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In recent years, N-methoxybenzyl-methoxyphenylethylamine (NBOMe) derivatives, a class of designer hallucinogenic drugs, have become popular drugs of abuse. These drugs have been the cause of severe intoxications and even deaths. They act as 5-HT2A receptors agonists and have been reported to produce serotonin-like syndrome with bizarre behavior, severe agitation and seizures persisting for as long as 3 days. The most commonly reported derivatives are 25I-NBOMe, 25B-NBOMe and 25C-NBOMe, respectively 2-(4-iodo-2,5-dimethoxyphenyl)- N-[(2-methoxyphenyl) methyl]ethanamine, N-(2-methoxybenzyl)- 2,5-dimethoxy-4-bromophenethylamine and N-(2-methoxybenzyl)- 2,5-dimethoxy-4-chlorophenethylamine. Like many low dose hallucinogenic drugs these compounds are often sold on blotter paper. Three different types of commercially available blotter papers reported to contain NBOMe derivatives were obtained. These blotter papers were screened using Direct Analysis in Real Time AccuTOFTM mass spectrometry followed by confirmation and quantification by high-performance liquid chromatography triple quadrapole mass spectrometry. The major drug present on each of the three blotter products was different, 25I-NBOMe, 25C-NBOMe or 25B-NBOMe. The blotter papers were also found to have minute amounts of two or three NBOMe derivative impurities of 25H-NBOMe, 25I-NBOMe, 25C-NBOMe, 25B-NBOMe and/or 25D-NBOMe. [ABSTRACT FROM AUTHOR]

Introduction: The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits ranging from improved mood and enhanced creativity to an increased sense of meaning and connectedness in life. While research on microdosing is still lagging behind the shift in public opinion, several papers have been published in the last five years which attempted to assess the effects of microdosing. Methods: This review paper aimed to critically analyze the research practices used in the recent wave of microdosing research: We reviewed 15 papers published before the closing date of this review in March 2022. Results: Our review concludes that it is premature to draw any conclusions about the efficacy or safety of microdosing since the research quality cannot be considered confirmatory. Discussion: We propose some potential causes for the current state of the literature and some suggestions for how these causes may be ameliorated. [ABSTRACT FROM AUTHOR]

New psychoactive substances (NPS) have been associated with fatalities and severe injuries in a number of cases in the United States and have led investigators to rethink traditional drug monitoring protocols. Of particular interest are the variable phenethylamine chemical structures known as 'NBOMes', which pose an emerging threat to public health with incidence steadily growing over the past decade. In this study, direct sample analysis (DSA)-time of flight mass spectrometry was employed to leverage rapid and sensitive ambient ionization mass spectrometry without chromatographic separation as verified with an authentic case sample. Samples for method development were prepared at Boston University School of Medicine's Biomedical Forensic Sciences program (Boston, MA) and analyzed at the State of Maine Health and Environmental Testing Laboratory's Forensic Chemistry Section (Augusta, ME). Preliminary method development work was performed at the University of Central Florida (Orlando, FL). DSA without any extraction step in addition to the evaluation of methanol, dichloromethane and hexane extractions were conducted. Methanol was found to not be a suitable extraction solvent for DSA analysis of these compounds. For the screening of NBOMe designer drug variables on blotter paper, DSA-TOFMS was successful at reducing analysis time to ∼15s per sample, for qualitative identification for the selected analytes of interest. The analysis of an authentic forensic case sample by DSA-TOFMS using the method development parameters demonstrates its utility in forensic laboratories. 25C-NBOMe was identified with an exact mass accuracy of 0.60ppm. [ABSTRACT FROM AUTHOR]

Near-death experiences (NDEs) and psychedelic drug experiences (YDEs) enable access to dimensions of non-ordinary sensation, perception, and insight beyond typical day-to-day phenomenology. Both are associated with a dissolution of conventional spatio-temporal conceptual distinctions, and a corresponding sense of connectedness and unity. Moreover, NDEs and YDEs have shown a remarkable ability to reduce the anxiety that people associate with death. In two recent papers, we showed that multi-person virtual reality experiences (VREs) designed within the 'numadelic' aesthetic (where bodies are represented as light energy rather than material objects) can elicit psychometric results comparable to YDEs. It nevertheless remains an open question why numadelic aesthetics achieve the observed results, especially given that the vast majority of VREs represent bodies as typically perceived in the 'real-world'. This article describes the origins of the numadelic aesthetic from subjective accounts of NDE phenomenology, and attempts to unravel mechanistic aspects of the numadelic aesthetic by embedding it within a more general theoretical framework. Specifically, we elaborate a 2-axis schematic grounded in predictive coding models of cognition and matter-energy ideas from physics. One axis tracks 'structural specificity', and the other tracks 'symbolic rigidity'. The majority of VREs, which emphasize photorealistic fidelity to content derived from 'day-to-day' phenomenology, are characterized by high structural specificity and high symbolic rigidity. Such approaches collapse imaginative potential into a limited low-entropy space of 'exogenous' possibility, unlike the high-entropy brain states associated with YDEs. In contrast, aesthetic domains characterized by low structural specificity and low symbolic rigidity are less concerned with fidelity to phenomenological priors, offering an expansive, 'uncollapsed' high-entropy possibility space into which participants can project meaning and corresponding endogenous insights can arise (e.g., as occurs in NDEs and YDEs). Situated within this theoretical framing, the numadelic aesthetic emerges as a practical example of an un-collapsed approach to representation, helping to explain the experimental observations within previous papers. Moreover, the theoretical framing suggests various experimental tests, and lays the groundwork for applying numadelic aesthetics to model NDEs, to help address the anxiety often associated with death. [ABSTRACT FROM AUTHOR]

This paper addresses the possible effects of psychedelic drugs, notably psilocybin, on moral bio‐enhancement (MBE). It will be argued that non‐psychedelic substances, such as oxytocin, serotonin/serotonin reuptake inhibitors, or vasopressin, have indirect effects on M(B)E, whereas psilocybin has direct effects. Additionally, morality and happiness have been shown to operate in a circularly supportive relationship. It will be argued that psilocybin also has more direct effects on the augmentation of human happiness than non‐psychedelic substances. Hence, psilocybin multiplies its effects on morality and on moral enhancement (as well as on happiness) if compared with non‐psychedelic substances. Still, caution is advised if psilocybin is being used, and the correct dosage should be prescribed by an appropriate physician. Furthermore, the use of psilocybin has additional effects on moral enhancement and happiness if combined with meditation, preferably under the guidance of an experienced meditation specialist. [ABSTRACT FROM AUTHOR]

Objective: This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Methods: The Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to structure and report the findings for this review. A literature search included the MEDLINE database up until December 2022. We included randomized or open-label human studies of MDMA, psilocybin, mescaline, LSD, DMT, or cannabis reporting non-emotionally charged neurocognitive outcomes ("cold cognition") measured through validated neuropsychological tests. Results: A total of 43 full-text papers on MDMA (15), cannabis (12), LSD (6), psilocybin (9), DMT/ayahuasca (1), and mescaline (0) were included, mostly on healthy subjects. A single article on MDMA's effects on cognition in subjects with PTSD was included; there were no studies on psychedelics and neurocognition in MDD. Most of the studies on healthy subjects reported detrimental or neutral effects on cognition during the peak effect of psychedelics with a few exceptions (e.g., MDMA improved psychomotor function). Performance on the type of neurocognitive dimension (e.g., attention, memory, executive function, psychomotor) varies by type of psychedelic, dosage, and cognitive testing. Conclusions: Small samples and a lack of uniformed methods across studies preclude unequivocal conclusions on whether psychedelics enhance, decrease, or have no significant effect on cognitive performance. It is foreseen that psychedelics will soon become an available treatment for various psychiatric disorders. The acute and long-term effects on cognition caused by psychedelics should be assessed in future studies. [ABSTRACT FROM AUTHOR]

This research aims to conceptualize cognitive liberty and the psychedelic humanities by examining their constitutive elements. The importance of this study lies in the fact that it is widespread to talk about psychedelic science nowadays, but there is a significant gap in the research. For instance, the role and importance of the humanities need to be acknowledged. Regarding cognitive liberty, this research considers that people have the right to use or refrain from using emerging neurotechnologies and psychedelics. People’s freedom of choice vis-à-vis these technologies must be protected, in particular with regard to coercive and non-consensual uses. Firstly, an analysis will be carried out of the constitutive elements of cognitive liberty, especially within the context of a philosophical approach. Secondly, this research will address some arguments for the philosophical uses of psychedelics. Finally, this paper will discuss the scope and significance of psychedelic humanities as a vein of research. Cognitive liberty is a crucial concept for the psychedelic humanities, likely to broaden our understanding of consciousness studies and reflect on ethical and social issues related to scientific research. Cognitive liberty is an update of freedom of thought according to the challenges of the 21st century. In addition, this paper will highlight the possible philosophical uses of psychedelic substances to broaden the research scope since, at present, the ritual and therapeutic uses of psychedelics have the most significant legitimacy. Recognition of philosophical uses demonstrates that learning from non-clinical uses of psychedelics is possible. The psychedelic humanities represent an underexplored avenue of research that can contribute to a better understanding of the interplay between science and culture. [ABSTRACT FROM AUTHOR]

Recent research has demonstrated the potential of psychedelic therapy for mental health care. However, the psychological experience underlying its therapeutic effects remains poorly understood. This paper proposes a framework that suggests psychedelics act as destabilizers, both psychologically and neurophysiologically. Drawing on the 'entropic brain' hypothesis and the 'RElaxed Beliefs Under pSychedelics' model, this paper focuses on the richness of psychological experience. Through a complex systems theory perspective, we suggest that psychedelics destabilize fixed points or attractors, breaking reinforced patterns of thinking and behaving. Our approach explains how psychedelic-induced increases in brain entropy destabilize neurophysiological set points and lead to new conceptualizations of psychedelic psychotherapy. These insights have important implications for risk mitigation and treatment optimization in psychedelic medicine, both during the peak psychedelic experience and during the subacute period of potential recovery. [ABSTRACT FROM AUTHOR]

In this article, the author attempts to pull together information and opinion relevant to an assessment of the religious significance of psychedelic drugs. The author states that the evidence indicates that these substances are not dangerous if responsibly used, and that they are non-habit-forming. Most researchers agree that a physiological tolerance is built up with regular use. The author discusses some of the results of his brief study on sixteen students who had taken LSD in their college campus. There were a number references to self-objectification, and to gains in insight about oneself. There was great variation in the degree of love experienced; some felt closer to other persons, others felt more separated and isolated. Certain types of inner events are experienced as fearful and hallucinatory by some subjects, and ecstatic, religious and highly beneficial by others. The relation between preparation for the drug session and the nature of the experience is problematical. One clear result of research so far is that set and setting are of considerable importance in determining what happens.

Introduction and purpose: Nowadays, when mental disorders are considered by the World Health Organisation as a global burden, the potential usage of psychedelic drugs as supportive therapy is gaining more attention worldwide. The aim of this paper is to summarize the usefulness of psilocybin - representative of psychedelics - in psychiatric venues. In this review we describe its properties, efficacy and adverse events in treating depression, trauma and obsessivecompulsive disorders. Brief description of the state of knowledge: Psilocybin demonstrates a safety profile which does not differ from standard drugs used in therapies of psychiatric disorders. Positive results of its administration were noticed on different psychiatric scales and are considered as clinically meaningful. With depression being the most common mental disease and growing demand for new remedies, most of the conducted research is concentrated on this subject, but there is also some evidence of its purpose in the treatment of trauma and obsessive-compulsive disorders. Conclusions: Psilocybin merits further research as foregoing results of conducted studies are pointing to its efficacy. Psychedelic-assisted therapies may create noteworthy opportunities to current matter in the standard treatment of psychiatric disorders and there is a possibility that in the future in some cases they will be considered as the first line treatment. Nevertheless, still more data is needed to determine its placement in the treatments. [ABSTRACT FROM AUTHOR]

The ego is one of the most central psychological constructs in psychedelic research and a key factor in psychotherapy, including psychedelic-assisted forms of psychotherapy. Despite its centrality, the ego-construct remains ambiguous in the psychedelic literature. Therefore, we here review the theoretical background of the ego-construct with focus on its psychodynamic conceptualization. We discuss major functions of the ego including ego boundaries, defenses, and synthesis, and evaluate the role of the ego in psychedelic drug action. According to the psycholytic paradigm, psychedelics are capable of inducing regressed states of the ego that are less protected by the ego's usual defensive apparatus. In such states, core early life conflicts may emerge that have led to maladaptive ego patterns. We use the psychodynamic term character in this paper as a potential site of change and rearrangement; character being the chronic and habitual patterns the ego utilizes to adapt to the everyday challenges of life, including a preferred set of defenses. We argue that in order for psychedelic-assisted therapy to successfully induce lasting changes to the ego's habitual patterns, it must psycholytically permeate the characterological core of the habits. The primary working principle of psycholytic therapy therefore is not the state of transient ego regression alone, but rather the regressively favored emotional integration of those early life events that have shaped the foundation, development, and/or rigidification of a person's character - including his or her defense apparatus. Aiming for increased flexibility of habitual ego patterns, the psycholytic approach is generally compatible with other forms of psychedelic-assisted therapy, such as third wave cognitive behavioral approaches. [ABSTRACT FROM AUTHOR]

This paper aims to present conceptual metaphors employed to discuss psychedelics in texts published online by organizations popularizing knowledge about psychedelic substances. The foundation of this investigation comprises Cognitive Grammar, Conceptual Metaphor Theory, and Corpus Linguistics. A corpus of 160 texts on medical research, mental health, and therapy published in 2020 is built to enable quantitative and qualitative analysis. The investigation reveals the existence of the conceptual metaphors: psychedelic experience is a trip (a single experience that requires return and may involve adventurous, sacred, challenging aspects), psychedelic experience is a journey (a set of experiences (trips), integration process, and development, may involve healing), psychedelic substance is a tool / bridge / vehicle / agent providing access. The study of collocates of the word "psychedelic" also suggests the conceptualization of the psychedelic substances and/or experience as medicine in the analyzed corpus. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had a devastating impact on the health and wellbeing of the global population. This paper presents the results of a longitudinal transcultural study that was begun at the peak of the pandemic (in April, 2020). An online survey was used to collect data from English-, Spanish-, and Portuguese-speaking participants. The survey collected information about sociodemographics, lifestyle activities, COVID-19-related circumstances, and drug use (with an emphasis on hallucinogenic drugs), as well as involving psychometric questionnaires. Users of hallucinogenic drugs had higher psychological well-being and lower scores on psychopathology scales, both at baseline and during follow-ups. This difference was larger when users were distinguished by frequency of use, as regular users scored higher on psychological well-being and lower on psychopathology scales. Subjects with more psychological distress had lower scores for all scales of post-traumatic growth, but if they were regular hallucinogens users, they had higher scores for post-traumatic growth. When comparing the results between cultural contexts, heterogeneous results were obtained. There were more English-speaking regular users of hallucinogenic drugs. Further research should analyse the potential role of hallucinogens in large-scale catastrophes, with a special focus on post-traumatic growth. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Bioethics / Revue canadienne de bioéthique is the property of Ecole de Sante Publique de l'Universite de Montreal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Contemporary research on serotonergic psychedelic compounds has been rife with references to so-called 'mystical' subjective effects. Several psychometric assessments have been used to assess such effects, and clinical studies have found quantitative associations between 'mystical experiences' and positive mental health outcomes. The nascent study of psychedelic-induced mystical experiences, however, has only minimally intersected with relevant contemporary scholarship from disciplines within the social sciences and humanities, such as religious studies and anthropology. Viewed from the perspective of these disciplines--which feature rich historical and cultural literatures on mysticism, religion, and related topics--'mysticism' as used in psychedelic research is fraught with limitations and intrinsic biases that are seldom acknowledged. Most notably, existing operationalizations of mystical experiences in psychedelic science fail to historicize the concept and therefore fail to acknowledge its perennialist and specifically Christian bias. Here, we trace the historical genesis of the mystical in psychedelic research in order to illuminate such biases, and also offer suggestions toward more nuanced and culturally-sensitive operationalizations of this phenomenon. In addition, we argue for the value of, and outline, complementary 'non-mystical' approaches to understanding putative mystical-type phenomena that may help facilitate empirical investigation and create linkages to existing neuro-psychological constructs. It is our hope that the present paper helps build interdisciplinary bridges that motivate fruitful paths toward stronger theoretical and empirical approaches in the study of psychedelic-induced mystical experiences. [ABSTRACT FROM AUTHOR]

Copyright of Estudios Atacameños is the property of Estudios Atacamenos and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This publication reports analytical properties of a new hallucinogenic substance identified in blotter papers seized from the drug market, namely 25C-NBOMe [2-(4-chloro-2,5-dimethoxyphenyl)-N-(2- methoxybenzyl)ethanamine]. The identification was based on results of comprehensive study including several analytical methods, i.e., GC-EI-MS (without derivatization and after derivatization with TFAA), LC-ESI-QTOF-MS, FTIR and NMR. The GC-MS spectrum of 25C-NBOMe was similar to those obtained for other representatives of the 25-NBOMe series, with dominant ions observed at m/z = 150, 121 and 91. Fragment ions analogic to those in 2C-C (4-chloro-2,5-dimethoxy-β-phenylethanamine) were also observed, but their intensities were low. Derivatization allowed the determination of molecular mass of the investigated substance. The exact molecular mass and chemical formula were confirmed by LC-QTOF-MS experiments and fragmentation pattern under electrospray ionization was determined. The MS/MS experiments confirmed that the investigated substance was N-(2-methoxy)benzyl derivative of 2C-C. The substance was also characterized by FTIR spectroscopy to corroborate its identity. Final elucidation of the structure was performed by NMR spectroscopy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Participants in MDMA- and psychedelic-assisted psychotherapy often emerge from these treatments with new beliefs about themselves and the world. Studies have linked changed beliefs with mystical experiences reported by some participants during drug sessions. While there has been some debate about the epistemic value of drug-induced mystical experiences, and about the need for consent to treatments that may alter metaphysical beliefs, less attention has been given to the sense of authenticity that attends these experiences. In this paper, I consider the intersubjective context in which these changed beliefs arise. I suggest that the sense of authenticity people experience with MDMA- and psychedelic-assisted psychotherapy derives from a simultaneous feeling of knowing and being known. The medications used in these treatments reduce the defensive barriers which ordinarily prevent powerful feelings from being intersubjectively shared, allowing the subject to experience knowing and being known with the therapist and/or internalized or imagined others. In explaining this thesis, I discuss Ratcliffe's "existential feeling;" ipseity in incipient psychosis and psychedelic states; Winnicott's notions of the True Self, omnipotence, creativity, and transitional phenomena; implicit relational knowing and moments of meeting; infant-mother dyad research; predictive processing and the relaxed beliefs model of psychedelic action; the role of the "partner in thought" in knowing and feeling known. I propose that a "transitional space" model of MDMA- and psychedelic- assisted psychotherapy is well-suited for working through "not-me" or dissociated experience [ABSTRACT FROM AUTHOR]

The word "psychedelic" (psyche (i.e., the mind or soul) and delos (i.e., to show)) has Greek origin and was first coined by psychiatrist Humphry Osmond in 1956, who had been conducting research on lysergic acid diethylamide (LSD) at the time. Psychedelic drugs such as N,N-DMT/DMT (N,N-dimethyltryptamine), 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), LSD (lysergic acid diethylamide), MDMA (3,4-methylenedioxymethamphetamine) and psilocybin have had significant value as an entheogen in spiritual, religious (shamanic) and sociocultural rituals in Central and South American cultures for thousands of years. In the 1960s, the globalization of these drugs and their subsequent spread outside of their indigenous, old-world cultures, led to the subsequent implementation of strict drug control laws in many Western countries. Even today, psychedelics are still classified as Schedule I drugs, resulting in a still lingering negative stigmatization/perception, vilification, and ultimate criminalization of psychedelics. This controversy still lingers and still limits scientific research and full medical acceptance. For many years up until recently, the spiritual, religious and medicinal value of these drugs could not be explored in a scientific context. More recently, a second wave of psychedelic research is now focusing on psychedelics as neuropharmaceuticals to treat alcohol and tobacco addiction, general mood and anxiety disorders and cancer-related depression. There is now a vast array of promising evidence-based data to confirm the years of anecdotal evidence of the medicinal values of psychedelics. Natural therapeutic alternatives such as psychedelic drugs may provide a safe and efficacious alternate to conventional drugs used to treat mood and anxiety disorders. In a Western context in particular, psychedelic drugs as therapeutic agents for mood and anxiety disorders are becoming increasingly of interest amidst increasing rates of such disorders globally, changing social constructions, the implementation of government regulations and increasing investment opportunities, that ultimately allow for the scientific study to generate evidenced-based data. Alternative psychotherapeutic interventions are gaining interest also, because of their low physiological toxicity, relatively low abuse potential, safe psychological effects, and no associated persisting adverse physiological or psychological effects during and after use. On the other hand, conventional psychotic drugs and anti-depressants are becoming less favorable because of their adverse side effects. Psychedelic neuropharmaceutical interventions may with medical oversight be the solution to conventional psychiatric disorders such as depression and anxiety, and an alternative to conventional psychiatric treatment options. This paper will review the therapeutic potential of psychedelic drugs as alternative therapeutic options for mood and anxiety disorders in a controlled, clinical setting, where the chances of adverse psychological episodes occurring are mitigated. [ABSTRACT FROM AUTHOR]

Religious experiences and their truth, nature, and influence remain controversial. This is despite their wide cultural expression and significant grounding in research. Personal experiences that are deemed "religious" are often critiqued for being culturally influenced and psychologically misleading, implying that this ought to discredit them. This paper seeks not to argue for the truth or falsity of these kinds of experiences, but rather to offer an autoethnographic response to how these experiences have functioned in this researcher's life. The response is contextualized broadly within the study of religious experience and contributes towards that field. Three forms of religious and spiritual experiences are offered narratively, from my early Charismatic experience, to synchronous encounters, as well as the exploration of psilocybin. It is suggested that these experiences are broadly shared, and that they can be personally as well as socially transformative. Although they are autoethnographic in nature, all three forms are situated within the context from which they emerged. [ABSTRACT FROM AUTHOR]

Psychedelics are experiencing a renaissance in clinical research. In recent years, an increasing number of studies on psychedelic-assisted treatment have been conducted. So far, the results are promising, suggesting that this new (or rather, rediscovered) form of therapy has great potential. One particular reason for that appears to be the synergistic combination of the pharmacological and psychotherapeutic interventions in psychedelic-assisted treatment. But how exactly do these two interventions complement each other? This paper provides the first account of the interaction between pharmacological and psychological effects in psychedelic-assisted treatment. Building on the relaxed beliefs under psychedelics (REBUS) hypothesis of Carhart-Harris and Friston and the contextual model of Wampold, it argues that psychedelics amplify the common factors and thereby the remedial effects of psychotherapy. More precisely, psychedelics are assumed to attenuate the precision of high-level predictions, making them more revisable by bottom-up input. Psychotherapy constitutes an important source of such input. At best, it signalizes a safe and supportive environment (cf. setting) and induces remedial expectations (cf. set). During treatment, these signals should become incorporated when high-level predictions are revised: a process that is hypothesized to occur as a matter of course in psychotherapy but to get reinforced and accelerated under psychedelics. Ultimately, these revisions should lead to a relief of symptoms. [ABSTRACT FROM AUTHOR]

Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. They also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. In this study (NCT03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). By the end of the dosing day, participants reported the intensity of their acute experience using the 30-item Mystical Experience Questionnaire (MEQ) and an open-form qualitative report from home. Persisting psychological effects attributed to the psilocybin experience were measured using the Persisting Effects Questionnaire (PEQ) 3-months after administration. Using a linear latent-variable model we show that the MEQ total score is positively associated with the later emergence of positive PEQ effects (p = 3 × 10−5). Moreover, the MEQ subscales "Positive Mood" (p corr = 4.1 × 10−4) and "Mysticality" (p corr = 2.0 × 10−4) are associated with positive PEQ whereas the subscales "Transcendence of Time and Space" (p corr = 0.38) and "Ineffability" (p corr = 0.45) are not. Using natural language pre-processing, we provide the first qualitative descriptions of the "Complete Mystical Experience" induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the Universe, familial love, and the experience of profound beauty. Combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects. [ABSTRACT FROM AUTHOR]

Background: We are confronted with dire statistics that document our current mental health crisis. New treatment modalities are desperately needed to address escalating mental suffering and trauma. Psychedelic medicines are attracting increased attention in psychiatry as effective treatment for a range of conditions. The mechanisms of actions and context necessary to maximize their full healing potential represent a radical departure from current psychiatric frameworks and present an opportunity to reimagine psychiatry as a healing art. Objective: Psychedelic psychotherapy leverages biological, psychological, and spiritual domains to harness innate healing potentials. A novel psychotherapeutic methodology utilizing psychedelic medicines as catalyzing agents is presented, one that provides a developmental model to promotes self-actualization. The paper outlines transformational psychotherapy, the therapeutic process and corresponding practice implications. Conclusion: Psychedelic psychotherapy represents a paradigm shift in healing, one that promotes self-integration and whole health. These shifts in internal health are correspondingly reflected in enhanced empathy, improved relatedness, and increased capacity for social connection. Much of human suffering and disregard for the planet is a reflection of our own collective inner impoverishment, fundamental disconnects, and unaddressed trauma. Psychedelic psychotherapy offers a healing approach to restore beauty and health to both the inner and outer worlds we inhabit. [ABSTRACT FROM AUTHOR]

Background: Chronic Pain is among the leading causes of disability worldwide with up to 60% of patients suffering from comorbid depression. Psychedelic-assisted therapy has recently been found effective in treating a host of mental health issues including depression and has historically been found to be useful in treating pain. Reports of self-medication for chronic pain using psychedelic drugs have been widely documented, with anecdotal evidence indicating widespread success in a range of pathologies. Aims: In preparation for an upcoming trial, to better understand how those with lived experience of chronic pain self-medicate with psychedelic drugs, and to establish, in detail, their therapeutic protocols and practices for success. Methods: As part of patient-involvement (PI) for an upcoming trial in this population, 11 individuals who reported self-medicating with psychedelic drugs took part in a 1-h semi-structured discussion, which was then transcribed and thematically analyzed. Results: Across a range of psychedelic substances and doses, reported pain scores improved substantially during and after psychedelic experiences. Two processes, Positive Reframing and Somatic Presence, were reliably identified as playing a role in improvements in mental wellbeing, relationship with pain, and physical (dis)comfort. Inclusion of other strategies such as mindfulness, breathwork, and movement were also widely reported. Due to the data's subjective nature, this paper is vulnerable to bias and makes no claims on causality or generalisability. Together, these results have been used to inform study design for a forthcoming trial. Conclusion: This pre-trial PI work gives us confidence to test psychedelic therapy for chronic pain in a forthcoming controlled trial. The results presented here will be instrumental in improving our ability to meet the needs of future study participants. [ABSTRACT FROM AUTHOR]

Within the context of scientific research, patient and public involvement (PPI) is defined as research performed "with" or "by" patients and members of the public, rather than "to," "about", or "for" them. When carried out systematically and thoughtfully, PPI has the potential to strengthen the quality and impact of research by fostering accountability, transparency, and relevance. There exist numerous guidelines, frameworks and tools for supporting PPI, however, these do not account for the unique challenges faced in psychedelic research. This paper describes the co-design of guidance intended to help build, evaluate and improve PPI in psychedelic research. A steering group was formed to design and run a co-design workshop alongside public collaborators. Insights from this workshop were analyzed and refined into a comprehensive and readily usable guide for planning PPI specific to the field of psychedelic research. Core values emerging from the process focused on the essential importance of trust, learning, purpose and inclusivity. It is hoped that this guidance will be a starting point for incorporating PPI in future psychedelic research, so that it can grow and adapt as this burgeoning field of research progresses. [ABSTRACT FROM AUTHOR]

Archival collections hold tangible documentation of the range of human experience. Diaries, letters, photographs, audio recordings, reports, and other paper and film-based materials tell the stories of people's lives. Using examples from the vast parapsychology archives and rare book collections at the University of West Georgia, this paper will share people's first-hand accounts of extraordinary incidents or of their supernatural abilities, from the profound to the disappointing, and from the unexpected to the purposefully sought, including near-death experiences, extrasensory perception, and psychedelic drug use. [ABSTRACT FROM AUTHOR]

Background: Mandrake (Mandragora spp.) is one of the most famous medicinal plant in western cultures since Biblical times and throughout written history. In many cultures, mandrake is related to magic and witchcraft, which is said to have a psychosomatic effect (especially when mandrake contains narcotic compounds) in addition to the pharmacological influence, as occurs with other narcotic magical plants. Due to its unique properties and related myths, it is not surprising that this plant has many names in many languages. Methods: This paper presents an attempt to reconstruct the historical, ethnobotanical, and folkloristic roots of 292 vernacular names of Mandragora spp. in forty-one languages. We used the plant's morphological data, philology, myths and legends, medicinal properties and uses, as well as historical evidence and folkloric data, to explain meaning, origin, migration, and history of the plant's names. Results: The names were classified into the following main categories: Derivatives of mandragora (19 languages), alraun (7) and of yabroukh (5). The salient groups of the plant's vernacular names are related to: Anthropomorphism (33 names in 13 languages); Similarity to other plants (28/9); Supernatural agents (28/9); Narcotic effects (21/8); Leaves, fruits, and seeds (21/8); Aphrodisiac properties (17/10); Use of a dog (15/9); Gallows (14/5); Black magic, sorcery, witchcraft (13/8), and Medicinal use (11/7). Conclusions: This frequency distribution of the mandrake's vernacular names reflects its widespread reputation as related to the doctrine of signatures, beliefs in its supernatural, natural, and mythic powers, and to a lesser extent, its uses in magic and medicine. A spatiotemporal analysis of the mandrake's names supports the old idea that the pulling ceremonies for this plant originated in the Near East and that various other myths related to this plant may have originated in different places and periods. [ABSTRACT FROM AUTHOR]

In our recent paper on adolescent cannabis use and risk of psychosis we found out that heavy cannabis use was associated with increased risk of any psychotic disorder or condition during 15 years of follow-up. We reported in the paper also that when the psychosis diagnoses were analysed separately, both schizophrenia spectrum disorder (HR = 11.18, 95% CI 3.16-39.62) and psychotic depression (HR = 9.74, 95% CI 3.83-24.73) are associated with cannabis use, whereas similar associations were not found for schizophrenia, bipolar disorder with psychotic episodes and other psychosis. Whether substance use contributes to an increased risk across different psychosis categories differentially is a matter requiring replication, and we think that in future it would be worthwhile studying affective psychoses under their own category if sample size permits. [Extracted from the article]

There is considerable evidence from the literature that psychedelics, such as N,N -dimethyltryptamine (DMT), are safe and effective treatments for depression. However, clinical administration to induce psychedelic effects and expensive psychotherapy-assisted treatments likely limit accessibility to the average patient. There is emerging evidence that DMT promotes positive behavioral changes in vivo at sub-hallucinogenic dosages, and depending on the target indication, subjecting patients to high, bolus dosages may not be necessary. Due to rapid metabolic degradation, achieving target levels of DMT in subjects is difficult, requiring IV administration, which poses risks to patients during the intense hallucinogenic and subjective drug effects. The chemical and physical properties of DMT make it an excellent candidate for non-invasive, transdermal delivery platforms. This paper outlines the formulation development, in vitro , and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioral and pharmacokinetic studies were performed with lead patch formulation (F5) in male and female Swiss Webster mice, and resulting DMT levels in plasma and brain samples were quantified using LC/MS/MS. Notable differences were seen in female versus male mice during IV administration; however, transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose. The IV half-life of DMT was extended by 20-fold with administration of the transdermal delivery system at sub-hallucinogenic plasma concentrations not exceeding 60 ng/mL. Results of a translational head twitch assay (a surrogate for hallucinogenic effects in non-human organisms) were consistent with absence of hallucinations at low plasma levels achieved with our TDDS. Despite the reported low bioavailability of DMT, the non-invasive transdermal DMT patch F5 afforded an impressive 77 % bioavailability compared to IV at two dosages. This unique transdermal delivery option has the potential to provide an out-patient treatment option for ailments not requiring higher, bolus doses and is especially intriguing for therapeutic indications requiring non-hallucinogenic alternatives. [Display omitted] [ABSTRACT FROM AUTHOR]

Meditation, psychedelics, and other similar practices or induction methods that can modulate conscious experience, are becoming increasingly popular in clinical and non-clinical settings. The phenomenology associated with such practices or modalities is vast. Many similar effects and experiences are also reported to occur spontaneously. We argue that this experiential range is still not fully described or understood in the contemporary literature, and that there is an ethical mandate to research it more extensively, starting with comprehensive documentation and definition. We review 50 recent clinical or scientific publications to assess the range of phenomena, experiences, effects, after-effects, and impacts associated with a broad variety of psychoactive compounds, meditative practices, and other modalities or events. This results in a large inventory synthesizing the reports of over 30,000 individual subjects. We then critically discuss various terms and concepts that have been used in recent literature to designate all or parts of the range this inventory covers. We make the case that specialized terminologies are needed to ground the nascent research field that is forming around this experiential domain. As a step in this direction, we propose the notion of “emergence” and some of its derivatives, such as “emergent phenomenology,” as possibly foundational candidates. [ABSTRACT FROM AUTHOR]

It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short‐term stressor or drug‐induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic‐like experiences over time. Theoretical and practical implications of this model are discussed. [ABSTRACT FROM AUTHOR]

The human need to find meaning in life and the human need for connection may be two sides of the same coin, a coin forged in the developmental crucible of attachment. Our need for meaningfulness can be traced to our developmental need for connection in the attachment relationship. The free energy principle dictates that in order to resist a natural tendency towards disorder self-organizing systems must generate models that predict the hidden causes of phenomenal experience. In other words, they must make sense of things. In both an evolutionary and ontogenetic sense, the narrative self develops as a model that makes sense of experience. However, the self-model skews the interpretation of experience towards that which is predictable, or already "known." One may say it causes us to "take things personally." Meaning is felt more acutely when defenses are compromised, when the narrative self is offline. This enables meaning-making that is less egocentrically motivated. Dreams, psychosis, and psychedelic states offer glimpses of how we make sense of things absent a coherent narrative self. This has implications for the way we understand such states, and lays bare the powerful reach of attachment in shaping what we experience as meaningful. [ABSTRACT FROM AUTHOR]

Background: Impairments in social cognition are known to be a key factor in several psychiatric and neurodevelopmental disorders. Interest in psychedelic drugs has increased in recent years, with significant research identifying psychedelic and hallucinogenic drugs as modulators of social cognition. However, more research is necessary before psychedelics are implemented in clinical settings as treatments for social cognition defects. Therefore, this study describes a scoping review protocol which will be used to analyze the body of literature on psychedelic drugs as modulators of social cognition in patients with psychiatric and neurodevelopmental disorders. Methods: This scoping review protocol was developed using the JBI Scoping Review Methodology Group's description of how to conduct a scoping review. The guidelines identified by this group as well as a search strategy developed with the assistance of a research librarian will be applied to a search of several peer-reviewed journals, including MEDLINE (Ovid), PsycINFO, EMBASE (Elsevier), and Scopus (Elsevier). Each study extracted will be screened in a two-step screening process, including a title and abstract screen, and a full-text screen. One independent individual will complete both steps of the screening, and a second independent individual will review the completed screening. Discussion: An understanding of the current literature on psychedelic drugs as modulators of social cognition will provide insight into what is presently known on the subject, and any gaps in the literature that can be addressed in future studies. The knowledge gained from this scoping review could lead to a new treatment for social cognition defects in clinical populations. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Post-traumatic stress disorder is a psychiatric condition following an extreme event that causes a near death of an involved individual. Since conventional treatments using selective serotonin reuptake inhibitors do not consistently yield therapeutic success, alternative substances are being explored as potential solutions. This study aims to compile information regarding the outcomes of utilizing psychedelics in individuals diagnosed with PTSD. Brief description of the state of knowledge: In July 2023, after a number of clinical trials and 20-year-long efforts to overturn the impact of a prohibition, Australia became the first country to allow doctors, in clinical development and under strict control, to use the 3,4-methyl enedioxy methamphetamine (MDMA) commonly known as ecstasy, as well as psylocybin in patients with post-traumatic stress disorder or depression [1]. There is a noticeable annual growth of inquiries on PubMed involving the keywords "psychedelics" and "therapeutic", amounting to 92 in 2000 and topped by 738 searches in 2023, whereas the total number of results consists of 8415 positions. Therapeutic effects of psychedelics are becoming more recognized over time. Summary: Post-Traumatic Stress Disorder (PTSD) is a complex condition that affects both the psychological and somatic aspects of the body. Thus, a multidimensional intervention is indicated. The use of psychedelics might contribute to improvements not only in the severity of PTSD but also in depression or pain. Further research on a larger group of participants should be carried out to assess the potential role of psychedelics in conventional medicine in the future, alongside psychotherapy. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions. [ABSTRACT FROM AUTHOR]

Modern clinical research on psychedelics is generating interesting outcomes in a wide array of clinical conditions when psychedelic-assisted psychotherapy is delivered to appropriately screened participants and in controlled settings. Still, a number of patients relapse or are less responsive to such treatments. Individual and contextual factors (i.e., set and setting) seem to play a role in shaping the psychedelic experience and in determining clinical outcomes. These findings, coupled with data from literature on the effectiveness of psychotherapy, frame the therapeutic context as a potential moderator of clinical efficacy, highlighting the need to investigate how to functionally employ environmental and relational factors. In this review, we performed a structured search through two databases (i.e., PubMed/Medline and Scopus) to identify records of clinical studies on psychedelics which used and described a structured associated psychotherapeutic intervention. The aim is to construct a picture of what models of psychedelic-assisted psychotherapy are currently adopted in clinical research and to report on their clinical outcomes. Ad-hoc and adapted therapeutic methods were identified. Common principles, points of divergence and future directions are highlighted and discussed with special attention toward therapeutic stance, degree of directiveness and the potential suggestive effects of information provided to patients. [ABSTRACT FROM AUTHOR]

Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD. [ABSTRACT FROM AUTHOR]

Introduction: It is a basic principle of the "psychedelic" treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value. Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ ISRCTN14426797 [ABSTRACT FROM AUTHOR]

This article provides an overview of the psychological and neural mechanisms of psychedelic compounds and their potential use in treating mental health and medical conditions. It discusses the therapeutic effects of psychedelics on various mental health conditions, including depression, anxiety disorders, autism, PTSD, and substance use disorders. The article explores the cellular, molecular, network, and circuit-level mechanisms through which psychedelics work, as well as the psychological and behavioral effects they produce. It also highlights the role of mystical experiences, reactivations, ayahuasca-induced personal death experiences, and environmental factors in psychedelic therapy. The article concludes by emphasizing the importance of interdisciplinary research and responsible use of psychedelics in psychiatry and mental health. The document includes references to studies and clinical trials that investigate the use of psychedelics in the treatment of mental health conditions, such as depression, anxiety, and alcohol dependence. These studies suggest that substances like ayahuasca, psilocybin, and MDMA may have positive effects on symptoms and outcomes for individuals with these conditions. However, further research is needed to fully understand the efficacy and safety of these treatments. [Extracted from the article]

Introduction: A growing body of literature is investigating the difficulties that some individuals encounter after psychedelic experiences. Existing research has explored the nature and predictors of these difficulties; however, a research gap exists in understanding how individuals endeavour to cope with such difficulties. Methods: The current study collected data from an international cohort of 608 participants who reported experiencing difficulties that persisted for at least one day after a psychedelic experience. They provided written data on how they used coping strategies to alleviate these difficulties. The qualitative analysis of the written data on coping was conducted using Structured Tabular Thematic Analysis. Results: A wide range of individual and social coping strategies were employed that were found helpful. The most common individual strategies were meditation and prayer, followed by self-educational activities such as reading and journaling. The most prevalent forms of social coping involved seeking support from friends or family members, followed by obtaining assistance from a therapist or coach. Features of social coping that were reported to be helpful included feeling heard/accepted, a non-judgemental attitude and sharing similar experiences. Discussion: Our findings hold potential for informing the design of therapeutic interventions and educational resources aimed at enhancing positive outcomes for those experiencing extended difficulties after psychedelic use. [ABSTRACT FROM AUTHOR]

Introduction and aim: It is important to understand how mental health practitioners view recent findings on psychedelic-assisted psychotherapy (PAP) as there is potential this treatment may be incorporated into clinical practice. The aim of our study was to explore how psychiatrists who are not involved in psychedelic research and who are located in the European region perceive psychedelics and PAP. Methods: We conducted online semi-structured interviews with 12 psychiatry specialists and psychiatry trainees from8 European countries. Data were analyzed using a general inductive approach informed by codebook thematic analysis. Results: Based on the interviews, we developed four main themes and 14 subthemes, including (1) Psychedelics hold potential, (2) Psychedelics are dangerous, (3) Future of psychedelics is uncertain, and (4) Psychiatry is ambivalent toward psychedelics. Discussion: Our respondents-psychiatrists acknowledged the potential of PAP but remained cautious and did not yet perceive its evidence base as robust enough. Education on psychedelics is lacking in medical and psychiatric training and should be improved to facilitate the involvement of mental health experts in decision-making on PAP. [ABSTRACT FROM AUTHOR]

Because psychedelics have been found to increase psychological traits like openness, mental flexibility, and interpersonal perceptiveness, some researchers believe that psychedelics could help individuals cope with the psychological effects of discrimination. However, it is still unclear whether psychedelic use can help manage the internalized stigma that deters formal mental health treatment. This study investigates the impact of six measures of psychedelic use (MDMA, psilocybin, DMT, ayahuasca, peyote/mescaline, and LSD) on psychological distress (Kessler Psychological Distress Scale) and internalized stigma. The study used data from the National Survey of Drug Use and Health (NSDUH) from 2008 to 2019, with a sample size of 458,372 participants. Ordinary least square regression models were conducted using Stata 18. Gender analysis found that among men, ayahuasca use was linked to reduced stigma perception associated with higher distress. For women, DMT use was linked to reduced stigma perceptions when experiencing higher distress. However, results find that individuals who have used MDMA and psilocybin reported heightened perceptions of stigma associated with increased psychological distress. Among women, MDMA and psilocybin use was associated with a higher perception of stigma when they experienced distress. These findings suggest that, overall, psychedelics may not reduce the impact of distress on the perception of stigma, especially for women. [ABSTRACT FROM AUTHOR]

Rationale: Psychedelic research re-emerged from a period of suppression into the so-called psychedelic renaissance. In parallel, most media reporting has shifted from the overstatement of the risks of psychedelics to overly positive hype. As the empirical evidence is more equivocal than frequently portrayed, the conclusions about the effectiveness of psychedelics should be considered preliminary. Poor science communication about psychedelics' therapeutic potential may lead potential participants or patients to feel misled and policy decisions to be misinformed. An evidence-informed characterization of their risks and benefits is needed. Objectives: This article assesses the state of psychedelic research for treating depression and the effect sizes of psychedelics on therapeutic outcomes, the risk of bias, and the prevalence of adverse effects. We review research on the risks and benefits of psychedelics and discuss how the following depression treatments have shown decreasing effect sizes over time: (1) cognitive behavioral therapy, (2) mindfulness interventions, (3) selective serotonin reuptake inhibitors, and (4) ketamine. We speculate that a similar trend may occur for psychedelic treatments. Results and conclusions: It is likely that larger and better-controlled psychedelic trials will demonstrate smaller effect sizes that are more comparable to other conventional and emerging treatments for mood disorders. Clear science communication is critical for setting public expectations and psychedelic policy. With this evidence-based assessment, we aim to cut through the misinformation about the benefits, risks, and future prospects of psychedelic treatments. [ABSTRACT FROM AUTHOR]

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20–50 Hz) and mid (50–100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs. [ABSTRACT FROM AUTHOR]

Background: Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer's disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. Methods: 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aβ accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated. Results: chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aβ accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD. Conclusion: The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD. [ABSTRACT FROM AUTHOR]

The current psychedelic renaissance intersects with Christian practices in two key ways. First, as psychedelic-assisted therapy (PAT) becomes more common, Christians undergoing therapeutic medical treatment may seek outside support for integrating into their religious lives mystical experiences that occur during psychedelic sessions. Second, with increasing legal access to psychedelics, more Christians may explore their spiritual potential outside of a medical context, either individually with spiritual guides or collectively in organized retreats. Many will have mystical encounters related to the Divine. Whether the experience involves the overwhelming presence or absence of the Divine, these Christians, too, will seek integration support. This essay argues that the Bible can serve as a rich source for such integration, because it contains significant material about mystical experiences marked by altered states of consciousness. First, I summarize the importance of the psychedelic renaissance, especially the scientific studies being conducted, as it relates to Christian practices of spiritual formation. Second, I explore new work being conducted by biblical scholars regarding embodied religious experiences with the Divine (and others), including mystical experiences. Third, I consider the Apostle Paul's embodied mystical experience, with special attention to 2 Corinthians 12:1–10, as one example of biblical material that might intersect with or inform psychedelic mystical encounters that contemporary Christians might experience (whether in a medical therapeutic or non-medical spiritual formation setting). Finally, I indicate directions for further research and discussion. [ABSTRACT FROM AUTHOR]

The human brain is a complex system, whose activity exhibits flexible and continuous reorganization across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. Here, we investigate healthy participants taking the serotonergic psychedelic N,N -dimethyltryptamine (DMT) with the Harmonic Decomposition of Spacetime (HADES) framework that can characterize how different harmonic modes defined in space are expressed over time. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition (DMT and non-DMT), we detect a decrease specifically in the second functional harmonic, which represents the uni- to transmodal functional hierarchy of the brain, supporting the leading hypothesis that functional hierarchy is changed in psychedelics. Moreover, HADES' dynamic spacetime measures of fractional occupancy, life time and latent space provide a precise description of the significant changes of the spacetime hierarchical organization of brain activity in the psychedelic state. [ABSTRACT FROM AUTHOR]