Interrupting the Psychedelic Experience Through Contextual Manipulation to Study Experience Efficacy.
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ABSTRACT:
SUBMITTER: Roseman L
PROVIDER: S-EPMC11250380 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Interrupting the Psychedelic Experience Through Contextual Manipulation to Study Experience Efficacy.
Roseman Leor L Erritzoe David D Nutt David D Carhart-Harris Robin R Timmermann Christopher C
JAMA network open 20240701 7
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Project description: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 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg 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.
| S-EPMC5776504 | biostudies-literature
Project description:Background: Recent years have seen a resurgence of research on the potential of psychedelic substances to treat addictive and mood disorders. Historically and contemporarily, psychedelic studies have emphasized the importance of contextual elements ('set and setting') in modulating acute drug effects, and ultimately, influencing long-term outcomes. Nevertheless, current small-scale clinical and laboratory studies have tended to bypass a ubiquitous contextual feature of naturalistic psychedelic use: its social dimension. This study introduces and psychometrically validates an adapted Communitas Scale, assessing acute relational experiences of perceived togetherness and shared humanity, in order to investigate psychosocial mechanisms pertinent to psychedelic ceremonies and retreats. Methods: In this observational, web-based survey study, participants (N = 886) were measured across five successive time-points: 2 weeks before, hours before, and the day after a psychedelic ceremony; as well as the day after, and 4 weeks after leaving the ceremony location. Demographics, psychological traits and state variables were assessed pre-ceremony, in addition to changes in psychological wellbeing and social connectedness from before to after the retreat, as primary outcomes. Using correlational and multiple regression (path) analyses, predictive relationships between psychosocial 'set and setting' variables, communitas, and long-term outcomes were explored. Results: The adapted Communitas Scale demonstrated substantial internal consistency (Cronbach's alpha = 0.92) and construct validity in comparison with validated measures of intra-subjective (visual, mystical, challenging experiences questionnaires) and inter-subjective (perceived emotional synchrony, identity fusion) experiences. Furthermore, communitas during ceremony was significantly correlated with increases in psychological wellbeing (r = 0.22), social connectedness (r = 0.25), and other salient mental health outcomes. Path analyses revealed that the effect of ceremony-communitas on long-term outcomes was fully mediated by communitas experienced in reference to the retreat overall, and that the extent of personal sharing or 'self-disclosure' contributed to this process. A positive relationship between participants and facilitators, and the perceived impact of emotional support, facilitated the emergence of communitas. Conclusion: Highlighting the importance of intersubjective experience, rapport, and emotional support for long-term outcomes of psychedelic use, this first quantitative examination of psychosocial factors in guided psychedelic settings is a significant step toward evidence-based benefit-maximization guidelines for collective psychedelic use.
| S-EPMC8114773 | biostudies-literature
Project description:Rhythms in the pseudo-steady state (PSS) levels of reactive species (RS), particularly superoxide and hydroxyl radicals, exist in cancer cells. The RS rhythm characteristics, particularly frequency and amplitude, are entrained (reset) by the anticancer compounds/drugs. In this work, we show for the first time that the phase of the RS rhythm at which the drug is added is significantly important in determining the cytotoxicity of anticancer compounds/drugs such as menadione and curcumin, in two different cancer cell lines. Curcumin, the more effective of the two drugs (IC50 = 15 µM, SiHa; 6 µM, HCT116) induced reset of superoxide and hydroxyl rhythms from 15.4 h to 9 h, and 25 h to 11 h respectively, as well as caused increases in these radical levels. However, menadione (IC50 = 20 µM, SiHa; 17 µM, HCT116) affected only the superoxide levels. Drug treatment at different time points/phase of the RS rhythm resulted in a maximum of 27% increase in cytotoxicity, which is significant. Further, we report for the first time, an unexpected absence of a correlation between the intracellular PSS RS and antioxidant levels; thus, the practice of using antioxidant enzyme levels as surrogate markers of intracellular oxidative stress levels may need a re-consideration. Therefore, the RS rhythm could be a fundamental/generic target to manipulate for improved cancer therapy.
| S-EPMC6994657 | biostudies-literature
Project description:The hippocampus contains neural representations capable of supporting declarative memory. Hippocampal place cells are one such representation, firing in one or few locations in a given environment. Between environments, place cell firing fields remap (turning on/off or moving to a new location) to provide a population-wide code for distinct contexts. However, the manner by which contextual features combine to drive hippocampal remapping remains a matter of debate. Using large-scale in vivo two-photon intracellular calcium recordings in mice during virtual navigation, we show that remapping in the hippocampal region CA1 is driven by prior experience regarding the frequency of certain contexts and that remapping approximates an optimal estimate of the identity of the current context. A simple associative-learning mechanism reproduces these results. Together, our findings demonstrate that place cell remapping allows an animal to simultaneously identify its physical location and optimally estimate the identity of the environment.
| S-EPMC8893323 | biostudies-literature
Project description:BackgroundOver the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap.AimHere, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes.MethodIndividuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively.ResultsRelative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16.ConclusionThese results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.
| S-EPMC9353970 | biostudies-literature
Project description:RationaleClassic psychedelics are currently being studied as novel treatments for a range of psychiatric disorders. However, research on how psychedelics interact with other psychoactive substances remains scarce.ObjectivesThe current study aimed to explore the subjective effects of psychedelics when used alongside cannabis.MethodsParticipants (n = 321) completed a set of online surveys at 2 time points: 7 days before, and 1 day after a planned experience with a serotonergic psychedelic. The collected data included demographics, environmental factors (so-called setting) and five validated questionnaires: Mystical Experience Questionnaire (MEQ), visual subscales of Altered States of Consciousness Questionnaire (ASC-Vis), Challenging Experience Questionnaire (CEQ), Ego Dissolution Inventory (EDI) and Emotional Breakthrough Inventory (EBI). Participants were grouped according to whether they had reported using no cannabis (n = 195) or low (n = 53), medium (n = 45) or high (n = 28) dose, directly concomitant with the psychedelic. Multivariate analysis of covariance (MANCOVA) and contrasts was used to analyse differences in subjective effects between groups while controlling for potential confounding contextual 'setting' variables.ResultsThe simultaneous use of cannabis together with classic serotonergic psychedelics was associated with more intense psychedelic experience across a range of measures: a linear relationship was found between dose and MEQ, ASC-Vis and EDI scores, while a quadratic relationship was found for CEQ scores. No relationship was found between the dose of cannabis and the EBI.ConclusionsResults imply a possible interaction between the cannabis and psychedelic on acute subjective experiences; however, design limitations hamper our ability to draw firm inferences on directions of causality and the clinical implications of any such interactions.
| S-EPMC9110465 | biostudies-literature
Project description:BackgroundAlongside a recent revival in the use of psychedelics in clinical settings, there have been increases in the prevalence of recreational use, with many using psychedelics to deal with difficult emotions or to improve well-being. While clinical research is conducted in carefully controlled settings, this is not necessarily the case for recreational use. In this mixed methods online survey study, we aimed to develop an understanding of frequently used psychedelic harm reduction practices in recreational settings and how their use relates to the psychedelic experience. We also aimed to characterise users' first and most recent psychedelic trips to understand how harm reduction changes with experience.MethodsParticipants (n = 163) recounted their first and most recent psychedelic experience by providing details about the harm reduction practices they employed and completing the Challenging Experience Questionnaire (CEQ) and Emotional Breakthrough Inventory (EBI). We also asked open-ended questions for a more in-depth qualitative understanding of their views on psychedelic harm reduction.ResultsUsing ANOVA, we observe greater use of harm reduction practices for participants' most recent versus first psychedelic experience and that use of these practices is positively associated with EBI scores and negatively associated with CEQ scores (particularly for the first experience). Participants engaged in a wide range of harm reduction practices and we provide details of those which are most commonly used and those which are deemed most important by experienced users. Our qualitative analysis indicated that participants were largely positive about psychedelics and many recounted profound positive experiences. While specifics of the drug they were taking was important for aspects of harm reduction, participants largely focused on the importance of ensuring a good "set and setting" for enhancing positive effects.ConclusionsOur research helps us understand how engagement in harm reduction may increase with experience. Our mixed methods data shed light on the perceived importance of different harm reduction practices and examine their association with the psychedelic experience itself. Together, our research has important implications for the development of psychedelic harm reduction advice and provides opportunities for future research to explore the importance of these different practices in more detail.
| S-EPMC9310449 | biostudies-literature
Project description:This study aimed to develop and validate a short-form version of the AWE-S (AWE-SF) within psychedelic samples, to reduce participant burden while maintaining psychometric integrity. Across five studies, we first replicated the original six-factor structure of the AWE-S through exploratory and confirmatory factor analyses (Study 1), leading to the creation of the 12-item AWE-SF (Study 2-3). We then established the AWE-SF's initial and predictive validity by correlating it with relevant emotional, psychedelic, and well-being outcomes (Study 4-6). The AWE-SF demonstrated strong positive associations with positive emotions and was also linked to openness to experience. Moreover, the AWE-SF effectively predicted both mystical-type and challenging psychedelic experiences, as well as long-term well-being outcomes such as life satisfaction and psychological richness. In particular, the facets of connection and vastness were associated with positive emotional states and mystical-type experience, while accommodation and self-loss were associated with negative emotional states and challenging psychedelic experience. These findings suggest that the AWE-SF is a robust, reliable, and accessible tool for measuring awe experience.
| S-EPMC11616893 | biostudies-literature
Project description:Psychedelic-assisted therapy research for depression and PTSD has been fast tracked in the United States with the Food and Drugs Administration (FDA) granting breakthrough designations for MDMA (post-traumatic stress disorder) and psilocybin (major depressive disorder). The psychotherapeutic treatments accompanying these psychedelics have not been well-studied and remain controversial. This article reviews the challenges unique to psychedelic-assisted therapy and introduces a newly optimised psychological flexibility model that adapts Contextual Behavioural Science (CBS)/Acceptance and Commitment Therapy (ACT) to those multiple challenges, including ego inflation, traumatic memories, and the perceived presence of entities. A methodology aligned with biological mechanisms, psychological processes and therapeutic contexts may be advantageous for improving outcomes. This model expands ACT by integrating practices and data from psychedelic-assisted therapy research into a Contextual Behavioural Science framework, allowing both fields to inform each other. Psychological flexibility processes are questioned and adapted to a psychedelic context, and interventions that operationalise these processes are considered. The principle through-line of the paper is to consider varied constructs of Self, as understood by these fields, and integrates respective elements of varied self-models, interventions and data into a Spectrum of Selves model for psychedelic-assisted therapy. Secondly the paper examines how to select and retain new self-perspectives and their corresponding behaviours systemically, drawing from evolutionary science principles. A case example of such behavioural reinforcement is provided, as well as a psychedelic integration checklist to guide the practical implementation of such an approach. This method can enable a coherent therapeutic framework with clear operational relationships between (1) problematic behaviour patterns that an individual wishes to address (2) the guided psychedelic experiences of that individual, and (3) the barriers to maintaining any changes, thus increasing theoretical-practical coherence, broadening treatment benefits and reducing relapse in psychedelic-assisted therapy. Research questions for further developing a CBS-consistent psychedelic-assisted therapy are offered.
| S-EPMC8689588 | biostudies-literature
Project description:BackgroundSubjective experiences seem to play an important role in the enduring effects of psychedelic experiences. Although the importance of the subjective experience on the impact of psychedelics is frequently discussed, a more detailed understanding of the subtypes of psychedelic experiences and their associated impacts on mental health has not been well documented.MethodsIn the current study, machine learning cluster analysis was used to derive three subtypes of psychedelic experience in a large (n = 985) cross sectional sample.ResultsThese subtypes are not only associated with reductions in anxiety and depression symptoms and other markers of psychological wellbeing, but the structure of these subtypes and their subsequent impact on mental health are highly reproducible across multiple psychedelic substances.LimitationsData were obtained via retrospective self-report, which does not allow for definitive conclusions about the direction of causation between baseline characteristics of respondents, qualities of subjective experience, and outcomes.ConclusionsThe present analysis suggests that psychedelic experiences, in particular those that are associated with enduring improvements in mental health, may be characterized by reproducible and predictable subtypes of the subjective psychedelic effects. These subtypes appear to be significantly different with respect to the baseline demographic characteristics, baseline measures of mental health, and drug type and dose. These findings also suggest that efforts to increase psychedelic associated personal and mystical insight experiences may be key to maximizing beneficial impact of clinical approaches using this treatment in their patients.
| S-EPMC9887654 | biostudies-literature