History repeating: guidelines to address common problems in psychedelic science.

Research in the last decade has expressed considerable optimism about the clinical potential of psychedelics for the treatment of mental disorders. This optimism is reflected in an increase in research papers, investments by pharmaceutical companies, patents, media coverage, as well as political and legislative changes. However, psychedelic science is facing serious challenges that threaten the validity of core findings and raise doubt regarding clinical efficacy and safety. In this paper, we introduce the 10 most pressing challenges, grouped into easy, moderate, and hard problems. We show how these problems threaten internal validity (treatment effects are due to factors unrelated to the treatment), external validity (lack of generalizability), construct validity (unclear working mechanism), or statistical conclusion validity (conclusions do not follow from the data and methods). These problems tend to co-occur in psychedelic studies, limiting conclusions that can be drawn about the safety and efficacy of psychedelic therapy. We provide a roadmap for tackling these challenges and share a checklist that researchers, journalists, funders, policymakers, and other stakeholders can use to assess the quality of psychedelic science. Addressing today's problems is necessary to find out whether the optimism regarding the therapeutic potential of psychedelics has been warranted and to avoid history repeating itself.

Awe arises in reaction to exceeded rather than disconfirmed expectancies.

Awe is a fascinating emotion, associated with positive consequences such as greater prosociality, generosity, and epistemic openness. Unfortunately, in spite of the weighty consequences of awe, the exact way in which it arises, and what it entails, is still a puzzle. Particularly puzzling is the question of whether awe is the result of expectancy violation. While awe is thought to arise in reaction to expectancy-violating objects or events, classical expectancy violations (e.g., a red queen of spades playing card) do not tend to cause awe. To shed light on this problem, we distinguished two types of expectancy violations-those that disconfirm and those that exceed one's expectancies-and we investigated whether awe is more likely to arise in reaction to one versus the other. We also looked at what appraisals constitute and are most important to the awe experience and how they structurally interact. To do this, we utilized network analysis and mapped out the network structure of appraisals linked to awe and to expectancy violations. Across two experimental studies (N = 823), we demonstrated that awe arises in reaction to exceeded (rather than disconfirmed) expectancies and that appraisals linked to exceeded expectancies (vastness and uniqueness) are central to awe, while appraisals linked to disconfirmed expectancies (uncertainty and inconsistency) are peripheral to the awe experience. Taken together, our investigation sheds new light on psychologists' understanding of expectancy violations and reveals when and how awe arises and what it entails. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ayahuasca and Public Health II: Health Status in a Large Sample of Ayahuasca-Ceremony Participants in the Netherlands.

Ayahuasca is a plant decoction in traditional Amazonian medicine. Its ritual use has been internationalized, leading to policy challenges that countries should address. This study evaluates the impact of regular ayahuasca ceremony participation on health by assessing the health status of 377 participants in ayahuasca ceremonies in the Netherlands using validated health indicators. A questionnaire was developed and administered to study participants. The questionnaire included several health indicators with public health relevance (e.g., BMI, diet, physical activity) and psychometrically validated questionnaires (ELS and COPE-easy). The data retrieved through health indicators was compared to normative Dutch data. Participants (50.1% women) were mostly Dutch (84.6%) with a mean age of 48.8 years (SD = 11.6). Compared to normative Dutch data, regular participants in ayahuasca ceremonies showed better general well-being, fewer chronic or lifestyle-related diseases, more physical activity, and a more balanced diet. Participants also used less alcohol during the COVID-19 pandemic, and although they used more illegal drugs than the general population, they did not report associated harms. Our findings suggest that regular participation in ayahuasca ceremonies is not linked to relevant health harms. This data could help drug policymakers to develop and implement evidence-based public policies.

Pharmacological, neural, and psychological mechanisms underlying psychedelics: A critical review.

This paper provides a critical review of several possible mechanisms at different levels of analysis underlying the effects and therapeutic potential of psychedelics. At the (1) biochemical level, psychedelics primarily affect the 5-HT2A receptor, increase neuroplasticity, offer a critical period for social reward learning, and have anti-inflammatory properties. At the (2) neural level, psychedelics have been associated with reduced efficacy of thalamo-cortical filtering, the loosening of top-down predictive signaling and an increased sensitivity to bottom-up prediction errors, and activation of the claustro-cortical-circuit. At the (3) psychological level, psychedelics have been shown to induce altered and affective states, they affect cognition, induce belief change, exert social effects, and can result in lasting changes in behavior. We outline the potential for a unifying account of the mechanisms underlying psychedelics and contrast this with a model of pluralistic causation. Ultimately, a better understanding of the specific mechanisms underlying the effects of psychedelics could allow for a more targeted therapeutic approach. We highlight current challenges for psychedelic research and provide a research agenda to foster insight in the causal-mechanistic pathways underlying the efficacy of psychedelic research and therapy.

The Einstein effect provides global evidence for scientific source credibility effects and the influence of religiosity.

People tend to evaluate information from reliable sources more favourably, but it is unclear exactly how perceivers' worldviews interact with this source credibility effect. In a large and diverse cross-cultural sample (N = 10,195 from 24 countries), we presented participants with obscure, meaningless statements attributed to either a spiritual guru or a scientist. We found a robust global source credibility effect for scientific authorities, which we dub 'the Einstein effect': across all 24 countries and all levels of religiosity, scientists held greater authority than spiritual gurus. In addition, individual religiosity predicted a weaker relative preference for the statement from the scientist compared with the spiritual guru, and was more strongly associated with credibility judgements for the guru than the scientist. Independent data on explicit trust ratings across 143 countries mirrored our experimental findings. These findings suggest that irrespective of one's religious worldview, across cultures science is a powerful and universal heuristic that signals the reliability of information.

Effects of psilocybin microdosing on awe and aesthetic experiences: a preregistered field and lab-based study.

There is an increased societal trend to engage in microdosing, in which small sub-hallucinogenic amounts of psychedelics are consumed on a regular basis. Following subjective reports that microdosing enhances the experience of nature and art, in the present study we set out to study the effects of psilocybin microdosing on feelings of awe and art perception. In this preregistered combined field- and lab-based study, participants took part in a microdosing workshop after which they volunteered to self-administer a psilocybin microdose or a placebo for three consecutive weeks, while the condition was kept blind to the participants and researchers. Following a 2-week break, the condition assignment was reversed. During each block, participants visited the lab twice to measure the effects of psilocybin microdosing vs. placebo. We used standardized measures of awe, in which participants reported their experiences in response to short videos or when viewing abstract artworks from different painters. Our confirmatory analyses showed that participants felt more awe in response to videos representing funny animals and moving objects in the microdosing compared to the placebo condition. However, about two-third of our participants were breaking blind to their experimental condition. Our exploratory findings suggest that expectancy-effects may be a driving factor underlying the subjective benefits of microdosing.

Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study.

BACKGROUND: Microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. Research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoceptive processing. AIMS: In this preregistered study, we investigated whether psilocybin microdoses alter self-reported interoceptive awareness and whether repeated microdosing over 3 weeks modulates emotion processing and reduces symptoms of anxiety and depression. METHODS: We used a double-blind, placebo-controlled, within-subject crossover design. Participants completed the Multidimensional Assessment of Interoceptive Awareness Questionnaire 1½ h after self-administering their second dose (or placebo), and the emotional go/no-go task and the shortened Depression Anxiety Stress Scale 1½ h after self-administering their seventh dose. RESULTS: Our confirmatory analyses revealed that psilocybin microdosing did not affect emotion processing or symptoms of anxiety and depression compared with placebo. Our exploratory analyses revealed that psilocybin microdosing did not affect self-reported interoceptive awareness, that symptoms of depression and stress were significantly reduced in the first block compared with baseline, that participants broke blind in the second block and that there was no effect of expectations. Further research in a substance-naïve population with clinical range anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing.

Social Adaptation in Context: The Differential Role of Religiosity and Self-Esteem in Vulnerable vs. Non-vulnerable Populations - A Registered Report Study.

There is evidence that religiosity and self-esteem are positively related, while self-esteem and religiosity in turn predict successful social adaptation. Moreover, self-esteem has been shown to be directly related to social adaptation in vulnerable contexts. In this registered report study, we tested the hypothesis that religiosity has a positive influence on social adaptation for people living in vulnerable contexts and that self-esteem is a mediator of this relationship. Evidence from this study indicates that neither there is any effect of religiosity on social adaptation nor on self-esteem, independent of whether people live in vulnerable contexts or not.

Working with Weirdness: A Response to "Moving Past Mysticism in Psychedelic Science".

In response to a recent call to rid psychedelic science of the concept of mystical experience, we argue that acknowledging the varieties and weirdness of psychedelic experiences should be at the heart of any research program on this topic. We highlight the rich tradition and scientific tools for studying mystical-type experiences, their relevance for understanding the therapeutic effects of psychedelics, as well as the need for more diversity in the experiences and participants included in this research.

A predictive processing framework of tool use.

In this paper I introduce the theory of predictive processing as a unifying conceptual framework to account for the human ability to use and innovate tools. I explain the basic concepts of predictive processing and illustrate how this framework accounts for the development of tool use in young infants and for findings in the neuropsychological and neuroscientific literature. Then, I argue that the predictive processing model needs to be complemented with a functional-evolutionary perspective, according to which the developmental and neurocognitive mechanisms should be understood in relation to the adaptive function that tools subserve. I discuss cross-cultural and comparative studies on tool use to illustrate how tools could facilitate a process of cumulative cultural and technological evolution. Furthermore, I illustrate how central premises of the predictive processing framework, such as the notion of Bayesian inference as a general principle and the role of prediction-error-updating, speak to central debates in evolutionary psychology, such as the massive modularity hypothesis and the trade-off between exploitation and innovation. Throughout the paper I make several concrete suggestions for future studies that could be used to put the predictive processing model of tool use to the test.

The role of meta-analysis and preregistration in assessing the evidence for cleansing effects.

Lee and Schwarz interpret meta-analytic research and replication studies as providing evidence for the robustness of cleansing effects. We argue that the currently available evidence is unconvincing because (a) publication bias and the opportunistic use of researcher degrees of freedom appear to have inflated meta-analytic effect size estimates, and (b) preregistered replications failed to find any evidence of cleansing effects.

Religious belief and cognitive conflict sensitivity: A preregistered fMRI study.

In the current preregistered fMRI study, we investigated the relationship between religiosity and behavioral and neural mechanisms of conflict processing, as a conceptual replication of the study by Inzlicht et al., (2009). Participants (N=193) performed a gender-Stroop task and afterwards completed standardized measures to assess their religiosity. As expected, the task induced cognitive conflict at the behavioral level and at a neural level this was reflected in increased activity in the anterior cingulate cortex (ACC). However, individual differences in religiosity were not related to performance on the Stroop task as measured in accuracy and interference effects, nor to neural markers of response conflict (correct responses vs. errors) or informational conflict (congruent vs. incongruent stimuli). Overall, we obtained moderate to strong evidence in favor of the null hypotheses that religiosity is unrelated to cognitive conflict sensitivity. We discuss the implications for the neuroscience of religion and emphasize the importance of designing studies that more directly implicate religious concepts and behaviors in an ecologically valid manner.

Broadening Your Mind to Include Others: The relationship between serotonergic psychedelic experiences and maladaptive narcissism.

RATIONALE: Recent research has shown that classical serotonergic psychedelic (CSP) drugs may be used to ameliorate certain health issues and disorders. Here we hypothesised that CSP experiences, through their ability to induce awe and ego-dissolution, may result in a reduction of maladaptive narcissistic personality traits, such as a strong sense of entitlement and lack of empathy. OBJECTIVES: Our objective was to investigate whether high levels of awe and ego dissolution during recent CSP experiences are associated with currently lower levels of maladaptive narcissism. METHODS: In this pre-registered high-powered (N = 414) study, we used an online retrospective survey asking participants to describe their 'most awe-inspiring, impressive, significant, or emotionally intense experience', as well as several validated scales to test our hypothesis. RESULTS: A statistically significant mediation model indicated that recent CSP-induced experiences were associated with currently increased feelings of connectedness and affective empathetic drive, which in turn were associated with decreased exploitative-entitled narcissism. This relationship held even when taking into account sensation-seeking personality features. We found no evidence for feelings of ego dissolution to have the same effect. CONCLUSIONS: Feelings of awe, but not ego dissolution, during recent CSP experiences were associated with increased feelings of connectedness and empathy, which in turn were associated with decreased levels of maladaptive narcissism personality features. This suggests that CSPs hold therapeutic potential for disorders involving connectedness and empathy, such as the treatment of pathological narcissism, and that the induction of connectedness through awe appears to be the driving force behind this potential.

The relationship between individual differences in gray matter volume and religiosity and mystical experiences: A preregistered voxel-based morphometry study.

The neural substrates of religious belief and experience are an intriguing though contentious topic. Here, we had the unique opportunity to establish the relation between validated measures of religiosity and gray matter volume in a large sample of participants (N = 211). In this registered report, we conducted a confirmatory voxel-based morphometry analysis to test three central hypotheses regarding the relationship between religiosity and mystical experiences and gray matter volume. The preregisterered hypotheses, analysis plan, preprocessing and analysis code and statistical brain maps are all available from online repositories. By using a region-of-interest analysis, we found no evidence that religiosity is associated with a reduced volume of the orbito-frontal cortex and changes in the structure of the bilateral inferior parietal lobes. Neither did we find support for the notion that mystical experiences are associated with a reduced volume of the hippocampus, the right middle temporal gyrus or with the inferior parietal lobes. A whole-brain analysis furthermore indicated that no structural brain differences were found in association with religiosity and mystical experiences. We believe that the search for the neural correlates of religious beliefs and experiences should therefore shift focus from studying structural brain differences to a functional and multivariate approach.

Experimentally induced awe does not affect implicit and explicit time perception.

The effects of emotion on time perception are elusive: depending on the intensity, valence and arousal of the situation, implicit and explicit time perception seems to slow down or speed up. Awe is a strong and powerful positive emotion that is typically elicited in response to vast stimuli and therefore inducing awe may be optimally suited for studying the relationship between emotion and time perception. In two studies we investigated whether the experience of awe would result in an expanded perception of time. Participants watched awe-eliciting, positive and neutral videos and simultaneously conducted a temporal bisection task, in which they classified vibrotactile stimuli as short or long. As expected awe videos elicited stronger feelings of awe than positive and control videos, while they were matched with positive videos in terms of subjective valence and arousal. However across both studies we did not find consistent effects of awe on implicit and retrospective time perception. Only in the first study, stronger subjective feelings of awe were associated with an increased dilation of time perception. The current findings indicate that lab-induced awe does not affect implicit and explicit time perception and we suggest that more ecologically valid ways to induce awe may be required in future studies.

Absorption and spiritual experience: A review of evidence and potential mechanisms.

Some people seem to have a 'talent' for spiritual experience: they readily sense the presence of supernatural beings, receive special messages from God, and report intense feelings of self-transcendence, awe and wonder. Here we review converging strands of evidence to argue that the trait of 'absorption' captures a general proclivity for having spiritual experiences. Participants scoring highly on the Tellegen Absorption Scale report vivid experiences of hearing God's voice during prayer, intense mystical experiences in response to psychedelics or placebo brain-stimulation, and strong feelings of presence and transcendence when confronted with natural beauty, virtual reality, or music. Several mechanisms may help to explain the relationship between absorption and spiritual experience. We suggest that absorption captures an experiential mindset that intensifies inner and outer sensory experience in ways that reflect both prior expectation and novel sensory engagement. It seems to enable that which must be imagined to feel more real.

The neural correlates of the awe experience: Reduced default mode network activity during feelings of awe.

In the present fMRI study, we aimed to obtain insight into the key brain networks involved in the experience of awe-a complex emotion that is typically elicited by perceptually vast stimuli. Participants were presented with awe-eliciting, positive and neutral videos, while they were instructed to get fully absorbed in the scenery or to count the number of perspective changes. By using a whole-brain analysis we found that several brain regions that are considered part of the default mode network (DMN), including the frontal pole, the angular gyrus, and the posterior cingulate cortex, were more strongly activated in the absorption condition. But this was less the case when participants were watching awe videos. We suggest that while watching awe videos, participants were deeply immersed in the videos and that levels of self-reflective thought were as much reduced during the awe videos, as during the perspective counting condition. In contrast, key regions of the fronto-parietal network (FPN), including the supramarginal gyrus, the medial frontal gyrus, and the insula, were most strongly activated in the analytical condition when participants were watching awe compared to positive and neutral videos. This finding underlines the captivating, immersive, and attention-grabbing nature of awe stimuli that is considered to be responsible for reductions in self-reflective thought. Together these findings suggest that a key feature of the experience of awe is a reduced engagement in self-referential processing, in line with the subjective self-report measures (i.e., participants perceived their self to be smaller).

Getting absorbed in experimentally induced extraordinary experiences: Effects of placebo brain stimulation on agency detection.

Previous work demonstrated that placebo brain stimulation can function as an experimental tool to elicit mystical and quasi-mystical (i.e., extraordinary) experiences. However, it has not yet been investigated whether these effects result from mere sensory deprivation and individual differences in suggestibility, or whether expectancy manipulations are crucial in eliciting these effects. In this study, we showed that extraordinary experiences could be systematically manipulated by means of an expectancy manipulation using a within-subjects design, while controlling for suggestibility effects. We further observed that participants' score on the Tellegen absorption scale, an individual difference measure reflecting people's propensity to get immersed in external stimuli or mental imagery, is related to the frequency and intensity of such experiences. Finally, we investigated the relationship between extraordinary experiences and agency detection, which has been hypothesized to be associated to supernatural beliefs and experiences. The experimental induction of extraordinary experiences did not result in increased agency detection.