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.

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.

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.

Regional personality assessment through social media language.

OBJECTIVE: We explore the personality of counties as assessed through linguistic patterns on social media. Such studies were previously limited by the cost and feasibility of large-scale surveys; however, language-based computational models applied to large social media datasets now allow for large-scale personality assessment. METHOD: We applied a language-based assessment of the five factor model of personality to 6,064,267 U.S. Twitter users. We aggregated the Twitter-based personality scores to 2,041 counties and compared to political, economic, social, and health outcomes measured through surveys and by government agencies. RESULTS: There was significant personality variation across counties. Openness to experience was higher on the coasts, conscientiousness was uniformly spread, extraversion was higher in southern states, agreeableness was higher in western states, and emotional stability was highest in the south. Across 13 outcomes, language-based personality estimates replicated patterns that have been observed in individual-level and geographic studies. This includes higher Republican vote share in less agreeable counties and increased life satisfaction in more conscientious counties. CONCLUSIONS: Results suggest that regions vary in their personality and that these differences can be studied through computational linguistic analysis of social media. Furthermore, these methods may be used to explore other psychological constructs across geographies.

Ethical Issues Regarding Nonsubjective Psychedelics as Standard of Care.

Evidence suggests that psychedelics bring about their therapeutic outcomes in part through the subjective or qualitative effects they engender and how the individual interprets the resulting experiences. However, psychedelics are contraindicated for individuals who have been diagnosed with certain mental illnesses, on the grounds that these subjective effects may be disturbing or otherwise counter-therapeutic. Substantial resources are therefore currently being devoted to creating psychedelic substances that produce many of the same biological changes as psychedelics, but without their characteristic subjective effects. In this article, we consider ethical issues arising from the prospect of such potential "nonsubjective" psychedelics. We are broadly supportive of efforts to produce such substances for both scientific and clinical reasons. However, we argue that such nonsubjective psychedelics should be reserved for those special cases in which the subjective effects of psychedelics are specifically contraindicated, whereas classic psychedelics that affect subjective experience should be considered the default and standard of care. After reviewing evidence regarding the subjective effects of psychedelics, we raise a number of ethical concerns around the prospect of withholding such typically positive, meaningful, and therapeutic experiences from most patients.

Psychedelics and Consciousness: Distinctions, Demarcations, and Opportunities.

Psychedelic substances produce unusual and compelling changes in conscious experience that have prompted some to propose that psychedelics may provide unique insights explaining the nature of consciousness. At present, psychedelics, like other current scientific tools and methods, seem unlikely to provide information relevant to the so-called "hard problem of consciousness," which involves explaining how first-person experience can emerge. However, psychedelics bear on multiple "easy problems of consciousness," which involve relations between subjectivity, brain function, and behavior. In this review, we discuss common meanings of the term "consciousness" when used with regard to psychedelics and consider some models of the effects of psychedelics on the brain that have also been associated with explanatory claims about consciousness. We conclude by calling for epistemic humility regarding the potential for psychedelic research to aid in explaining the hard problem of consciousness while pointing to ways in which psychedelics may advance the study of many specific aspects of consciousness.

Differences in brain morphometry associated with creative performance in high- and average-creative achievers.

Nearly everyone has the ability for creative thought. Yet, certain individuals create works that propel their fields, challenge paradigms, and advance the world. What are the neurobiological factors that might underlie such prominent creative achievement? In this study, we focus on morphometric differences in brain structure between high creative achievers from diverse fields of expertise and a 'smart' comparison group of age-, intelligence-, and education-matched average creative achievers. Participants underwent a high-resolution structural brain imaging scan and completed a series of intelligence, creative thinking, personality, and creative achievement measures. We examined whether high and average creative achievers could be distinguished based on the relationship between morphometric brain measures (cortical area and thickness) and behavioral measures. Although participants' performance on the behavioral measures did not differ between the two groups aside from creative achievement, the relationship between posterior parietal cortex morphometry and creativity, intelligence, and personality measures depended on group membership. These results suggest that extraordinary creativity may be associated with measurable structural brain differences, especially within parietal cortex.

Differences in brain activity patterns during creative idea generation between eminent and non-eminent thinkers.

An influential model of the neural mechanisms of creative thought suggests that creativity is manifested in the joint contributions of the Default Mode Network (DMN; a set of regions in the medial PFC, lateral and medial parietal cortex, and the medial temporal lobes) and the executive networks within the dorsolateral PFC. Several empirical reports have offered support for this model by showing that complex interactions between these brain systems account for individual differences in creative performance. The present study examined whether the engagement of these regions in idea generation is modulated by one's eminence in a creativity-related field. Twenty (n â€‹= â€‹20) healthy eminent creators from diverse fields of expertise and a 'smart' comparison group of sixteen (n â€‹= â€‹16) age- and education-matched non-eminent thinkers were administered a creative generation task (an adaptation of the Alternative Uses Task) and a control perceptual task, while undergoing functional magnetic resonance imaging (fMRI). The participants' verbal responses were recorded through a noise-canceling microphone and were later coded for fluency and accuracy. Behavioral and fMRI analyses revealed commonalities between groups, but also distinct patterns of activation in default mode and executive brain regions between the eminent and the non-eminent participants during creative thinking. We interpret these findings in the context of the well-documented contributions of these regions in the generation of creative ideas as modulated, in this study, by participants' creative eminence.

Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis.

Importance: A clear and comprehensive understanding of risks associated with psychedelic-assisted therapy is necessary as investigators extend its application to new populations and indications. Objective: To assess adverse events (AEs) associated with classic psychedelics, particularly serious AEs (SAEs) and nonserious AEs (NSAEs) requiring medical or psychiatric evaluation. Data Sources: The search for potentially eligible studies was conducted in the Scopus, MEDLINE, PsycINFO, and Web of Science databases from inception through February 8, 2024. Study Selection: Two independent reviewers screened articles of classic psychedelics (lysergic acid diethylamide [LSD], psilocybin, dimethyltryptamine [DMT], and 5-methoxy-N,N-dimethyltryptamine [5-MeO-DMT]) involving administration in clinical or research contexts. Data Extraction and Synthesis: AE data were extracted and synthesized by 2 reviewers and were used for random-effects meta-analysis of AE frequency and heterogeneity. Risk of bias assessment focused on AE ascertainment (eg, systematic assessment and quality of follow-up). Main Outcomes and Measures: A hybrid approach was used for capture of all reported AEs following high-dose classic psychedelic exposure and confirmatory capture of AEs of special interest, including suicidality, psychotic disorder, manic symptoms, cardiovascular events, and hallucinogen persisting perception disorder. AEs were stratified by timescale and study population type. Forest plots of common AEs were generated, and the proportions of participants affected by SAEs or NSAEs requiring medical intervention were summarized descriptively. Results: A total of 214 unique studies were included, of which 114 (53.3%) reported analyzable AE data for 3504 total participants. SAEs were reported for no healthy participants and for approximately 4% of participants with preexisting neuropsychiatric disorders; among these SAEs were worsening depression, suicidal behavior, psychosis, and convulsive episodes. NSAEs requiring medical intervention (eg, paranoia, headache) were similarly rare. In contemporary research settings, there were no reports of deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders following administration of high-dose classic psychedelics. However, there was significant heterogeneity in the quality of AE monitoring and reporting. Of 68 analyzed studies published since 2005, only 16 (23.5%) described systematic approaches to AE assessment, and 20 studies (29.4%) reported all AEs, as opposed to only adverse drug reactions. Meta-analyses of prevalence for common AEs (eg, headache, anxiety, nausea, fatigue, and dizziness) yielded comparable results for psilocybin and LSD. Conclusions and Relevance: In this systematic review and meta-analysis, classic psychedelics were generally well tolerated in clinical or research settings according to the existing literature, although SAEs did occur. These results provide estimates of common AE frequencies and indicate that certain catastrophic events reported in recreational or nonclinical contexts have yet to be reported in contemporary trial participants. Careful, ongoing, and improved pharmacovigilance is required to understand the risk and benefit profiles of these substances and to communicate such risks to prospective study participants and the public.

Unveiling the underlying structure of awe in virtual reality and in autobiographical recall: an exploratory study.

Over the last two decades, awe has attracted the attention of an increasing number of researchers. The use of virtual reality has been identified as one of the most effective techniques for eliciting awe, in addition to more personalized methods for inducing emotion, such as autobiographical recall. However, previous measures of awe were unable to uncover the hidden structure of this experience. Awe experience scale (AWE-S) has been validated as a comprehensive measure of contingent awe in English, providing new opportunities for analysis. In this two-phases study, we investigated whether the latent structure of the experience of awe evoked by the autobiographical recall technique (Study 1) overlapped with that induced by exposing participants to a validated virtual reality awe-eliciting training (Study 2). The original English AWE-S structure held both in autobiographical recall induction and virtual reality-based elicitation. Despite evidence of overlap between English and Italian structures, low correlations were found between Italian trait measures used to test the concurrent validity of the AWE-S in the Italian sample and AWE-S state dimensions. This study highlights cultural differences in awe experience, trait, and state variations, and provides new insights into the standardized induction of this emotion through simulated environments.

Centering and flourishing: an online intervention study assessing the effects of a Christian contemplative practice on stress-reduction and human flourishing.

Despite widespread engagement in contemplative religious practices, comparatively little research has been conducted on their potential effects on well-being. Furthermore, few studies have focused on how an explicitly religious framing may impact the outcomes of such practices. In this online randomized controlled trial (N = 702), we tested the well-being effects of a contemplative prayer practice called Centering Prayer on self-identifying Christians. We compared 1) presenting the practice with an explicitly religious framing (experimental condition), 2) presenting the practice without an explicitly religious framing (active control), and 3) presenting simple instructions to reflect on the day, without any instructions regarding a meditation-like practice (passive control). After randomization into one of these three conditions, participants were asked to complete their assigned practice daily for 28 days. We hypothesized that the religious framing version of the practice would increase well-being over the active and passive control conditions. Well-being was assessed at three follow-up time points: one day, one week, and one month after the practice period. We found no group differences between the conditions on our primary outcome measure of well-being at one-week post-intervention. Each group increased in well-being from baseline to follow-up. We found significant group differences on acute measures of spiritual experience, the Mystical Experience Questionnaire (MEQ-30) and Daily Spiritual Experience Questionnaire (DSES). These results suggest that a religious framing may not enhance well-being effects but may alter spiritual outcomes related to contemplative practices.

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).

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.

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.

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.

Developing an Ethics and Policy Framework for Psychedelic Clinical Care: A Consensus Statement.

Importance: As government agencies around the globe contemplate approval of the first psychedelic medicines, many questions remain about their ethical integration into mainstream medical practice. Objective: To identify key ethics and policy issues related to the eventual integration of psychedelic therapies into clinical practice. Evidence Review: From June 9 to 12, 2023, 27 individuals representing the perspectives of clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists convened at the Banbury Center at Cold Spring Harbor Laboratory. Prior to the meeting, attendees submitted key ethics and policy issues for psychedelic medicine. Responses were categorized into 6 broad topics: research ethics issues; managing expectations and informed consent; therapeutic ethics; training, education, and licensure of practitioners; equity and access; and appropriate role of gatekeeping. Attendees with relevant expertise presented on each topic, followed by group discussion. Meeting organizers (A.L.M., I.G.C., D.S.) drafted a summary of the discussion and recommendations, noting points of consensus and disagreement, which were discussed and revised as a group. Findings: This consensus statement reports 20 points of consensus across 5 ethical issues (reparations and reciprocity, equity, and respect; informed consent; professional boundaries and physical touch; personal experience; and gatekeeping), with corresponding relevant actors who will be responsible for implementation. Areas for further research and deliberation are also identified. Conclusions and Relevance: This consensus statement focuses on the future of government-approved medical use of psychedelic medicines in the US and abroad. This is an incredibly exciting and hopeful moment, but it is critical that policymakers take seriously the challenges ahead.

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.