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Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics

Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics PERSPECTIVE published: 02 August 2021 doi: 10.3389/fpsyt.2021.680064 Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics 1 2 3 4 Nicolas Langlitz , Erika Dyck , Milan Scheidegger and Dimitris Repantis 1 2 Department of Anthropology, The New School for Social Research, New York, NY, United States, Department of History, University of Saskatchewan, Saskatoon, SK, Canada, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland, Charité – Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Berlin, Germany The revival of psychedelic research coincided and more recently conjoined with psychopharmacological research on how drugs affect moral judgments and behaviors. This article makes the case for a moral psychopharmacology of psychedelics that examines whether psychedelics serve as non-specific amplifiers that enable subjects to (re-)connect with their values, or whether they promote specific Edited by: moral-political orientations such as liberal and anti-authoritarian views, as recent Michael James Winkelman, Arizona State University, United States psychopharmacological studies suggest. This question gains urgency from the fact Reviewed by: that the return of psychedelics from counterculture and underground laboratories to Fabrizio Schifano, mainstream science and society has been accompanied by a diversification of their University of Hertfordshire, United Kingdom users and uses. We propose bringing the pharmacological and neuroscientific literature Brian D. Earp, into a conversation with historical and anthropological scholarship documenting the full University of Oxford, United Kingdom spectrum of moral and political views associated with the uses of psychedelics. This Ido Hartogsohn, Bar-Ilan University, Israel paper sheds new light on the cultural plasticity of drug action and has implications for the *Correspondence: design of psychedelic pharmacopsychotherapies. It also raises the question of whether Dimitris Repantis other classes of psychoactive drugs have an equally rich moral and political life. dimitris.repantis@charite.de Keywords: psychedelics, hallucinogens, morality and values, extrapharmacological variables, anthropology, Specialty section: ethnography, history, psychotherapy This article was submitted to Psychopharmacology, a section of the journal INTRODUCTION: A NEW FIELD OF RESEARCH Frontiers in Psychiatry Received: 31 March 2021 Since the 2000s, neuropsychopharmacologists have grown interested in the neurochemical Accepted: 09 June 2021 foundations of moral behaviors. Experimental paradigms from social psychology and behavioral Published: 02 August 2021 economics have been used to study the effects of drugs, for example how antidepressants such as Citation: citalopram enhanced harm aversion and affected people’s inclination to retaliate against unfairness Langlitz N, Dyck E, Scheidegger M (1), how oxytocin affected one’s readiness to trust others (2) and motivated both in-group favoritism and Repantis D (2021) Moral and out-group derogation (3), how regular users of stimulants showed less prosocial behavior Psychopharmacology Needs Moral (4), or how MDMA and LSD increased emotional empathy and altruism (5). Analogous to Inquiry: The Case of Psychedelics. moral psychology, a field that emerged at about the same time, this rapidly growing body of Front. Psychiatry 12:680064. research gave birth to a new subfield that could aptly be called “moral psychopharmacology.” doi: 10.3389/fpsyt.2021.680064 Frontiers in Psychiatry | www.frontiersin.org 1 August 2021 | Volume 12 | Article 680064 Langlitz et al. Moral Psychopharmacology Needs Moral Inquiry THE CONTEXT DEPENDENCE OF interventions. Thereby, the question of how drugs affect human relationships and what makes a good relationship comes into PSYCHEDELICS VARIES THEIR MORAL the purview of psychiatric drug treatment. In the clinical EFFECTS context, moral psychopharmacology moves from the limited ecological validity of behavioral economic games and moral In the case of psychedelics, research on their moral effects is dilemma experiments to issues that are highly relevant to of particular importance. Politically, psychedelic drug use is the moral fabric of everyday life (even if the intricacies likely to increase and take place in a variety of non-medical of romantic relationships or family life have not figured contexts as a number of jurisdictions introduce decriminalizing prominently in moral philosophy). In this respect, the moral legislation concerning psychedelics. In May 2021, for example, psychopharmacology of all drugs that affect social behavior Psilonautica and Drug Science, two UK-based organizations, appears significant. Notably, recent studies highlight how revealed findings from a study showing that a majority of psychedelics and empathogens modulate conscious decision- the British public support the medical use of psychedelics making and behavioral orientations in various psycho-socio- for trauma-based injuries and end-of-life anxiety. American environmental domains (5, 10, 11). The pronounced context- cities like Denver, Oakland and Santa Cruz went further and dependence of psychedelics and their application in the context decriminalized psilocybin, and in 2020 the state of Oregon of different psychotherapeutic approaches or non-clinical uses decriminalized psilocybin and approved it for medical use. gives particular urgency to the question of how they affect The legal prohibition on psychedelics is beginning to change, people’s moral judgment and behavior. After all, the moral effects but its regulatory future remains context specific. Scientifically, might not be one-dimensional, simply increasing or decreasing the moral psychopharmacology of psychedelics is especially regard for others as concerns about moral “enhancement” and interesting because their effects have long been shown to depend “degradation” imply [(12, 13), p. 233–35, 261–63]. Instead, the crucially on extra-pharmacological factors. Since the 2010s, what moral effects of psychedelics appear to differ depending on the is colloquially called “set and setting,” the subject’s mindset and context of their use and the mind-set of the user. their social and physical environment, has attracted renewed The successful mainstreaming of psychedelics through interest in the revival of psychedelic research. Carhart-Harris medical research has introduced these substances to populations et al. (6) argued that the drugs’ 5HT receptor agonism renders 2a beyond the so-called psychedelic research community. The the psychedelic experience exceptionally sensitive to context, growing diversity of users and uses broadens the range of both internal and external. While common psychophysiological extra-pharmacological factors that shape the drugs’ moral effects on serotonin-mediated neurobehavioral circuits may effects. Historical and ethnographic research can complement shape some of the cross-cultural similarities in patterns of contemporary neuropsychopharmacology studies with studies psychedelic use and experiences, their cultural desirability is of cultural contexts that examine other sets and settings in mostly shaped by political factors (7). What distinguishes relation to drug uses and effects. While members of the research in this vein from research on the placebo effect is that, American counterculture used LSD, mescaline, and psilocybin as in the case of psychedelics, the effects of extra-pharmacological psychopharmacological tools to liberate individuals from the ills factors appear to be pharmacologically mediated and amplified. of their society, Huichol youth ingested peyote buttons to become It is part of psychedelic drug action to blur the line between full members of their own society (14, 15), and Native American the pharmacological and the nonpharmacological, between drug Church worshippers consumed peyote to foster indigenous action and social context. resistance to North American colonialism (16, 17). In the 1960s, This context-dependence is also of clinical importance as psychedelics were taken to experience a mystical union that users psychedelic-assisted therapy of depression and other psychiatric claimed fostered a sense of universal love, but anthropologists conditions combines pharmacotherapy with psychotherapy, have also described Amazonian societies that used them in rituals actively mobilizing extra-pharmacological factors to improve to prepare for violent intergroup conflict (18–20). At present, treatment outcomes (even though ongoing randomized psychedelic therapists and progressive intellectuals suggest that controlled trials do not explicitly focus on the psychotherapeutic psychedelic experiences could help to work through the cultural contribution). The subjective experience shaped by set and trauma of racist discrimination (21, 22), and one study found that setting might not just be epiphenomenal but causally related intense psychedelic experiences predicted liberal political views, to the drugs’ therapeutic effects (8). Although interactions openness, and nature relatedness, while negatively predicting with other people crucially affect how patients experience the authoritarian political views [(23); but see (24)]. At the same effects of psychedelics, in medical research, it is often a mere time, a budding traditionalist scene finds inspiration in the afterthought that drug treatments of psychiatric patients have significant implications for their social relationships (9). Outside right-wing writer and psychonaut Ernst Jünger and, according to media reports, psychedelics might also play a role in the of a clinical setting, these contextual features will be even more difficult to assess, predict, or control. political radicalization of far-right groups in the United States This relationship to cultural context opens up a dimension (25–27). A moral psychopharmacology of psychedelics needs to of moral psychopharmacology directly relevant to clinical explain how pharmacological and extrapharmacological factors work, which cannot be guided only by considerations of interact to produce such seemingly contradictory varieties of the normal and the pathological that usually inform medical psychedelic experience. Frontiers in Psychiatry | www.frontiersin.org 2 August 2021 | Volume 12 | Article 680064 Langlitz et al. Moral Psychopharmacology Needs Moral Inquiry TAKING PSYCHEDELIC RESEARCH psychedelic apprenticeships to different therapeutic goals and ethical projects. Subjects undergoing drug-induced mystical BEYOND THE TWO-CULTURE DIVIDE experiences might even be steered toward religious conversion and New Age spiritualities—a prospect that has raised concern A well-established but potentially misleading account of the moral and political versatility of psychedelics draws from among psychedelic psychotherapists who seek to secularize the an older naturalist ontology that suggests that there is one field and worry about the abuse of power on the part of guides and therapists (40, 41). nature and many cultures that interpret it differently. It has inspired a neat division of labor between the disciplines: The context sensitivity of psychedelics entails that randomized placebo-controlled trials are insufficient for appreciating the neuropsychopharmacologists study the effects of drugs on the brain, cultural anthropologists and historians study how different full range of their possible effects, nor do they capture the diverse ways in which consumers may encounter psychedelics in groups of humans make sense of them at different points in time. In recent decades, however, both the ontological and medical and non-medical settings alike. If the pharmacological activity of a drug changes the relationship between a living the epistemological divide between the two cultures of the natural sciences on the one hand and the humanities and thing and its environment in ways that depend on the living thing’s mindset and the particular quality of the interpretive social sciences on the other hand have been called into question from very different angles. Culture is no longer environment, then the environment would be inscribed in the observed pharmacological effect—even if the placebo the exclusive domain of the humanities and human sciences effects were subtracted from the effects of the verum. In the but has become an object of research in cultural neuroscience and cultural primatology (28, 29). The same is true for related 1950s, anthropologist Anthony Wallace had already noted that Euro-American subjects who had received mescaline in the ontological categories such as the mind, which used to organize the disciplinary divide between Geistes- and Naturwissenschaften laboratory reported very different psychotropic effects than Native Americans who had eaten peyote buttons in religious in the German-speaking world but is now the subject matter of evolutionary and brain research. This new naturalism has ceremonies. At a time when placebo-controlled trials only just emerged as the gold standard of pharmacological research, inspired research programs in the social sciences that have sought to break down the barrier between the natural and the human Wallace proposed to complement them by culture-controlled trials that tested the same drug at the same dosage under by presenting the scientific objects of the natural sciences as constructed by humans (30–32). While these challenges to the different social and cultural circumstances [(13), p. 116–26, 185– 92; (42)]. Reanimating this largely forgotten approach today dichotomies of nature/culture, nature/human, or mind/matter might not be equally compelling across all areas of study, they are would provide moral psychopharmacology with an opportunity germane to a class of psychoactive drugs whose effects depend to import experimental paradigms from social, moral, and political psychology. on their users’ personalities, expectations, and cultural beliefs as well as the social setting in which they are ingested. Studying the moral effects of psychedelics raises epistemological challenges “UPSTREAM” DESIGN OF NEW USES OF that extend across the divide between the natural sciences and the humanities (33). PSYCHEDELICS More recently, extra-pharmacological factors have attracted The ethical plasticity of psychedelic-induced experiences attention in psychedelic research, which again stimulates interdisciplinary debates and transdisciplinary collaborations poses a formidable bioethical problem. Usually, bioethics offers a moral evaluation of the social consequences of new (34, 35). The experiential diversity of psychedelic states calls for novel approaches combining phenomenological methods biotechnologies or pharmaceuticals. For example, debates and empirical research to better understand the structure and over antidepressants or so-called cognitive enhancers assumed that the drugs have certain effects established by clinical dynamics of altered states of consciousness that go beyond their conceptualization as “brain states”. Social anthropologist David observation and psychopharmacological experiment, while bioethicists evaluated the social consequences of these Dupuis, clinical psychologist Rosalind Watts, and neuroscientist Christopher Timmermann propose moving beyond research that effects downstream from pharmacology and proposed how to regulate the drugs’ applications. A growing body of bioethical correlates first-person reports and third-person measurements of brain activity and attend to the second-person dimension literature on psychedelics evaluates the use of psychedelics to neurochemically enhance the sense of meaning in psychedelic- of what they call “psychedelic apprenticeship” (36). Their focus on the social mediation of psychedelic-induced experiences assisted psychotherapy and their use to develop virtues, suppress vices, and enhance moral behavior (43, 44). What distinguishes can account for why psychedelics have turned out to be a “double-edged sword” that can either benefit or harm their the notion of psychedelic moral enhancement, as advocated by users—or even do both at the same time. Psychedelics have some authors, from traditional notions is that it recognizes that been shown to increase suggestibility while concealing this amplifying particular aspects of prosociality produces trade-offs influence of others by endowing visions with a noetic quality, and adverse effects. For example, MDMA boosts prosocial a deep sense of having obtained unmediated knowledge that behavior toward members of one’s in-group but not toward requires no external validation or evidence (37–39). This more the outgroup, which can result in a redistribution of limited variable set of outcomes opens up the possibility of harnessing resources (45). However, if psychedelics reduced their users’ Frontiers in Psychiatry | www.frontiersin.org 3 August 2021 | Volume 12 | Article 680064 Langlitz et al. Moral Psychopharmacology Needs Moral Inquiry sense of self-importance, they might free up resources in favor of of the psychedelic experience. From a regulatory perspective, both neighbors and strangers, increasing other-regard solely at a it will still largely depend on randomized placebo-controlled cost to egocentric motivations (46, 47). trials, whether psychedelics will have a wide or a restricted role This model of bioethics presupposes conceptions of what as prescription medicines. The goal is not to replace but to counts as moral and measures technologies against them. complement those trials, as a wide range of contextual variables It is based on a separation of technology and morality, are likely to determine the therapeutic benefits of psychedelics. means and ends. However, psychedelics present a case where An upstream approach to the morally transformative effects of the means transform the ends. Although a recent trial by psychedelics places psychopharmacologists, psychiatrists, social Carhart-Harris et al. comparing psilocybin and escitalopram researchers, and humanities scholars side by side to study, in long-standing, moderate-to-severe major depressive disorder assess, and redesign psychedelic experiences in their social, did not show significant difference in antidepressant effects, cultural, and historical contexts (57, 58). Ideally, laboratories it produced secondary effects on qualitative dimensions of and clinical trial sites would embed anthropological, sociological, psychosocial functioning that transformed patients’ attitudes and philosophical observers instead of keeping them cordoned toward themselves, others, and the world (48). Notably, off in their respective university departments. Ethnographic patients from other trials undergoing conventional treatment descriptions and comparisons of the uses of psychedelic drugs at for depression reported that medications and short-term talk different sites, including non-medical sites, could be fed back into therapies tended to reinforce their sense of disconnection the fashioning of new uses. First-hand familiarity with research and avoidance, whereas psychedelic treatment encouraged and therapeutic practices as well as everyday personal contact connection and acceptance or a sense of “reconnecting” enable members of different disciplines to inform each other’s with past values that had faded over the years (49–51). thinking and devise approaches that make good use of the context Of course, these experiential reports leave open whether dependence of psychedelics in light of ongoing discussions of people actually reconnect with their own values, what role what constitutes a good use. their heightened suggestibility plays in this process, and whether the pharmacological modulation of affective relations CONCLUSION: EXTENDING RESEARCH to the world and to others privileges certain moral and AND DEVELOPMENT INTO THE maybe even political transformations over others. Do different EXTRA-PHARMACOLOGICAL REALM psychedelic compounds produce different moral effects and ethical orientations? How do psychedelics compare with other If moral psychopharmacology took it upon itself to develop classes of psychotropic drugs? Whatever the mechanism, forms of psychedelic apprenticeship for the currently sprawling variability, and scope of such pharmacological transvaluation medical and non-medical applications of psychedelics, it would of values, it led psychiatrist William Smith and medical extend pharmaceutical research and development into the ethicist Dominic Sisti to call for an enhanced consent process extra-pharmacological realm. Such a design process needs acknowledging that patients might experience significant shifts to be informed by best practices in clinical psychology in their ethical outlook and worldview, which they cannot fully and cognate fields, but, intellectually, it cannot hide behind foresee from the perspective of their pre-therapeutic self (52). professional prescriptions because what counts as good and The challenge is to invent new research practices that observe and bad is precisely what is at stake here. It is an open reflect on the combining of neurochemistry and morality in the philosophical question that has to be answered in a recursive laboratories and clinics where this amalgamation is happening. process of psychopharmacological experimentation, clinical Another challenge involves observing how psychedelics and ethnographic observation, historical research, and ethical are used beyond the laboratory and the clinic, turning reflection. The evaluation of new uses of different drugs in psychopharmacology into a field science by adopting practices the laboratory, the clinic, and in the wild should not be from ethnopharmacology, ecology, and other areas of field confined to the armchair, removed from these spaces and biology. For instance, battery-powered EEG equipment already the experiences they engender. That is why research and allows one to study in naturalistic settings how ayahuasca, development of psychedelics in context also requires research and an Amazonian jungle environment, guidance by experienced development of knowledge cultures that bridge the gap between ayahuasceros, and other variables concur in their effect on brain neuropsychopharmacology, social research, and the humanities. waves, and placebo-controlled field experiments seek to tease It is an empirical question whether such a blending of moral apart the impact of pharmacological and extra-pharmacological psychopharmacology with moral inquiry would remain confined factors in such an ayahuasca ceremony (53, 54). Other field to psychedelics because of their peculiar pharmacological sciences such as cultural primatology that use recent advances properties, or whether it could become a model for working with in statistics to explain how complex interactions between large other classes of psychotropic substances as well. numbers of ecological factors shape animal behavior might provide further methodological inspiration for how to study the interplay between pharmacological and extrapharmacological DATA AVAILABILITY STATEMENT factors [e.g., (29, 55), p.180–90; (56)]. Finally, the challenge is to study historical uses of psychedelics The raw data supporting the conclusions of this article will be as natural experiments that shed light on the context dependence made available by the authors, without undue reservation. Frontiers in Psychiatry | www.frontiersin.org 4 August 2021 | Volume 12 | Article 680064 Langlitz et al. 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Carhart-Harris RL, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Conflict of Interest: The authors declare that the research was conducted in the Murphy R, et al. Trial of psilocybin versus escitalopram for depression. N Eng absence of any commercial or financial relationships that could be construed as a J Med. (2021) 384:1402–11. doi: 10.1056/NEJMoa2032994 potential conflict of interest. 49. Carhart-Harris RL, Erritzoe D, Haijen E, Kaelen M, Watts R. Psychedelics and connectedness. Psychopharmacology. (2018) 235:547–50. doi: 10.1007/s00213-017-4701-y Publisher’s Note: All claims expressed in this article are solely those of the authors 50. Noorani T, Garcia-Romeu A, Swift TC, Griffiths RR, Johnson MW. and do not necessarily represent those of their affiliated organizations, or those of Psychedelic therapy for smoking cessation: qualitative analysis the publisher, the editors and the reviewers. Any product that may be evaluated in of participant accounts. J Psychopharmacol. (2018) 32:756–69. this article, or claim that may be made by its manufacturer, is not guaranteed or doi: 10.1177/0269881118780612 endorsed by the publisher. 51. Watts R, Day C, Krzanowski J, Nutt D, Carhart-Harris RL. Patients’ accounts of increased ‘connectedness’ and ‘acceptance’ after psilocybin Copyright © 2021 Langlitz, Dyck, Scheidegger and Repantis. This is an open-access for treatment-resistant depression. J Humanist Psychol. (2017) article distributed under the terms of the Creative Commons Attribution License (CC doi: 10.1177/0022167817709585 BY). The use, distribution or reproduction in other forums is permitted, provided 52. Smith WR, Sisti D. Ethics and ego dissolution: the case of psilocybin. J Med the original author(s) and the copyright owner(s) are credited and that the original Ethics. (2020). doi: 10.1136/medethics-2020-106070. [Epub ahead of print]. publication in this journal is cited, in accordance with accepted academic practice. 53. Hoffmann E, Keppel Hesselink JM, da Silveira Barbosa Y. Effects of a No use, distribution or reproduction is permitted which does not comply with these psychedelic, tropical tea, ayahuasca, on the electroencephalographic (EEG) terms. Frontiers in Psychiatry | www.frontiersin.org 6 August 2021 | Volume 12 | Article 680064 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Frontiers in Psychiatry Pubmed Central

Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics

Frontiers in Psychiatry , Volume 12 – Aug 2, 2021

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PERSPECTIVE published: 02 August 2021 doi: 10.3389/fpsyt.2021.680064 Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics 1 2 3 4 Nicolas Langlitz , Erika Dyck , Milan Scheidegger and Dimitris Repantis 1 2 Department of Anthropology, The New School for Social Research, New York, NY, United States, Department of History, University of Saskatchewan, Saskatoon, SK, Canada, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland, Charité – Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Berlin, Germany The revival of psychedelic research coincided and more recently conjoined with psychopharmacological research on how drugs affect moral judgments and behaviors. This article makes the case for a moral psychopharmacology of psychedelics that examines whether psychedelics serve as non-specific amplifiers that enable subjects to (re-)connect with their values, or whether they promote specific Edited by: moral-political orientations such as liberal and anti-authoritarian views, as recent Michael James Winkelman, Arizona State University, United States psychopharmacological studies suggest. This question gains urgency from the fact Reviewed by: that the return of psychedelics from counterculture and underground laboratories to Fabrizio Schifano, mainstream science and society has been accompanied by a diversification of their University of Hertfordshire, United Kingdom users and uses. We propose bringing the pharmacological and neuroscientific literature Brian D. Earp, into a conversation with historical and anthropological scholarship documenting the full University of Oxford, United Kingdom spectrum of moral and political views associated with the uses of psychedelics. This Ido Hartogsohn, Bar-Ilan University, Israel paper sheds new light on the cultural plasticity of drug action and has implications for the *Correspondence: design of psychedelic pharmacopsychotherapies. It also raises the question of whether Dimitris Repantis other classes of psychoactive drugs have an equally rich moral and political life. dimitris.repantis@charite.de Keywords: psychedelics, hallucinogens, morality and values, extrapharmacological variables, anthropology, Specialty section: ethnography, history, psychotherapy This article was submitted to Psychopharmacology, a section of the journal INTRODUCTION: A NEW FIELD OF RESEARCH Frontiers in Psychiatry Received: 31 March 2021 Since the 2000s, neuropsychopharmacologists have grown interested in the neurochemical Accepted: 09 June 2021 foundations of moral behaviors. Experimental paradigms from social psychology and behavioral Published: 02 August 2021 economics have been used to study the effects of drugs, for example how antidepressants such as Citation: citalopram enhanced harm aversion and affected people’s inclination to retaliate against unfairness Langlitz N, Dyck E, Scheidegger M (1), how oxytocin affected one’s readiness to trust others (2) and motivated both in-group favoritism and Repantis D (2021) Moral and out-group derogation (3), how regular users of stimulants showed less prosocial behavior Psychopharmacology Needs Moral (4), or how MDMA and LSD increased emotional empathy and altruism (5). Analogous to Inquiry: The Case of Psychedelics. moral psychology, a field that emerged at about the same time, this rapidly growing body of Front. Psychiatry 12:680064. research gave birth to a new subfield that could aptly be called “moral psychopharmacology.” doi: 10.3389/fpsyt.2021.680064 Frontiers in Psychiatry | www.frontiersin.org 1 August 2021 | Volume 12 | Article 680064 Langlitz et al. Moral Psychopharmacology Needs Moral Inquiry THE CONTEXT DEPENDENCE OF interventions. Thereby, the question of how drugs affect human relationships and what makes a good relationship comes into PSYCHEDELICS VARIES THEIR MORAL the purview of psychiatric drug treatment. In the clinical EFFECTS context, moral psychopharmacology moves from the limited ecological validity of behavioral economic games and moral In the case of psychedelics, research on their moral effects is dilemma experiments to issues that are highly relevant to of particular importance. Politically, psychedelic drug use is the moral fabric of everyday life (even if the intricacies likely to increase and take place in a variety of non-medical of romantic relationships or family life have not figured contexts as a number of jurisdictions introduce decriminalizing prominently in moral philosophy). In this respect, the moral legislation concerning psychedelics. In May 2021, for example, psychopharmacology of all drugs that affect social behavior Psilonautica and Drug Science, two UK-based organizations, appears significant. Notably, recent studies highlight how revealed findings from a study showing that a majority of psychedelics and empathogens modulate conscious decision- the British public support the medical use of psychedelics making and behavioral orientations in various psycho-socio- for trauma-based injuries and end-of-life anxiety. American environmental domains (5, 10, 11). The pronounced context- cities like Denver, Oakland and Santa Cruz went further and dependence of psychedelics and their application in the context decriminalized psilocybin, and in 2020 the state of Oregon of different psychotherapeutic approaches or non-clinical uses decriminalized psilocybin and approved it for medical use. gives particular urgency to the question of how they affect The legal prohibition on psychedelics is beginning to change, people’s moral judgment and behavior. After all, the moral effects but its regulatory future remains context specific. Scientifically, might not be one-dimensional, simply increasing or decreasing the moral psychopharmacology of psychedelics is especially regard for others as concerns about moral “enhancement” and interesting because their effects have long been shown to depend “degradation” imply [(12, 13), p. 233–35, 261–63]. Instead, the crucially on extra-pharmacological factors. Since the 2010s, what moral effects of psychedelics appear to differ depending on the is colloquially called “set and setting,” the subject’s mindset and context of their use and the mind-set of the user. their social and physical environment, has attracted renewed The successful mainstreaming of psychedelics through interest in the revival of psychedelic research. Carhart-Harris medical research has introduced these substances to populations et al. (6) argued that the drugs’ 5HT receptor agonism renders 2a beyond the so-called psychedelic research community. The the psychedelic experience exceptionally sensitive to context, growing diversity of users and uses broadens the range of both internal and external. While common psychophysiological extra-pharmacological factors that shape the drugs’ moral effects on serotonin-mediated neurobehavioral circuits may effects. Historical and ethnographic research can complement shape some of the cross-cultural similarities in patterns of contemporary neuropsychopharmacology studies with studies psychedelic use and experiences, their cultural desirability is of cultural contexts that examine other sets and settings in mostly shaped by political factors (7). What distinguishes relation to drug uses and effects. While members of the research in this vein from research on the placebo effect is that, American counterculture used LSD, mescaline, and psilocybin as in the case of psychedelics, the effects of extra-pharmacological psychopharmacological tools to liberate individuals from the ills factors appear to be pharmacologically mediated and amplified. of their society, Huichol youth ingested peyote buttons to become It is part of psychedelic drug action to blur the line between full members of their own society (14, 15), and Native American the pharmacological and the nonpharmacological, between drug Church worshippers consumed peyote to foster indigenous action and social context. resistance to North American colonialism (16, 17). In the 1960s, This context-dependence is also of clinical importance as psychedelics were taken to experience a mystical union that users psychedelic-assisted therapy of depression and other psychiatric claimed fostered a sense of universal love, but anthropologists conditions combines pharmacotherapy with psychotherapy, have also described Amazonian societies that used them in rituals actively mobilizing extra-pharmacological factors to improve to prepare for violent intergroup conflict (18–20). At present, treatment outcomes (even though ongoing randomized psychedelic therapists and progressive intellectuals suggest that controlled trials do not explicitly focus on the psychotherapeutic psychedelic experiences could help to work through the cultural contribution). The subjective experience shaped by set and trauma of racist discrimination (21, 22), and one study found that setting might not just be epiphenomenal but causally related intense psychedelic experiences predicted liberal political views, to the drugs’ therapeutic effects (8). Although interactions openness, and nature relatedness, while negatively predicting with other people crucially affect how patients experience the authoritarian political views [(23); but see (24)]. At the same effects of psychedelics, in medical research, it is often a mere time, a budding traditionalist scene finds inspiration in the afterthought that drug treatments of psychiatric patients have significant implications for their social relationships (9). Outside right-wing writer and psychonaut Ernst Jünger and, according to media reports, psychedelics might also play a role in the of a clinical setting, these contextual features will be even more difficult to assess, predict, or control. political radicalization of far-right groups in the United States This relationship to cultural context opens up a dimension (25–27). A moral psychopharmacology of psychedelics needs to of moral psychopharmacology directly relevant to clinical explain how pharmacological and extrapharmacological factors work, which cannot be guided only by considerations of interact to produce such seemingly contradictory varieties of the normal and the pathological that usually inform medical psychedelic experience. Frontiers in Psychiatry | www.frontiersin.org 2 August 2021 | Volume 12 | Article 680064 Langlitz et al. Moral Psychopharmacology Needs Moral Inquiry TAKING PSYCHEDELIC RESEARCH psychedelic apprenticeships to different therapeutic goals and ethical projects. Subjects undergoing drug-induced mystical BEYOND THE TWO-CULTURE DIVIDE experiences might even be steered toward religious conversion and New Age spiritualities—a prospect that has raised concern A well-established but potentially misleading account of the moral and political versatility of psychedelics draws from among psychedelic psychotherapists who seek to secularize the an older naturalist ontology that suggests that there is one field and worry about the abuse of power on the part of guides and therapists (40, 41). nature and many cultures that interpret it differently. It has inspired a neat division of labor between the disciplines: The context sensitivity of psychedelics entails that randomized placebo-controlled trials are insufficient for appreciating the neuropsychopharmacologists study the effects of drugs on the brain, cultural anthropologists and historians study how different full range of their possible effects, nor do they capture the diverse ways in which consumers may encounter psychedelics in groups of humans make sense of them at different points in time. In recent decades, however, both the ontological and medical and non-medical settings alike. If the pharmacological activity of a drug changes the relationship between a living the epistemological divide between the two cultures of the natural sciences on the one hand and the humanities and thing and its environment in ways that depend on the living thing’s mindset and the particular quality of the interpretive social sciences on the other hand have been called into question from very different angles. Culture is no longer environment, then the environment would be inscribed in the observed pharmacological effect—even if the placebo the exclusive domain of the humanities and human sciences effects were subtracted from the effects of the verum. In the but has become an object of research in cultural neuroscience and cultural primatology (28, 29). The same is true for related 1950s, anthropologist Anthony Wallace had already noted that Euro-American subjects who had received mescaline in the ontological categories such as the mind, which used to organize the disciplinary divide between Geistes- and Naturwissenschaften laboratory reported very different psychotropic effects than Native Americans who had eaten peyote buttons in religious in the German-speaking world but is now the subject matter of evolutionary and brain research. This new naturalism has ceremonies. At a time when placebo-controlled trials only just emerged as the gold standard of pharmacological research, inspired research programs in the social sciences that have sought to break down the barrier between the natural and the human Wallace proposed to complement them by culture-controlled trials that tested the same drug at the same dosage under by presenting the scientific objects of the natural sciences as constructed by humans (30–32). While these challenges to the different social and cultural circumstances [(13), p. 116–26, 185– 92; (42)]. Reanimating this largely forgotten approach today dichotomies of nature/culture, nature/human, or mind/matter might not be equally compelling across all areas of study, they are would provide moral psychopharmacology with an opportunity germane to a class of psychoactive drugs whose effects depend to import experimental paradigms from social, moral, and political psychology. on their users’ personalities, expectations, and cultural beliefs as well as the social setting in which they are ingested. Studying the moral effects of psychedelics raises epistemological challenges “UPSTREAM” DESIGN OF NEW USES OF that extend across the divide between the natural sciences and the humanities (33). PSYCHEDELICS More recently, extra-pharmacological factors have attracted The ethical plasticity of psychedelic-induced experiences attention in psychedelic research, which again stimulates interdisciplinary debates and transdisciplinary collaborations poses a formidable bioethical problem. Usually, bioethics offers a moral evaluation of the social consequences of new (34, 35). The experiential diversity of psychedelic states calls for novel approaches combining phenomenological methods biotechnologies or pharmaceuticals. For example, debates and empirical research to better understand the structure and over antidepressants or so-called cognitive enhancers assumed that the drugs have certain effects established by clinical dynamics of altered states of consciousness that go beyond their conceptualization as “brain states”. Social anthropologist David observation and psychopharmacological experiment, while bioethicists evaluated the social consequences of these Dupuis, clinical psychologist Rosalind Watts, and neuroscientist Christopher Timmermann propose moving beyond research that effects downstream from pharmacology and proposed how to regulate the drugs’ applications. A growing body of bioethical correlates first-person reports and third-person measurements of brain activity and attend to the second-person dimension literature on psychedelics evaluates the use of psychedelics to neurochemically enhance the sense of meaning in psychedelic- of what they call “psychedelic apprenticeship” (36). Their focus on the social mediation of psychedelic-induced experiences assisted psychotherapy and their use to develop virtues, suppress vices, and enhance moral behavior (43, 44). What distinguishes can account for why psychedelics have turned out to be a “double-edged sword” that can either benefit or harm their the notion of psychedelic moral enhancement, as advocated by users—or even do both at the same time. Psychedelics have some authors, from traditional notions is that it recognizes that been shown to increase suggestibility while concealing this amplifying particular aspects of prosociality produces trade-offs influence of others by endowing visions with a noetic quality, and adverse effects. For example, MDMA boosts prosocial a deep sense of having obtained unmediated knowledge that behavior toward members of one’s in-group but not toward requires no external validation or evidence (37–39). This more the outgroup, which can result in a redistribution of limited variable set of outcomes opens up the possibility of harnessing resources (45). However, if psychedelics reduced their users’ Frontiers in Psychiatry | www.frontiersin.org 3 August 2021 | Volume 12 | Article 680064 Langlitz et al. Moral Psychopharmacology Needs Moral Inquiry sense of self-importance, they might free up resources in favor of of the psychedelic experience. From a regulatory perspective, both neighbors and strangers, increasing other-regard solely at a it will still largely depend on randomized placebo-controlled cost to egocentric motivations (46, 47). trials, whether psychedelics will have a wide or a restricted role This model of bioethics presupposes conceptions of what as prescription medicines. The goal is not to replace but to counts as moral and measures technologies against them. complement those trials, as a wide range of contextual variables It is based on a separation of technology and morality, are likely to determine the therapeutic benefits of psychedelics. means and ends. However, psychedelics present a case where An upstream approach to the morally transformative effects of the means transform the ends. Although a recent trial by psychedelics places psychopharmacologists, psychiatrists, social Carhart-Harris et al. comparing psilocybin and escitalopram researchers, and humanities scholars side by side to study, in long-standing, moderate-to-severe major depressive disorder assess, and redesign psychedelic experiences in their social, did not show significant difference in antidepressant effects, cultural, and historical contexts (57, 58). Ideally, laboratories it produced secondary effects on qualitative dimensions of and clinical trial sites would embed anthropological, sociological, psychosocial functioning that transformed patients’ attitudes and philosophical observers instead of keeping them cordoned toward themselves, others, and the world (48). Notably, off in their respective university departments. Ethnographic patients from other trials undergoing conventional treatment descriptions and comparisons of the uses of psychedelic drugs at for depression reported that medications and short-term talk different sites, including non-medical sites, could be fed back into therapies tended to reinforce their sense of disconnection the fashioning of new uses. First-hand familiarity with research and avoidance, whereas psychedelic treatment encouraged and therapeutic practices as well as everyday personal contact connection and acceptance or a sense of “reconnecting” enable members of different disciplines to inform each other’s with past values that had faded over the years (49–51). thinking and devise approaches that make good use of the context Of course, these experiential reports leave open whether dependence of psychedelics in light of ongoing discussions of people actually reconnect with their own values, what role what constitutes a good use. their heightened suggestibility plays in this process, and whether the pharmacological modulation of affective relations CONCLUSION: EXTENDING RESEARCH to the world and to others privileges certain moral and AND DEVELOPMENT INTO THE maybe even political transformations over others. Do different EXTRA-PHARMACOLOGICAL REALM psychedelic compounds produce different moral effects and ethical orientations? How do psychedelics compare with other If moral psychopharmacology took it upon itself to develop classes of psychotropic drugs? Whatever the mechanism, forms of psychedelic apprenticeship for the currently sprawling variability, and scope of such pharmacological transvaluation medical and non-medical applications of psychedelics, it would of values, it led psychiatrist William Smith and medical extend pharmaceutical research and development into the ethicist Dominic Sisti to call for an enhanced consent process extra-pharmacological realm. Such a design process needs acknowledging that patients might experience significant shifts to be informed by best practices in clinical psychology in their ethical outlook and worldview, which they cannot fully and cognate fields, but, intellectually, it cannot hide behind foresee from the perspective of their pre-therapeutic self (52). professional prescriptions because what counts as good and The challenge is to invent new research practices that observe and bad is precisely what is at stake here. It is an open reflect on the combining of neurochemistry and morality in the philosophical question that has to be answered in a recursive laboratories and clinics where this amalgamation is happening. process of psychopharmacological experimentation, clinical Another challenge involves observing how psychedelics and ethnographic observation, historical research, and ethical are used beyond the laboratory and the clinic, turning reflection. The evaluation of new uses of different drugs in psychopharmacology into a field science by adopting practices the laboratory, the clinic, and in the wild should not be from ethnopharmacology, ecology, and other areas of field confined to the armchair, removed from these spaces and biology. For instance, battery-powered EEG equipment already the experiences they engender. That is why research and allows one to study in naturalistic settings how ayahuasca, development of psychedelics in context also requires research and an Amazonian jungle environment, guidance by experienced development of knowledge cultures that bridge the gap between ayahuasceros, and other variables concur in their effect on brain neuropsychopharmacology, social research, and the humanities. waves, and placebo-controlled field experiments seek to tease It is an empirical question whether such a blending of moral apart the impact of pharmacological and extra-pharmacological psychopharmacology with moral inquiry would remain confined factors in such an ayahuasca ceremony (53, 54). Other field to psychedelics because of their peculiar pharmacological sciences such as cultural primatology that use recent advances properties, or whether it could become a model for working with in statistics to explain how complex interactions between large other classes of psychotropic substances as well. numbers of ecological factors shape animal behavior might provide further methodological inspiration for how to study the interplay between pharmacological and extrapharmacological DATA AVAILABILITY STATEMENT factors [e.g., (29, 55), p.180–90; (56)]. Finally, the challenge is to study historical uses of psychedelics The raw data supporting the conclusions of this article will be as natural experiments that shed light on the context dependence made available by the authors, without undue reservation. Frontiers in Psychiatry | www.frontiersin.org 4 August 2021 | Volume 12 | Article 680064 Langlitz et al. 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Carhart-Harris RL, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Conflict of Interest: The authors declare that the research was conducted in the Murphy R, et al. Trial of psilocybin versus escitalopram for depression. N Eng absence of any commercial or financial relationships that could be construed as a J Med. (2021) 384:1402–11. doi: 10.1056/NEJMoa2032994 potential conflict of interest. 49. Carhart-Harris RL, Erritzoe D, Haijen E, Kaelen M, Watts R. Psychedelics and connectedness. Psychopharmacology. (2018) 235:547–50. doi: 10.1007/s00213-017-4701-y Publisher’s Note: All claims expressed in this article are solely those of the authors 50. Noorani T, Garcia-Romeu A, Swift TC, Griffiths RR, Johnson MW. and do not necessarily represent those of their affiliated organizations, or those of Psychedelic therapy for smoking cessation: qualitative analysis the publisher, the editors and the reviewers. Any product that may be evaluated in of participant accounts. J Psychopharmacol. (2018) 32:756–69. this article, or claim that may be made by its manufacturer, is not guaranteed or doi: 10.1177/0269881118780612 endorsed by the publisher. 51. Watts R, Day C, Krzanowski J, Nutt D, Carhart-Harris RL. Patients’ accounts of increased ‘connectedness’ and ‘acceptance’ after psilocybin Copyright © 2021 Langlitz, Dyck, Scheidegger and Repantis. This is an open-access for treatment-resistant depression. J Humanist Psychol. (2017) article distributed under the terms of the Creative Commons Attribution License (CC doi: 10.1177/0022167817709585 BY). The use, distribution or reproduction in other forums is permitted, provided 52. Smith WR, Sisti D. Ethics and ego dissolution: the case of psilocybin. J Med the original author(s) and the copyright owner(s) are credited and that the original Ethics. (2020). doi: 10.1136/medethics-2020-106070. [Epub ahead of print]. publication in this journal is cited, in accordance with accepted academic practice. 53. Hoffmann E, Keppel Hesselink JM, da Silveira Barbosa Y. Effects of a No use, distribution or reproduction is permitted which does not comply with these psychedelic, tropical tea, ayahuasca, on the electroencephalographic (EEG) terms. Frontiers in Psychiatry | www.frontiersin.org 6 August 2021 | Volume 12 | Article 680064

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