Clinical trials investigating psychedelic compounds for depression and anxiety-related disorders are yielding promising preliminary results. Psychedelics produce profound alterations in brain function-such as suppression of the default mode network and thalamocortical dysregulation-leading to intense subjective experiences including ego dissolution and mystical-type states.While often described as meaningful or therapeutic, these effects can also be unpredictable or distressing. Because of these effects, which require labor-intensive, potentially cost-challenging preparation, administration, integration sessions, and exclude individuals with psychiatric vulnerabilities (e.g., bipolar disorder, borderline personality disorder, schizophrenia), questions remain about their real-world scalability. Consequently, there is growing interest in the possibility of dissociating the therapeutic benefits of psychedelics from their consciousness-altering effects.In this perspective, we examine emerging clinical and preclinical evidence investigating this scientifically timely and pressing question. Pharmacological strategies such as serotonin 2A receptor (5-HT2AR) antagonism and the development of "biased" psychedelic analogues or psychedelic-inspired compounds with reduced or null psychedelic potential may represent potential routes through which therapeutic efficacy may be retained even in the absence of psychedelic experiences. Current preclinical data suggest that downstream molecular and network-level mechanisms may mediate therapeutic effects independently of 5-HT2AR-driven subjective states.Whether these mechanisms can fully substitute for the experiential component of psychedelic therapy remains to be determined. Nonetheless, confirming this dissociation could mark a turning point in psychopharmacology, enabling the development of next-generation psychedelic-inspired treatments that may be more scalable, accessible, and appropriate for a broader range of psychiatric populations.

ABSTRACT This essay focuses on the writings and trip reports of several key figures of the first psychedelic revolution from an eco-critical perspective. Although the Earth Movement can be said to have emerged from the countercultural ethos of activists heavily influenced by the psychedelic revolution, the relationship of these earliest psychedelic advocates – such as Ken Kesey and Timothy Leary – to nature and to ecology has never been carefully examined. The larger issue of psychedelic biophilia comes into play in this investigation: to what extent is it accurate to say that LSD and other psychedelic experiences promote a love of nature and an ecological consciousness? In addition to the writings of Kesey and Leary, this essay examines the contributions and insights of Jane Dunlap (a.k.a. the well-known nutritionist Adelle Davis) and an incident from the 2011 film The Magic Trip, based on footage filmed by the Merry Pranksters in 1964.

Psychometric validation of the French version of the five-dimensional altered states of consciousness questionnaire (5D-ASC) and associated 11 OAV subscales.

ABSTRACTPurposeExpectations strongly shape participant experiences in clinical trials, contributing to placebo effects that complicate interpretation of outcomes. While quantitative tools exist to measure expectations, their subjective and multidimensional nature, especially for individuals with treatment‐resistant depression (TRD), remains underexplored. This study aimed to explore the motivations and expectations of participants in psychedelic clinical trials.MethodSeventeen semi‐structured interviews were conducted with individuals prior to screening for two TRD clinical trials involving 5‐MeO‐DMT or psilocybin at a German university hospital. Two matched follow‐up interviews were also completed after trial participation. Data were analyzed thematically to identify overarching themes and subthemes.FindingsTwo main themes emerged: motivations and expectations, each with four subthemes. Motivations included hope, demoralization, prior psychedelic experience, and social motivation. Expectations involved anticipated symptom reduction, perceived mechanisms of change during the psychedelic experience, the role of setting, and retrospective expectations. Many participants viewed trial participation as a last resort due to chronic illness and previous treatment failures. In two cases, retrospective accounts suggested that initially cautious expectations were reinterpreted as stronger after participation.ConclusionExpectations in psychedelic trials are complex and may evolve over time. These findings highlight the need to systematically address expectancy in trial design, informed consent, and interpretation of clinical outcomes, particularly in treatment‐resistant populations.

Psychedelic-assisted therapy and integration are gaining renewed recognition as an effective mental health intervention. However, occupational therapy (OT) is largely missing from psychedelic integration practices despite clear overlap integration objectives. This project involved a comprehensive review of the literature, along with practitioner interviews and a survey to examine current integration practices and identify opportunities for OT involvement. Findings suggest that OT’s focus on performance patterns and functional outcomes indicate that the profession can support measurable, sustainable, and goal-directed change following psychedelic experiences, making OT a critical yet underutilized contributor to psychedelic integration and this evolving mental health modality.

Psychedelics have received considerable attention due to their potential in treating psychiatric disorders. The "setting" during psychedelic-assisted therapy (PAT) is recognized as playing a central role in the experience, during which music features prominently. Although music is theorized as directing and shaping psychedelic sessions, its precise contribution to acute experience and therapeutic outcomes is unclear. This scoping review aimed to map quantitative research on the interplay of psychedelics and music by consolidating existing evidence, identifying gaps, and where possible, reporting on effects of psychedelics and music on subjective (e.g., psychological) and objective (e.g., biological) outcomes. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, relevant papers were identified through electronic databases (MEDLINE, Embase, PsychINFO, Scopus) using terms associated with psychedelic compounds, psychedelic-assisted therapy, and music. Papers were restricted to quantitative studies published in peer-reviewed journals investigating human subjects within therapeutic and controlled experimental contexts, focusing on interactions between music and psychedelics. A total of 19 papers (total human sample = 330) met inclusion criteria. Psilocybin and LSD were the most studied psychedelic compounds; no studies were found investigating MDMA and music. Characteristics of music conditions across studies have been limited. The findings suggest that music modulates the psychedelic experience through: (1) amplifying and intensifying emotions, (2) recruiting brain networks involved in meaning-attribution and visual imagery, and (3) increasing overall neural entropy. Considerable gaps remain in understanding mechanisms of action and how music is delivered to optimize therapeutic response, due in part to methodological inconsistencies and small sample sizes. This review underscores the critical role of music in shaping psychedelic experiences and therapeutic outcomes.

Recent clinical trials have suggested the safety and efficacy of psychedelic therapy for treatment-resistant depression, posttraumatic stress disorder, addiction, and end-of-life distress. While neurobiological mechanisms such as 5-HT2A receptor activation, increased neural entropy, and default mode network modulation have been well-characterized, significantly less attention has been given to the emergence of unconscious material within psychedelic states. This article introduces a psychodynamically informed framework for understanding and working with such material in clinical contexts. Drawing on psychoanalytic theory, we explore how psychedelic compounds may facilitate access to preverbal, dissociated, and developmentally embedded psychic content, often expressed through somatic experience, symbolic imagery, and unconstrained affect. Using the four standard phases of psychedelic screening, preparation, psychedelic treatment session, and follow-up or integration, we present a structured psychodynamic lens, integrating conceptual theory with illustrative clinical vignettes. These fictional composites, informed by publicly funded clinical research programs, highlight how unspoken experience, affective intensity, and shifts in psychic structure may unfold within the psychedelic experience. We argue that consideration of unconscious communication, symbolic processes, and defensive functioning can foster greater clinical depth. This article advances the position that psychoanalytic models, though underrepresented in current psychedelic research, offer valuable tools for conceptualizing mechanisms of change beyond symptom reduction. As psychedelic treatments approach regulatory approval and broader clinical use, such perspectives may play an important role in future research, training, supervision, and individualized care models.

Classical psychedelics such as N,N-dimethyltryptamine (DMT) modulate consciousness via serotonergic receptor agonism, and are increasingly investigated for their psychotherapeutic potential. When combined with the monoamine oxidase A (MAO-A) inhibitor harmine-mimicking the pharmacological profile of ayahuasca-oral DMT induces a psychedelic experience lasting 4-5 h. While some neuroimaging studies have characterized effects of DMT on functional connectivity and electroencephalography its impact on cerebral energy metabolism remains largely unexplored. We assessed the cerebral metabolic rate for glucose consumption (CMRglc) with [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) and linear graphic analysis following buccal DMT + harmine (90 mg DMT, 120 mg harmine) versus placebo in a single-blind, crossover design in 14 healthy males. Scans were acquired during peak drug effects (100-170 min post-administration). Global CMRglc increased by 12.5% under DMT+harmine versus placebo (t = 2.58, p = 0.011). Vertex- and network-wise analyses revealed widespread cortical increases, particularly in higher-order brain networks. Exploratory analyses found a significant positive correlation between global CMRglc and harmine plasma levels, but not with DMT plasma levels, subjective intensity ratings. A psychedelic dose of DMT + harmine globally increased cerebral glucose metabolism, recapitulating a classic finding for psilocybin, and suggesting a potential metabolic signature of the psychedelic state. Clinical trial registry name and URL incl. registration number: Molecular Imaging Study of Harmine/DMT: a Basic Research Approach (HaD-PET) https://clinicaltrials.gov/study/NCT06252506.

For English, the validated part of Psychedelic Experience Scale (PES48) is a four-factor structure called the Mystical Experience Questionnaire (MEQ30). The other validated part of the PES48 consists of four more factors: two more mystical factors (paradoxicality and connectedness, which together with the MEQ30 form the MEQ40), and two more non-mystical factors (visual experience and distressing experience). However, this latter four-factor part of the PES48 has thus far only been validated for the German version of the PES48. We investigated whether the overall eight-factor structure of the PES48 (which includes the MEQ30 four-factor structure) can also be validated, and thus potentially be put to good use in English. Data from 280 English PES measurements (145 different healthy participants) from four placebo-controlled studies with low to high doses of psilocybin were included. The reliability of the eight subscales was evaluated using measures of internal consistency. The validity of the factor structure was assessed through model fit indices from confirmatory factor analysis. English results were then also compared with the German PES validation data set from Stocker etal. (2024). Six of the eight subscales (mystical, positive mood, transcendence of time and space, ineffability, connectedness, distressing experience) of the English PES48 show high internal consistency, one subscale (paradoxicality) shows good, and one (visual experience) acceptable internal consistency. Both MEQ models (MEQ30 and MEQ40) show similar fits (acceptable to good model fits). In English, both MEQ models show better fits than in German. All six MEQ40 scale means of the English data are higher compared to German data. The findings suggest that the eight-factor PES48 is also a valid psychometric tool in English. With the MEQ40 part of the PES48, one can measure mystical experience with a still wider conceptual breath than with the MEQ30. Furthermore, one can also measure non-mystical visual and distressing states in an overall more comprehensive and broader conceptualization of the psychedelic experience. Higher MEQ40 scale means for the English than the German study participants could inspire future research into the role of setting in relation to mystical experience.

Background/Aim Increased attention is being paid toward Psychedelic Assisted Psychotherapy (PAP) and how this can support priority populations such as trans people. The current study analyses trans people’s naturalistic psychedelic experiences shared on the social media platform Reddit to inform PAP. Methods 225 posts from between 2019 and 2024 were recorded from the subreddits r/trans and r/asktransgender and were assessed for inclusion. Codes and themes were extracted from the data using structured tabular thematic analysis. Results Four themes were identified. The first acknowledged how psychedelic-induced altered states can lead to self-acceptance, gender euphoria, and gender realization. The second explored how psychological release during psychedelic trips can also facilitate a journey of self-acceptance. The third explored how these experiences can function as a catalyst for change. The last theme explored how psychedelic-induced altered states can simultaneously support and exasperate gender dysphoria. Conclusion This work highlights how psychedelics can have both ‘healing’ (e.g., gender euphoria, self-acceptance) and “harming” (e.g., exacerbated dysphoria and grief) qualities for trans individuals. As such, clinical applications need to consider this duality and integrate it to inform responsive and affirming PAP protocols.

ABSTRACT Psychedelic-assisted psychotherapies (PAPs) pose ethical challenges that existing normative frameworks cannot adequately address. This paper argues that the convergence of belief relaxation (the loosening of high-level predictive priors) and context amplification (the heightened influence of environmental cues on experiential content) generates a condition I call transient epistemic vulnerability: a state in which the individual’s fundamental orientations toward meaning, value, and reality become structurally open to revision under heightened sensitivity to the normative dimensions of the therapeutic environment. Drawing on Clifford Geertz’s analysis of the fusion of ethos and worldview, I argue that psychedelic experiences replicate a mechanism whereby normative commitments come to appear as descriptive features of reality under asymmetric conditions of interpretive power. I critically examine four leading proposals (Letheby, McGovern et al. Bortolotti, Bublitz) and argue that each remains within an epistemic register when the more fundamental challenge is ethical and contextual: the conditions of power, vulnerability, and interpretive authority under which beliefs and existential orientations form. I introduce normative capture to describe the risk that patients’ orientations will be shaped by unexamined features of the therapeutic context, and propose structural reflexivity as a middle position between therapeutic passivity and active epistemic guidance. Five normative principles are outlined.

ABSTRACT Limited research suggests that distinct intentions covary with acute experiences and subsequent outcomes. Nevertheless, data on the types of intentions set by users remain scarce, and their effects lack clarity. This study uses a retrospective, mixed-methods, cross-sectional approach to investigate intention-setting among psychedelic users. We establish a taxonomy of intentions in naturalistic use and examine how domain-specific intentions correlate with acute effects and changes in well-being. Additionally, we test qualities for effective intention-setting. The most common intentions focus on self-discovery and personal growth, as well as healing and mental health. Participants reported that intention-setting provided direction and cognitive focus, as well as positive emotional anchoring. Intentions related to mental health, self-expansion, and physical health were associated with greater subjective effects, including mystical experiences, emotional breakthroughs, and challenging experiences, as well as improved well-being and reductions in dysfunctional attitudes. In contrast, recreational intentions were unrelated to reductions in dysfunctional attitudes and correlated negatively with changes in well-being. Finally, intentions that were specific, relevant, and integrated after the psychedelic experience correlated with improvements in well-being. Unexpectedly, flexible intentions covaried with worse outcomes. These data suggest that specific, relevant, integrated intentions focused on self-discovery and mental health might offer the most benefits.

ABSTRACT This study examines psychedelic integration among Brazilian users by validating a Brazilian Portuguese version of the Psychedelic Integration Scales (PIS), developed through translation and cultural adaptation to ensure relevance and applicability within the Brazilian sociocultural context. A cross-sectional survey was conducted with 1379 participants recruited online. Confirmatory Factor Analysis supported a unidimensional structure for the Brazilian version of the scale (PIS-BR), with satisfactory internal consistency (α = 0.95) and strong evidence of validity based on the relationship with external variables with mystical experience (r = 0.636, p < .01) and positivity (r = 0.352, p < .01). Qualitative analysis of open-ended responses, supported by AI-assisted methods and reviewed by researchers, identified diverse integration strategies, including personal reflection and self-analysis, psychotherapy and professional support, spiritual and meditative practices, connection with nature, social sharing and support networks, personal and relational transformation, and difficulties in integration. This study contributes to understanding psychedelic integration processes in a culturally distinct context. Despite limitations related to sampling and cross-sectional design, the findings provide valuable insights for future research on the conceptualization, measurement, and cultural variability of psychedelic integration beyond the acute effects of these experiences.

Eating disorders (EDs) have complex presentations with high rates of comorbidities and low recovery rates. Current treatment options often lack sufficiency in improving ED symptoms. Psychedelic-assisted therapies represent a novel treatment approach for the treatment of EDs, with research documenting preliminary positive evidence. However, psychedelics have their own challenges and risks which need to be considered within an ED population to inform study design and future clinical application. The primary aim of this meta-synthesis was to integrate existing qualitative data on the experience of using psychedelics in ED treatment from the perspectives of both individuals with EDs and providers (e.g. clinicians, ceremony leaders), using meta-ethnography to generate new interpretative insights. The methods followed the seven steps of a meta ethnographic approach. An electronic search of three databases (PubMed, Medline, and PsycINFO) was conducted. Papers were included if they were qualitative studies exploring the use of typical or atypical psychedelics, from the perspective of either a provider or individual experiencing an ED. A total of eight studies were included. From the data we identified five meta-themes that together depict how psychedelic experiences may act as catalysts for transformation. Our interpretive narrative posits that core transformative processes (Mind-Body-Spirit, Emotional Processing), unfold within specific contextual conditions (Navigating Challenges and Risks, Enabling Safe and Supportive Experiences), and lead to meaningful outcomes (Therapeutic Improvements). Meta- and sub-themes reflect ED-specific elements, highlighting that psychedelics may improve emotion processing and enhance perception of and connection with the body and the self, which is pertinent to ED recovery. Themes also indicate the increased risk for adverse side effects with low weight and other physical vulnerabilities associated with EDs. The themes and interpretive narratives identified in this meta-synthesis suggest that to achieve therapeutic outcomes, ED-specific contextual conditions are required to facilitate internal processes during psychedelic therapy for EDs. This includes minimising the uncertainty that typifies EDs through exploration of expectations and autonomy in selection of setting elements (e.g. lighting, music, eye-mask) or collaboratively agreeing strategies for if anxiety spikes. Further, facilitators should require dual competency in psychedelic treatment and ED psychopathology and treatment.

While prior research links psychedelic use to improved psychological outcomes, less is known about whether psychedelic exposure relates to engagement with formal mental health care when treatment is recognized as needed. Using publicly available, de-identified pooled data from the National Survey on Drug Use and Health (2008–2019), this study examines whether lifetime psychedelic use is associated with missed needed mental health treatment and whether psychedelic exposure moderates the relationship between psychological distress and unmet care, with attention to gender differences. Regression analyses indicate that psychedelic use is not independently associated with lower odds of missing needed treatment once psychological distress is accounted for. However, psychedelic exposure is associated with a weaker relationship between distress and missed care: as psychological distress increases, individuals with prior psychedelic use—particularly men—exhibit a smaller increase in missed needed treatment compared to non-users. Gender-stratified analyses show that this buffering pattern is evident for men across multiple substances, whereas among women, only MDMA demonstrates a comparable moderating effect. These findings suggest that psychedelic use does not uniformly increase engagement with mental health care but is associated with gendered differences in how psychological distress translates into disengagement. Situated within the Medical Sociological and Social Epidemiological Psychedelics Paradigm, the results highlight how structural inequality shapes the behavioral translation of psychedelic experiences, producing diminished returns for women despite comparable levels of distress.

Psilocybin-assisted psychotherapy shows promise in alcohol use disorder (AUD), but therapeutic mechanisms remain poorly understood. Previous qualitative studies have described potential processes such as gaining insights, altered self-perception, connectedness, and changes in coping, yet findings remain limited and inconsistent in AUD, and little is known about early markers of therapeutic response. We conducted a mixed quantitative-qualitative analysis of first integration sessions in the Psilocybin Alcohol Depression (PAD) randomized controlled trial. Only participants randomized to the 25mg psilocybin group were included in this analysis. Recently detoxified patients with AUD and persisting depressive symptoms underwent semi-structured integration interviews the day after dosing. Transcripts were analyzed with IRaMuTeQ software using the Reinart descending hierarchical classification. Associations with abstinence at 3months were examined. Twenty participants were included (55% male, median age 49); 55% were abstinent at 3months. The corpus comprised 127,760 words, with 88% classified into two stable classes. Class 1 (44% of text segments) described sensory and emotional aspects of the psychedelic experience (physical sensations, visual phenomena, emotions, setting) and was predominantly elicited by non-responders. Class 2 (56%) reflected active cognitive processes and inner dialogue, including cognitive restructuring, distancing from habitual patterns, commitment to change, and work on pre-elicited intentions related to alcohol. Abstinence at 3months was significantly associated with references to family connections, pleasant emotions, adaptive processing of fear, and revisiting alcohol-related triggers with new coping strategies, while non-abstinence was associated with negative emotions, physical pain, disappointment, and suppressive coping. Responders were distinguished by narratives of inner dialogue and adaptive coping, while non-responders emphasized sensory and affective descriptions and suppressive coping. Inner dialogue may constitute a distinct therapeutic mechanism, highlighting the importance of preparation and integration in psilocybin-assisted psychotherapy.

Trip sitting or just sitting? Session facilitators substantially influence psychedelic experiences in clinical trials but not in healthy ones.

Reports of resurfaced repressed memories during psychedelic experiences have circulated for decades and still emerge today. However, the veracity of repressed memories remains debated, and the mechanisms through which psychedelics might recover alleged repressed memories are unclear. This scoping review aimed to provide an overview of the literature on repressed memory in the context of psychedelics. It examined how repressed memory was defined, which substances were predominantly discussed, which mechanisms were proposed to explain their effects, and whether these mechanisms were empirically supported. A scoping review was conducted in line with PRISMA-ScR guidelines. Web of Science, PubMed, PsycINFO and Google Scholar were searched for relevant publications. Fifty-three sources met eligibility criteria. Data were charted on study design, psychedelic substance, definitions of repressed memory, results, and proposed mechanisms. Most publications focused on lysergic acid diethylamide (LSD) in relation to repressed memory. Few sources provided a definition of repressed memory. Proposed mechanisms on how psychedelics might influence repressed memory included psychoanalytical reductions of defensive memory blockades and neurobiological alterations of executive control. However, empirical support for these mechanisms was limited. The included literature did not offer a coherent explanation on how psychedelics could recover repressed memories, nor consistent evidence that they did so reliably. Future work should provide clear definitions of repressed memory in the context of psychedelics, test proposed effects of psychedelics on memory and executive control across multiple psychedelic substances, include placebo-controlled designs, and account for the potential occurrence of false memories.

Background: Institutional review boards (IRBs) are gatekeepers of psychedelic research, deciding whether and under what conditions it may proceed. Yet IRB understanding, attitudes, perspectives, and concerns regarding psychedelics and psychedelic research have not previously been studied. These factors are important to assessing whether US IRBs are likely to be over- or underprotective of psychedelic research participants and to helping psychedelic investigators address key IRB concerns. Methods: A total of 529 current IRB chairs were invited to participate in an electronic survey conducted in October–November 2024. The sample included chairs at US organizations affiliated with psychedelic studies registered on ClinicalTrials.gov, the top 100 NIH-funded organizations, and organizations in states with more and less favorable psychedelic policies; IRB chairs affiliated with the Department of Veterans Affairs and two commercial IRBs were also included. Survey domains included psychedelic experience, understanding and attitudes about psychedelics, confidence reviewing psychedelic protocols, concern about aspects of psychedelic administration research compared to other research, views on risks associated with psychedelic administration research, perspectives on participant protections, and resource needs. Results: Overall, 212 IRB chairs completed at least 80% of the survey (42.7% response rate), a third of whom (34.9%) reported professional experience with psychedelics. Participants often reported lacking knowledge about psychedelic risks/benefits (35–51%) and selected neutral responses to questions examining their attitudes about psychedelics (35–47%). Most (61–78%) reported similar confidence reviewing psychedelic and nonpsychedelic protocols. Many IRB chairs (33–53%) reported heightened concern about psychedelic administration research, including legal, employment, and other social risks, expectations of benefit leading to bias, participant safety, consent challenges, and inclusion of vulnerable populations; about half (47.2%) reported heightened institutional risk compared to other research. Most agreed with requiring extensive monitoring of psychedelic administration sessions (82.9%) but expressed wide-ranging views on other protections. Conclusions: Rather than reflecting a broadly conservative approach to psychedelic research, IRB chairs often expressed a neutral attitude toward psychedelics alongside some uncertainty, while noting concerns that align with unsettled issues in the field. Gaps in IRB knowledge regarding psychedelic risks/benefits can be addressed in research protocols, while the field must continue to work toward consensus on best practices for participant protection.

ABSTRACT This article presents the results of a Cognitive Linguistic analysis of metaphors used in a series of interviews by a single healthy volunteer following four moderate-to-high dosing sessions with psilocybin. The interviews were conducted by members of a human psychedelic research lab in a deep-sampling fMRI and EEG brain imaging study, allowing the participant to recount experiences under the effects of the compound. The goal of this case analysis is to make theoretically informed inferences about the participant’s cognitive-phenomenal processes during the interviews and the psychedelic experiences. To this end, we use Conceptual Metaphor Theory to explain how the participant consistently uses metaphors that frame abstract introspective events in terms of more concrete, visible and interpersonal events. This instantiates a cognitive frame that is known as the Observer’s Model. The metaphor themes we identify also imply a recurring sense of cognitive defusion and heightened metacognitive awareness during the psilocybin sessions. Moreover, we find that literal descriptions of hallucinatory visual experiences correlate semantically with metaphorical expressions, suggesting that metaphorical thinking plays a role in motivating those experiences. We link these linguistic-analytical results to neuroscientific findings about psychedelics and explore psychological and therapeutic implications.