This review (2024) examines the acute subjective effects of classic psychedelics, their relationship to risks and therapeutic benefits, and the current limitations in measuring these effects. It discusses existing measures, their construct validity, and predictive value for outcomes, while proposing recommendations for improving conceptualization and measurement in future research.
The administration of classic psychedelics has been associated with well-being and mental health benefits as well as risks and adverse events. The acute subjective effects of psychedelics might have a causal role in these risks and therapeutic benefits, but inconsistencies and limitations in the conceptualization and measurement of these acute subjective effects hinder research and clinical advances. In this Review, we outline current characterizations and psychometric examinations of the acute subjective effects of psychedelics, evaluate the construct validity of commonly used measures and describe findings showing that specific acute subjective effects predict certain outcomes. We discuss how to balance the limitations of existing measures with methodological advances in practice and elaborate on well-known methods and other psychological processes that can help inform the creation of new measures. We suggest actionable recommendations for how the field can transcend current conceptualizations and provide guidance on best practices until the next generation of measures is validated.
Classic psychedelics such as psilocybin, DMT, mescaline and LSD produce a distinctive set of acute subjective effects that alter perception, cognition and affect. These effects range from positive experiences—visual alterations, heightened affect, connectedness, insight and moments rated as highly meaningful—to challenging states including anxiety, fear, dissociation and confusion that can require therapeutic support. Although several clinical studies have reported therapeutic benefits (for example, in mood and substance-use disorders), these findings are preliminary because of limitations in design, sample size and blinding, and serious adverse experiences (for example, psychosis or increased suicidality) have been observed in some cases, emphasising the need for careful assessment of both risks and benefits. Yaden and colleagues set out to clarify how acute subjective effects have been conceptualised and measured, to evaluate the construct validity of commonly used instruments, and to examine empirical relations between specific acute effects and later outcomes. The Review contrasts two broad explanatory classes—higher-level subjective processes versus lower-level pharmacological and neurobiological mechanisms—surveys psychometric approaches (broad versus narrow measures), assesses threats to validity, and offers concrete recommendations to improve measurement practices and guide future research and clinical applications.
Papers cited by this study that are also in Blossom
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Journal of Psychopharmacology (2017)
Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)
Forstmann, M., Yudkin, D. A., Prosser, A. M. B. et al. · PNAS (2020)
The paper is a narrative review rather than a report of a new empirical study; the extracted text does not clearly report a systematic search strategy, databases searched or formal inclusion/exclusion criteria. Instead, the investigators synthesise existing empirical findings, psychometric evaluations and theoretical models across several literatures: clinical and non-clinical psychedelic trials, neurobiology and preclinical work, and measurement development studies. Their approach emphasises construct validation using the Standards for Educational and Psychological Testing framework. Specifically, the authors evaluate response-process evidence (how respondents understand and remember experiences), test-content evidence (coverage and representativeness of items), external aspects of construct validity (convergent, discriminant and criterion relations) and validity generalisation (across populations, cultures, substances and settings). They review both broad-spectrum instruments (for example, the Mystical Experience Questionnaire, 5-Dimensional and 11-Dimensional Altered State of Consciousness scales, Hallucinogen Rating Scale) and narrower tools focused on specific constructs (for example, Ego Dissolution Inventory, Emotional Breakthrough Inventory, Watts Connectedness Scale, Challenging Experience Questionnaire), and draw on examples from clinical trials, correlational studies and neuroimaging and pharmacological manipulations (for example, ketanserin blockade of 5-HT2A receptors) to illustrate measurement and mechanism issues. Where relevant, the Review integrates psychometric findings (factor structure, correlations between scales, model fit), experimental manipulations linking receptor activity to subjective intensity, and preclinical evidence. The authors also discuss qualitative and response-process techniques (cognitive interviewing, think-aloud protocols, probe-based methods) as complementary methods to improve item validity, while noting that much existing validation work remains limited in scope and sample diversity.
The Review summarises empirical associations between acutely measured subjective effects and later outcomes, while also documenting inconsistencies. Several clinical and non-clinical studies reported that higher scores on measures of “mystical-type” or related experiences immediately after a session correlate with improved outcomes weeks to months later. Examples include correlations from psilocybin studies in people with life-threatening cancer: Mystical Experience Questionnaire scores correlated with reduced anxiety (r = -0.59), reduced depression (r = -0.41) and increased life satisfaction (r = 0.53) at 5-week follow-up; a second sample reported a correlation with follow-up depression of r = -0.49. In treatment-resistant depression, the oceanic boundlessness factor predicted lower depression at week 5 (r = -0.44), and in another depression study the mystical factor (b = -0.35) and the Emotional Breakthrough Inventory (b = -0.42) predicted lower depression at week 6. An early tobacco-cessation open-label study found that a States of Consciousness Questionnaire score predicted biologically confirmed abstinence weeks later (r = -0.56). Not all findings are consistent, however. A long-term follow-up of a psilocybin-based depression treatment found increases in well-being at 6 and 12 months but no reliable decreases in depression; in another trial the total score on an 11-Dimensional Altered State of Consciousness scale did not predict persisting therapeutic benefits, although its oceanic boundlessness subscale did (r = -0.40, p = 0.04). The authors underline that correlations do not prove causation and that unobserved lower-level neurobiological processes (for example, plasticity) could underlie both subjective reports and clinical change. On the neurobiological front, psychedelics act primarily at serotonergic 5-HT2 receptors, with 5-HT2A activation linked to subjective effects and neural plasticity. Pharmacological blockade with the 5-HT2A antagonist ketanserin reduces or abolishes many acute subjective features in humans; rodent 'head-twitch' responses are similarly attenuated. Positron emission tomography studies reported receptor occupancy and signalling covarying with subjective intensity (reported β = 0.34). Three systems-level neurobiological models are described: cortico-striato-thalamo-cortical disruption of thalamic gating, a claustro-cortical misalignment hypothesis, and the 'relaxed beliefs under psychedelics' model with the entropic brain hypothesis; neuroimaging findings provide some support but are preliminary and sometimes contradictory. Regarding measurement, the authors contrast broad and narrow approaches. Broad instruments trace back to the Good Friday experiment and include the Mystical Experience Questionnaire (30 items, positively valenced) and multidimensional scales such as the 5-Dimensional and 11-Dimensional Altered State of Consciousness scales; narrow measures target constructs like insight, awe, acceptance, connectedness, emotional breakthrough and ego dissolution. Psychometric problems are documented: some scales show poor model fit (for example, earlier versions of the Abnormal Mental States Questionnaire), items with ambiguous language, under-representation of negatively valenced experiences in some measures, and frequent co-administration of positive and negative measures (for example, pairing the Mystical Experience Questionnaire with the Challenging Experience Questionnaire). The review highlights construct-irrelevant threats to validity. Acute cognitive impairments under psychedelics (attentional and memory deficits) can impair immediate or retrospective reporting; delayed measurement increases memory error; expectancy and halo effects may bias endorsements; and shared method variance can inflate correlations between scales. Empirical overlap between constructs was noted: the Mystical Experience Questionnaire correlates highly with the oceanic boundlessness factor (r = 0.93) and substantially with the Ego Dissolution Inventory (r_s = 0.74), suggesting conceptual convergence or possible measurement redundancy. Generalisability is limited because most validations use Western, educated, industrialised, rich, democratic (WEIRD) samples, often volunteers with prior psychedelic interest. The authors report that response-process validation (for example, cognitive interviewing) is under-represented in the literature. Finally, the investigators report methodological recommendations encountered in the literature: use of cognitive interviewing and probe methods to improve item comprehension, improved active placebos and blinding, recruitment of psychedelic-naïve participants to reduce expectancy bias, standardised timing of post-dose assessments, multi-method validation (self-report, interviews, behavioural and biological measures), and analytic approaches including latent variable modelling, network analysis as complementary tools, semantic-network approaches and hierarchical (bass-ackwards) factor exploration.
Yaden and colleagues interpret the accumulated evidence as indicating that acute subjective effects are relevant to understanding therapeutic benefits and risks of psychedelics, but they caution that causal claims remain unsettled. The authors present two complementary mechanistic perspectives: one emphasises higher-level subjective and cognitive-affective processes (insight, emotional breakthrough, connectedness, ego dissolution) that may mediate lasting change, while the other stresses lower-level pharmacological and neurobiological effects (notably 5-HT2A-related plasticity) that could either drive therapeutic change directly or produce subjective experiences that accompany change. Both avenues, they argue, merit empirical testing. With respect to measurement, the authors conclude that existing instruments provide useful information but exhibit important limitations in content coverage, response-process validity, external validity and generalisability. They note substantive conceptual overlap across many scales (for example, constructs related to interconnection or unity recur across instruments), but also warn that high correlations may reflect shared method variance or ambiguous item wording rather than identical latent constructs. The Review therefore advocates a plural but principled measurement strategy: combine top-down theory with bottom-up, data-driven item generation and qualitative vetting, and use multi-method approaches to establish convergent and discriminant validity. Key limitations acknowledged include the predominance of WEIRD samples, underuse of response-process validation methods, potential recall and expectancy biases in retrospective self-report, heterogeneous psychometric quality of scales and preliminary, sometimes contradictory, neuroimaging findings. The authors recommend concrete research practices to address these gaps: better active placebos and blinding to reduce demand characteristics, recruitment of more diverse and psychedelic-naïve samples to improve generalisability, standardised assessment timing post-dose, and the incorporation of ecological and temporal measurement methods (digital phenotyping, experience sampling, temporal graphical representations). For future research and practice, the Review proposes an iterative programme of measure development that pairs qualitative techniques (cognitive interviewing, micro-phenomenological interviews) with quantitative psychometrics (latent variable modelling, hierarchical factor analyses, and complementary network analyses), pre-registered hypotheses about nomological networks, multi-trait multi-method validation, and collaborative multi-laboratory approaches (for example, adversarial collaborations and multiverse analyses) to enhance robustness. Such advances, the authors suggest, will help clarify which acute subjective features predict beneficial or adverse long-term outcomes and thereby improve the translation of psychedelic science into clinical and policy contexts.
In the context of society-wide stagnation of well-being levels and high rates of mental illness, these initial findings have attracted substantial -although often overeager -interest. Whether the impacts on well-being and the specific therapeutic benefits of psychedelics hinge upon their subjective effects remains an ongoing discussion. Some research suggested that the acute subjective effects of psychedelics are not necessary to produce therapeutic benefits. According to this viewpoint, lower-level neurobiological processes such as neural plasticity and neurogenesisare sufficient to account for the therapeutic benefits of psychedelics. By contrast, emerging work suggests that acute subjective effects related to higherlevel neurobiological, cognitive and affective processes involved in recalling, engaging with and making meaning of the psychedelic experience might play a critical role in the full and enduring therapeutic benefits of psychedelics. The issue of whether acute subjective effects are causally relevant to the therapeutic benefits of psychedelics must ultimately be adjudicated empirically. As scientific and public interest in psychedelics and their therapeutic potential continues to grow, conceptual clarity, data-driven insights and best practices in measuring acute subjective effects must be advanced to understand therapeutic mechanisms and optimize potential applications of psychedelics. Measures have often followed from examinations of mental states referred to as exceptional, religious, spiritual, mystical, self-transcendent, awe or peak experiences, and the broadly defined constructs of non-ordinary experiences and altered states of consciousness (Box 1). Psychedelic researchers have drawn on these sources and findings, sometimes explicitly and sometimes working in parallel, to create psychometric
Classic psychedelics -such as psilocybin, dimethyltryptamine (DMT), mescaline and lysergic acid diethylamide (LSD) -produce a host of acute subjective effects that differ from the effects of other moodaltering drugs and broadly impact cognition, perception and affect. The acute subjective effects of psychedelics include changes such as visual alterations, heightened affect, a sense of connectedness, emotional breakthrough, ineffability, synaesthesia, disembodiment or insightfulness. Psychedelics also commonly elicit challenging psychological content and negative emotions such as anxiety and fear, existential struggle, social disconnection and depersonalization, and states of confusion that lead people to put themselves in physically or socially risky situations and can sometimes require therapeutic support. However, classic psychedelics have been rated as less risky in terms of harm to self and others than other psychoactive substances that are routinely used recreationally. In several trials of non-clinical samples, the majority of participants rated the experience as among the most meaningful of their entire lives. As the lifetime prevalence of recreational psychedelic use is currently around 16% in the United States, and on the rise, quantifying and balancing the risks and benefits of recreational psychedelic use -especially compared to other psychoactives-is a topic of ongoing ethical and policy analysis. The clinical risk and benefit profiles of psychedelic substances are also actively being investigated. Several studies have documented therapeutic benefits of psilocybin on mood and substance use disorders. These studies must be considered preliminary owing to issues of design, sample size and blinding, and caution ought to remain the rule regarding clinical recommendationsbecause psychedelics can elicit serious adverse experiences (such as psychosis, dissociation and suicidal ideation) even in controlled research settings. However, clinical studies have generally reported increased well-being and therapeutic benefits, although adverse events, such as headache and nausea, and serious adverse events, such as increased suicidality, were also noted (for example, serious adverse events were reported in 4% of patients with neuropsychiatric disorders).
The Varieties of Religious Experience: A Study in Human Nature 142 was published in 1902. This book provided the foundation for the psychological study of intense and meaningful altered states of consciousness for more than a century. When approaching the subject of what was referred to as 'religious experience' or 'mystical experience', the phrase 'forms of consciousness' was also used. The book introduced the term 'mystical experience' as it is used in contemporary psychedelic research, although it was defined much more broadly than current constructs, and also popularized the term 'mystical experience' to refer to some of the most subjectively intense of the experiences. However, the author explicitly pointed out that the use of the term 'mystical' was not intended to suggest supernaturalism or non-rationalism. Four marks were introduced to define mystical experiences: transiency (lasting for a brief period), passivity (the experiences feel overwhelming), noetic (the sense that the experience feels real and as if the person is gaining knowledge) and ineffability (difficulty or impossibility to put the experience fully into words). In 1960, Mysticism and Philosophybuilt on this initial work and explicitly added that feelings of unity or interconnectedness were fundamental features of mystical experiences. This characterization influenced the design of some of the most widely used scales to assess mystical experiences. In particular, this work informed the initial iteration of the Mystical Experience Questionnaire used in the 'Good Friday experiment'and the Mysticism scale, which was created to capture a wide variety of mystical-type experiences including drug-induced, practice-induced (for example, meditation) and spontaneous experiences. Picking up on this initial work, survey studies conducted in the 1970s in the United Kingdom on religious experiences included questions covering mystical experiences. By the 2000s, large-scale polling companies such as Gallup and the General Social Survey conducted surveys on these experiences using questions such as "Would you say that you have ever had a 'religious or mystical experience' -that is, a moment of sudden religious insight or awakening?", overall finding a 35% endorsement rate in the United States and the United Kingdom 139 .
the Review, we refer to classic psychedelics using the generic term 'psychedelics'. We first present the subjective and neurobiological effects of psychedelics that are proposed to be implicated in the mechanisms driving therapeutic change. We then consider broad and narrow approaches to the construct of acute subjective effects and evaluate the construct validity of the measures that have been developed to assess such effects. We examine the measures' strengths and limitations through the lens of response processes, test content, external aspects of construct validity and validity generalization, and engage in the active debate regarding which and to what degree previous theories should be used when advancing towards precise and comprehensive models of subjective psychedelic experiences and their clinical outcomes. Next, we discuss some psychological science insights that could inform understanding of the acute subjective effects of psychedelics. Indeed, psychedelic science has developed measures of subjective effects constructs that assess psychological processes (such as emotions or self-identity), often without incorporating insights from betterstudied psychological constructs. We focus on these connections to help with the interpretation of the therapeutic benefits of psychedelics. Finally, we argue that data-driven and qualitatively vetted measures should be the pillars of the field's best practices as it moves beyond current conceptualizations and measures.
In this section, we provide an overview of the literature on two potential mechanisms underlying the therapeutic benefits of psychedelics: acute subjective effects involving higher-level neurobiological processes, and lower-level pharmacological and neurobiological effects. We discuss empirical relationships between acute subjective effects and positive therapeutic changes as well as the potential relevance of both mechanisms to the therapeutic benefits of psychedelics.
Existing measures of acute subjective effects captured during or directly after psychedelic experiences often correlate with positive therapeutic responses weeks or months later. The Mystical Experience Questionnaire (a measure comprising subscales related to feelings of unity, positive mood, transcendence of time and space, and ineffability) was positively correlated with persisting beneficial outcomes in individuals with a life-threatening cancer diagnosis in two independent samples. In the first study, scores on the questionnaire administered immediately after a psilocybin session correlated with outcome measures assessed 5 weeks later, including anxiety (r = -0.59), depression (r = -0.41) and life satisfaction (r = 0.53). Similar results were found in the second study, which reported a correlation between acutely assessed mystical-type experiences and follow-up depression scores (r = -0.49). Correlations have also been found in samples of individuals with mental health conditions. The oceanic boundlessness factor is a subscale of the 5-Dimensional Altered States of Consciousness scale that assesses feelings of positive mood, spiritual experience, feelings of connection, derealization and depersonalization. This factor predicted lower depression scores at week 5 (r = -0.44) in a treatment-resistant depression study. Scores on the 'mystical' factor of the Mystical Experience Questionnaire (b = -0.35) and the Emotional Breakthrough Inventory (b = -0.42) -a measure of productive mental engagement with emotional challenges involving exploration and resolution -predicted lower depression at week 6 in a depression study. Furthermore, scores on the States of Consciousness Questionnaire (an early 43-item version of the Mystical Experience Questionnaire) predicted biologically confirmed abstinence weeks later (r = -0.56) in an open-label tobacco cessation study. When and how the acute subjective effects predict persisting therapeutic benefits is still being investigated. A systematic review indicated that mystical-type experiences (defined by feelings of unity, positive mood, ineffability, transcendence of time and space, and noetic quality) measured immediately after psychedelic experiences were generally associated with well-being outcomes measured weeks or months after the use of psychedelics among non-clinical samples, and negatively associated with anxiety. However, findings are not always consistent. Scores on the Mystical Experience Questionnaire predicted persisting increases in well-being (r = 0.50) at 6-month and 12-month follow-ups but not decreases in depression in a long-term follow-up study of a psilocybin-based depression treatment. The total score of the 11-Dimensional Altered State of Consciousness scale assessed immediately after psychedelic experiences did not correlate with persisting therapeutic benefits in another psilocybin-based depression treatment study. But in this study, the oceanic boundlessness factor subscale did predict a persisting therapeutic response (r = -0.40; p = 0.04). These findings suggest that the acute subjective effects of psychedelics might play a role in their therapeutic benefits. However, correlations do not definitely indicate that the subjective effects of psychedelics cause therapeutic outcomes. Unobserved variables related to acute subjective effects and therapeutic benefits simultaneously might explain a statistical relationship between them. For example, lower-level physiological processes involved in adaptive neural plasticity could, potentially, underlie the subjective experiences that are associated with the therapeutic benefits of psychedelics. According to this view, the acute subjective effects could be considered epiphenomenal.
Psychedelics are partial or full agonists of serotonergic 5-HT 2 receptors. This effect on 5-HT 2A receptors has been found to mediate the relationship between psychedelic administration and increased neural plasticity. Psychedelics are broadly active across 5-HT 2 receptors, but the G-protein-coupled receptor 5-HT 2A is particularly relevant, because blocking 5-HT 2A (for example, using the 5-HT 2A antagonist ketanserin) reduces or eliminates the acute subjective effects of psychedelics in humans. Following administration of psychedelics, participants who were administered the 5-HT 2A antagonist ketanserin reported lower ratings on the 5-Dimensional Altered State of Consciousness subscales measuring oceanic boundlessness, visionary restructuralization (visuals and other perceptual changes) and anxious ego dissolution (characterized by paranoia, thought disorder, and anxiously experienced loss of sense of self and self-world boundary), relative to participants who did not receive ketanserin. Blocking 5-HT 2A in rodents that had been administered psychedelics reduced or eliminated the 'head twitch response', a behavioural response that indexes the effects of serotonergic agonists such as psychedelics in rodents. Furthermore, 5-HT 2A receptor occupancy and signalling, indexed using positron emission tomography, have been observed to covary with acute subjective intensity in humans (assessed via self-report Likert-scale ratings and correlated with acute subjective experience such as mystical-type experience) (β = 0.34). Three main emerging neurobiological models suggest that the acute subjective effects of psychedelics might stem from systems-level
changes in the brain. First, the cortico-striato-thalamo-cortical model proposes that, by impacting 5-HT 2A receptors in multiple parts of this circuit's feedback loop, psychedelics disrupt thalamic gating. Such modulation of the information flow through the brain's architecture potentially accounts for the acute subjective effects of psychedelics. This model is supported by results showing a correlation between the total score of the 5-Dimensional Altered State of Consciousness scale and global brain connectivity in the somatomotor network. Second, the claustro-cortical circuit model proposes that psychedelic-initiated 5-HT 2A activation leads to a misalignment between the claustrum and the cortex, prompting atypical cognitive control. Indeed, higher total scores on the Mystical Experience Questionnaire were associated with lower claustrum variance and amplitude of low-frequency fluctuations. Finally, the 'relaxed beliefs under psychedelics' model suggests that psychedelics reduce the constraints that higher-level cortical networks (such as the default mode, frontoparietal and salience networks) typically place on lower levels (such as the visual cortex, amygdala, hippocampus and thalamus), leading to increased bottom-up information flow. Results showing correlations between ego dissolution (involving an attenuated sense of self and self-world boundary) and reductions in connectivity in the default mode network (parahippocampus and retrosplenial cortex) support this model. Within the latter model, the entropic brain hypothesis holds that patterns of functional brain activation and connectivity become dynamically unstable under psychedelics. According to a preprint that is undergoing peer review, higher blood concentration of psilocin and higher reported subjective intensity of the psychedelic experience are associated with the activity of brain regions being more likely to alternate unpredictably among correlated, non-correlated and anticorrelated (greater entropy in covarying relations between regions). Given that such relations between regions over time index diverse cognitive states, these patterns might relate to the variable and shifting perceptual, cognitive and affective states represented in the acute subjective effects. However, neuroimaging studies in this area have produced contradictory findings and remain relatively preliminary. Preclinical research can help with understanding the therapeutic benefits of psychedelics. Identifying common therapeutic mechanisms across mammalian species offers avenues for better understanding the physiological, neurological and behavioural underpinnings of clinical outcomes of psychedelic use. Although experiences involving 'existential' meanings are of course unlikely to be present in rodent models, an array of subjective experiences might be shared across mammalian species (without any linguistic element) including feelings of attachment, approach orientation, social engagement, fear and the reversal of despair. There is evidence in rodent models that psychedelics can produce anti-depressant-like effects and that certain subjectively perceived contextual factors can contribute to overall efficacy of psychedelics. Findings from this area of research might prove an important addition to the debate about how relevant acute subjective effects are to the persisting therapeutic benefits of psychedelics among humans. Despite the research advances on the mechanisms that might lead to therapeutic benefits, questions remain regarding how helpful these pharmacological and neurobiological findings are to understanding the acute subjective effects of psychedelics. The diverse range of psychometric scales used to measure acute subjective effects have been constructed via varying standards of psychometric validation. Together with frequent misconceptions (Box 2), these limitations have raised questions about the reported relationships across acute subjective effects measures and between neurobiological mechanisms and clinical outcomes. A better understanding of the development, structure and construct validity of existing scales could help to guide improvements of these measures.
Psychometric measures of the acute subjective effects of psychedelics have followed two general streams: scales that aim to capture a broad spectrum of subjective effects including perceptual changes (mostly used in European research), and scales that adopt a narrower focus to capture more specific and generally explicitly valenced effects (mostly used in US and UK research). In this section, we review common measures from both streams (Table).
A highly influential measure of the acute subjective effects of psychedelics emerged from the 'Good Friday experiment', which involved administering psilocybin to seminary students who were observing a church service. Based on previous work, this study measured the acute subjective effects of psychedelics using nine categories: internal unity (reduced sense of self or individuality), external unity (connection with the external world), transcendence of time and space (change in usual senses of time or space), deeply felt positive mood, sense of sacredness, objectivity and reality, paradoxicality (insights or sensations that seem to integrate opposites), alleged ineffability (experience seems beyond language) and persisting positive changes in attitude and/or behaviour. Participants given psilocybin endorsed these categories at higher levels than participants in the control group, who were given the psychoactively inert substance niacin. The Mystical Experience Questionnaire, which was created during a more rigorous replication of this initial study, includes four factors that capture a broad range of subjective experiences: mysticaltype experiences (authoritative sense of unity and sacredness), altered perceptions of time and space (various changes in the senses of time and space), positive mood (emotions such as awe and reverence) and ineffability (sense that the experience cannot be expressed in words). Progressive psychometric validation processes led to the development of the contemporary version of the 30-item version of the Mystical Experience Questionnaire, which is frequently used in empirical studies of the acute subjective effects of psychedelics. Given this questionnaire's developmental lineage and operationalization of 'mystical experience', it is positively valenced in that its items do not explicitly ask about negative or challenging experiences. For this reason, the Challenging Experience Questionnaire, which focuses on negative valence, is routinely co-administered. Another broad acute subjective effects measure is the Aussergewohnliche Psychische Zustande 64 (translated into English as the Abnormal Mental States Questionnaire). This measure drew on the theory that altered states of consciousness could be defined in similar terms regardless of their origin or trigger. The questionnaire features 158 items (reduced from an initial set of 800 items) with a binary response styleand three factors capturing oceanic boundlessness (feelings of connection to the world and other persons in general, invoking Freudian terminology), dread of ego dissolution (anxiety) and visionary restructuralization. This questionnaire and the related Aussergewöhnliche Bewusstseinszustände scalewere found to have poor psychometric properties, such as inadequate relative model fit (the comparative fit index) and absolute model fit (root mean square error of approximation).
The term 'altered state of consciousness' suggests an extremely broad set of possible mental states. All psychoactive drugs (such as caffeine, amphetamines or opioids) could be said to induce an altered state of consciousness. Although the term is often used in psychedelic research to refer to narrower kinds of experience, the definition of the construct is often left ambiguous. The 5-Dimensional Altered State of Consciousness scalewas developed to specifically measure predefined facets of this construct, and a reanalysis of the Aussergewöhnliche Bewusstseinszustände scale resulted in an 11-factor measure called the 11-Dimensional Altered States of Consciousness scale. Other measures also aim to provide broad coverage of acute subjective effects. For instance, the Hallucinogen Rating Scale 69 covers somaesthesia (perception of bodily sensations), affect, perception, cognition, volition and subjective intensity of the experience, but has received little psychometric evaluation. The Ayahuasca Experience Inventorywas designed to capture cognitive, emotional and physical states experienced under the acute effects of ayahuasca during Shipibo-Conibo-led ceremonies, and consists of three factors: clarity (peace and self-connection), reappraisal (cognitive reappraisal of negative beliefs about the self and others and initiative to enact change) and discomfort (unpleasant feelings of torment and isolation). Although not specifically designed to index psychedelic experience, the Inventory of Non-Ordinary Experiencesaims to capture a comprehensive range of phenomena ranging from love and pain to seeing ghosts and out-of-body and psychic phenomena. This inventory focuses on item-level validity (each item is a variable) and, as such, its superordinate dimensionality is unknown, limiting its utility in clinical research contexts. Respondents across at least two cultures (United States and India) reportedly understand the items, but the term 'non-ordinary experience' is non-specific and therefore presents similar conceptual problems to 'altered state of consciousness'. Non-ordinarity could be attributed to any vast number of experiences
The characterization and quantification of the acute subjective effects of psychedelics has led to several widespread misconceptions involving the labels of the constructs, the relevance of previous scholarly work on construct creation and claims about the comprehensiveness of a measure. The first misconception relates to some contemporary perspectives that theological premises about an ultimate reality are necessarily built into the construct 'mystical experience'. This misconception derives from a tendency to fixate on the label of the construct and to assume that it must refer to whatever colloquial sense the term connotes. Some scholars might attribute a common, colloquial meaning of the term necessarily referring to something supernatural or otherwise non-rational 169 . However, the term 'mystical experience' also has a technical meaning that refers to a cluster of subjective experiences. This latter sense of the term has been used in some highly influential workand in contemporary measures of mystical experiences. Multiple common meanings of a term can interfere with effective science communication by needlessly triggering misleading connotations, which might be a pragmatic reason to abandon these labels entirely. However, to do so might also obscure the long scholarly history and discourse surrounding these terms. In our view, it is the operationalized definition that matters 171 , along with the items themselves that are used in the instrument. Furthermore, contemporary scales are not operationalized to test a metaphysical supposition but to measure the degree to which a subjective experience has occurred that can be descriptively selfreported. Overall, researchers should keep in mind the technical rather than colloquial meaning of constructs. The second common misconception is the view that a history of scholarly discourse on a construct undermines the possibility of a construct having psychometric validity. For example, there has been much focus on the idea that mystical experiences involve a perception of contentlessness during states of unity. Some have claimed that this idea has had a pernicious influence on some early researchers, and discounted the validity of measures that bear any relation to this work 172 . However, this concept no longer appears in the items of contemporary measures. Additionally, factors related to feelings of interconnection have been recovered in many different scales and are supported by qualitative research across a diverse set of scholarly and theoretical work, suggesting an overlap between the original terms and assessments that do not share the same theoretical lineage. Similar arguments have raised concerns regarding measures of ego dissolution and oceanic boundlessness, given the Freudian roots of these labels 172 ; yet factors related to changes to the self have been documented in several other scales that have also been reliably used to elucidate the subjective effects of psychedelics. Although some scholarship has been particularly influential in promoting specific measures, and (perhaps stemming from this scholarship) most psychedelic research has been conducted in Western, educated, industrialized, rich and democratic contexts 107 , psychometric evidence of convergence on some common factors cannot be completely dismissed simply on the basis of scholarly exegesis -as these are open empirical questions. Such scholarly analyses suggest the need for more scientific work in creating more data-driven measures with cross-cultural validity and vetted with qualitative processes. A third common misconception is that measures of acute subjective effects are intended to be comprehensive, that is, to capture all the possible effects of psychedelics for all participants. This is not the case. Psychedelic experiences involve a vast number of acute subjective effects, but few of them would be of interest for researchers and fewer would be relevant for the prediction of persisting positive or negative outcomes. Choices must be made to capture some subset of effects in keeping with the principle of parsimony and practical measurement realities. Relatedly, low scores in individual items have been suggested to undermine a scale's validity and utility as a measure. But a measure will often pick up a subjective effect that predicts benefit -as demonstrated empirically -without requiring the subjective effect in question to always occur or always be associated with benefit or detriment. Additionally, scores are generally expressed in group averages and the correlations with persisting effects are usually only moderate, which means that there will be many cases that occur off the regression line. Such misconceptions are widespread across various disciplines and deserve increased science education efforts, especially when studies are reported to the public.
regardless of their relation to intense alterations of consciousness such as those associated with psychedelic experiences.
Measures that adopt a narrow approach to capture specific subjective effects of psychedelics largely assess psychological states that are usually considered productive or pleasant (positively valenced). These measures include the Psychological Insight Questionnaire, focused on new understandings and realizations from the psychedelic experience; the Awe Experience Scale, a multidimensional measure of the emotion of awe; the Acceptance/Avoidance-Promoting Experiences Questionnaire, which measures the respondent's degree of acceptance during intense subjective experiences; the Watts Connectedness Scale, focused on feelings of connectedness to other people and things; the Emotional Breakthrough Inventory, which measures beneficial affective experiences; and the Ego Dissolution Inventory, which measures both feelings of connection and ego dissolution. Measures related to mental illness and aversive experience generally assess states commonly considered to be unpleasant (negatively valenced). Although these measures have been administered in psychedelic research contexts, most of them were not created specifically for psychedelic drug administration studies. The Addiction Research Center Inventory, which is often used to assess behaviour related to psychoactive substances of abuse, assesses a psychotomimetic factor. This measure was designed specifically to differentiate LSD from other drugs and is considered to provide a measure of dysphoria, perhaps because it was developed through studies in prisoners, who generally reported that the experience was unpleasant (probably owing, in part, to the specific setting). The Psychotomimetic States Inventoryis explicitly oriented to measuring mental illness. The Challenging Experience Questionnaire 9 is among the few negatively valenced measures created specifically for use in psychedelic contexts that is still commonly administered, generally along with the Mystical Experience Questionnaire.
Both the narrower and the broader approaches to assessing subjective effects have advantages and trade-offs. The narrower approach helps identify active ingredients of experiences specifically linked to persisting negative or positive effects at a granular level, pertaining to specific aspects of the subjective effects of psychedelics. However, by design, a narrow approach might miss important aspects of the experiences. By contrast, the broad approach provides a fuller picture of possible states but might not index some specific effects or might obscure or subsume important narrow states at subordinate levels of the construct hierarchy. As this field matures, models of acute psychedelic experience are likely to become increasingly complex and encompassing of factors across these narrow and broad measures. This increasing model complexity and comprehensiveness should fulfil aims for a detailed and close to comprehensive representation of relevant phenomenological and cognitive states of psychedelic experiences, as well as pragmatic aims of predicting persisting risks and benefits. These measures must also be possible to administer during or immediately after the acute subjective effects of psychedelics. Evaluating how well existing scales assess the construct they were designed to capture can inform specific research and development recommendations.
Quantifying participants' acute subjective experiences using retrospective accounts is central to psychedelic science. However, retrospective measurement raises important concerns regarding construct validity, which is defined by how well a test or measure assesses what it is intended to assess. Psychological science offers methods to assess the validity of quantitative measures of mental operations, traits and phenomena that cannot be directly observed using latent constructs, such as the Standards for Educational and Psychological Testing. In this section, we evaluate the construct validity of common measures of the acute subjective effects of psychedelics with reference to four sources outlined by these standards.
The response process refers to whether a measure facilitates respondents' engagement in mental operations that are theoretically relevant to the construct being measured. In the context of acute psychedelic measurement, response process evidence addresses whether respondents engage in cognitive processes such as understanding the specific construct being described in questionnaire items (for example, ego dissolution) and accurately remembering whether the construct corresponds to respondents' prior psychedelic experience. Furthermore, ensuring response process validation of acute subjective measures involves addressing construct-irrelevant factors, which are factors in the response process -other than the theoretical attribute under examination -that contribute to respondent ratings. Results of cognitive tasks administered during the acute subjective effects of psychedelics using standardized computer programs in controlled laboratory settings have shown overall performance deficits, probably owing to a reduced attentional capacity under the acute effects of psychedelics. Indeed, deficits were found on the inhibition of return task, which targets attention specifically. Reduced performance on the Frankfurt Attention Inventory, the Stroop task, the go/no-go testand other working memory taskshave also been observed. These acute cognitive deficits raise concerns about the cognitive functioning of respondents as they complete retrospective measures shortly following acute subjective effects. Of note, psychoactive effects have been observed to linger for some time at a markedly low intensity, referred to as 'afterglow'. Declarative episodic memory error could conceivably function as a construct-irrelevant factor. Psychedelics alter cognitive functioning, which might undermine respondents' ability to precisely recall and gauge the acute subjective effects. Psychedelic administration during memory encoding impairs recollection (free recall tasks) and enhances familiarity of previously learned stimuli. Answering questions about one's previous experiences involves recognition (a feeling of familiarity for a previously encountered stimulus) rather than free recall (precise recollection). Thus, these findings do not necessarily suggest serious memory deficits on self-reporting measures, which aid recall by providing descriptions of experiential content. However, memory of mental objects under high doses (>25 mg psilocybin) has not been evaluated. In addition, the delay between the experience and the respondents' reporting might contribute to retrospective memory deficits because memories fade over time. Some validation efforts have relied on data involving longer delays of days to weeks before reporting, which can increase measurement error and decrease validity. Preconceived judgements of psychedelic experiences are a second construct-irrelevant factor that might decrease validity. Meaningful and positive impressions of psychedelic experiences and positive expectancycould influence respondents' opinions and answers to the measures (halo effect). Participants might generally endorse positively valenced attributes (such as connectedness and emotional breakthrough) rather than responding precisely about the more specific qualities of their personal experience. Similarly, respondents' ideas regarding the utility and significance of psychedelic experiences could influence their responses. For example, a respondent with prior knowledge of psychedelic-induced mystical-type experiences might believe that psychedelics are useful for mystical-type experience and be more likely to endorse mystical-type experience items. To the extent that respondents believe researchers are looking for positive outcomes, respondents might present a favourable picture of positive change following psychedelics, thereby succumbing to demand characteristics.
Content validity refers to the representativeness of content within a measure relevant to the theoretical attribute. In the context of acute subjective measurement, test content evidence bears on whether a measure is too broad, too narrow or fails to include important facets of the underlying construct. A measure could be considered too broad if it includes phenomena outside the psychedelic experience or experiences irrelevant to capturing features related to the clinical outcomes it is concerned with. A measure could be considered too narrow if it fails to include relevant phenomena (construct under-representation). For example, measures that do not include ego dissolution when conceptualizing experiences of connectedness or unity (or vice versa) might be considered too narrow. Similarly, experiences of emotional breakthrough might fit within the broader construct of acceptance-related experience. Another issue relevant to test content is whether different aspects of psychedelic experiences should be distinguished from each other. For example, unusual experiences can be distinguished into two components: the primary phenomenological features of an event (what the event was like or seemed like) and the secondary interpretations (subjective appraisals of emotional valence, significance and cause). However, given the close association between experiences
and interpretations, whether these components are straightforwardly separable is unclear. Measures of acute subjective effects have expanded considerably, and new measures continue to be created to provide a more nuanced assessment. For example, a measure has been constructed that captures acceptance-related and avoidance-related acute subjective effects. Similarly, some existing measures have been criticized for understating negatively valenced experiences, and studies often balance the assessment of the psychedelic experience by co-administering the Challenging Experience Questionnaire, which focuses on negative valence. Wide-ranging measures exist that carefully consider both positively and negatively valenced subjective effects (for example, the 11-Dimensional Altered State of Consciousness scale). Finally, it is unclear whether the collective body of existing measures is sufficiently representative of all the relevant acute subjective effects that occur during psychedelic experiences. Microphenomenologists are engaged in expanding the phenomenological and cognitive content space of the psychedelic experience. For example, one project is applying the micro-phenomenological interview method to record first-person experiential descriptions of psychedelic experiences in order to inform the construction of psychometric tools that better assess the structure and content of acute subjective effects 100 .
The external aspects of construct validity refer to whether a measure exhibits theoretically consistent patterns of convergent, discriminant and criterion relations with other measured attributes and outcomes. Comparisons of the measurement scores with other variables can provide evidence on whether an assessed measure or attribute is meaningfully distinct (discriminant validity) or overlapping (convergent validity) with other measures or constructs that assess acute subjective psychedelic experiences. Similarly, the relationships between measures of the acute subjective effects of psychedelics and outcome variables provide information about the usefulness of the measure in predicting clinical benefits, such as less severe depression symptoms (criterion validity). In general, measures of the acute subjective effects of psychedelics show evidence of convergent, discriminant and criterion validity. Regarding convergent and discriminant validity, the tests have been generally limited to associations with other acute subjective effects of psychedelics from self-report constructs. By contrast, convergent and discriminant validity have been reported for the 11-Dimensional Altered State of Consciousness scale factors relative to ordinary mood states. Discriminant validity (low or null association) has been observed for the Challenging Experience Questionnaire relative to a set of positively valenced measures (Mystical Experience Questionnaire, Ego Dissolution Inventory, Emotional Breakthrough Inventory, Avoidance-Promoting Experiences and Psychological Insight Questionnaire). Convergent validity has been observed across the same latter set of measuresand was confirmed between the negatively valenced Acceptance/Avoidance-Promoting Experiences Questionnaire subscale (avoidant-related experience) and the Challenging Experience Questionnaire. One limitation in this literature is that the thresholds for establishing convergent and discriminant validity are vague. For example, a correlation of r ~ 0.50 between the Emotional Breakthrough Inventory and the Mystical Experience Questionnaire was interpreted as support for convergent validity in one study, and a larger correlation (r s = 0.74) between the Mystical Experience Questionnaire and the Ego Dissolution Inventory was interpreted as support for discriminant validity in another study. Differences in interpretation would be justified if precise theory-driven predictions of the relations between constructs were formulated a priori. However, such predictions have generally been absentor, when specified, limited to whether the correlations between constructs were high or low, without further specification. In addition to challenges with interpretation, three other notable limitations exist. First, it is unclear whether predicted convergent and discriminant nomological network patterns hold up across different methods of measurement (multi-trait, multi-method approach 101 ). The convergence or discriminance between two constructs would be more compelling if self-report measures and interviews supported the overlap or separation. Second, the temporal association or dissociation of different acute attributes during the psychedelic experience is unknown. The duration of psychoactive effects might influence convergent validity, dependent on the type of psychedelic compounds, doses and their pharmacological routes. For example, psilocybin has psychoactive periods that can last for around 6 hours, and distinct acute subjective effects might occur at different time points, but participants might report them as occurring at the same time due to how the self-report measures are presented. Thus, a high correlation across diverse attributes might be related to the temporal realities of psilocybin administration. Third, very seldomly have measures been validated out of sample. Such practices would ensure replication and support generalizability. The literature is clearer concerning criterion validity, although not without gaps. The capacity to predict future outcomes is an important part of a construct's nomological network and identity, and particularly important for evaluating the therapeutic utility of subjective effects of psychedelics. In general, some acute subjective effects have been associated with persisting beneficial changes. Factors that showed a positive correlation with persisting positive outcomes include mystical-type experience, insight, emotional breakthroughand ego dissolution. By contrast, challenging (negatively valenced) experiences have shown generally null or only slightly negative relations with persisting beneficial changes. Findings are mixed regarding other longer-term outcomes such as personality and spiritual-type belief changes that could, potentially, inform a greater specificity of predictive relations. Although subsequent validation in prospective studies generally follows initial investigations 103 , criterion outcomes have been measured using retrospective indices of change, which are more likely than prospective measures to be vulnerable to placebo and expectancy effects.
Validity generalization refers to whether the properties and interpretations of a measure's score are the same across different people, population groups, cultures, drugs and administration settings. Measures have generally been validated only in samples characterized as Western, educated, industrialized, rich and democratic. Validation surveys are frequently explicit about the topic of research and usually do not compensate volunteers, and therefore might attract a high concentration of psychedelic enthusiasts who are likely to differ from the general population. In addition, setting types (for example, supportive versus alienating settings) could drive diverse acute experiences across individuals, given their sensitivity to the features of their setting. Qualitative work has also shown some cultural variations in subjective experiences that are not captured by existing scales.
The interpretation of the terms used in self-report items depends on subjective connotations, which can become problematic if the items are ambiguous or otherwise difficult to understand. For example, a respondent who is not religious and who does interpret the phrase 'religious aspects' as referring to a religious doctrine might not endorse the item, although they might have had an experience that fits with another sense of the term 'religious' (such as involving pervasive feelings that life is precious). These diverse connotations might introduce systematic error in studies of culturally and ethnically diverse samples. Participants' confusion about the description of an experience in measures and items has also been raised as a potential source of invalidity. For example, the item "I experienced a touch of eternity" might introduce an error if participants have difficulty determining and reporting what level of experience they had. Current measures have typically improved on previous assessments that had even more confusing items, such as items with double negatives 111 or less validated factor structure. But some items in current measures remain confusing and might result in inaccurate measurements of individuals' experiences. In sum, we found some empirical support for the validity of current measures of acute psychedelic experiences according to the Standards for Educational and Psychological Testing criteria. However, there are several limitations and threats to the validity of current measures.
There is consensus among construct validity theorists that predictions about a construct's nomological network should be made a priori and based on theory. However, in practice, theoretical predictions are frequently informed by observed empirical relations in an iterative and ongoing process, and inferences about theoretical attributes are frequently guided by psychometric results from network analyses and latent variable modelling in a bottom-up manner 112 . To the degree that measures meaningfully reflect the theoretical attribute being examined, researchers can learn about constructs by reference to their nomological network. There is some degree of convergence across measures of the acute subjective effects of psychedelics -particularly across subscales within measures -despite the substantially different theoretical backgrounds motivating the different measures. For example, nearly all measures have a factor involving feelings of interconnection, which is assessed with items referring to unity, oneness (the cognitive state of oneself and external and internal phenomena being undifferentiated), connectedness, relationality or boundlessness. Specific cases of this example are the mystical factor in the Mystical Experience Questionnaire, the ego dissolution factor in the Ego Dissolution Inventory, the connectedness factor in the Awe Experience Scale and the oceanic boundlessness factor in the 5-Dimensional Altered State of Consciousness scale. Overall, these subscale-level measures correlate highly and, in some cases, so do the total measure scores. For example, the Mystical Experience Questionnaire showed a high correlation with the oceanic boundlessness dimension of the 5-Dimensional Altered State of Consciousness scale (r = 0.93)and with factors of the Awe Experience Scale (range of semantic network analysis values 0.77-0.83) 113 , and the mystical factor of the Mystical Experience Questionnaire showed high correlation with the Ego Dissolution Inventory (r s = 0.74). Thus, factors from separate existing scales used to measure the acute effects of psychedelics display conceptual overlap, an observation which might inform future quantitative and qualitative studies (Fig.). Nevertheless, factors unrelated to a scale's intended constructs can contribute to the high correlations between measures. For example, the oceanic boundlessness subscale of the 11-Dimensional Altered State of Consciousness scale (such as experience of unity and insightfulness) correlates with the Mystical Experience Questionnaire total (r = 0.93), but they might measure different latent variables and the correlations might be driven by construct-irrelevant factors; scales and items might be assumed to tap into the same construct based only on their semantic similarity. Empirically establishing common latent factors would require that the scales separately show good construct validity in the first place. Psychedelic experiences are out of the ordinary, and imprecisely recollected (or ineffable) features of the experience might be difficult to report in linguistic categories. A respondent might endorse two different terms pointing to distinct experiences because the terms prompt retrieval of an acute subjective experience that bears at least some resemblance to both but is, in fact, not completely captured by either. Thus, high correlations between some measures and subscales could be driven by spurious variance attributable to the measurement method rather than the measured construct (shared method variance). In general, it will be important for scientists to balance concerns about parsimony on the one hand (which would motivate convergence so as to reduce the number of constructs) and discriminance on the other (which would motivate retaining meaningful demarcations between constructs). Current measures are not rendered entirely useless, despite their limitations. However, there are numerous ways in which psychedelic researchers can enhance the ability of acute psychedelic measures to more accurately measure their intended construct validly. Foremost among these are qualitative processes and response process techniques to reduce construct-irrelevant factors. One such qualitative process, cognitive interviewing, is a technique within response process validation in which researchers examine how respondents understand items. Another example is think-aloud protocols, in which respondents are asked to talk through their cognitive processes while responding to items 117 . The probe-based method 118 directs respondents' attention to parts of a measure that might be confusing (for example, "What does the term 'unity' mean to you?", "Can you repeat the question I just asked you in your own words?"). Finally, cognitive interviews would be valuable in understanding how well respondents comprehend the language and concepts used in acute subjective measures of psychedelic experience. Unfortunately, response process validity evidence is under-represented in psychedelic research. Some initiatives have applied these techniques using open-ended responses rather than cognitive interviews. For example, the response process evaluation method 121 uses open-ended responses and iterative measurement to probe whether respondents understand each item, and has been used to establish item-level validity in the Inventory of Non-Ordinary Experiences in the United States and India. There are ongoing scientific efforts that aim to expand the representativeness of content related to psychedelic experience and capture a more nuanced representation of the subjective effects. The evaluations of the convergent, discriminant and criterion validity of the measures can be improved through precise pre-registered hypotheses, the application of multi-trait, multi-method approaches that provide a comprehensive examination of the constructs, inquiry into the temporal aspects of the experiences and characterizing construct-irrelevant factors to reduce potential artefactual associations. Although construct-irrelevant variance weakens a measure's validity and is a crucial object of future study, it might not entirely
compromise a measure's capacity to adequately signal the underlying theoretical construct. Indeed, there is no direct evidence of a pernicious influence of construct-irrelevant variance in the context of acute psychedelic measurement as of yet, so further study is needed, but improvements should nonetheless proceed in the meantime. Using study design techniques can help to mitigate judgement biases. For example, improving active placebo conditions so that they are indistinguishable from classic psychedelic experience can keep participants blinded, a necessary condition for properly placebo-controlled trials. Recruiting individuals without psychedelic use history and with low knowledge of psychedelics can help to preserve blinding and reduce reporting biases such as the halo effect. In the context of clinical trials, measures are included to provide information to predict future therapeutic or adverse responses and to make progress in identifying potential therapeutic mechanisms. Beyond existing measures, a more principled, systematic approach is needed to construct future measures. A more nuanced approach can help to correct current limitations in representativeness and the discrepancies between the pursued aims of the measures and their content. Importantly, new measures should be explicit about the theoretical assumptions used to identify the acute subjective effects of interest.
The psychedelic sciences have made relevant scientific advances in understanding acute subjective effects and linking these effects to other variables such as future therapeutic benefits, risks and changes in neurobiology. However, one potential problem in psychedelic science is that psychedelic experiences have been approached somewhat separately from ordinary cognitive and psychological states. Measures of the acute subjective effects of psychedelics often seem to include psychological processes that are better studied in psychological science more generally, such as emotions, feelings of connection, metaphysical beliefs and changes to the senses of time, space and the self. The relationship between the specific constructs as defined in psychedelic science versus psychological science is yet to be empirically established, but identifying potential associations could enable links between psychedelic science and mainstream cognitive, affective and clinical psychology, and help to understand the therapeutic impact of psychedelics. An in-depth inquiry into how acute affective changes (both positive and negative) might translate into persisting therapeutic benefits and risks represents a promising direction for psychedelic research. Positive affect is a common psychological construct that has been studied for several decades, and substantial evidence supports theories that outcomes such as a broadening of one's thought-action repertoire can promote the building of psychosocial resources 124 . Several studies have focused on positive affect as an outcome measure assessed weeks after a psychedelic experience, but it has rarely been featured among therapeutically relevant mechanisms of persisting therapeutic benefits, despite work suggesting that positive emotions may underlie psychedelics' therapeutic outcomes 125 . Similarly, negative affect is a commonly assessed component of challenging psychedelic experiences, which can include feelings of anxiety, fear and paranoia. Facets of affect can be identified in measures of the acute subjective effects of psychedelics, such as the positive mood factor of the Mystical Experience Questionnaire and the blissfulness factor of the 11-Dimensional Altered State of Consciousness scale, or the anxiety subscale of the Challenging Experience Questionnaire and in sub-scales of the 11-Dimensional Altered State of Consciousness scale. Awe is among the most relevant emotions related to the acute subjective effects of psychedelics, given the information overload and enormity of perceived meaning often involved in the acute subjective effects, and the extensive inner worlds, connectedness and small self often reported during psychedelic states. Awe is more generally defined in terms of two appraisal dimensions: the perception of vastness (both literal and figurative) and the need for cognitive accommodation (incorporating unexpected experiences into one's mental schemata). Awe has been investigated across several triggers, such as natural scenery, virtual reality, videos (for example, nature documentaries) and witnessing other people engaging in acts of excellence and virtue, and has been found to promote learningand decrease dependence on internal knowledge (what an individual already knows). In psychedelic research contexts, awe has been proposed as a major therapeutic mechanism of psychedelics. The 11-Dimensional Altered State of Consciousness scale and the Mystical Experience Questionnaire scales assess awe explicitly (for example, with the item 'sense of awe or awesomeness'). Feeling connected -as opposed to isolated -might result in beneficial psychological effects. The need to belong is a well-established psychological motivation 137 and a well-replicated finding is that the negative consequences of loneliness are legion. Connectedness is a sense of relatedness and enhanced feelings of association with the self, others and/or the wider world (aspects of one's environment or broader context). Connectedness is not merely an emotion; there is a low correlation between feelings of connection and emotions, but connectedness is related to positive emotions, including awe. A sense of connectedness is explicit in most measures of the acute subjective effects of psychedelics, such as the 11-Dimensional and 5-Dimensional Altered State of Consciousness scales' experience of unity and oceanic boundlessness factors, and the Mystical Experience Questionnaire's mystical factor and measures devoted entirely to feelings of connectedness like the Watts Connectedness Scale. There are semantic distinctions between the terms used to assess connectedness across scales, but their connotations are similar, as evidenced by items being clustered together algorithmically based on similar participants' responses across samples. There are some acute subjective effects of psychedelics that could be considered related to religious and/or spiritual beliefs or Psychedelic experiences comprise an enormous number of possible subjective effects, only some of which existing measures capture. Some of these effects could be conceptually defined as a sense of connectedness, perceptual alterations, changes in affect and cognition, modified sense of time, space, and the self, and physiological sensations (larger circles). A diverse set of sub-scales or factors, which can represent clusters of items (smaller circles) within scales, might capture some aspect of the subjective effects. There might be conceptual overlap across the factors' definitions and the items that comprise the scales. Additional aspects of the subjective experience of psychedelics are yet to be captured by measures (which could be conceptualized as the blank space in the background of the figure). These factors are conceptually arranged for demonstration purposes and require future empirical work to determine dimensionality.
attributions, which have been studied in the field of psychology of religion and spirituality 140 . Such religious or spiritual qualities are captured by items such as the oceanic boundlessness and spiritual experience factors in the 11-Dimensional and 5-Dimensional Altered State of Consciousness scales. God-encounter 8 and entity-encounter experienceshave been examined in psychedelic research and are also often explored within the field of the psychology of religion. The therapeutic relevance of such experiences and attributions is unclear (and raises ethical and clinical challenges 141 ). Furthermore, the more specific noetic quality 142 might warrant specific attention in relation to metaphysical beliefs. Psychedelic states are usually associated with a feeling of hyper-realness or the sense that the experience is somehow 'realer than real'. The noetic quality might facilitate a process of imbuing certain elements of experience and knowledge with positive value. Understanding the sense of realness individuals ascribe to spiritual experiences might assist scientists in making sense of religious and/or spiritual beliefs, interpretations or attributions that sometimes follow psychedelic experiences. The senses of time, space and the self are quite fundamental faculties, or categories, of consciousness and have been studied in the psychological sciences using several methods. The fact that these senses can be altered with psychedelics could present opportunities to study each of them individually and how they relate to one another. For example, a neuroimaging study on temporal, social and spatial distance found a common cortical region that tracks the senses of time, space and the self 144 , showing some degree of overlap. Systematic work in the psychology of time perception has linked time perception to attention and spatial awareness to research on proprioception and peri-personal space. Changes in the sense of time and space during the acute subjective effects of psychedelics are captured by most measures. Self-reported changes to the sense of space can occur in terms of both one's immediate surroundings as well as with one's body in relation to one's surroundings. Acute insights that are deemed persuasive, helpful and meaningful represent another core aspect of psychedelic experience that has been associated with positive long-term changesand therapeutic value in clinical trials. Although there may be distinct neurobiological processes underlying psychedelic-mediated insights, such insights may very well share processes in common with other forms of insight studied by previous scientists in the context of problemsolving and learning. For example, early pioneer research on chimpanzees 149 observed the derivation of sudden and novel solutions to difficult problems following periods of contemplation, and research on rats 150 demonstrated a capacity for learning that was not mediated by operant or classical conditioning (latent learning). We encourage the connection of psychedelic science to contemporary scientific inquiries into psychological processes underlying psychological insight. In sum, psychedelic experiences include changes to affect, cognition and perception that relate to better-known processes in the psychological sciences. In moving beyond existing measures for the subjective experiences of psychedelics, elaborating on these links to existing areas of study could help avert the field of psychedelic science from reinventing constructs and failing to build upon pre-existing knowledge.
The acute subjective effects of psychedelics are relevant to understanding the risks, benefits and mechanisms of psychedelics, and could inform research on non-psychedelically triggered altered states of consciousness. Our overview of the existing literature indicates that theories and measures approach the acute subjective effects of psychedelics using diverse conceptualizations (from broad to narrow), that measures assess diverse constructs (some of which have poor construct validity), and that diverse scales and subscales might measure similar latent constructs in some cases. Psychedelic science is no longer in its infancy; however, precisely measuring the acute subjective effects of psychedelics is one of the field's dimensions that requires further development and maturation. Reconciling measures and methods between psychedelic and psychological science might be challenging, but it is undoubtedly a worthwhile future direction for the field. Although existing measures were created following a rationale and involved psychometric validation, items were generally drawn from a loose collection of top-down theoretical assumptions and from qualitative and anecdotal data. Relying on top-down approaches can pose serious content validity threats if the theory is overly constraining and relevant aspects of the construct are missed. To overcome current limitations, cognitive data from controlled laboratory contexts should be complemented with behavioural data from ecologically valid contexts using methods such as digital phenotyping and natural language processing. Experience sampling methods and temporal graphical approaches (illustrations of subjective effects over the course of an experience) could help to describe the acute subjective effects as they occur, and administering a series of short psychoactive experiences could help to reduce the range of acute subjective effects reported from a longer drug administration session. Researchers should also consider more rigorous designs to improve validity. Effective blinding and examining participants' expectations and prior knowledge of psychedelics might mitigate biased responding. Including participants from diverse cultural and sociodemographic backgrounds will increase generalizability, and measurement invariance techniques (such as structural equation modelling) can help to identify whether the factor structure of acute subjective effects differs across various groups, settings and drugs and whether they continue to predict therapeutically relevant outcomes. To enable quantitative comparisons across studies, we recommend a standardized administration of valid existing measures including testing at standard time points after dosing, assessing positive and negative experiences, and considering broad and narrow measures to answer targeted hypotheses. Ultimately, these improvements should help the applied utility of existing measures for predicting therapeutic outcomes across groups. When considering future directions, determining whether existing latent constructs are recovered through a bottom-up and more datadriven process is important. Theoretical (top-down) and data-driven atheoretical (bottom-up) approaches to construct validation are not incompatible. Bottom-up approaches can facilitate the discovery of boundaries between constructs that inform theory and can be subsequently subject to rigorous testing. Although we advocate for moving beyond current conceptualizations and measures, we acknowledge the inevitable need to use psychometric self-report measures as a method. Accordingly, we support a broad measurement approach that pulls from an array of data from acute subjective psychedelic experiences and ordinary cognitive state measures. Going forward, we recommend a bottom-up, principled and systematic process that uses conceptually adequate criteria and qualitative vetting to select candidate items and an iterative dimensionality-reduction process
(factor and network analysis)to capture a comprehensive picture of the subjective effects of psychedelics. Quantitative techniques are available for such a systematic process. Latent variable modelling is useful to reduce method variance by creating latent variables from several variables that differ in method but reflect the same acute subjective effect (for example, assess the same effect across self-report and semi-structured interviews), and to deliver new latent variables supported by the identification of shared variance across constructs. Network analysis can be used to model how acute subjective states covary and interact with each other within a network 161 . However, one of the principles of network theoryis that variables are interrelated owing to direct interactions rather than external causal factors. It is unclear how this principle would apply in the present context. For this reason, we do not believe network analysis should entirely replace latent variable modelling (but, rather, complement it), and network modelling does not preclude integrating latent variables. Relatedly, semantic network analysis -which assesses word similarity, word importance and latent semantic analysis between different scales -can be used to determine how much a new scale's items might overlap with those of existing scales prior to data collection, potentially saving resources and helping to promote discriminant semantic validity. Constructs are likely to be organized at superordinate and subordinate levels of a hierarchy. A straightforward method for characterizing this hierarchy is the bass-ackwards approach 164 , in which an ascending number of principal components or factors are gradually extracted to unfold hierarchical relations. This method could be applied to a granular array of acute subjective experiences to delineate divisions between constructs, which could be obscured if only larger attributes at a superordinate level of construct hierarchy (for example, mysticaltype experience scores) are included as variables. Some scholars might be concerned that this approach will result in losing the distinctiveness of more granular features of acute experience, and over-favour parsimony. However, granular features are not lost in a hierarchical model of constructs; they are represented at lower levels of the hierarchy, just as lower-level personality facets are represented in the five-factor model of personality. Qualitative, iterative and evidence-based approaches to item development that use meta-surveys and interviews to probe sources of construct-irrelevant variance are a crucial component of validity that quantitative approaches neglect. Response process techniques such as cognitive interviewing and the response process evaluation method 121 could be applied simultaneously to the mentioned techniques to ensure the validity of existing and next-generation items. Additionally, team science approaches, in which multiple researchers and laboratories collaborate to examine a particular research topic, can help better elucidate the robustness of a particular finding. Adversarial collaborations such as many-analysts approaches in which numerous independent research teams analyse the same dataset to address a research question can help mitigate individual-researcher bias 166 . Multiverse approaches that conduct target analyses across a comprehensive set of alternatively processed datasets might clarify the robustness of an effect across different data processing methods (for example, by excluding cases or transforming variables). The field of psychometric measures has advanced, and nextgeneration measures ought to be developed to improve on and surpass existing paradigms to understand the acute subjective effects of psychedelics. After all, the questions of what psychedelic experiences are like and how these experiences impact persisting risks and benefits is of urgent interest to scientists and the public, and systematically asking people about their experiences will be a necessary part of any scientific answer. Published online: 3 September 2024
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