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      Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects

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          Abstract

          Background

          There is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic “ayahuasca” for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspired by ayahuasca, which contain specific and standardized active components, are a potential remedy.

          Methods

          We investigated subjective acute and persisting effects of a novel formulation containing the reversible monoamine oxidase inhibitor harmine (orodispersible tablet containing 100 mg MAO-I) and N,N-dimethyltryptamine (incremental intranasal dosing of up to 100 mg DMT), compared with two other conditions, namely harmine alone and placebo, in a crossover RCT in 31 healthy male subjects.

          Results

          DMT + harmine, but not harmine alone, induced a psychedelic experience assessed with the 5D-ASC rating scale [global score: F(2,60) = 80.21, p < 0.001] and acute experience sampling items over time, characterized by psychological insights [PIQ, F(2,58.5) = 28.514, p < 0.001], emotional breakthroughs [EBI, F(2,60) = 26.509, p < 0.001], and low scores on the challenging experience questionnaire [CEQ, F(2,60) = 12.84, p < 0.001]. Participants attributed personal and spiritual significance to the experience (GSR) with mainly positive persisting effects (PEQ) at 1- and 4-months follow-up. Acute drug effects correlated positively with persisting effects. We found no changes in trait measures of personality, psychological flexibility, or general well-being, and no increases in psychopathology (SCL-90-R) were reported.

          Discussion and Conclusion

          Our results suggest that the experience induced by the standardized DMT + harmine formulation induces a phenomenologically rich psychedelic experience, demonstrates good psychological safety and tolerability, is well tolerated, and induces beneficial psychological processes that could possibly support psychotherapy. Further studies are required to investigate the psychotherapeutic potential in patients.

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          The weirdest people in the world?

          Behavioral scientists routinely publish broad claims about human psychology and behavior in the world's top journals based on samples drawn entirely from Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies. Researchers - often implicitly - assume that either there is little variation across human populations, or that these "standard subjects" are as representative of the species as any other population. Are these assumptions justified? Here, our review of the comparative database from across the behavioral sciences suggests both that there is substantial variability in experimental results across populations and that WEIRD subjects are particularly unusual compared with the rest of the species - frequent outliers. The domains reviewed include visual perception, fairness, cooperation, spatial reasoning, categorization and inferential induction, moral reasoning, reasoning styles, self-concepts and related motivations, and the heritability of IQ. The findings suggest that members of WEIRD societies, including young children, are among the least representative populations one could find for generalizing about humans. Many of these findings involve domains that are associated with fundamental aspects of psychology, motivation, and behavior - hence, there are no obvious a priori grounds for claiming that a particular behavioral phenomenon is universal based on sampling from a single subpopulation. Overall, these empirical patterns suggests that we need to be less cavalier in addressing questions of human nature on the basis of data drawn from this particularly thin, and rather unusual, slice of humanity. We close by proposing ways to structurally re-organize the behavioral sciences to best tackle these challenges.
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            The WHO-5 Well-Being Index: a systematic review of the literature.

            The 5-item World Health Organization Well-Being Index (WHO-5) is among the most widely used questionnaires assessing subjective psychological well-being. Since its first publication in 1998, the WHO-5 has been translated into more than 30 languages and has been used in research studies all over the world. We now provide a systematic review of the literature on the WHO-5.
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              Preliminary psychometric properties of the Acceptance and Action Questionnaire-II: a revised measure of psychological inflexibility and experiential avoidance.

              The present research describes the development and psychometric evaluation of a second version of the Acceptance and Action Questionnaire (AAQ-II), which assesses the construct referred to as, variously, acceptance, experiential avoidance, and psychological inflexibility. Results from 2,816 participants across six samples indicate the satisfactory structure, reliability, and validity of this measure. For example, the mean alpha coefficient is .84 (.78-.88), and the 3- and 12-month test-retest reliability is .81 and .79, respectively. Results indicate that AAQ-II scores concurrently, longitudinally, and incrementally predict a range of outcomes, from mental health to work absence rates, that are consistent with its underlying theory. The AAQ-II also demonstrates appropriate discriminant validity. The AAQ-II appears to measure the same concept as the AAQ-I (r=.97) but with better psychometric consistency. Copyright © 2011. Published by Elsevier Ltd.
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                Author and article information

                Contributors
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                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                08 January 2024
                2023
                : 14
                : 1302559
                Affiliations
                [1] 1Psychedelic Research and Therapy Development, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, University of Zurich , Zurich, Switzerland
                [2] 2Department of Psychology, University of Zurich , Zurich, Switzerland
                [3] 3Neuroscience Center Zurich, University of Zurich and ETH , Zurich, Switzerland
                [4] 4Department of Health Science and Technology, ETH , Zurich, Switzerland
                [5] 5Institute of Pharmacology and Toxicology, University of Zurich , Zurich, Switzerland
                [6] 6Department of Forensic Pharmacology and Toxicology, University of Zurich , Zurich, Switzerland
                [7] 7MoMiLab, IMT School for Advanced Studies Luca , Lucca, Italy
                [8] 8Department of Psychosomatic Medicine and Psychotherapy, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany
                [9] 9Biopsychology, Department of Psychology, TUD Dresden University of Technology , Dresden, Germany
                [10] 10Experimental Psychopathology and Psychotherapy, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, University of Zurich , Zurich, Switzerland
                Author notes

                Edited by: Yasmin Schmid, University Hospital of Basel, Switzerland

                Reviewed by: Friederike Holze, University Hospital of Basel, Switzerland; Martin Madsen, Neurobiology Research Unit, Rigshospitalet, Denmark

                *Correspondence: Helena D. Aicher, helena.aicher@ 123456uzh.ch

                These authors have contributed equally to this work and share first authorship

                ‡ORCID: Helena D. Aicher, https://orcid.org/0000-0001-5915-7086

                Article
                10.3389/fpsyt.2023.1302559
                10804806
                38264636
                d7ee4af2-c3ed-4075-b964-69d0f6d2b490
                Copyright © 2024 Aicher, Mueller, Dornbierer, Suay, Elsner, Wicki, Meling, Caflisch, Hempe, Steinhart, Mueller, Von Rotz, Kleim and Scheidegger.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 September 2023
                : 15 December 2023
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 93, Pages: 16, Words: 12138
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We gratefully acknowledge grant funding that supported this publication from the SNSF Swiss National Science Foundation (HA, Doc.CH Grant P0ZHP1_191935; MS, and DM, Spark CRSK-1_196833), from the Bioentrepreneur Fellowship UZH (DD, BIOEF-18-009), from the Forschungskredit PostDoc UZH (MS, Grant No. FK-18-052), from the BIAL Foundation (MS and DM, No. 333/20), from the Reconnect Foundation (DM), and from private donations (MM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
                Categories
                Psychiatry
                Original Research
                Custom metadata
                Psychopharmacology

                Clinical Psychology & Psychiatry
                ayahuasca,ayahuasca analog,dmt,harmine,therapeutic potential,psychological processes,psychometrics,subjective effects

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