Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study.

Recent studies suggest psychedelic use may be associated with changes in a variety of beliefs or belief-like states, including increased 1) mind perception, 2) non-naturalistic beliefs, and 3) Atheist-Believer status (e.g. believer, agnostic, or nonbeliever). We conducted a prospective longitudinal study among participants (N = 657) who planned to have a psilocybin experience outside a laboratory setting. We asked participants about their beliefs concerning mind perception of various entities, specific metaphysical positions, and Atheist-Believer status both before (and after their experience. Replicating previous findings, we observed increases in mind perception across a variety of living and non-living targets (e.g. plants, rocks). However, we found little to no change in metaphysical beliefs (e.g. dualism) or Atheist-Believer status. Taken together, these findings contrast with those from cross-sectional studies that psilocybin experiences result in changes to Atheist-Believer status and non-naturalistic beliefs but support the relevance of mind perception and mentalization.

Valuing the Acute Subjective Experience.

Psychedelics, including psilocybin, and other consciousness-altering compounds such as 3,4-methylenedioxymethamphetamine (MDMA), currently are being scientifically investigated for their potential therapeutic uses, with a primary focus on measurable outcomes: for example, alleviation of symptoms or increases in self-reported well-being. Accordingly, much recent discussion about the possible value of these substances has turned on estimates of the magnitude and duration of persisting positive effects in comparison to harms. However, many have described the value of a psychedelic experience with little or no reference to such therapeutic benefits, instead seeming to find the experience valuable in its own right. How can we make sense of such testimony? Could a psychedelic experience be valuable even if there were no persisting beneficial effects? If so, how? Using the concept of psychological richness, combined with insights from the philosophy of aesthetics and the enhancement literature, this essay explores potential sources of value in the acute subjective experience, apart from the value derived from persisting beneficial effects.

Large language models could change the future of behavioral healthcare: a proposal for responsible development and evaluation.

Large language models (LLMs) such as Open AI's GPT-4 (which power ChatGPT) and Google's Gemini, built on artificial intelligence, hold immense potential to support, augment, or even eventually automate psychotherapy. Enthusiasm about such applications is mounting in the field as well as industry. These developments promise to address insufficient mental healthcare system capacity and scale individual access to personalized treatments. However, clinical psychology is an uncommonly high stakes application domain for AI systems, as responsible and evidence-based therapy requires nuanced expertise. This paper provides a roadmap for the ambitious yet responsible application of clinical LLMs in psychotherapy. First, a technical overview of clinical LLMs is presented. Second, the stages of integration of LLMs into psychotherapy are discussed while highlighting parallels to the development of autonomous vehicle technology. Third, potential applications of LLMs in clinical care, training, and research are discussed, highlighting areas of risk given the complex nature of psychotherapy. Fourth, recommendations for the responsible development and evaluation of clinical LLMs are provided, which include centering clinical science, involving robust interdisciplinary collaboration, and attending to issues like assessment, risk detection, transparency, and bias. Lastly, a vision is outlined for how LLMs might enable a new generation of studies of evidence-based interventions at scale, and how these studies may challenge assumptions about psychotherapy.

Strong Bipartisan Support for Controlled Psilocybin Use as Treatment or Enhancement in a Representative Sample of US Americans: Need for Caution in Public Policy Persists.

The psychedelic psilocybin has shown promise both as treatment for psychiatric conditions and as a means of improving well-being in healthy individuals. In some jurisdictions (e.g., Oregon, USA), psilocybin use for both purposes is or will soon be allowed and yet, public attitudes toward this shift are understudied. We asked a nationally representative sample of 795 US Americans to evaluate the moral status of psilocybin use in an appropriately licensed setting for either treatment of a psychiatric condition or well-being enhancement. Showing strong bipartisan support, participants rated the individual's decision as morally positive in both contexts. These results can inform effective policy-making decisions around supervised psilocybin use, given robust public attitudes as elicited in the context of an innovative regulatory model. We did not explore attitudes to psilocybin use in unsupervised or non-licensed community or social settings.

Characterizing empathy and compassion using computational linguistic analysis.

Many scholars have proposed that feeling what we believe others are feeling-often known as "empathy"-is essential for other-regarding sentiments and plays an important role in our moral lives. Caring for and about others (without necessarily sharing their feelings)-often known as "compassion"-is also frequently discussed as a relevant force for prosocial motivation and action. Here, we explore the relationship between empathy and compassion using the methods of computational linguistics. Analyses of 2,356,916 Facebook posts suggest that individuals (N = 2,781) high in empathy use different language than those high in compassion, after accounting for shared variance between these constructs. Empathic people, controlling for compassion, often use self-focused language and write about negative feelings, social isolation, and feeling overwhelmed. Compassionate people, controlling for empathy, often use other-focused language and write about positive feelings and social connections. In addition, high empathy without compassion is related to negative health outcomes, while high compassion without empathy is related to positive health outcomes, positive lifestyle choices, and charitable giving. Such findings favor an approach to moral motivation that is grounded in compassion rather than empathy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

IUPHAR-review: The integration of classic psychedelics into current substance use disorder treatment models.

Substance use disorders (SUDs) have an enormous impact on public health. With classic psychedelic-assisted therapies showing initial promise in treating multiple SUDs, it is possible that these treatments will become legally available options for patients with SUDs in the future. This article highlights how classic psychedelic-assisted therapies might be integrated into current clinical practice. We first describe contemporary evidence-based treatments for SUDs and highlight how classic psychedelic-assisted therapies might fit within each treatment. We suggest that classic psychedelic-assisted therapies can be integrated into most mainstream evidence-based SUD treatments that are currently used in clinical settings, indicating broad compatibility of classic psychedelics with contemporary SUD treatment paradigms.

Psychedelic Science, Contemplative Practices, and Indigenous and Other Traditional Knowledge Systems: Towards Integrative Community-Based Approaches in Global Health.

As individuals and communities around the world confront mounting physical, psychological, and social threats, three complimentary mind-body-spirit pathways toward health, wellbeing, and human flourishing remain underappreciated within conventional practice among the biomedical, public health, and policy communities. This paper reviews literature on psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems to make the case that combining them in integrative models of care delivered through community-based approaches backed by strong and accountable health systems could prove transformative for global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that can generate positive effects on health, well-being, and prosocial behavior, and combining them appears to have synergistic effects. Traditional knowledge systems can be rich sources of ethnobotanical expertise and repertoires of time-tested practices. A decolonized agenda for psychedelic research and practice involves engaging with the stewards of such traditional knowledges in collaborative ways to codevelop evidence-based models of integrative care accessible to the members of these very same communities. Going forward, health systems could consider Indigenous and other traditional healers or spiritual guides as stakeholders in the design, implementation, and evaluation of community-based approaches for safely scaling up access to effective psychedelic treatments.

Acute Subjective Effects of Psychedelics within and Beyond WEIRD Contexts.

Reports of psychedelic experiences may contain similarities and differences across cultural contexts, but most current characterizations and quantifications of psychedelic experiences come from Western medical and naturalistic settings. In this article, we begin with a brief history of the diversity of psychedelic use in non-Western settings. We then compare and contrast accounts of psychedelic experiences within and beyond Western, educated, industrialized, rich, and democratic (WEIRD) contexts. We focus on specific reports of direct testimony of the acute subjective effects of psychedelics experienced across these contexts. We compare themes from each of these various contexts, with special emphasis on psychometric measures such as the mystical experiences questionnaire (MEQ), the five-dimensional altered states of consciousness (5D-ASC) scale, the Survey of God Encounters, and the Survey of Entity Encounters, the Challenging Experiences Questionnaire, and the Inventory of Nonordinary Experiences (INOE). Finally, we offer recommendations for future research to quantify these similarities and differences across cultures to assess them empirically in the future.

Positive psychology psychoeducation makes a small impact on undergraduate student mental health: Further curriculum innovation and better well-being research needed.

OBJECTIVES: Courses on well-being are increasingly evaluated to see how they may promote mental health in college. We examined the impact of a course on students' well-being, anxiety, and depression. METHODS: Subjects were undergraduates enrolled in the "Science of Happiness," (SOH) (n = 105), and "Child and Adolescent Psychopathology," (CAP) (n = 114). Well-being measures included the PERMA Profiler and Satisfaction with Life Scale (SWLS) at the beginning and conclusion of the semester. The Depression Anxiety and Stress Scale - 21 items (DASS-21) measured psychopathology. RESULTS: There were significant improvements on the SWLS 1.28 (p = .038; d = .264) in SOH. There was no improvement for the PERMA Profiler in either group, and no differences between groups. There was no significant change on the DASS-21 for SOH subjects. CONCLUSIONS: Undergraduate courses that deliver positive psychology psychoeducation have a small effect size even in non-randomized studies. Future curriculum innovation is needed and better research to validate positive psychology psychoeducation.

Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use.

BACKGROUND: Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggest that psilocybin's effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period. AIMS: To learn the extent to which antidepressants may diminish the effects of psilocybin-containing mushrooms both concurrently and after discontinuation of antidepressants. METHODS: Online retrospective survey of individuals with use of psilocybin mushrooms (1) with an antidepressant and/or (2) within 2 years of discontinuing an antidepressant. Participants who took mushrooms with an antidepressant and either took the same dose pre-antidepressant or took the same dose with other people not on antidepressant reported the strength of drug effects relative to their expectation. Participants who took mushrooms following discontinuation of an antidepressant also reported the presence of weakened effects. RESULTS: In reports (n = 611) of taking mushrooms with an antidepressant, probabilities [95% CI] of weaker than expected drug effects were 0.47 [0.41-0.54] (selective serotonergic reuptake inhibitors, SSRIs), 0.55 [0.44-0.67] (serotonin norepinephrine reuptake inhibitors, SNRIs) and 0.29 [0.2-0.39] (bupropion). Following SSRI/SNRI discontinuation (n = 1,542 reports), the probability of reduced drug effects was not significantly different from the earliest post-discontinuation timepoint (within 1 week) until 3-6 months, probability = 0.3 [0.20-0.46], p = 0.001. A sensitivity analysis found that removing responses involving fluoxetine, which has an especially long half-life, did not significantly alter this result. CONCLUSIONS: SSRI/SNRIs appear to weaken psilocybin drug effects relative to a non-serotonergic antidepressant. This dampening effect may last as long as 3 months following antidepressant discontinuation.

Predicting U.S. county opioid poisoning mortality from multi-modal social media and psychological self-report data.

Opioid poisoning mortality is a substantial public health crisis in the United States, with opioids involved in approximately 75% of the nearly 1 million drug related deaths since 1999. Research suggests that the epidemic is driven by both over-prescribing and social and psychological determinants such as economic stability, hopelessness, and isolation. Hindering this research is a lack of measurements of these social and psychological constructs at fine-grained spatial and temporal resolutions. To address this issue, we use a multi-modal data set consisting of natural language from Twitter, psychometric self-reports of depression and well-being, and traditional area-based measures of socio-demographics and health-related risk factors. Unlike previous work using social media data, we do not rely on opioid or substance related keywords to track community poisonings. Instead, we leverage a large, open vocabulary of thousands of words in order to fully characterize communities suffering from opioid poisoning, using a sample of 1.5 billion tweets from 6 million U.S. county mapped Twitter users. Results show that Twitter language predicted opioid poisoning mortality better than factors relating to socio-demographics, access to healthcare, physical pain, and psychological well-being. Additionally, risk factors revealed by the Twitter language analysis included negative emotions, discussions of long work hours, and boredom, whereas protective factors included resilience, travel/leisure, and positive emotions, dovetailing with results from the psychometric self-report data. The results show that natural language from public social media can be used as a surveillance tool for both predicting community opioid poisonings and understanding the dynamic social and psychological nature of the epidemic.

A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression.

Objectives: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis. Design: Reanalysis of a two-arm double-blind placebo controlled trial. Participants: Fifty-nine patients with MDD. Interventions: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups. Outcome measures: Quick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A. Results: Using Bayes factors and 'skeptical priors' which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a 'clinically meaningful amount' (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin's non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis. Conclusions: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful--and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments. Trial registration number: NCT03429075.

Psychedelics, Meaningfulness, and the "Proper Scope" of Medicine: Continuing the Conversation.

Psychedelics such as psilocybin reliably produce significantly altered states of consciousness with a variety of subjectively experienced effects. These include certain changes to perception, cognition, and affect,1 which we refer to here as the acute subjective effects of psychedelics. In recent years, psychedelics such as psilocybin have also shown considerable promise as therapeutic agents when combined with talk therapy, for example, in the treatment of major depression or substance use disorder.2 However, it is currently unclear whether the aforementioned acute subjective effects are necessary to bring about the observed therapeutic effects of psilocybin and other psychedelics. This uncertainty has sparked a lively-though still largely hypothetical-debate on whether psychedelics without subjective effects ("nonsubjective psychedelics" or "non-hallucinogenic psychedelics") could still have the same therapeutic impact, or whether the acute subjective effects are in fact necessary for this impact to be fully realized.3,4,5.

AI-based analysis of social media language predicts addiction treatment dropout at 90 days.

The reoccurrence of use (relapse) and treatment dropout is frequently observed in substance use disorder (SUD) treatment. In the current paper, we evaluated the predictive capability of an AI-based digital phenotype using the social media language of patients receiving treatment for substance use disorders (N = 269). We found that language phenotypes outperformed a standard intake psychometric assessment scale when predicting patients' 90-day treatment outcomes. We also use a modern deep learning-based AI model, Bidirectional Encoder Representations from Transformers (BERT) to generate risk scores using pre-treatment digital phenotype and intake clinic data to predict dropout probabilities. Nearly all individuals labeled as low-risk remained in treatment while those identified as high-risk dropped out (risk score for dropout AUC = 0.81; p < 0.001). The current study suggests the possibility of utilizing social media digital phenotypes as a new tool for intake risk assessment to identify individuals most at risk of treatment dropout and relapse.

Reconsidering "dissociation" as a predictor of antidepressant efficacy for esketamine.

RATIONALE: The relationship between subjective drug experience and antidepressant outcomes for ketamine derivatives is poorly understood but of high clinical relevance. Esketamine is the patented (S)-enantiomer of ketamine and has regulatory approval for psychiatric applications. OBJECTIVES: We examined the relationship between acute dissociation, as measured by the Clinician-Administered Dissociative States Scale (CADSS), and antidepressant efficacy, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), for esketamine across the 4-week induction phase of treatment. METHODS: This post hoc analysis combined data (N = 576) from the TRANSFORM-1 and TRANSFORM-2 clinical trials of esketamine for treatment-resistant depression. Linear mixed models were performed using total MADRS score as the outcome variable with the following independent variables: baseline MADRS score, treatment condition × time interaction, and CADSS × time interaction. To assess whether initial dissociation predicted rapid antidepressant benefit with esketamine, a separately planned regression was performed with day 2 MADRS as the outcome variable with the following dependent variables: baseline MADRS, treatment condition, and day 1 CADSS. RESULTS: The linear mixed model did not show any effect of a CADSS × time interaction (p = 0.7). Looking solely at the effect of day 1 CADSS on day 2 MADRS revealed that each additional CADSS point was associated with a - .04 [95% CI - .08, - .002] (p = .04) decrease in MADRS score. CONCLUSIONS: We found no evidence of a clinically significant positive or negative association between dissociation and antidepressant effect for esketamine. Our findings suggest that subsequent inquiry in this area will benefit from improved characterization of drug experiences relevant to therapeutic outcomes.