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This study aimed to evaluate the alcohol consumption among professional truck and bus drivers using direct ethanol biomarkers, and to explore its relationship with anxiety, depression, and stress. The assessment of potential harmful drinking was conducted through the measurement of direct biomarkers: phosphatidylethanol (PEth), ethyl glucuronide (EtG), and ethyl sulfate (EtS), using dried blood spots (DBS). Additionally, self-reported data from the Alcohol Use Disorders Identification Test (AUDIT-C) were used. Emotional states, including depression, anxiety, and stress, were evaluated using the Depression, Anxiety, and Stress Scale (DASS-21). A total of 97 drivers participated in the study, with the majority being male (96%) and identified as truck drivers (75.3%). Among them, 43.3% reported working more than 10 h daily. The majority of volunteers exhibited normal levels of stress (81.4%), anxiety (83%), and depression (86.6%). According to the AUDIT-C assessment, 30.9% were categorized as having a moderate risk, while 11.3% were deemed to be at high risk for harmful alcohol consumption behavior. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) levels, indicating recent ethanol consumption, were detected in 14.4% of the drivers. In contrast, the long half-life metabolite PEth (16:0-18:1) was present in 88.7% of the volunteers. A moderate correlation (rs = 0.45, p <.01) was observed between PEth levels and AUDIT-C scores. The Receiver Operating Characteristic (ROC) curve, utilizing a PEth threshold of ≥ 59.0 ng ml−1, displayed 78% sensitivity and 73% specificity in effectively distinguishing high risk for alcohol intake. Notably, no significant associations were found between alcohol consumption and levels of stress, depression, and anxiety. The study findings indicate a noteworthy proportion of drivers engaging in regular alcohol consumption alongside a demanding workload. Notably, PEth measurements highlighted an underreporting within the AUDIT-C self-reports. These results lend robust support for the utilization of biomarkers in assessing alcohol consumption patterns among drivers. [ABSTRACT FROM AUTHOR]

Objective: Psilocybin-assisted therapy has shown promising efficacy on clinical depressive symptoms. However, diverse psychological support or psychotherapy was performed with psilocybin treatment. This study aimed to explore the association of psychological protocols with the efficacy of psilocybin-assisted therapy for depressive symptoms. Method: Five major databases were systemic searched for clinical trials addressing psilocybin-assisted therapy for patients with clinical depressive symptoms. A Bayesian random-effects meta-analysis and meta-regression were performed. The effect size was mean difference (with 95% credible interval) measured by 17-Item Hamilton Depression Rating Scale. Results: There were 10 eligible studies including 515 adult patients with clinically diagnosed depression. The psychological protocols could be categorized into four types: (i) manualized directive psychotherapy(k=1); (ii) manualized nondirective psychological support (k=3), (iii) non-manualized nondirective psychological support (k=5); and (iv) non-manualized supportive psychotherapy (k=1). The pooled standard mean difference of psilocybin-assisted therapy was 10.08 (5.03-14.70). Conclusion: Compared with manualized nondirective psychological support, the other three psychological approaches did not differ significantly. The improvement of depressive symptoms was not associated with the psychological protocols in adult patients receiving psilocybin-assisted therapy [ABSTRACT FROM AUTHOR]

Psychedelic substances, which can occasion mystical experiences, are sometimes used for religious and spiritual reasons. Despite strong links between psychedelics and spirituality, no previous systematic review has investigated connections between psychedelics and indicators of long-term spiritual growth. Thus, 34 empirical studies were analyzed with 19,724 total participants from 32 independent samples. A variety of methodologies were used among the reviewed studies, and some studies included international samples. Results showed that psychedelics—especially classic psychedelics (e.g., psilocybin, LSD, and DMT)—have been studied more often in this context than other substances. Findings indicate that psychedelic use is linked with a variety of subjective indicators of spiritual growth, including stronger perceived connections with the divine, a greater sense of meaning, increased spiritual faith, increased engagement in religious and spiritual practices, an increase in feelings of unity and self-transcendence, positive changes in worldview, increased connectedness with others, and reduced fear of death. Many studies that reported on one of these indicators also reported on others, implying a co-occurrence of these facets during and after psychedelic experiences. Spiritual growth was often related to mystical experiences, with higher mystical experience ratings associating positively with perceived spiritual growth. [ABSTRACT FROM AUTHOR]

The resurgence of interest in psychedelic substances for psychiatric treatment has sparked both excitement and scepticism within the scientific community. This paper addresses the moralisation and hype surrounding psychedelic therapies. Through a systematic review of the literature and a detailed case study, we illustrate that the therapeutic effect of psychedelics is not solely pharmacological but is instead facilitated by their ability to enhance psychotherapy. The paper explores the historical context of psychedelics in psychiatry, their mechanism of action, and evidence of their efficacy in treating depression. We highlight the necessity of integrating psychedelics with psychotherapeutic interventions and emphasise the importance of methodological rigour and ethical standards in psychedelic research and practice. By presenting an informed understanding of psychedelic treatments, we advocate for their consideration as legitimate alternatives alongside traditional therapies, offering a potential paradigm shift in psychiatric care. [ABSTRACT FROM AUTHOR]

AbstractDepression is a serious psychiatric disorder with a high incidence of morbidity and mortality and psilocybin with psychotherapy has emerged as a promising potential in the treatment of depressive disorders. A review of psilocybin use in patients with depressive disorders is presented.A search was conducted investigating the use of psilocybin in patients with depressive disorders and treatment resistant depression via PubMed/MEDLINE, EMBASE, and Google Scholar in October 2023; all publication types were permitted and limited for English-language. Keyword search terms included: “psilocybin” or “psychedelics” and “depression”, or “major depressive disorder”, or “treatment-resistant depression”. Controlled and uncontrolled clinical trials utilizing psilocybin with psychological support for major depressive disorder and treatment-resistant depression, as well as in patients with depression and cancer related anxiety have demonstrated immediate and sustained antidepressant and anxiolytic effects. Psilocybin has a favorable safety profile and was well-tolerated in clinical trials. Psilocybin’s abuse potential is low and clinical research suggests the potential of psilocybin to produce rapid and lasting antidepressant effects up to 12 months post-treatment. Psilocybin may offer a valuable contribution as an option to the currently available pharmacological and psychotherapeutic agents for patients with major depressive disorders, treatment-resistant depression as well as for patients with depression and comorbid terminal cancer. Future studies are needed to demonstrate these findings and any synergistic interaction between psilocybin and the psychological support offered to patients during sessions. [ABSTRACT FROM AUTHOR]

Current pharmacological treatments for major depressive disorder (MDD) are often only partially effective, with many patients experiencing no significant benefit, leading to treatment-resistant depression (TRD). Psilocybin, a classical serotonergic psychedelic, has emerged as a notable emerging treatment for such disorders. The aim of this systematic review and meta-analysis is to summarize and discuss the most recent evidence about the therapeutic effects of single-dose and two-dose psilocybin administration on the severity of depressive symptoms, as well as compare the efficacy of these interventions among patients with a primary diagnosis of MDD or TRD. Articles were collected from EBSCOhost and PubMed following the PRISMA guidelines, yielding 425 articles with 138 duplicates. After screening 287 records, 12 studies met the eligibility criteria and were included in the review. A quantitative analysis of the studies indicates that psilocybin is highly effective in reducing depressive symptoms severity among patients with primary MDD or TRD. Both single-dose and two-dose psilocybin treatments significantly reduced depressive symptoms severity, with two-dose administration sometimes yielding more pronounced and lasting effects. However, it is unclear if this was solely due to dosage or other factors. Future research should include standardized trials comparing these dosing strategies to better inform clinical practice. [ABSTRACT FROM AUTHOR]

• There is not sufficient evidence to demonstrate a causal relationship between seizures and use of classic psychedelics. • In the absence of concomitant use of other drugs, we found no increased risk of seizures related to use of classic psychedelics in non-epileptic individuals. • Risk of seizures might increase with the concomitant use of other substances, such as kambo or lithium. • Preliminary evidence suggests a possible protective effect of some psychedelics against seizures in animal models. Seizures are a concerning adverse event frequently associated with the use of psychedelics, and hence, studies involving these substances tend to exclude patients with past history of epilepsy. This is especially relevant because epileptic seizures are markedly increased in the population suffering from mental disorders, and psychedelic assisted therapy is being researched as a promising treatment for several of them. To determine the extent of the current literature on the relationship between classic psychedelics and seizures, a scoping review was performed using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). The search was conducted in PubMed, Web of Science, Google scholar, LILACS and Scielo, and both animal and human models were included. A total of 16 publications on humans, and 11 on animals, were found. The results are heterogeneous, but globally suggest that psychedelics may not increase the risk of seizures in healthy individuals or animals in the absence of other drugs. However, concomitant use of other substances or drugs, such as kambo or lithium, could increase the risk of seizures. Additionally, these conclusions are drawn from data lacking sufficient external validity, so they should be interpreted with caution. Future paths for research and a summary on possible neurobiological underpinnings that might clarify the relationship between classical psychedelics and seizures are also provided. [ABSTRACT FROM AUTHOR]

Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo. [ABSTRACT FROM AUTHOR]

Background: Voter initiatives in Oregon and Colorado authorize legal frameworks for supervised psilocybin services, but no measures monitor safety or outcomes. Aims: To develop core measures of best practices. Methods: A three-phase e-Delphi process recruited 36 experts with 5 or more years' experience facilitating psilocybin experiences in various contexts (e.g., ceremonial settings, indigenous practices, clinical trials), or other pertinent psilocybin expertise. Phase I, an on-line survey with qualitative, open-ended text responses, generated potential measures to assess processes, outcomes, and structure reflecting high quality psilocybin services. In Phase II, experts used seven-point Likert scales to rate the importance and feasibility of the Phase I measures. Measures were priority ranked. Qualitative interviews and analysis in Phase III refined top-rated measures. Results: Experts (n = 36; 53% female; 71% white; 56% heterosexual) reported currently providing psilocybin services (64%) for a mean of 15.2 [SD 13.1] years, experience with indigenous psychedelic practices (67%), and/or conducting clinical trials (36%). Thematic analysis of Phase I responses yielded 55 candidate process measures (e.g., preparatory hours with client, total dose of psilocybin administered, documentation of touch/sexual boundaries), outcome measures (e.g., adverse events, well-being, anxiety/depression symptoms), and structure measures (e.g., facilitator training in trauma informed care, referral capacity for medical/psychiatric issues). In Phase II and III, experts prioritized a core set of 11 process, 11 outcome, and 17 structure measures that balanced importance and feasibility. Conclusion: Service providers and policy makers should consider standardizing core measures developed in this study to monitor the safety, quality, and outcomes of community-based psilocybin services. [ABSTRACT FROM AUTHOR]

Psilocybin-assisted psychotherapy (PAP) is a promising treatment option for depression, with randomized controlled trials (RCTs) providing preliminary support for its safety and efficacy. However, there is a lack of consistency across existing treatment protocols and psychotherapeutic approaches. The objective of this review is to summarize and compare current psychotherapy methods of PAP in treating depression and distress in life-threatening illnesses. We sought to comprehensively summarize published psychotherapy protocols from clinical trials to provide insights for future practices. A systematic search of four databases (Embase, MEDLINE, PsycINFO, CINAHL) for data relating to psychotherapy protocols was conducted by two independent reviewers. In total, our search identified 1869 articles; after removing duplicates, we screened 1107 articles. We included 70 articles in the full-text review and determined that 28 were eligible for the final review. All protocols include sessions before (preparatory) and after (integration) the psychedelic dosing session with supportive monitoring. However, there was substantial variability and inconsistencies in all other aspects of therapy protocols (e.g., duration and number of sessions, model of therapy). Additionally, significant limitations were identified in the frequent need for more clarity in the description of therapeutic approaches. In published clinical trials, PAP has consisted of preparation, supportive dosing, and integration sessions. Beyond this basic framework, significant heterogeneity and lack of clarity were identified in reported psychotherapy protocols, meaning a validated and universally agreed upon protocol for PAP currently does not exist. Future studies should more clearly define and report psychotherapeutic components to identify the safest and most efficacious approaches to PAP. • We identified 1869 articles; screened 1107 articles, included 70 articles in the full-text review with 28 in the final review. • In clinical trials, psilocybin-assisted psychotherapy consisted of preparation, supportive dosing, and integration sessions. • Significant heterogeneity and lack of clarity were identified in reported psychotherapy protocols. • Future studies should improve reporting of psychotherapeutic practices to identify the safest and most efficacious approaches. [ABSTRACT FROM AUTHOR]

There is an increasing demand for effective treatments for depression, particularly for individuals grappling with treatment-resistant depression. Over recent years, a surge of interest has focused on exploring the safety and efficacy of psilocybin as a potential treatment for depression. However, preliminary findings from phase 2 studies have been inconclusive, prompting critical examination of issues such as maintaining blinding and the role of adjunctive psychotherapy. The maintenance of double-blinding and the role of adjunctive psychotherapy introduce biases that complicate the attainment of conclusive results in clinical research. Examining historical data reveals a recurrent pattern linked to the use of psychoactive substances, which starts with an excess of optimism and ends with general addictive behaviors and a heightened risk of serious public health problems. Considering these findings, a cautious and measured approach is imperative, given that the efficacy and safety of psilocybin treatment have yet to be unequivocally established. The potential for excessive optimism among researchers is a notable concern, as unwarranted enthusiasm may inadvertently facilitate the widespread adoption of this treatment without sufficient empirical support. In navigating the complexities of depression treatment, it is necessary to strike a balance between innovation and prudence to ensure evidence-based advancement of therapeutic approaches. [ABSTRACT FROM AUTHOR]

It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short‐term stressor or drug‐induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic‐like experiences over time. Theoretical and practical implications of this model are discussed. [ABSTRACT FROM AUTHOR]

Rationale: Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been surprisingly little empirical investigation of the "psychotherapy" in PAP, leaving critical questions about the necessary and sufficient components of PAP unanswered. Objectives: As clinical trials for psychedelic compounds continue the transition from safety- and feasibility-testing to evaluating efficacy, the role of the accompanying psychotherapy must be better understood to enhance scientific understanding of the mechanisms underlying therapeutic change, optimize clinical outcomes, and inform cost-effectiveness. Results: The present paper first reviews the current status of psychotherapy in the PAP literature, starting with recent debates regarding "psychotherapy" versus "psychological support" and then overviewing published clinical trial psychotherapy models and putative models informed by theory. We then delineate lessons that PAP researchers can leverage from traditional psychotherapy research regarding standardizing treatments (e.g., publish treatment manuals, establish eligibility criteria for providers), identifying mechanisms of change (e.g., measure established mechanisms in psychotherapy), and optimizing clinical trial designs (e.g., consider dismantling studies, comparative efficacy trials, and cross-lagged panel designs). Throughout this review, the need for increased research into the psychotherapeutic components of treatment in PAP is underscored. Conclusions: PAP is a distinct, integrative, and transdisciplinary intervention. Future research designs should consider transdisciplinary research methodologies to identify best practices and inform federal guidelines for PAP administration. [ABSTRACT FROM AUTHOR]

Background: Available evidence points to a possible role of Short Chain Fatty Acids (SCFAs) in mood disorders. This is the first systematic review to map the associations between SCFA levels and mood disorder symptoms. Methods: Following the PRISMA guidelines, the databases PubMed, Embase, and PsycINFO were searched for studies that assessed SCFA levels in human populations with mood disorder symptoms, or animal models of mood disorder. Risk of bias was assessed by the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) checklist. Results: 19 studies were included and could be divided into animal (n=8) and human studies (n=11), with the animal studies including 166 animals and 100 controls, and the human studies including 662 participants and 330 controls. The studies were characterized by heterogeneity and methodological challenges on multiple parameters, limiting the validity and transferability of findings. Notably, only two of the clinical studies assessed the presence of mood disorder with diagnostic criteria, and no studies of mania or bipolar disorder met the inclusion criteria. Discussion: Despite significant methodological limitations, associations between SCFA levels and depressive symptoms were reported in most of the studies. However, the direction of these associations and the specific SCFAs identified varied. The quantification of SCFA levels in mood disorders is an emerging yet sparsely studied research field. Although there is some evidence suggesting a link between SCFAs and depressive symptoms, the directionality of effects and mechanisms are unclear and the relation to manic symptoms is uninvestigated. [ABSTRACT FROM AUTHOR]

Purpose of Review: Self-awareness can be defined as the capacity of becoming the object of one's own awareness and, increasingly, it has been the target of scientific inquiry. Self-awareness has important clinical implications, and a better understanding of the neurochemical basis of self-awareness may help clarifying causes and developing interventions for different psychopathological conditions. The current article explores the relationship between neurochemistry and self-awareness, with special attention to the effects of psychedelics. Recent Findings: The functioning of self-related networks, such as the default-mode network and the salience network, and how these are influenced by different neurotransmitters is discussed. The impact of psychedelics on self-awareness is reviewed in relation to specific processes, such as interoception, body ownership, agency, metacognition, emotional regulation and autobiographical memory, within a framework based on predictive coding. Summary: Improved outcomes in emotional regulation and autobiographical memory have been observed in association with the use of psychedelics, suggesting higher-order self-awareness changes, which can be modulated by relaxation of priors and improved coping mechanisms linked to cognitive flexibility. Alterations in bodily self-awareness are less consistent, being potentially impacted by doses employed, differences in acute/long-term effects and the presence of clinical conditions. Future studies investigating the effects of different molecules in rebalancing connectivity between resting-state networks may lead to novel therapeutic approaches and the refinement of existing treatments. [ABSTRACT FROM AUTHOR]

The resurgence of interest in psychedelics as treatments for psychiatric disorders necessitates a better understanding of potential sex differences in response to these substances. Sex as a biological variable (SABV) has been historically neglected in medical research, posing limits to our understanding of treatment efficacy. Human studies have provided insights into the efficacy of psychedelics across various diagnoses and aspects of cognition, yet sex-specific effects remain unclear, making it difficult to draw strong conclusions about sex-dependent differences in response to psychedelic treatments. Compounding this further, animal studies used to understand biological mechanisms of psychedelics predominantly use one sex and present mixed neurobiological and behavioral outcomes. Studies that do include both sexes often do not investigate sex differences further, which may hinder the translation of findings to the clinic. In reviewing sex differences in responses to psychedelics, we will highlight the direct interaction between estrogen (the most extensively studied steroid hormone) and the serotonin system (central to the mechanism of action of psychedelics), and the potential that estrogen-serotonin interactions may influence the efficacy of psychedelics in female participants. Estrogen influences serotonin neurotransmission by affecting its synthesis and release, as well as modulating the sensitivity and responsiveness of serotonin receptor subtypes in the brain. This could potentially influence the efficacy of psychedelics in females by modifying their therapeutic efficacy across menstrual cycles and developmental stages. Investigating this interaction in the context of psychedelic research could aid in the advancement of therapeutic outcomes, especially for conditions with sex-specific prevalence. [ABSTRACT FROM AUTHOR]

The article explores the potential use of MDMA therapy for treating post-traumatic stress disorder (PTSD) and medication-resistant depression. It highlights that PTSD currently lacks effective medication options. However, an FDA panel recently deemed the treatment "unproven," which is a setback for advocates of MDMA therapy. The decision raises concerns about the data submitted by Lykos Pharmaceuticals, the company developing the treatment. The FDA advisory committee has raised various concerns about the efficacy, safety, blind study design, regulation of psychotherapy providers, potential unethical behavior, lack of diversity among participants, and potential bias in the sample. The committee voted that the human trials did not prove efficacy and that the risks of MDMA outweigh its benefits. While advocates for MDMA therapy remain hopeful, the recent ruling is seen as a setback for the use of psychedelics in mental health treatment. [Extracted from the article]

Objective: The objective of this systematic review is to determine the tolerability and safety of psilocybin in a variety of psychiatric and substance-dependence conditions. Data sources: A systematic review was conducted using Embase, PubMed, Cochrane Central, and Web of Science through September 2023 using the following terminology: "psilocybin" AND "mental-disease" OR "substance-dependence" AND "disease-therapy," in addition to other synonymous key words. Study selection and data extraction: Literature reporting acute effects and safety data following the use of psilocybin as the pharmacologic intervention in a clinical trial in adult patients with a psychiatric or substance-dependence condition were included. Following the application of inclusion and exclusion criteria, 16 studies were ultimately included in this review. Data synthesis: The most common treatment-emergent adverse effects reported were transient nausea and headache. Transient anxiety was reported as a frequent psychiatric effect, and 3 participants received a benzodiazepine for refractory anxiety during the psilocybin session. Psilocybin demonstrated modest increases in blood pressure and heart rate, and 1 participant received an antihypertensive for sustained hypertension during the psilocybin session. No cases of psilocybin-induced psychosis or Hallucinogen Persisting Perception Disorder were reported. Relevance to patient care and clinical practice: Treatment resistance remains a concern for psychiatric patients and novel therapies are needed to help alleviate the burden of morbidity and mortality. Psilocybin demonstrates promising acute and long-term safety that may allow for its use in psychiatric or substance-dependence conditions as an alternative to standards of care or in treatment-resistant patients. Conclusions: Psilocybin has demonstrated tolerability and safety in recent literature that has investigated its therapeutic potential in a variety of psychiatric or substance-dependence conditions. [ABSTRACT FROM AUTHOR]

Background: Impairments in social cognition are known to be a key factor in several psychiatric and neurodevelopmental disorders. Interest in psychedelic drugs has increased in recent years, with significant research identifying psychedelic and hallucinogenic drugs as modulators of social cognition. However, more research is necessary before psychedelics are implemented in clinical settings as treatments for social cognition defects. Therefore, this study describes a scoping review protocol which will be used to analyze the body of literature on psychedelic drugs as modulators of social cognition in patients with psychiatric and neurodevelopmental disorders. Methods: This scoping review protocol was developed using the JBI Scoping Review Methodology Group's description of how to conduct a scoping review. The guidelines identified by this group as well as a search strategy developed with the assistance of a research librarian will be applied to a search of several peer-reviewed journals, including MEDLINE (Ovid), PsycINFO, EMBASE (Elsevier), and Scopus (Elsevier). Each study extracted will be screened in a two-step screening process, including a title and abstract screen, and a full-text screen. One independent individual will complete both steps of the screening, and a second independent individual will review the completed screening. Discussion: An understanding of the current literature on psychedelic drugs as modulators of social cognition will provide insight into what is presently known on the subject, and any gaps in the literature that can be addressed in future studies. The knowledge gained from this scoping review could lead to a new treatment for social cognition defects in clinical populations. [ABSTRACT FROM AUTHOR]

Objective: To synthesise young person and family member perspectives on processes of change in family therapy for anorexia nervosa (AN), including systemic family therapy and manualised family-based treatments, to obtain an understanding of what helps and hinders positive change. Method: A systematic search of the literature was conducted to identify qualitative studies focussing on experiences of therapeutic change within family therapies for AN from the perspectives of young people and their families. Fifteen studies met inclusion criteria and underwent quality appraisal following which they were synthesised using a meta-synthesis approach. Results: Six overarching themes were generated: "A holistic focus on the young person's overall development"; "The therapeutic relationship as a vehicle for change"; "The therapist's confinement to a script and its impact on emotional attunement"; "A disempowering therapeutic context"; "Externalisation of the eating disorder (ED)"; and "The importance of family involvement". Positive change was helped by understanding and support given to the young person's overall development including their psychological, emotional, social and physical wellbeing, positive therapeutic relationships, relational containment within the family system and externalising conversations in which young people felt seen and heard. Positive change was hindered by inflexibility in the treatment approach, counter-effects of externalisation, negative experiences of the therapist, a narrow focus on food-intake and weight, as well as the neglect of family difficulties, emotional experiences, and psychological factors. Conclusions: Positive change regarding the young person's eating-related difficulties ensued in the context of positive relational changes between the young person, their family members, the therapist and treatment team, highlighting the significance of secure and trusting relationships. The findings of this review can be utilised by ED services to consider how they may adapt to the needs of young people and their families in order to improve treatment satisfaction, treatment outcomes, and in turn reduce risk for chronicity in AN. Plain English summary: This review synthesises the views of young people and their family members regarding their perspectives of therapeutic change within family therapies for Anorexia Nervosa (AN), including both manualised eating disorder-focussed family therapy models (family-based treatment; FBT and AN-focussed family therapy; FT-AN), as well as systemic family therapy (SyFT), to understand which aspects of these treatment approaches are helpful versus hindering to recovery from an eating disorder (ED). Parental involvement was crucial in facilitating the restoration of physical health through the process of parents taking temporary responsibility for the young person's eating behaviours until they can feed themselves again. However, treatment often failed to acknowledge and address the psychological and emotional difficulties that made the young person vulnerable to developing AN, as well as the psychological distress caused by increasing food-intake and weight. A positive therapeutic relationship in which families felt well supported by their therapist was important in providing containment during a time of familial strain and instability, yet there was a need for greater flexibility and individualisation within manualised ED-focussed family therapy approaches, particularly FBT. The findings highlight the importance of eliciting the young person's voice to enhance their personal agency in treatment and the value of therapeutic space to improve family functioning and enhance family unity. Lastly, they illuminate the need for manualised ED-focussed family therapy models to allow space for the therapist to emotionally attune to young people and families in order to contain their experience of distress. [ABSTRACT FROM AUTHOR]

Pain, a comorbidity of anxiety disorders, causes substantial clinical, social, and economic burdens. Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain‐associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100 mg kg−1) in alleviating pain‐associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety‐like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress‐related hormones including corticosterone, corticotropin‐releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVNCRH) is reduced after propofol treatment. Interestingly, artificially activating PVNCRH neurons through chemogenetics interfered with the anxiety‐reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVNCRH neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of γ‐aminobutyric acid type A receptor β3 (GABAAβ3) subunits in PVNCRH neurons diminished the anxiety‐relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain‐associated anxiety‐like behaviors using a single dose of propofol. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) stands as a formidable neurodegenerative ailment and a prominent contributor to dementia. The scarcity of available therapies for AD accentuates the exigency for innovative treatment modalities. Psilocybin, a psychoactive alkaloid intrinsic to hallucinogenic mushrooms, has garnered attention within the neuropsychiatric realm due to its established safety and efficacy in treating depression. Nonetheless, its potential as a therapeutic avenue for AD remains largely uncharted. This comprehensive review endeavors to encapsulate the pharmacological effects of psilocybin while elucidating the existing evidence concerning its potential mechanisms contributing to a positive impact on AD. Specifically, the active metabolite of psilocybin, psilocin, elicits its effects through the modulation of the 5-hydroxytryptamine 2A receptor (5-HT2A receptor). This modulation causes heightened neural plasticity, diminished inflammation, and improvements in cognitive functions such as creativity, cognitive flexibility, and emotional facial recognition. Noteworthy is psilocybin's promising role in mitigating anxiety and depression symptoms in AD patients. Acknowledging the attendant adverse reactions, we proffer strategies aimed at tempering or mitigating its hallucinogenic effects. Moreover, we broach the ethical and legal dimensions inherent in psilocybin's exploration for AD treatment. By traversing these avenues, We propose therapeutic potential of psilocybin in the nuanced management of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Psychoactive substances obtained from botanicals have been applied for a wide variety of purposes in the rituals of different cultures for thousands of years. Classical psychedelics from N,N′‐dimethyltryptamine, psilocybin, mescaline and various lysergamides cause specific alterations in perception, emotion and cognition by acting through serotonin 5‐HT2A receptor activation. Lysergic acid diethylamide, the first famous breakthrough in the field, was discovered by chance by Albert Hoffman in the Zurich Sandoz laboratory in 1943, and studies on its psychoactive effects began to take place in the literature. Studies in this area were blocked after the legislation controlling the use and research of psychedelic drugs came into force in 1967, but since the 1990s, it has started to be a matter of scientific curiosity again by various research groups. In particular, with the crucial reports of psychotherapy‐assisted psilocybin applications for life‐threatening cancer‐related anxiety and depression, a new avenues have been opened in the treatment of psychiatric diseases such as treatment‐resistant depression and substance addictions. An increasing number of studies show that psychedelics have a very promising potential in the treatment of neuropsychiatric diseases where the desired efficiency cannot be achieved with conventional treatment methods. In this context, we discuss psychedelic therapy, encompassing its historical development, therapeutic applications and potential treatment effects—especially in depression, trauma disorders and substance use disorders—within the framework of ethical considerations. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research. [ABSTRACT FROM AUTHOR]

In the past few years, psilocybin, a psychedelic compound found in “magic mushrooms” (psilocybin mushrooms), has undergone decriminalization in numerous cities across the US and has been legalized in Oregon and Colorado. Proponents of psilocybin decriminalization have emphasized its therapeutic potential in treating mental health disorders. Furthermore, psilocybin mushrooms are considered the safest psychedelic option, with lower potency and a reduced risk of overdoses and emergency hospitalizations compared to other prevalent psychedelics, such as LSD (lysergic acid diethylamide) and MDMA (3,4-methylenedioxymethamphetamine). We analyzed the impact of psilocybin reforms on public interest in psilocybin, as well as their cross-commodity effects on LSD and MDMA, utilizing extensive web-based search data. We observe a significant increase in psilocybin search volume and a notable reduction in search volume associated with LSD and MDMA. Our results are consistent nationwide across states, irrespective of their stance on psilocybin reforms. The shift in public interest toward psilocybin, which is considered the safest psychedelic, away from LSD and MDMA, carries positive implications for public health. [ABSTRACT FROM AUTHOR]

Background: Most studies examining the simultaneous use of cannabis with other drugs have focused on cannabis and alcohol, with fewer studies examining simultaneous use of cannabis with other drugs. The United States is currently experiencing an upward trend in psychedelic use and there is an increasing need to characterize cannabis and psychedelic drug interactions to best inform public health recommendations. Materials and Methods: A mixed methods field study design was used to survey participants (N = 128) on their lifetime co-use of cannabis with other drugs. Participants who reported lifetime co-use of cannabis and psychedelics (N = 63) were then asked open-ended questions about their most recent simultaneous co-use experience (i.e., how cannabis enhanced their psychedelic experience and whether they experienced any adverse reactions). We conducted a thematic analysis of responses describing how cannabis enhanced the psychedelic experience (N = 54). However, due to low response rate for participants reporting an adverse reaction (N = 7, 11.1%), responses to this question were not analyzed thematically and are instead presented individually. Results: Themes included tension reduction and balancing of drug effects (N = 27, 50%), enhancement to psychological processes (N = 11, 20.4%), intensified psychedelic drug effects (N = 12, 22.2%), enhanced psychedelic come-down experience (N = 8, 14.8%), and overall ambiguous enhancement (N = 7, 13%). Among participants reporting an adverse reaction, individual responses included increased anxiety and intensity of the experience, decreased sociability, increased negative affect, sleepiness, disassociation, and confusion. Conclusion: Additional research is warranted to better characterize cannabis and psychedelic drug interactions to best inform public health recommendations. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major source of morbidity and mortality worldwide, particularly for racial and ethnic minorities who face higher rates of hypertension and worse health-related outcomes. Recent research has reported on protective associations between classic psychedelics and hypertension; however, there is a need to explore how race and ethnicity may moderate such associations. Methods: We used data from the National Survey on Drug Use and Health (2005-2014) to assess whether race and ethnicity moderate the associations between classic psychedelic use - specifically psilocybin - and past year hypertension. Results: Hispanic identity moderated the associations between psilocybin use and past year hypertension. Furthermore, individuals who used psilocybin and identified as Non-Hispanic White had reduced odds of hypertension (aOR: 0.83); however, these associations were not observed for any other racial or ethnic groups in our study for individuals who used psilocybin. Conclusion: Overall, our results demonstrate that the associations between psychedelics and hypertension may vary by race and ethnicity. Longitudinal studies and clinical trials can further advance this research and determine whether such differences exist in causal contexts. [ABSTRACT FROM AUTHOR]

Introduction: Psilocybin, a naturally occurring serotonergic agonist in some mushroom species, has shown promise as a novel, fast-acting pharmacotherapy seeking to overcome the limitations of conventional first-line antidepressants. Studying psilocybin effects on cognition and emotional processing may help to clarify the mechanisms underlying the therapeutic potential of psilocybin and may also support studies with people suffering from depression. Thus, this review aims to provide a comprehensive overview of the current literature regarding the effects of psilocybin on these two key areas in both healthy and depressed populations. Method: A systematic search was performed on 29 January 2024, in the PubMed, EBSCOhost, Web of Science and SCOPUS databases. After duplicates removal, study selection was conducted considering pre-specified criteria. Data extraction was then performed. The quality assessment of the studies was carried out using the Cochrane Collaboration tools for randomized (RoB 2.0) and non-randomized (ROBINS-I) controlled trials. Results: Twenty articles were included, with 18 targeting healthy adults and two adults with depression. Results point to impairments within attentional and inhibitory processes, and improvements in the domains of creativity and social cognition in healthy individuals. In the population with depression, only cognitive flexibility and emotional recognition were affected, both being enhanced. The comparison of outcomes from both populations proved limited. Conclusions: Psilocybin acutely alters several cognitive domains, with a localized rather than global focus, in a dose- and time-dependent manner. However, the significant methodological constraints call for further research, in the context of depression and with standardized protocols, with longitudinal studies also imperative. [ABSTRACT FROM AUTHOR]

Aim: Recently, the relationship between diabetes and mental health has been widely studied. With the advent of continuous glucose monitoring (CGM), some researchers have been interested in exploring the association between glucose-related metrics and psychological aspects. These studies have primarily relied on self-report questionnaires which present some limitations. Therefore, the present multicenter study aims at testing potential associations between CGM metrics and affective processes derived from narratives about using a CGM sensor. Methods: An exploratory correlational design was used. Fifty-eight adults with type 1 diabetes using CGM were enrolled and invited to complete an online survey, where they replied to an open-ended question regarding their personal experience with the CGM sensor. Texts derived from the answers were analyzed through Linguistic Inquiry and Word Count, a widely used text analysis tool that can automatically identify and quantify linguistic patterns related to various psychological dimensions. Psycholinguistic measures were correlated with CGM metrics. Results: Higher levels of sadness/depression correlated with lower %TIR (r = − 339; p <.01) and higher %TAR (r =.342; p <.01). Conclusions: The study highlights the relationship between CGM metrics and psychological variables derived from patients' narratives. In particular, it is possible to hypothesize a positive role of %TIR in reducing depressive feelings in individuals with diabetes, as well as a negative role of depressive feelings in achieving desirable CGM outcomes. Additionally, there is a potential role of glycemic variability, particularly hyperglycemia, in the expression of depressive and sad feelings, which has been less studied compared to the effects of hypoglycemia. [ABSTRACT FROM AUTHOR]

Objectives: The Australian government recently rescheduled psilocybin and 3,4-methylenedioxymethamphetamine for limited clinical uses. This change has raised various regulatory concerns and challenges for the field of psychedelic-assisted therapy. To provide clarity, we aimed to comprehensively catalogue the matters relating to psychedelic-assisted therapy that are or could be regulated. Methods: We conducted a desktop review of the literature and current regulatory sources, semi-structured interviews with professionals who had expertise in fields relating to psychedelic-assisted therapy and a framework analysis to generate a taxonomy of relevant regulatory matters. In relation to each matter, we further identified what type of regulation (if any) currently applies to that matter, any uncertainty as to how the matter should be addressed in clinical practice in the context of current regulation and whether there are conflicting views as to how the matter could or should be further regulated. Results: The taxonomy is structured into six main regulatory domains, three of which have a substantial proportion of matters with uncertainty or conflicting views: Service Establishment, Practitioner, and Treatment Delivery. Key examples of such matters include the location of services and facilities required, which professionals are eligible to become psychedelic therapists, and with what qualifications and experience. Matters in the remaining three domains, Patient Evaluation, Drug Supply and Service Oversight, appear by comparison relatively settled, with regulation either well-established or thought unnecessary. Conclusions: The taxonomy provides a roadmap for health services establishing and implementing a psychedelic-assisted therapy program, or for government and other policymakers when determining areas that may require further regulation. [ABSTRACT FROM AUTHOR]

Grief, a common reaction to loss, can frequently become problematic or impairing. Available treatments for prolonged grief disorder are promising but leave room for considerable improvement. Qualitative accounts of psychedelic experiences after bereavement reveal themes that parallel core components of prolonged grief disorder therapy. However, few studies have investigated the therapeutic potential of psychedelics for symptoms of grief. The present study surveyed recreational psychedelic users (N = 363) who had suffered a bereavement event. They reported retrospective grief symptoms before and after the psychedelic experience as well as subjective reactions to the psychedelic, including emotional breakthroughs and challenging experiences. Results indicate improvements in grief symptoms after a psychedelic experience, with a large effect size (Cohen's d = 0.83). The occurrence of emotional breakthroughs was positively associated with improvements in symptoms of grief, while the converse relation was observed for challenging experiences. Findings provide preliminary evidence that support the development of a psychedelic-assisted therapy protocol to target symptoms of grief. Psychedelic-assisted therapy might offer an alternative to current grief treatment options. [ABSTRACT FROM AUTHOR]

There has been growth in the use of psychedelics by the global population in recent years. In addition to recreational and ritualistic use, recent research into psychedelics has brought advances for treating mental disorders. Understanding the specific circumstances in which psilocybin leads to positive outcomes may have important implications for the future of its clinical use and for harm reduction initiatives. This study aimed to investigate the positive effects from the consumption of psilocybin through public online self-reports. We sought to investigate health benefits promoted by the consumption of the substance, positive acute effects, and contextual details of these experiences. We analyzed 846 reports with the assistance of the IRaMuTeQ textual analysis software, adopting the procedures of Descending Hierarchical Classification, Correspondence Factor Analysis, and Specificities Analysis. The texts were grouped in 5 clusters, describing the content of mental experiences, cognitive processes, somatic experiences, perceptual alterations, and context of administration. The findings of this study reinforce central axes of the psychedelic experience, such as the presence of somatic and visual alterations, connectedness and feeling one with the world and effects of setting, as well as the beneficial character of mystical experiences this substance promotes, and the importance of the ego-dissolution phenomenon. [ABSTRACT FROM AUTHOR]

Evidence suggests that psilocybin has therapeutic benefit for treating depression. However, there is little consensus regarding the mechanism by which psilocybin elicits antidepressant effects. This systematic review summarizes existing evidence. Ovid MEDLINE, EMBASE, psychINFO, and Web of Science were searched, for both human and animal studies, using a combination of MeSH Terms and free-text keywords in September 2021. No other mood disorders or psychiatric diagnoses were included. Original papers in English were included. The PRISMA framework was followed for the screening of papers. Two researchers screened the retrieved articles from the literature search, and a third researcher resolved any conflicts. Of 2,193 papers identified, 49 were selected for full-text review. 14 articles were included in the qualitative synthesis. Six supported psilocybin's mechanism of antidepressant action via changes to serotonin or glutamate receptor activity and three papers found an increase in synaptogenesis. Thirteen papers investigated changes in non-receptor or pathway-specific brain activity. Five papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex. Several neuroreceptors, neurotransmitters, and brain areas are thought to be involved in psilocybin's ability to mitigate depressive symptoms. Psilocybin appears to alter cerebral blood flow to the amygdala and prefrontal cortex, but the evidence on changes in functional connectivity and specific receptor activity remains sparse. The lack of consensus between studies suggests that psilocybin's mechanism of action may involve a variety of pathways, demonstrating the need for more studies on psilocybin's mechanism of action as an antidepressant. [ABSTRACT FROM AUTHOR]

The drug experiences of women in Western society have been both sensationalized for their scandalous aspects and sterilized in clinical reports, but the role of women in the investigation of psychedelics in modern Western history is obscure, and the identities and activities of early women participants are often unknown. This paper explores some of the under-reported history of women's contributions to psychedelic exploration and research in the twentieth century. Mabel Luhan and Valentina Wasson represent women whose stories have entered the canon of psychedelic history but have failed to fully represent their individual impact. Wasson's work is often subsumed under that of her more well-known husband. Luhan is considered to be a psychedelic pioneer, but her pattern of interference in the politics of peyote in the Taos Pueblo is often overlooked. The poet Mary Barnard is well-known as a translator of Sappho, but her lyrical writing on psychedelics is less celebrated. Gertrude Paltin and Kay Parley are female therapists and authors whose valuable writing on psychedelics is almost unknown in the field. There remain many women whose significant contributions to the exploration and employment of psychedelics for spiritual development, personal discovery, individual betterment or therapeutic impact have not been well recorded. [ABSTRACT FROM AUTHOR]

The primary objective of this qualitative study was to explore the therapeutic trajectories of individuals undergoing psilocybin-assisted group therapy. This interpretive phenomenological analysis focused on an enriched study sample of gay-identified cisgender men (n = 9) with human immunodeficiency virus diagnosed before 1996 and clinically significant trauma symptoms. Microphenomenological interviews were carried out 1 day after participants' individual psilocybin sessions to elicit fine-grained descriptions of the psilocybin-assisted treatment. Two major thematic change processes were identified using Interpretive Phenomenological Analysis. During their psilocybin sessions, participants reported transitioning out of habitual, evaluative modes of processing and into mindful, experiential modes of processing (from "autopilot" to "meta-aware"). Freed from their emotionally avoidant tendencies, participants were able to process and release previously disowned feelings (grief, shame) and access relational and self-transcendent feelings and prosocial attitudes (joy, gratitude, love, care, compassion). The treatment also supported processes of meaning-making and the realization of posttraumatic growth (in psychological, relational, spiritual dimensions) as participants integrated past traumas into their life narratives and identities (from "trauma-dominant" to "growth-dominant"). These findings suggest that administering adjunctive group therapy with psilocybin may enhance the effectiveness of trauma processing by reinforcing social cohesion, safety, trust, and belonging. These data provide the first empirical suggestion of psilocybin's efficacy in alleviating trauma symptoms in a group-facilitated format and provide a deeper understanding of the potential psychological change processes involved in this novel treatment approach. [ABSTRACT FROM AUTHOR]

The therapeutic use of psilocybin in psychedelic-assisted therapy models is currently being tested for a variety of indications, necessitating the training of hundreds of therapists. At present, training programs do not include the provision of a psilocybin experience for therapists, and the last time such an experience was offered with a similar compound was through the Spring Grove LSD Training Study between 1969 and 1974. This article explores archival Spring Grove data to inform training programs and efforts to establish or provide training experiences with psilocybin or otherwise include experiences with nonordinary states of consciousness in the training of psychedelic therapists. [ABSTRACT FROM AUTHOR]

Psychedelic therapies intentionally combine a caring/healing environment, psychotherapy, and psychedelic medicine as a powerful means of treating intractable conditions of depression and posttraumatic stress disorder. This article utilizes the nursing theory of human caring science, as articulated by Jean Watson, to describe the essential and fundamental human caring qualities in psychedelic therapy. By mapping these qualities onto the traits of a psychedelic therapist, articulated by Janis Phelps and illustrating them with qualitative, exemplar data from a psilocybin assisted therapy study, we have created a nursing-informed philosophical theoretical framework with which to begin to examine questions related to trust enhancement between patient and therapist, therapeutic communication of openness to patient experiences, mutual learning between therapist and patient, the influence spiritual or psychedelic practices of the therapist on outcomes, optimizing therapeutic healing environments, and care of the physical body during psychedelic therapy sessions. This article is intended to identify themes and generate hypotheses for future nursing-informed psychedelic psychotherapy research. [ABSTRACT FROM AUTHOR]

Chronic pruritus (CP) is defined as an unpleasant sensation causing a desire to scratch and lasting > 6 weeks. It has a multifactorial etiology but is more frequently associated with chronic inflammatory dermatoses and systemic disorders. Psychogenic pruritus and neurological disorders are other less common etiologies, while, in some patients, it is idiopathic. CP appears to be processed by non-histaminergic pathway, contributing to its complexity and therapeutic challenge. Moreover, regardless of the etiology, it is multidimensional, including cognitive, motivational and affective components. There is a close link between psychological distress and pruritus, with particular clinical expression in chronic inflammatory dermatoses, involving the activation of the hypothalamic-pituitary-adrenal axis (and its cutaneous equivalent), the sympathetic nervous system, the release of hormones and peptides, the role of immune cells (T and B cells, macrophages) and immune-related cells in the skin (mast cells, dendritic cells and keratinocytes). Moreover, there is strong evidence that psychological factors influence the experience of pruritus. CP can also cause psychiatric disorders, including but not limited to anxiety and depression, and also lead to significant quality of life (QoL) impairment. Thereby, although a psychodermatological assessment should ideally be carried out in the context of a specific psychodermatology consultation, a brief mental health assessment could be part of the general dermatological approach to these patients. Considering that mental health, QoL and pruritus are closely linked, psychotherapeutic interventions and/or psychotropic drugs should thus be considered in some patients as an adjunct to the pharmacological treatment of CP. [ABSTRACT FROM AUTHOR]

Several fungi belonging to the genus Psilocybe , also called "magic mushrooms", contain the hallucinogenic drugs psilocybin and psilocin. They are chemically related to serotonin (5-HT). In addition to being abused as drugs, they are now also being discussed or used as a treatment option for depression. Here, we hypothesized that psilocybin and psilocin may act also on cardiac serotonin receptors and studied them in vitro in atrial preparations of our transgenic mouse model with cardiac myocytes-specific overexpression of the human 5-HT 4 receptor (5-HT 4 -TG) as well as in human atrial preparations. Both psilocybin and psilocin enhanced the force of contraction in isolated left atrial preparations from 5-HT 4 -TG, increased the beating rate in isolated spontaneously beating right atrial preparations from 5-HT 4 -TG and augmented the force of contraction in the human atrial preparations. The inotropic and chronotropic effects of psilocybin and psilocin at 10 µM were smaller than that of 1 µM 5-HT on the left and right atria from 5-HT 4 -TG, respectively. Psilocybin and psilocin were inactive in WT. In the human atrial preparations, inhibition of the phosphodiesterase III by cilostamide was necessary to unmask the positive inotropic effects of psilocybin or psilocin. The effects of 10 µM psilocybin and psilocin were abrogated by 10 µM tropisetron or by 1 µM GR125487, a more selective 5-HT 4 receptor antagonist. In summary, we demonstrated that psilocin and psilocybin act as agonists on cardiac 5-HT 4 receptors. • The hallucinogens psilocybin or psilocin are used as new treatment for depression. • In the human brain, they act mainly via 5-HT 2A serotonin receptors. • Hypothetically, that they may act also on cardiac 5-HT 4 serotonin receptors. • Here, we demonstrated that they act as agonists on human cardiac 5-HT 4 receptors. • Possibly, psilocybin or psilocin may have cardiac side effects. [ABSTRACT FROM AUTHOR]

This article underscores the critical role of social workers in harnessing the potential therapeutic benefits of psilocybin for treating major depressive disorder (MDD) and substance use disorder (SUD). Contemporary treatments for MDD often have side effects, and the success rate for SUD treatments remains low. The pervasiveness of MDD, combined with the challenges in treating SUD, highlights a need for innovative treatments. This article provides an overview of the resurgence of literature over the past two decades that illuminates the therapeutic promise of psilocybin for mental health treatment; clinical trials elucidate the efficacy of psilocybin-assisted therapy in mitigating MDD and demonstrate great promise in reducing SUD symptoms. The long-lasting posttreatment effect emphasizes its potential as a novel treatment modality. Furthermore, psilocybin's recognition as a "breakthrough therapy" by the U.S. Food and Drug Administration (FDA) and the accelerating pace of psychedelic reform bills indicate growing acceptance and interest in its therapeutic capacities. Psilocybin-assisted therapy emerges as a potent treatment option, showcasing remarkable effectiveness even after a single dose. Recommendations and pathways for social workers to be involved in psilocybin-assisted therapy investigation, advocacy, and implementation are provided. [ABSTRACT FROM AUTHOR]

Serotonergic psychedelics, such as psilocybin, alter perceptual and cognitive systems that are functionally integrated with the amygdala. These changes can alter cognition and emotions that are hypothesized to contribute to their therapeutic utility. However, the neural mechanisms of cognitive and subcortical systems altered by psychedelics are not well understood. We used resting-state functional magnetic resonance images collected during a randomized, double-blind, placebo-controlled clinical trial of 24 healthy adults under 0.2 mg/kg psilocybin to estimate the directed (i.e., effective) changes between the amygdala and 3 large-scale resting-state networks involved in cognition. These networks are the default mode network, the salience network, and the central executive network. We found a pattern of decreased top-down effective connectivity from these resting-state networks to the amygdala. Effective connectivity decreased within the default mode network and salience network but increased within the central executive network. These changes in effective connectivity were statistically associated with behavioral measures of altered cognition and emotion under the influence of psilocybin. Our findings suggest that temporary amygdala signal attenuation is associated with mechanistic changes to resting-state network connectivity. These changes are significant for altered cognition and perception and suggest targets for research investigating the efficacy of psychedelic therapy for internalizing psychiatric disorders. More broadly, our study suggests the value of quantifying the brain's hierarchical organization using effective connectivity to identify important mechanisms for basic cognitive function and how they are integrated to give rise to subjective experiences. [ABSTRACT FROM AUTHOR]

To map the studies reporting the use of psychedelics in clinical and non-clinical settings by people reporting an eating disorder (ED) and their outcomes. To be included, peer-reviewed articles had to be written in English or Spanish and had to address the usage of psychedelics by people reporting an ED. Searches were conducted on PubMed, Scopus, and Web of Science. Data on key study characteristics and the findings from the studies were charted using a standardised form. Two reviewers independently charted the data from the included articles. Quality appraisal was conducted for all included studies. Six studies reporting the use of ayahuasca, DMT/5-MEO-DMT, LSD/1P-LSD, San Pedro/mescaline, psilocybin, and ketamine were included. After the psychedelic experiences, many participants reported diminished ED symptoms, reductions in anxiety, self-harm, suicidality, and problematic substance use, significant improvements in depression and wellbeing, and changes in self-perception, and some showed complete remission. Several participants felt profound spiritual healing and reported achieving deep insights into the psychological origins of their ED. All the qualitative studies met 100% of the quality appraisal criteria, whereas the quantitative studies were rated from between 20% and 60%. All included studies suggest that psychedelics promise therapeutic value for eating disorders. These findings are preliminary, and randomised controlled trials are necessary to prove psychedelic-assisted psychotherapy efficacy and long-term implications for eating disorders. Major changes in drug policy are urgent to facilitate research about psychedelics. Trial registration: ClinicalTrials.gov identifier: NCT04661514. Trial registration: ClinicalTrials.gov identifier: NCT04052568. Trial registration: ClinicalTrials.gov identifier: NCT04505189. [ABSTRACT FROM AUTHOR]

Psilocybin is a serotonergic psychedelic believed to have therapeutic potential for neuropsychiatric conditions. Despite well-documented prevalence of perceptual alterations, hallucinations, and synesthesia associated with psychedelic experiences, little is known about how psilocybin affects sensory cortex or alters the activity of neurons in awake animals. To investigate, we conducted two-photon imaging experiments in auditory cortex of awake mice and collected video of free-roaming mouse behavior, both at baseline and during psilocybin treatment. In comparison with pre-dose neural activity, a 2 mg/kg ip dose of psilocybin initially increased the amplitude of neural responses to sound. Thirty minutes post-dose, behavioral activity and neural response amplitudes decreased, yet functional connectivity increased. In contrast, control mice given intraperitoneal saline injections showed no significant changes in either neural or behavioral activity across conditions. Notably, neuronal stimulus selectivity remained stable during psilocybin treatment, for both tonotopic cortical maps and single-cell pure-tone frequency tuning curves. Our results mirror similar findings regarding the effects of serotonergic psychedelics in visual cortex and suggest that psilocybin modulates the balance of intrinsic versus stimulus-driven influences on neural activity in auditory cortex. NEW & NOTEWORTHY: Recent studies have shown promising therapeutic potential for psychedelics in treating neuropsychiatric conditions. Musical experience during psilocybin-assisted therapy is predictive of treatment outcome, yet little is known about how psilocybin affects auditory processing. Here, we conducted two-photon imaging experiments in auditory cortex of awake mice that received a dose of psilocybin. Our results suggest that psilocybin modulates the roles of intrinsic neural activity versus stimulus-driven influences on auditory perception. [ABSTRACT FROM AUTHOR]

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Introduction and purpose: Post-traumatic stress disorder is a psychiatric condition following an extreme event that causes a near death of an involved individual. Since conventional treatments using selective serotonin reuptake inhibitors do not consistently yield therapeutic success, alternative substances are being explored as potential solutions. This study aims to compile information regarding the outcomes of utilizing psychedelics in individuals diagnosed with PTSD. Brief description of the state of knowledge: In July 2023, after a number of clinical trials and 20-year-long efforts to overturn the impact of a prohibition, Australia became the first country to allow doctors, in clinical development and under strict control, to use the 3,4-methyl enedioxy methamphetamine (MDMA) commonly known as ecstasy, as well as psylocybin in patients with post-traumatic stress disorder or depression [1]. There is a noticeable annual growth of inquiries on PubMed involving the keywords "psychedelics" and "therapeutic", amounting to 92 in 2000 and topped by 738 searches in 2023, whereas the total number of results consists of 8415 positions. Therapeutic effects of psychedelics are becoming more recognized over time. Summary: Post-Traumatic Stress Disorder (PTSD) is a complex condition that affects both the psychological and somatic aspects of the body. Thus, a multidimensional intervention is indicated. The use of psychedelics might contribute to improvements not only in the severity of PTSD but also in depression or pain. Further research on a larger group of participants should be carried out to assess the potential role of psychedelics in conventional medicine in the future, alongside psychotherapy. [ABSTRACT FROM AUTHOR]

Abstract As a proposed mediator between stigma-related stressors and negative mental health outcomes, HIV-related shame has been predictive of increased rates of substance use and difficulties adhering to antiretroviral treatment among people with HIV. These downstream manifestations have ultimately impeded progress toward national goals to End the HIV Epidemic, in part due to limited success of conventional psychotherapies in addressing HIV-related shame. In a pilot clinical trial (N = 12), receipt of psilocybin-assisted group therapy was associated with a large pre-post decrease in HIV-related shame as measured by the HIV and Abuse Related Shame Inventory, with a median (IQR) change of − 5.5 (− 6.5, − 3.5) points from baseline to 3-months follow-up (Z = − 2.6, p = 0.009, r = − 0.75). A paradoxical exacerbation of sexual abuse-related shame experienced by two participants following receipt of psilocybin raises critical questions regarding the use of psilocybin therapy among patients with trauma. These preliminary findings carry potential significance for the future of HIV care.

Abstract Background Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. Methods Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures. Discussion This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. Trial registration ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.