The revival of the psychedelic experience scale: Revealing its extended-mystical, visual, and distressing experiential spectrum with LSD and psilocybin studies.

BACKGROUND: Research with the Psychedelic Experience Questionnaire/Scale (PES) focuses on questions relating to mystical experience (Mystical Experience Questionnaire (MEQ)). The psychometric potential of the non-MEQ items of the PES remains largely unexplored. AIMS: We investigated whether the PES also yields subscales besides the MEQ30 subscales. METHODS: Data from 239 PES measurements (140 healthy participants) from six studies with moderate to high doses of lysergic acid diethylamide and/or psilocybin were included. New subscales (with items other than MEQ30) were created and validated as follows: (1) theoretical derivation of candidate items; (2) removal of items with rare experiences; (3) exploratory factor analysis; and (4) confirmatory factor analysis. Correlations of subscales within the PES and between the PES and the 5-Dimensional Altered States of Consciousness Scale (5D-ASC) were performed. In addition, a cluster analysis using all items (except rare experiences) was performed. RESULTS: The reliability of the four original factors of the MEQ30 was confirmed and four additional factors for the non-MEQ items were revealed: paradoxicality, connectedness, visual experience, and distressing experience. The first two additional factors were strongly correlated with the MEQ30 mystical subscale. Adding the new subscales to the MEQ30 subscales increased the explained variance with the 5D-ASC. The cluster analysis confirmed our main results and provided additional insights for future psychedelic psychometrics. CONCLUSION: The study yields a new validated 6-factor structure for extended mystical experience (MEQ40: MEQ30 + Paradoxicality + Connectedness) and covers psychedelic experience as a whole more comprehensively than has hitherto been possible within a single questionnaire (PES48). The entire PES (PES100) can also be used for further future psychedelic-psychometric research.

Acute Subjective Effects of Psychedelics within and Beyond WEIRD Contexts.

Reports of psychedelic experiences may contain similarities and differences across cultural contexts, but most current characterizations and quantifications of psychedelic experiences come from Western medical and naturalistic settings. In this article, we begin with a brief history of the diversity of psychedelic use in non-Western settings. We then compare and contrast accounts of psychedelic experiences within and beyond Western, educated, industrialized, rich, and democratic (WEIRD) contexts. We focus on specific reports of direct testimony of the acute subjective effects of psychedelics experienced across these contexts. We compare themes from each of these various contexts, with special emphasis on psychometric measures such as the mystical experiences questionnaire (MEQ), the five-dimensional altered states of consciousness (5D-ASC) scale, the Survey of God Encounters, and the Survey of Entity Encounters, the Challenging Experiences Questionnaire, and the Inventory of Nonordinary Experiences (INOE). Finally, we offer recommendations for future research to quantify these similarities and differences across cultures to assess them empirically in the future.

Reduced death anxiety as a mediator of the relationship between acute subjective effects of psychedelics and improved subjective well-being.

Research over the past several decades suggests that meaningful psychedelic experiences can engender long-term effects on subjective wellbeing. However, less research has investigated the psychological mechanisms through which these effects may emerge. In the present study, participants (N = 201) completed an online survey that retrospectively measured the acute effects of a meaningful psychedelic experience, as well as changes in subjective well-being and death anxiety. Reductions in death anxiety significantly mediated the effects of mystical experience on satisfaction with life, positive affect, and negative affect. Reductions in death anxiety did not mediate any of the effects of psychological insight. Although correlational, the findings are consistent with the hypothesis that some of the benefits of psychedelic-induced mystical experiences on subjective well-being may emerge due to reductions in death anxiety. Nevertheless, further research is needed to establish a causal effect of reduced death anxiety on well-being in the context of psychedelic experiences.

An Integrative Review of Measures of Spirituality in Experimental Studies of Psilocybin in Serious Illness Populations.

Background: Psilocybin-assisted therapies (PAT) are reemerging as a treatment for complex distress often prompting mystical experiences, enhanced meaning, and spiritual wellbeing. We sought to investigate how measures of spirituality are employed in experimental studies of PAT conducted with seriously ill adults. Methods: We included experimental studies of psilocybin conducted with seriously ill adults, which employed measures that contained spirituality and mysticism concepts within their domains or subdomains. Included studies were peer-reviewed and published in English language (up to December 2021). Results: Seven articles met our inclusion criteria. A total of 12 unique instruments were identified. The most frequently used instruments were the Mystical Experience Questionnaire (MEQ30), the Functional Assessment of Chronic Illness Therapy-Spirituality (FACIT-Sp-12), and the Demoralization Scale (DS-I/II) (used in four studies each), followed by the Persisting Effects Questionnaire (PEQ) (used in three studies). Overall, studies did not consistently define and contextualize spirituality domains and subdomains studied. Conclusions: Despite well-recognized significance of spirituality in PAT, there was considerable heterogeneity in number and types of spirituality measures employed across studies. There also seemed a lack of attention to defining and operationalizing spirituality and its domains and subdomains. This is notable as spirituality and overlapping concepts (eg mystical experiences) contributes substantially to this body of research and patients' therapeutic outcomes. Towards developing more rigorous science of spirituality in PAT research, there is a critical need to evaluate and refine measures of spirituality to enhance their utility and replicability, limit participant burden, and better contextualize spirituality-related findings and outcomes.

Psychosis and psychedelics: Historical entanglements and contemporary contrasts.

Experiences of psychedelics and psychosis were deeply entangled in scientific practices in the mid-20th century, from uses of psychedelic drugs that could model psychosis, to detailed phenomenological comparisons of endogenous and drug-induced madness. After the moral panic of the 1960s shut down psychedelic research, however, these two phenomena became disentangled. In the decades following, the science of psychosis transformed, shedding the language of psychoanalysis, and adopting the new scientific veneer of psychiatry. Today, as psychedelic science re-emerges, the research programs surrounding psychosis and psychedelics now stand in stark contrast. Here, I look closely at how these research programs respond to questions related to what is worth measuring, what is worth investigating, and how we ought to respond to these experiences. This comparison reveals radically different assumptions and values that guide each research paradigm and shape clinical practice. While psychedelic research often includes scales that seek to capture experiences of mysticism, meaningfulness, and ego dissolution, research related to psychosis focuses on the measurement of pathological symptoms and functioning. Research into psychosis primarily seeks universal and reductionist causal explanations and interventions, while psychedelic research embraces the importance of set and setting in shaping unique experiences. Responses to psychedelic crisis involve warmth, compassion, and support, while responses to psychotic experiences often involve restraint, seclusion, and weapons. I argue that these differences contain important lessons for psychiatry. However, as psychedelic research struggles to meet regulatory requirements and fit within the paradigm of evidence-based medicine, these differences may quickly dissolve.

Stairway to Heaven: A First-Person Account of Noesis.

ABSTRACT: Mystical and spiritual experiences have been reported throughout human history. Causal explanations for these range from psychopathology of mental illness, drugs such as hallucinogens, neurological disorders including temporal lobe epilepsy, and genuine mystical or spiritual awakening. There is a common core of phenomena in such experiences, as described both in historical accounts and recent research, but also evidence of cultural specificity. This article is a personal account of such an experience, which occurred in a postanesthetic state. A striking feature of the experience was noesis: a sense of revelation and complete understanding. I argue that while there must be a neural basis to these phenomena, it is difficult to reduce the subjective meaning of the experience purely to a brain dysfunction. Reconciling mechanism and meaning of such experiences remains a challenge for both neuroscience and philosophy.

Relationship between mysticism and severe odontogenic infections in Africa: what to do?

OBJECTIVE: This study is a case report of a severe odontogenic infection treated at Huambo Provincial Hospital, Angola. The case was made worse by local mysticism. CASE REPORT: A pregnant woman was treated for a severe odontogenic infection that caused descending mediastinitis and even a lumbar abscess. The patient died of this infection. A delay in attendance was crucial in this death. DISCUSSION: Patients from the African continent commonly experience life-threatening head and neck infections. These critical infections are rarely found in Europe or North America. The clinical situation is aggravated by local mysticism, along with poverty, lack of access to health facilities, and a shortage of skilled workers. Religious habits and the use of local herbs without scientific evidence can create difficult-to-manage situations. CONCLUSIONS: The authors believe this is the first report of an association between life-threatening odontogenic infection and mysticism. International collaboration, including teledentistry and continuing education, are critical to transforming this scene.

"Human as an Embodied Spirit": A Proposed Conceptual Model for Nursing Based on Iranian Mysticism and Wisdom.

Most nursing models are developed based on Western philosophy. The conceptual model of "human as an embodied spirit" based on Iranian mysticism and wisdom is presented in this article. This conceptual model was developed in 2 phases: first, using a derivation process, the concepts of the model were developed. Next, in a synthesis process, the conceptual model was constructed. Definitions and descriptions of each of the concepts of the model-the constitution of the physical body, the composition of graded soul, knowledge-based interventions, love-based interventions, balance, and harmony-and the relations between these concepts are presented in the article. This model gives equal value to the art and the science of nursing and integrates all dimensions of human being and related health problems in such a way that they can be explained and approached as a continuum. The next step is the testing of this model followed by the development of guidelines for education and practice.

Insular Stimulation Produces Mental Clarity and Bliss.

For the first time, an ecstatic aura has been evoked through the electrical stimulation of the dorsal anterior insula during presurgical invasive intracerebral monitoring in a patient who did not suffer from an ecstatic form of epilepsy. This case provides more evidence that the anterior insula is the major generator of such a mystical-type experience even in individuals with no underlying brain network changes related to a preexisting ecstatic epilepsy. ANN NEUROL 2022;91:289-292.

Epilepsy - from mysticism to science.

The understanding of epilepsy has been in progressive evolution since Antiquity, with scientific advances culminating in the last few decades. Throughout history, epilepsy was plagued by mystical misconceptions involving either demonic possessions, witchcraft, or divine interventions. This has frequently altered or even halted any real progress in its scientific understanding or its social perception. This metaphysical context is also at the core of the stigma revolving around this condition, some of which still lingering today. This review explores the origins of these mystical beliefs, and describes the chronological evolution of epilepsy from mysticism to science across different civilizations and eras.

Acute subjective effects in LSD- and MDMA-assisted psychotherapy.

BACKGROUND: Lysergic acid diethylamide (LSD) and 3,4-methylenedioxymethamphetamine (MDMA) were used in psychotherapy in the 1960s-1980s, and are currently being re-investigated as treatments for several psychiatric disorders. In Switzerland, limited medical use of these substances is possible in patients not responding to other treatments (compassionate use). METHODS: This study aimed to describe patient characteristics, treatment indications and acute alterations of mind in patients receiving LSD (100-200 µg) and/or MDMA (100-175 mg) within the Swiss compassionate use programme from 2014-2018. Acute effects were assessed using the 5 Dimensions of Altered States of Consciousness scale and the Mystical Experience Questionnaire, and compared with those in healthy volunteers administered with LSD or MDMA and patients treated alone with LSD in clinical trials. RESULTS: Eighteen patients (including 12 women and six men, aged 29-77 years) were treated in group settings. Indications mostly included posttraumatic stress disorder and major depression. Generally, a drug-assisted session was conducted every 3.5 months after 3-10 psychotherapy sessions. LSD induced pronounced alterations of consciousness on the 5 Dimensions of Altered States of Consciousness scale, and mystical-type experiences with increases in all scales on the Mystical Experience Questionnaire. Effects were largely comparable between patients in the compassionate use programme and patients or healthy subjects treated alone in a research setting. CONCLUSION: LSD and MDMA are currently used medically in Switzerland mainly in patients with posttraumatic stress disorder and depression in group settings, producing similar acute responses as in research subjects. The data may serve as a basis for further controlled studies of substance-assisted psychotherapy.

Dose-response relationships of psilocybin-induced subjective experiences in humans.

BACKGROUND: Psilocybin is the psychoactive component in Psilocybe mushrooms ('magic mushrooms'). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies. AIM: Establishing dose-response relationships of the subjective experiences induced by psilocybin in healthy study participants and a comparison of patient groups. METHOD: We applied a linear meta-regression approach, based on the robust variance estimation framework, to obtain linear dose-response relationship estimates on questionnaire ratings after oral psilocybin administration. Data were obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale. RESULTS: Psilocybin dose positively correlated with ratings on most factors and scales, mainly those referring to perceptual alterations and positively experienced ego dissolution. Measures referring to challenging experiences exhibited small effects and were barely modulated by dose. CONCLUSION: Psilocybin intensified almost all characteristics of altered states of consciousness assessed with the given questionnaires. Because subjective experiences are not only determined by dose, but also by individual and environmental factors, the results may only apply to controlled laboratory experiments and not to recreational use. This paper may serve as a general literature citation for the use of psilocybin in experimental and clinical research, to compare expected and observed subjective experiences.

Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings.

BACKGROUND: N,N-dimethyltryptamine is a short-acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date have addressed the neural and psychological effects of N,N-dimethyltryptamine alone, either administered intravenously or inhaled in freebase form, and none have been conducted in natural settings. AIMS: Our primary aim was to study the acute effects of inhaled N,N-dimethyltryptamine in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. "set" and "setting"), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming N,N-dimethyltryptamine in familiar and comfortable settings. METHODS: We combined state-of-the-art wireless electroencephalography with psychometric questionnaires to study the neural and subjective effects of naturalistic N,N-dimethyltryptamine use in 35 healthy and experienced participants. RESULTS: We observed that N,N-dimethyltryptamine significantly decreased the power of alpha (8-12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1-4 Hz) and gamma (30-40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of some features of mystical-type experiences. N,N-dimethyltryptamine also increased global synchrony and metastability in the gamma band while decreasing those measures in the alpha band. CONCLUSIONS: Our results are consistent with previous studies of psychedelic action in the human brain, while at the same time the results suggest potential electroencephalography markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.

Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches.

BACKGROUND: Growing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe and promising pharmacotherapy for treatment of mood and substance use disorders when administered as part of a structured intervention. In most trials to date, psilocybin dose has been administered on a weight-adjusted basis rather than the more convenient procedure of administering a fixed dose. AIMS: The present post hoc analyses sought to determine whether the subjective effects of psilocybin are affected by body weight when psilocybin is administered on a weight-adjusted basis and when psilocybin is administered as a fixed dose. METHODS: We analyzed acute subjective drug effects (mystical, challenging, and intensity) associated with therapeutic outcomes from ten previous studies (total N = 288) in which psilocybin was administered in the range 20 to 30 mg/70 kg (inclusive). Separate multivariate regression analyses examined the relationships between demographic variables including body weight and subjective effects in participants receiving 20 mg/70 kg (n = 120), participants receiving 30 mg/70 kg (n = 182), and participants whose weight-adjusted dose was about 25 mg (to approximate the fixed dose that is currently being evaluated in registration trials for major depressive disorder) (n = 103). RESULTS: In the 20 mg/70 kg and 30 mg/70 kg weight-adjusted groups, and in the fixed dose group, no significant associations were found between subjective effects and demographic variables including body weight or sex. Across a wide range of body weights (49 to 113 kg) the present results showed no evidence that body weight affected subjective effects of psilocybin. CONCLUSIONS: These results suggest that the convenience and lower cost of administering psilocybin as a fixed dose outweigh any potential advantage of weight-adjusted dosing.

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans.

BACKGROUND: Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal consciousness. AIMS: We evaluated whether pre-drug brain 5-HT2AR binding predicted the three phases of psilocybin subjective drug intensity (SDI) and retrospective self-report of mystical type experiences in healthy individuals. METHOD: Sixteen participants completed a pre-drug [11C]Cimbi-36 positron emission tomography scan to assess 5-HT2AR binding. On a separate day, participants completed a single psilocybin session (oral dose range 0.2-0.3 mg/kg), during which SDI was assessed every 20 min. The Mystical Experience Questionnaire (MEQ) was completed at the end of the session. The three SDI phases were modelled using segmented linear regressions. We evaluated the associations between neocortex 5-HT2AR binding and SDI/MEQ outcomes using linear regression models. RESULTS: Neocortex 5-HT2AR was statistically significantly negatively associated with peak plateau duration and positively with time to return to normal waking consciousness. It was also statistically significantly negatively associated with MEQ total score. CONCLUSION: This is the first study to investigate how individual brain 5-HT2AR binding predicts subjective effects of a single dose of psilocybin. Our findings reinforce the role of cerebral 5-HT2AR in shaping the temporal and mystical features of the psychedelic experience. Future studies should examine whether individual brain levels of 5-HT2AR have an impact on therapeutic outcomes in clinical studies.

Development of the Psychological Insight Questionnaire among a sample of people who have consumed psilocybin or LSD.

BACKGROUND: Several measures have been developed to examine acute psychedelic effects (e.g. mystical-type and challenging experiences), but no measure assesses acute psychologically insightful experiences that may occur during psychedelic experiences. AIM: The purpose of this study was to develop and examine the psychometric properties of the Psychological Insight Questionnaire. METHOD: A cross-sectional survey study among psilocybin and LSD users. Respondents (n=1661; Mage=22.9, standard deviation=8.5; Caucasian/White=83%; non-Hispanic=91%; men=72%; United States resident=66%) completed an Internet-based survey. RESULTS: The Psychological Insight Questionnaire consists of 23 items with two subscales: (a) Avoidance and Maladaptive Patterns Insights and (b) Goals and Adaptive Patterns Insights. Construct validity of the Psychological Insight Questionnaire was supported by strong correlations of the Psychological Insight Questionnaire (and Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights subscales) scores with the insight subscale of the Session Impacts Scale, and weak-to-moderate correlations with the Mystical Experiences and Challenging Experiences Questionnaires. Furthermore, Psychological Insight Questionnaire (and Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights subscales) scores were moderately-to-strongly correlated with retrospectively reported increases in psychological flexibility, and well-being/life satisfaction that were attributed to a memorable psychedelic experience. Lastly, incremental validity was established showing that the Psychological Insight Questionnaire (and Avoidance and Maladaptive Patterns Insights subscale) scores predict unique variance in changes in psychological flexibility, and Psychological Insight Questionnaire (and Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights subscales) scores predict changes in well-being and life satisfaction, beyond measures of acute mystical-type and challenging effects. CONCLUSIONS: The Psychological Insight Questionnaire has the potential to extend the understanding of the acute and enduring effects of psychedelics. Further longitudinal research is necessary to determine the long-term predictive validity of the Psychological Insight Questionnaire and to examine the role of psychological insight in predicting therapeutic outcomes.

Pivotal mental states.

This paper introduces a new construct, the 'pivotal mental state', which is defined as a hyper-plastic state aiding rapid and deep learning that can mediate psychological transformation. We believe this new construct bears relevance to a broad range of psychological and psychiatric phenomena. We argue that pivotal mental states serve an important evolutionary function, that is, to aid psychological transformation when actual or perceived environmental pressures demand this. We cite evidence that chronic stress and neurotic traits are primers for a pivotal mental state, whereas acute stress can be a trigger. Inspired by research with serotonin 2A receptor agonist psychedelics, we highlight how activity at this particular receptor can robustly and reliably induce pivotal mental states, but we argue that the capacity for pivotal mental states is an inherent property of the human brain itself. Moreover, we hypothesize that serotonergic psychedelics hijack a system that has evolved to mediate rapid and deep learning when its need is sensed. We cite a breadth of evidences linking stress via a variety of inducers, with an upregulated serotonin 2A receptor system (e.g. upregulated availability of and/or binding to the receptor) and acute stress with 5-HT release, which we argue can activate this primed system to induce a pivotal mental state. The pivotal mental state model is multi-level, linking a specific molecular gateway (increased serotonin 2A receptor signaling) with the inception of a hyper-plastic brain and mind state, enhanced rate of associative learning and the potential mediation of a psychological transformation.

Mystical-type experiences occasioned by ketamine mediate its impact on at-risk drinking: Results from a randomized, controlled trial.

BACKGROUND: Sub-anesthetic ketamine administration may be helpful for substance use disorders. Converging evidence suggests that the efficacy of ketamine for certain conditions may implicate a subset of its psychoactive effects. AIMS: The aim of this analysis is to evaluate whether the mystical-type effects of ketamine are critical for clinical efficacy in alcohol-dependent individuals. In this secondary analysis, we determine if a subset of the psychoactive effects of ketamine, the so-called mystical-type experience, mediates the effect of ketamine, when combined with motivational enhancement therapy, on at-risk drinking behavior in alcohol-dependent individuals interested in treatment. METHODS: Forty alcohol dependent adults were randomized to either a 52-minute infusion of ketamine or midazolam, which they received on a designated quit-day during the second week of a five-week motivational enhancement therapy regimen. Psychoactive effects were assessed following the infusion, and alcohol use was monitored for the subsequent 3 weeks at each twice-weekly visit. RESULTS: We found that ketamine leads to significantly greater mystical-type effects (by Hood Mysticism Scale) and dissociation (by Clinician Administered Dissociative States Scale) compared to the active control. Ketamine also led to significant reduction in at-risk drinking. The Hood Mysticism Scale, but not Clinician Administered Dissociative States Scale score, was found to mediate the effect of ketamine on drinking behavior. CONCLUSIONS: This trial adds evidence to the literature on the importance of mystical-type experiences in addiction treatment. Future research should continue to investigate the relationship between the psychoactive effects of psychedelic therapeutics and clinical outcomes for other substance use and mental health disorders.

Ecstatic expeditions: Fischl Schneersohn's "science of man" between modern psychology and Jewish mysticism.

This article examines Fischl Schneersohn's (1887-1958) "science of man" as a psychotherapeutic approach situated between modern psychology and Chassidic mysticism. While almost forgotten today, Schneersohn was a prolific writer, well-known in Yiddish-speaking circles as a psychologist, educationalist, novelist, and psychotherapist. As a descendant of an important dynasty of Chassidic rebbes, he grew up inside the Chabad movement, but followed a secular career. The first part of this article traces Schneersohn's biography from the outskirts of the Russian empire to Germany, Poland, the United States, and Palestine, and shows how his upbringing and historical experiences shaped his psychological works and his self-understanding as educationalist and psychotherapist. The second part examines Schneersohn's main work, Studies in Psycho-Expedition, which blended Chassidic mysticism and contemporary psychology in a way that was both idiosyncratic and unique. The psycho-sociological "science of man" was a modern psychological and psychotherapeutic approach, using specific methods to gain knowledge about the human mind, and to counteract and treat mental disorders, neuroses, and nervousness. At the same time, however, it was deeply influenced by Chassidic mysticism; revolving around the assumption of a universal human need for spiritual ecstasy. Schneersohn universalised, secularised, and reframed elements of the Kabbalah as a modern psychotherapy. By examining an almost forgotten psychotherapeutic approach outside the mainstream in its specific historical context, this article contributes to the history of the connection between religion and the psy-disciplines, as well as to ongoing debates about the role of spirituality and ecstasy in psychology and psychotherapy.