations from planet to planet, the Fremen finally settled on Arrakis, becoming its indigenous population. Experiential knowledge will be an important teacher to someone without any prior technical or technological training in sustaining a presence in spiritual realms. Techniques and technologies change the people and societies that use them. (shrink)

Assuming that one believes that individuals and states can morally defend values, beliefs, and institutions with force , one logically wants just combatants to possess the physical, mental, and spiritual capacities that will enable them to win the war. On the other hand, being a just combatant in a just war does not morally entitle that combatant to do anything to win that war. The moral requirement for just combatants to fight justly is codified in international law of war (...) and in state-specific legal documents such as the United States Uniform Code of Military Justice. While it is almost unequivocally clear to soldiers and civilians who soldiers cannot harm in the performance of their duties, and why these people are exempt from harm, it is less clear what the state itself can morally do to its own soldiers to enhance their chances of victory: can the state do anything to soldiers to give them an advantage on the field of battle?For United States soldiers and their counterparts in most Western liberal democracies, the answer is obviously no. Deeply embedded social and cultural norms in Western democracies mandate that the state set and enforce rigid lines which drill sergeants and earnest commanders cannot cross, even in the name of combat readiness, grounding these norms in notion of basic rights appealed to in the U.S. Constitution. In this essay, I argue against some types of drug-induced internal biotechnical enhancement of soldiers on the grounds that, in the present state of technology, it is not reasonable to suppose that the military can perform such enhancement operations on soldiers without causing irrevocable psychological damage that would certainly and unjustifiably alienate the soldiers from the very society they serve. (shrink)

The dinoflagellates, a diverse sister group of the malaria parasites, are the major agents causing harmful algal blooms and are also the symbiotic algae of corals. Dinoflagellate nuclei differ significantly from other eukaryotic nuclei by having extranuclear spindles, no nucleosomes and enormous genomes in liquid crystal states. These cytological characteristics were related to the acquisition of prokaryotic genes during evolution (hence Mesokaryotes), which may also account for the biochemical diversity and the relatively slow growth rates of dinoflagellates. The fact (...) that the proliferation of many dinoflagellates is sensitive to turbulence may be due to the physiological requirements of the genome's liquid crystal states. Mechanical stress and anti‐microtubule drugs induce cell cycle arrest mainly in G1, implicating a role for the permanent cortical microtubular cytoskeleton in mechanotransduction. The cell cycles of photosynthetic dinoflagellates are also gated by the circadian rhythm, with cell division occurring mainly at the end of the dark phase. Cell growth and the biosynthesis of many toxins occur during the light phase, corresponding to G1 in the cell cycle. The dinoflagellates also embody several options for coupling cell cycle progression to cell growth, enabling them to make the best use of available resources and possibly preparing them for a symbiotic existence. BioEssays 27:730–740, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

This pioneering book explores in depth the role of neurotransmitters in conscious awareness. The central aim is to identify common neural denominators of conscious awareness, informed by the neurochemistry of natural, drug induced and pathological states of consciousness. Chemicals such as acetylcholine and dopamine, which bridge the synaptic gap between neurones, are the 'neurotransmitters in mind' that form the substance of the volume, which is essential reading for all who believe that unravelling mechanisms of consciousness must include (...) these vital systems of the brain.Up-to-date information is provided on: Psychological domains of attention, motivation, memory, sleep and dreaming that define normal states of consciousness. Effects of chemicals that alter or abolish consciousness, including hallucinogens and anaesthetics. Disorders of the brain such as dementia, schizophrenia and depression considered from the novel perspective of the way these affect consciousness, and how this might relate to disturbances in neurotransmission.(Series B). (shrink)

This article investigates the distribution of power in Poland’s drug reimbursement policy in the early 2000s. We examine competing theoretical expectations suggested by neopluralism, historical institutionalism, corporate domination, and clique theory of the post-communist state, using data from a purposive sample of 109 semi-structured interviews and documentary sources. We have four concrete findings. First, we uncovered rapid growth in budgetary spending on expensive drugs for narrow groups of patients. Second, to achieve these favorable policy outcomes drug companies employed (...) two prevalent methods of lobbying: informal persuasion of key members of local cliques and endorsements expressed by patient organizations acting as seemingly independent “third parties.” Third, medical experts were co-opted by multinational drug companies because they relied on these firms for scientific and financial resources that were crucial for their professional success. Finally, there was one-way social mobility from the state to the pharmaceutical sector, not the “revolving door” pattern familiar from advanced capitalist countries, with deleterious consequences for state capacity. Overall, the data best supported a combination of corporate domination and clique theory: drug reimbursement in Poland was dominated by Western multinationals in collaboration with domestically based cliques. (shrink)