Harnessing placebo: Lessons from psychedelic science.

The randomized controlled trial (RCT) research design assumes that a drug's "specific" effect can be isolated, added, and subtracted from the "nonspecific" effect of context and person. While RCTs are helpful in assessing the added benefit of a novel drug, they tend to obscure the curative potential of extra-pharmacological variables, known as "the placebo effect." Ample empirical evidence suggests that person/context-dependent physical, social, and cultural variables not only add to, but also shape drug effects, making them worth harnessing for patient benefits. Nevertheless, utilizing placebo effects in medicine is challenging due to conceptual and normative obstacles. In this article, we propose a new framework inspired by the field of psychedelic science and its employment of the "set and setting" concept. This framework acknowledges that drug and nondrug factors have an interactive and synergistic relationship. From it, we suggest ways to reintegrate nondrug variables into the biomedical toolbox, to ethically harness the placebo effect for improved clinical care.

Technology and addiction: What drugs can teach us about digital media.

Comparisons between digital media and narcotic drugs have become increasingly common in the vigorous discussion on smartphone addiction and technology addiction. Commentators have used evocative terms such as "digital heroin," "electronic cocaine," and "virtual drugs" when discussing users' growing dependence on their devices. This article looks at the spreading discourse comparing digital media with drugs from a set of interdisciplinary perspectives including media studies, political economy, critical theory, science and technology studies, and addiction studies. It engages several key questions: To what extent can heavy smartphone use be considered an addiction, and how is it similar or different from drug addiction? How do the analogies between media and drugs fit within prevalent imaginaries of information technologies, and within the greater cultural themes and preoccupations of late capitalism? And finally, what can drugs teach us about the possible escape routes from our society's current predicament?

Set and setting in microdosing: an oft-overlooked principle.

RATIONALE: The use of psychedelics for medical and recreational purposes is rising. Contextual factors such as expectancy, intention, and sensory and social environment (set and setting) are widely recognized as moderating the effects of these substances. Nevertheless, clinical trials of microdosing - the ingestion of small, sub-hallucinogenic doses of psychedelics - rarely report their set and setting. This fact suggests that such factors are not considered important in the context of microdosing. OBJECTIVE: This paper challenges this assumption and makes the case for the crucial relevance of set and setting in microdosing practice. Building on set and setting theory and placebo theory, we explain why set and setting are of crucial importance in the case of microdosing. RESULTS: This reasoning helps elucidate the role of set and setting in determining the outcomes of microdosing and helps explain some of the contradictory results that have emerged in microdosing research in recent years. CONCLUSION: Set and setting are important constructs to be considered especially in the context of microdosing psychedelics. By reporting set and setting, the results of microdosing research can be made more reliable and consistent.

Modalities of the psychedelic experience: Microclimates of set and setting in hallucinogen research and culture.

Mid-20th-century American research on psychedelics evinced a stunning diversity of interpretations of hallucinogenic effects. While some researchers viewed psychedelics as invaluable tools for psychotherapy, others persisted in treating them as psychosis-inducing agents. As some groups considered psychedelics as catalysts for artistic creativity, others investigated their potential use as psychochemical weapons in the battlefield, or conversely as tools for spiritual ecstasy and revelation. This bewildering array of perceptions regarding the nature of hallucinogenic effects led to stark contrasts in the contexts (set and setting) of psychedelic research and experimentation, leading to wildly divergent outcomes and reports on the effects of the drugs, and strident disagreements between the actors in the field. Examining this remarkable historical moment of epistemological unclarity regarding psychedelics and their effects, this article describes how distinct scientific and cultural trends and moments of mid-20th-century America contributed to the creation of diverse microclimates of set and setting that reproduced investigator beliefs and attitudes and brought about a beguiling Pygmalion effect that left researchers befuddled and perplexed. I propose the concept of psychedelic modality to describe how distinct sociocultural microclimates lead to thematic aggregates in which distinct types of expectations, intentions as well as physical, social, and cultural environments all tend to cluster, producing characteristic outcomes and results. By exploring the historical context and consequences of the emergence of seven psychedelic modalities (psychotomimetic, military, psychotherapeutic, spiritual, artistic-creative, tech-innovative, and political) in mid-20th-century America, this article outlines the varieties of psychedelic experiences in their relationship with culture at large, and subcultures in particular.

Virtual Daime: When Psychedelic Ritual Migrates Online.

During the 2020 COVID-19 epidemic a variety of social activities migrated online, including religious ceremonies and rituals. One such instance is the case of Santo Daime, a Brazilian rainforest religion that utilizes the hallucinogenic brew ayahuasca in its rituals. During the pandemic, multiple Santo Daime rituals involving the consumption of ayahuasca took place online, mediated through Zoom and other online platforms. The phenomenon is notable since the effects of hallucinogens are defined by context (set and setting) and Santo Daime rituals are habitually governed by punctilious regulations aimed at directing the experience of participants. The abrupt move to online space thus augurs significant implications in the context of hallucinogenic rituals. This paper looks at this development and its repercussions for entheogenic rituals, as it asks how do psychedelic rituals change when they move online? Building on the author's previous work on set and setting in the Santo Daime religion, the paper introduces accounts from 12 semi-structured interviews with daimistas participating in online daime rituals, approached through the prism of set and setting, and the study of online religiosity. The analysis points at several key dynamics emerging in the context of virtual rituals. The migration online allowed for the continuation of Santo Daime entheogenic rituals at a time of social distancing, fostered a sense of global brotherhood and opened new possibility for religious participation and learning. Concurrently, online ritual produced an impoverished ritual experience and novel types of challenges including a higher potential for distractions, technical difficulties, and low sensory fidelity. Other novel challenges included social anxiety and an in-built tension between the social and spiritual dimensions of ritual. Finally, some participants were concerned by the cultural context of online rituals: technological mediation, consumerism, commodification, and digital divide. The limitations of digital technology appear amplified by the highly immersive, body oriented, experientially intensified context of the psychedelic experience. This paper contributes to the literature on the extra-pharmacological factors shaping experiences with psychedelics, as well as to the literature on the consequences of the adoption of digital media technologies during the COVID-19 pandemic.

Cyberdelics in context: On the prospects and challenges of mind-manifesting technologies.

The concept of cyberdelics emerged in the 1980s and 1990s as an umbrella term denoting the nexus connecting cybernetic (digital) technologies and psychedelic (mind manifesting) drugs. Cyberdelic technologies, in particular the then newly emerging field of virtual reality, were touted by psychedelic cultural icons including Timothy Leary and Terence McKenna as auguring a new era of digital mind-expansion where psychedelic experiences will be recreated online inside virtual worlds. Cyberdelic culture waned in the 2000s. However, recent years have seen the return of the cyberdelic imaginary, following on the heels of a psychedelic resurgence and a renewed interest in virtual reality technologies and their use in therapy. Cyberdelic advocates speak of the necessity of creating transformative technologies that steer humanity away from mindless consumerism and distractedness, and towards expanded states of awe, presence, and transcendence. Nevertheless, much like psychedelics, cyberdelic technologies are seen as running against the grain of current sociocultural arrangements and economic models which threaten to quell their transformative potential. Research on psychedelics within the humanities over the past decade has emphasized the role of cultural set and setting: the significance of the cultural embeddedness of these psychoactive agents and the dependence of their effects on surrounding sociocultural conditions. Building on the notion of information technologies as mind-manifesting technologies, this paper sets out to consider what psychedelics can teach us about cyberdelics: how the principles of set and setting and current discussions within the psychedelic humanities can inform our understanding of the resurgence of interest in cyberdelic media, its prospects, and challenges.

Set and Setting in the Santo Daime.

Set and setting is a fundamental concept in the field of psychedelic drug research, which points to the profound dependence of psychedelic effects on psychological, social, and cultural factors. Santo Daime is a Brazilian religion that makes elaborate use of ordering principles, techniques, and symbology to shape and direct the effects of the hallucinogenic brew ayahuasca. This paper systematically explores the tapestry of, inter alia, symbolic, social, cultural, psychological, aesthetic and musical elements that participate in the shaping of the psychedelic experience in the context of the Santo Daime ayahuasca religion. The methodically rich under the hood description of the mechanics of entheogenic initiation within the Santo Daime tradition provides a template for future studies of the role of context in psychedelic experimentation.

The Meaning-Enhancing Properties of Psychedelics and Their Mediator Role in Psychedelic Therapy, Spirituality, and Creativity.

Past research has demonstrated to the ability of psychedelics to enhance suggestibility, and pointed to their ability to amplify perception of meaning. This paper examines the existing evidence for the meaning-enhancing properties of psychedelics, and argues that the tendency of these agents to enhance the perception of significance offers valuable clues to explaining their reported ability to stimulate a variety of therapeutic processes, enhance creativity, and instigate mystical-type experiences. Building upon previous research, which suggested the potential role of psychedelic meaning-enhancement in enhancing placebo response, the paper explores the mechanisms by which the meaning-amplifying properties of psychedelics might also play a role in enhancing creativity, as well as in effecting mystical-type experiences. The wider social and public-health implications of this hypothesis are discussed, and suggestions are made as to the various ways in which scientific understanding of the meaning-enhancing properties of psychedelics might be advanced and utilized.

Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology.

Placebo response theory and set and setting theory are two fields which examine how non-biological factors shape the response to therapy. Both consider factors such as expectancy, preparation and beliefs to be crucial for understanding the extra-pharmacological processes which shape the response to drugs. Yet there are also fundamental differences between the two theories. Set and setting concerns itself with response to psychoactive drugs only; placebo theory relates to all therapeutic interventions. Placebo theory is aimed at medical professionals; set and setting theory is aimed at professionals and drug users alike. Placebo theory is primarily descriptive, describing how placebo acts; set and setting theory is primarily prescriptive, educating therapists and users on how to control and optimize the effects of drugs. This paper examines how placebo theory and set and setting theory can complement and benefit each other, broadening our understanding of how non-biological factors shape response to drugs and other treatment interventions.