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Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Key Points: Question: Will a single psychedelic dose of psilocybin with psychotherapy demonstrate evidence for efficacy and/or safety in drug-free, treatment-resistant participants with bipolar II depression? Findings: In this nonrandomized open-label trial of 15 individuals with bipolar II depression, most participants met remission criteria on the Montgomery-Åsberg Depression Rating Scale 3 weeks after a single 25-mg psilocybin dose, and most remained in remission 12 weeks postdose with no increase in mania/hypomania symptoms or suicidality. Meaning: The findings suggest efficacy and safety of psilocybin in bipolar II depression and support further study of psychedelics in this population. This open-label nonrandomized open-label trial evaluates the safety and efficacy of single-dose psilocybin with psychotherapy for depressive episodes in individuals with bipolar disorder. Importance: Bipolar II disorder (BDII) is a debilitating condition frequently associated with difficult-to-treat depressive episodes. Psilocybin has evidence for rapid-acting antidepressant effects but has not been investigated in bipolar depression. Objective: To establish the safety and efficacy of psilocybin in patients with BDII in a current depressive episode. Design, Setting, and Participants: This was a 12-week, open-label nonrandomized open-label trial conducted at Sheppard Pratt Hospital. Participants aged 18 to 65 years with BDII, a current depressive episode longer than 3 months, and documented insufficient benefit with at least 2 pharmacologic treatments during the current episode were invited to participate. Of 70 approached, 19 met inclusion criteria and were enrolled. The trial was conducted between April 14, 2021, and January 5, 2023. Interventions: A single dose of synthetic psilocybin, 25 mg, was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing. Therapists met with patients for 3 sessions during pretreatment, during the 8-hour dosing day, and for 3 integration sessions posttreatment. Main Outcomes and Measures: The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures included MADRS scores 12 weeks posttreatment, the self-rated Quick Inventory of Depression Symptoms-Self Rating (QIDS-SR), and the self-rated Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), each completed at baseline and all subsequent visits. Safety measures included the Columbia Suicide Severity Rating Scale (CSSRS) and the Young Mania Rating Scale (YMRS) completed at each visit. Results: Of the 15 participants in this study (6 male and 9 female; mean [SD] age, 37.8 [11.6] years), all had lower scores at week 3, with a mean (SD) change of −24.00 (9.23) points on the MADRS, (Cohen d = 4.08; 95% CI, −29.11 to −18.89; P <.001). Repeat measures analysis of variance showed lower MADRS scores at all tested posttreatment time points, including the end point (Cohen d = 3.39; 95% CI, −33.19 to −16.95; adjusted P <.001). At week 3, 12 participants met the response criterion (50% decrease in MADRS), and 11 met remission criterion (MADRS score ≤10). At the study end point, 12 patients met both response and remission criteria. QIDS-SR scores and Q-LES-Q-SF scores demonstrated similar improvements. YMRS and CSSRS scores did not change significantly at posttreatment compared to baseline. Conclusions and Relevance: The findings in this open-label nonrandomized open-label trial suggest efficacy and safety of psilocybin with psychotherapy in BDII depression and supports further study of psychedelics in this population. [ABSTRACT FROM AUTHOR]

We describe trends in psilocybin exposures among adolescents and young adults as reported to US poison centers over the past decade. We queried the National Poison Data System for cases involving psilocybin during January 1, 2013–December 31, 2022. Persons aged 13–25 years were included. We examined exposures to psilocybin by demographics, clinical effects, level of care, and medical outcome. During the 10-year study period, 4,055 psilocybin-involved exposures were reported among adolescents and young adults, 2,667 (65.8%) being single substance exposures. Most single substance cases received medical attention (adolescents: 75.3% [n = 1,176], young adults: 72.1% [n = 797]). We did not find significant change in the number of cases during 2013–2018. Cases started increasing in 2019. In 2022, cases more than tripled among adolescents and more than doubled among young adults, compared to 2018 (p <.0001). Continued national surveillance is critical to determine the impact of psilocybin exposures on youth as it becomes increasingly available. [ABSTRACT FROM AUTHOR]

• Evidence-based mental telehealth treatment for firefighters is effective. • Delivery of the unified protocol (UP) reduces posttraumatic stress disorder symptom severity in firefighters. • Delivery of the UP reduces alcohol use behaviors in firefighters. • The UP can be successfully applied to telehealth for firefighters. Firefighters protect the public despite significant risk to their health and well-being stemming from frequent trauma exposure and other occupational stressors. A minority of firefighters develop posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), or related mental health problems, such as depression or anxiety. These problems frequently co-occur and are linked with high neuroticism and difficulties with emotion regulation. Thus, efficient treatment for this population should be transdiagnostic and target neuroticism. Moreover, logistical challenges and stigma represent barriers to care in firefighters. We addressed these challenges by culturally adapting the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders and delivering it to 61 firefighters via videoconferencing, of whom 49 completed treatment. The adaptation process is described, and two case vignettes are presented. In the total sample, large effect size improvements were observed in symptoms of PTSD, depression, and psychological aspects of quality of life at posttreatment and 1-month follow-up. For anxiety, improvements were medium at posttreatment and large at follow-up. Medium effects were observed on reductions in AUD symptoms and in the other aspects of quality of life (physical health, social relationships, and environmental) at posttreatment and follow-up. Reductions in suicide risk were small in the total sample and moderate among those who screened positive for being at suicide risk at pretreatment. Similarly promising results were observed in the subsamples of participants who screened positive for PTSD, AUD, and co-occurring PTSD–AUD at pretreatment, with large improvements in AUD symptoms observed in those who screened positive for AUD at pretreatment. This is the first study to report on the unified protocol delivered via telehealth. The treatment completion rate was high (80.3%). The current study contributes to the emerging literature on the unified protocol for PTSD and AUD. The current findings support the utility of this treatment for PTSD and AUD, consistent with the underlying approach of targeting neuroticism across diagnostic categories. [ABSTRACT FROM AUTHOR]

Objective: The primary aim of this qualitative study was to delineate psychological mechanisms of change in the first randomized controlled trial of psilocybin-assisted psychotherapy to treat alcohol use disorder (AUD). Theories regarding psychological processes involved in psychedelic therapy remain underdeveloped. Method: Participants (N = 13) mostly identified as non-Hispanic and White, with approximately equal proportions of cisgender men and women. Participants engaged in semistructured interviews about their subjective experiences in the study. Questions probed the nature of participants' drinking before and after the study as well as coping patterns in response to strong emotions, stress, and cravings for alcohol. Verbatim transcripts were coded using Dedoose software, and content was analyzed with interpretive phenomenological analysis. Results: Participants reported that the psilocybin treatment helped them process emotions related to painful past events and helped promote states of self-compassion, self-awareness, and feelings of interconnectedness. The acute states during the psilocybin sessions were described as laying the foundation for developing more self-compassionate regulation of negative affect. Participants also described newfound feelings of belonging and an improved quality of relationships following the treatment. Conclusion: Our results support the assertion that psilocybin increases the malleability of self-related processing, and diminishes shame-based and self-critical thought patterns while improving affect regulation and reducing alcohol cravings. These findings suggest that psychosocial treatments that integrate selfcompassion training with psychedelic therapy may serve as a useful tool for enhancing psychological outcomes in the treatment of AUD. Public Health Significance Statement This study demonstrated the importance of psychological factors that influence outcomes in psilocybinassisted therapy for alcohol use disorder (AUD). Our findings suggest that psilocybin treatment prompted meaningful and enduring improvements in self-compassion and affect regulation. These psychological processes may help individuals with AUD cope with difficult emotions and stress and prevent relapse by encouraging adaptive coping responses. [ABSTRACT FROM AUTHOR]

This article explores the potential for mediation as a means of resolving disputes within the psilocybin industry. Psilocybin, found in magic mushrooms, has been used by Indigenous communities for spiritual purposes and is now being studied for its therapeutic benefits. While some states have decriminalized or legalized psilocybin, it remains federally illegal. The article suggests that implementing a mediation-first approach could be beneficial in resolving industry disputes, as mediation is seen as a less burdensome and more therapeutic alternative to litigation. The article also discusses the legal complexities and operational challenges faced by businesses in the cannabis and psilocybin industries, highlighting the need for federal action to address these challenges. Additionally, the article provides an overview of the regulatory frameworks for psilocybin consumption in Oregon and Colorado, emphasizing the aim of providing safe access to psilocybin for individuals with mental health challenges. The text also discusses the potential risks of psychedelic therapy, the vulnerability of the psychedelic industry to lawsuits, and the benefits of alternative dispute resolution (ADR), specifically mediation, in the American legal system. It suggests that mediation can help mitigate legal and financial risks and promote positive outcomes for businesses in the psilocybin industry. [Extracted from the article]

Research on psychotropics is gaining more popularity worldwide and support from drug regulatory agencies, which recognise the unmet medical needs of certain patient communities, such as patients with mental disorders and patients with cancer who experience depression. Cannabinoids and psilocybin have shown promising results in preclinical studies and clinical trials, but the current clinical evidence is scarce, and the regulatory requirements are strict due to high potential for drug abuse. The US FDA has recently released a draft, non-binding guidance on clinical trials with psychedelics. Europe is currently falling behind the US and Canada in terms of regulating psychotropic substances. The article provides a general introduction on conducting clinical trials with psychotropics and the regulatory require - ments (as of October 2023) when submitting marketing authorisation application. In the near future, as more data becomes available, research on psychotropics will definitely shape the European regulatory landscape. [ABSTRACT FROM AUTHOR]

Hypoglycemic encephalopathy (HE) is a type of encephalopathy resulting from extremely low blood glucose level. Symptoms are not specific and can be misdiagnosed very often. It can occur during deep and/or prolonged hypoglycemia, which may be a result of inadequately controlled diabetes. Here, we report a case of an 11-year old male patient diagnosed with type 1 diabetes mellitus treated with the use of insulin pump who was admitted to the Pediatric Neurology Department because of multiple incidents of seizures. Boy was found unconscious by his mother. The blood glucose level on the glucometer was 35 mg/dl. It turned out that the reason of hypoglycemia was inadequate insulin dosing. He was given intravenous glucose by the ambulance service without improvement in the state of consciousness. Brain MRI revealed in both cerebral hemispheres, symmetrically, elevated white matter signal, mainly in the subcortex and cortex of the frontal and occipital and parietal lobes with features of diffusion restriction. EEG revealed generalized slow brain activity, without obvious epileptiform. Boy was provided with a variety of antiepileptic drugs. Unfortunately, none of them yielded with satisfactory results so far and the patient is still suffering from drug-resistant epilepsy. In conclusion, glucose is one of the key metabolic agents for the proper brain function and any imbalances in its blood level may impair the neuronal computation. Thus, it is extremely important, especially among diabetic patients, to control glucose blood level and avoid any disturbances, as they may lead to severe consequences, such as HE and drug-resistant epilepsy. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aims to evaluate the impact of psilocybin on patients experiencing psychiatric symptoms, with a focus on health-related quality of life (HRQoL) and safety. Method of Research: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed database and identified studies published from January 2011 to December 2021 pertaining to the impact of psilocybin on psychiatric symptoms. Two authors independently conducted a focused analysis and reached a final consensus on five studies meeting the specific selection criteria. Study bias was addressed using the Cochrane risk of bias tool. Results: The impact of psilocybin on psychiatric symptoms was examined in five randomized controlled trials (RCTs). Four studies administered 1 to 2 doses of psilocybin, with doses ranging from 14mg/70kg to 30mg/70kg, and one study administered a fixed dose of 25mg to all participants. Administration of psilocybin resulted in significant and sustained reduction in symptoms of anxiety and depression, enhanced sense of wellbeing, life satisfaction, and positive mood immediately after psilocybin administration and up to six months after conclusion of treatment. All studies included some form of psychotherapy, and none reported serious adverse effects. Conclusion: RCTs show the efficacy of psilocybin in the treatment of anxiety and depression symptoms, as well as improvement in HRQoL, and no serious side effects. However, additional research is necessary to characterize predictors of treatment response, patient screening requirements, effectiveness in broader clinical populations, and guidelines for psilocybin-assisted psychotherapy. [ABSTRACT FROM AUTHOR]

Psychedelics and related compounds have shown efficacy for the treatment of a variety of conditions that are prevalent among older adults, including mood disorders, the psychological distress associated with a serious medical illness, post-traumatic stress disorder (PTSD), and prolonged grief disorder. Psychedelics also have properties that could help provide therapeutic benefits for patients with dementing disorders, as well as promoting personal growth among healthy older adults. This article focuses on psilocybin, a classic psychedelic, and MDMA, a substituted amphetamine with properties similar to classic psychedelics. Both act on the 5HT2A receptor. Psychedelics can be safely administered to healthy adults in controlled conditions. However, both psilocybin and MDMA can increase blood pressure and heart rate, which could be a concern if used in older adults with cardiovascular disease. Very few older adults or patients with serious comorbidities have been included in clinical trials of psychedelics to date, raising the question of how generalizable study results are for the patients that most geropsychiatrists will be treating. Research on the neurophysiologic and mechanistic effects of psychedelics in older adults could also provide insights into the aging brain that could have clinical applications in the future. Given the potential of psychedelic compounds to benefit older adults, more research is needed to establish safety and efficacy among older adults, particularly those with multi-morbidity. [ABSTRACT FROM AUTHOR]

This article analyzes how and why Timothy Leary established a psychedelic research center in Zihuatanejo, Mexico in the summers of 1962 and 1963. We analyze the reaction Mexican authorities and academics had to this event, the part the press played in public portrayal, the rise of psychedelic drug tourism, and the effect this center had on the local community and wider counterculture. Modern history of psychedelics in Mexico-including Leary's influence-has seldom been studied. We contribute to the history of psychoactive substances by integrating a transnational perspective that focuses on people and events in Mexico and the United States, and on how international travel and the exchange of knowledge jointly constructed a fundamental part of the psychedelic movement. Based on historical and ethnographic sources, we argue that moral panic around drugs, fears over social and cultural changes, sensationalist press coverage, a rigid political system, and rifts with the local community contributed to the closure of the Zihuatanejo Project. More broadly, we note how these factors influenced the Mexican government and society 's reaction to the jipi movement throughout the 1960s. [ABSTRACT FROM AUTHOR]

Background: Migraine is a common neurovascular disorder with a pathophysiology related to the serotonin (5-hydroxytryptamine; 5-HT) system. Pharmacologic modulation of 5-HT receptors has demonstrated efficacy in the acute treatment of migraines. Psilocybin, a classic psychedelic with 5-HT receptor activity, has demonstrated therapeutic potential in the management of neuropsychiatric conditions. To date, no reports have investigated the effect of psilocybin administered acutely during a migraine episode. Case presentation: The case of a 33-year-old male patient with a history of migraines with aura, who had acute administration of oral psilocybin (in the form of the dried fruiting body of Psilocybe cubensis mushrooms) at migraine onset is presented. Headache intensity was rated hourly using the Numerical Rating Scale (NRS) and compared to three previous migraines. Profound reductions in headache intensity and emetic episodes were reported during the migraine treated acutely with oral psilocybin administration, compared to three previous migraines. Discussion: The severe, disabling, and treatment-resistant nature of migraines warrants continued surveillance for novel pharmacologic interventions. The established congruous pathophysiology of migraine and pharmacology of psilocybin, via the 5-HT receptor system, positions psilocybin as a potential therapeutic target. Conclusion: While this report highlights the potential role of psilocybin in the acute management of migraines, it is essential to note that it should not be considered a basis for guiding clinical practice at this point. Further research is necessary to establish the safety and efficacy of psilocybin as a treatment option for migraines. [ABSTRACT FROM AUTHOR]

This document is a comment and response to a study published in JAMA Psychiatry regarding the use of psilocybin in treating bipolar depression. The authors raise three concerns about the study. Firstly, they argue that the study should not have been titled a nonrandomized controlled trial because there was no control group. Secondly, they point out that the study did not adhere to the most recent criteria for defining treatment-resistant bipolar depression. Lastly, they criticize the study design for not including a control group, which they believe is necessary to assess efficacy and safety. The authors also express concerns about the lack of blinding, the use of psychotherapy and additional pharmacotherapy, and the reporting of certain secondary outcomes. They recommend the use of a checklist to assess validity threats in psychedelic science in the future. [Extracted from the article]

A recent study published in JAMA Psychiatry explores the potential use of psilocybin, a compound found in certain mushrooms, for the treatment of bipolar II depression. The study involved 15 participants with bipolar II depression who were given a high dose of psilocybin alongside psychological support. The results showed significant improvements in depression symptoms, with 80% of participants meeting criteria for response and remission. Importantly, there were no significant adverse events reported. While the study has limitations, such as a small sample size and lack of a control group, it provides preliminary evidence for the safety and potential efficacy of psilocybin in treating bipolar II depression. However, caution should be exercised in generalizing these findings to bipolar I disorder, which is characterized by more severe manic episodes. Further research is needed to explore the long-term effects and risks associated with psilocybin treatment. [Extracted from the article]

• The default mode network (DMN) may serve as a hub for real-time sensory synthesis. • Post-traumatic stress disorder (PTSD) has identified perceptual challenges as a core feature of the disorder. • The hierarchical predictive coding framework synthesizes these lines of research into a novel theoretical model. Humans rely on internal models from sensory information to predict future action, and the default mode network (DMN) plays a pivotal role in this process. These models, however, can become distorted or disrupted in cases of post-traumatic stress disorder (PTSD) because traumatic stress can maladaptively alter how humans understand themselves and predict what happens in the world around them. Here, we examine the relationship between PTSD and this predictive phenomenon known as hierarchical predictive coding implicated in the DMN. We postulate that a hierarchical predictive coding framework will help researchers and clinicians more effectively explain the neural and psychological effects of PTSD among individuals who live with this condition, which may contribute to more targeted research and treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients diagnosed with major depressive disorder (MDD) who fail to respond to two or more antidepressants are often considered to have treatment-resistant depression (TRD). Many of the current options for TRD have significant side effect profiles, are expensive, and are difficult to access. There has been a revival of psychedelic research in recent years that shows promising results in the treatment of TRD. Case Presentation: Here, the case of a 43-yearold man with TRD is presented. TRD symptoms were greatly interfering with his life. He underwent psychological testing, lab work, adequate trials of numerous medications, transcranial magnetic stimulation (TMS), and electroconvulsive therapy, all without adequate relief of his symptoms. The patient began self-administering a microdosing regimen of psilocybin and experienced significant improvement of MDD symptoms, as characterized by Hamilton Depression Rating Scale (HDRS). Discussion: In recent years, multiple randomized, controlled trials (RCTs) have shown the benefit of psilocybin in the treatment of varying types of depression. One trial evaluated psilocybin and escitalopram as treatments for depression, and psilocybin was found to be superior. Conclusion: This case suggests the possible benefit of psilocybin in the setting of TRD, as outlined in recent research. Additional research is needed to confirm these observations. [ABSTRACT FROM AUTHOR]

Narrative therapy has been absent from the burgeoning body of structuralist literature on the psychedelic renaissance. This paper argues that structuralist approaches limit the application of principles of client empowerment. It demonstrates applications of politicised narrative practices to supporting client safety, agency and meaning-making. Thin pathologising and/or structuralist descriptions of problems were deconstructed, along with the politics of problems and psychedelic contexts. Clients were supported to develop preferred stories and identities through second-story development, and to richly describe intentional states and/or preferred identities. When used in psychedelic harm reduction, narrative therapy can support safety, empowerment and rich meaning-making. [ABSTRACT FROM AUTHOR]

This article is a response to comments made about a study on the use of psilocybin to treat bipolar depression. The first concern raised was about the study being described as a nonrandomized controlled trial, as there was no comparator group. The authors agreed to amend the subtitle to a nonrandomized open-label trial to avoid confusion. The second concern was that the study did not evaluate resistance to prior antidepressant treatments based on specific criteria, but instead used a widely used and validated instrument. The third criticism was that open-label trials of a novel compound in a novel illness target may not provide much useful information, but the authors argued that their study was important in providing the first clinical experience of using psilocybin in patients with treatment-resistant bipolar depression. They acknowledged the limitations of their study and the need for further research. [Extracted from the article]

CorrectionThe Original Investigation titled "Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes: A Nonrandomized Open-Label Trial,"[1] published on December 6, 2023, was corrected to revise the study type in the title and text from "a nonrandomized controlled trial" to "a nonrandomized open-label trial." This article was corrected online. [Extracted from the article]

This systematic review analyzes the current literature on the potential therapeutic use of classic psychedelics (i.e., psilocybin, lysergic acid diethylamide [LSD], N,N-dimethyltryptamine [DMT], 5-methoxy-N,N-dimethyltryptamine [5-MeO-DMT], mescaline, and other classic psychedelic analogs utilized in preclinical models) in obsessive-compulsive disorder (OCD) and related disorders. Our search identified 23 articles meeting our predetermined eligibility criteria, comprising 2 non-systematic reviews, 11 preclinical studies investigating the use of classic psychedelics or analogs in preclinical models of OCD, 8 case studies or case reports, and 2 clinical trials. This review provides an up-to-date synthesis of psychedelic OCD research, bridging preclinical findings, historical case reports, and initial clinical trial outcomes. Psilocybin appears to be the most widely used classic psychedelic and is well-tolerated in both OCD and body dysmorphic disorder (BDD) populations, with some participants experiencing significant symptom reduction. This review contributes to our understanding of the potential of classic psychedelics (in particular LSD and psilocybin) as novel therapeutic interventions for OCD and related disorders, offering insights into future research directions and clinical applications in this emerging field. • This systematic review identified 23 articles meeting predetermined eligibility criteria: 2 non-systematic reviews, 11 preclinical models of OCD, 8 case studies or case reports, and 2 clinical trials. • This review provides an up-to-date synthesis of psychedelic OCD research, bridging preclinical findings, historical case reports, and initial clinical trial outcomes. • Psilocybin appears to be well-tolerated in both OCD and body dysmorphic disorder (BDD), with some participants experiencing significant symptom reduction. • There seems to be a notable lack of persisting effects of psilocybin on OCD, which requires repeated dosing to maintain symptom reduction, compared with other mental health conditions. • As Patient demand for and widespread interest in psychedelic therapies continues to grow, we hope to ensure proper standardization, replication, and evaluation of this research. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that psychedelics may be useful for treating a range of different neuropsychiatric conditions that currently have limited treatment options. On May 4–6, 2021, leaders from academia and industry discussed a variety of issues related to the development and adoption of psychedelic drugs for different conditions during the virtual Psychedelic Therapeutics and Drug Development Conference. Selected topics from the conference are presented below. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [ABSTRACT FROM AUTHOR]

Neuroinflammation has emerged as a central pathology common to several acute and chronic brain diseases. Recent studies have displayed the anti-inflammatory properties of naturally occurring compounds derived from mushrooms and plants could potentially reduce neuroinflammation and disease progression. In this study, we aimed to investigate the impact of psilocybin and eugenol, as well as their combinations, on neuroinflammation. To induce inflammation through the gut-brain axis, we employed a colitis mouse model via oral feeding of dextran sulfate sodium (DSS). By administering various concentrations and combinations of treatments, both before and after inducing inflammation, we sought to assess the synergistic anti-inflammatory effects of psilocybin and eugenol. Our findings revealed oral psilocybin and eugenol post-treatment significantly reduced the expression of pro-inflammatory cytokines and inflammatory mediators in the brain, including IL-1β, IL-6, and COX-2. Notably, combined treatment of psilocybin and eugenol exhibited the strongest reduction in IL-6 levels when compared to the DSS group. While both psilocybin and eugenol possess anti-inflammatory effects, the combined treatment overall did not demonstrate synergistic reductions in neuroinflammation across all markers. This study adds to the growing body of evidence supporting the therapeutic potential of psilocybin and eugenol in psychiatric and neurodegenerative inflammatory disorders. Further research is necessary to elucidate the underlying mechanisms of their anti-inflammatory effects and to evaluate their efficacy in clinical settings. • Dextran sulfate sodium induced neuroinflammation through the gut-brain axis. • Pretreatment with psilocybin and/or eugenol did not prevent neuroinflammation. • Post-treatment with psilocybin and/or eugenol decreased neuroinflammation. • Psilocybin and eugenol post-treatment demonstrated the most promising results. • Psilocybin and eugenol demonstrate dose-dependent synergy. [ABSTRACT FROM AUTHOR]

This paper introduces a framework for impact-centered design that maps the direct and indirect psychological, social, and behavioral effects resulting from human-product interactions, as well as the strategic pathways that designers utilize to achieve these effects. The framework was created through a series of expert workshops in which 186 design cases were analyzed. The framework includes three basic levels. At the base, user-product interaction evokes three types of direct product experience: aesthetic experience, experience of meaning, and emotional experience. The second level describes more indirect and long-term types of impact: on behaviors, attitudes, (general) experiences, and users' and stakeholders' knowledge. The third and final level represents the general quality of life and society. This paper details the characteristics of and theoretical models underlying the various impact areas, provides illustrative student design cases, and describes how the impact areas relate to each other and how design can influence them. Design research can help increase the designer's influence by contributing theoretical models that explain the various relationships in the impact areas. We propose a three-part classification of these models to get an overview of the current state of knowledge of each impact area, and to discuss the different ways in which models can guide designers. In the discussion, we offer four action points to help set a concerted agenda for impact-centered design research. [ABSTRACT FROM AUTHOR]

There is a long history of psychedelic use throughout history. A great deal of research was conducted on the possible benefits of psychedelics until LSD and psilocybin became street drugs in the 1960s with reported negative effects. Declared illegal in the late 1960s, research slowed on the benefits of such drugs. A new version of the "street" use of psychedelics has emerged in the form of microsoding, particularly by entrepreneurs and Silicon Valley engineers. This paper reviews the history of psychedelics, possible benefits for creativity and openness for entrepreneurs, and how the issue should be addressed in an entrepreneurship classroom. [ABSTRACT FROM AUTHOR]

Despite their different etiologies, three types of spiritually transformative experiences (STEs)--near-death experiences, psilocybin experiences, and meditative experiences of cosmic consciousness --appear to have attributes that are common to a broad range of mystical experiences, including an experience of expanded awareness. In addition, all three appear to be associated with profound and lasting transformations in the lives of experiencers. Finally, these three experiences appear to share some common neural correlates. In this article, we discuss similarities in case studies of these STEs, in data from controlled clinical research studies on their transformative effects, as well as from neurophysiological data correlated with the occurrence of the STEs themselves. In all three STEs, research shows a reduction in neural activity in the major centers of the brain, including the Default Mode Network, the foundation of egoic stories involving the narrative related to oneself and the world in which one lives. It is proposed that during these STEs, reduced neural activity in areas of the brain that normally act as a filter or reducing valve mechanism opens the capacity to expanded awareness, which is associated with lasting transformation in the lives of experiencers. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the use of ClO2 on disinfection of two different growing substrates commonly used in oyster mushroom cultivation. Cottonseed hull (CSH) and wheat straw (WS) were immersed for periods of 10, 20, 30 and 40 min in different ClO2 concentrations (2, 4 and 8 mL/L). The control substrates were immersed in just water at the same times. Efficiency of treatments was evaluated for yield, biological efficiency (BE) and average mushroom weight. Yield and BEs ranged between 93.8–348.5 g/kg and 29.3–108.9% in CSH and 55.3–314.0 g/kg and 14.6–89.7% in WS, respectively. The highest yield and BE were obtained at 4 mL/L concentration of ClO2 and 30 min immersion time in WS and at 4 mL/L concentration of ClO2 and 20 min immersion time in CSH substrate. The results revealed that ClO2 would be a viable and promising technique for disinfection of substrates for oyster mushroom cultivation. [ABSTRACT FROM AUTHOR]

Psychedelic-assisted therapy is based on the premise that psychedelic substances can act as catalysts or adjuncts to psychotherapeutic processes. Recent clinical trials involving psychedelic-assisted therapy have generally employed a similar three-part structure consisting of preparation, support during the dosing sessions, and subsequent "integration." However, the content of these sessions and the frame through which the therapists approach participants and understand the clinical process has thus far been inconsistent among studies. In designing a manualized therapy protocol for a small clinical trial of psilocybin-assisted therapy for major depressive disorder, our group sought to delineate an explicit and replicable, evidence-based model that intentionally builds upon both the neurobiological actions of the medication and the phenomenology of the drug experience. Having identified considerable concordance in proposed mechanisms of change between Acceptance and Commitment Therapy (ACT) and psilocybin therapy, we employed ACT as an overarching psychotherapeutic framework. We hypothesize that the psilocybin experience can provide direct experiential contact with ACT processes that increase psychological flexibility, and that these deeply felt experiences may in turn be reinforced during ACT-informed follow-up therapy sessions. In this paper, we describe the rationale for selecting ACT, areas of potential synergism between ACT and psilocybin-therapy, the basic structure of our treatment model, and limitations to this approach. • Psychedelic-assisted therapies have potential in a variety of mental disorders. • Psilocybin therapy and ACT are synergistic as both foster psychological flexibility. • The psilocybin experience can provide experiential contact with core ACT processes. • Psilocybin-assisted therapy of depression may be optimized by integrating ACT. [ABSTRACT FROM AUTHOR]

Psychedelic assisted therapy comprises three stages: Preparation, Psychedelic Session, and Integration. Preparation is key for maximising the potential of a beneficial psychedelic experience and integration is important for prolonging improvements. The psychological flexibility model (PFM) appears to be a promising one to guide psychedelic preparation and integration. This paper proposes a model that utilises the PFM as informed by a previously published qualitative study of patient accounts of change processes in psilocybin therapy that identified themes of acceptance and connection as associated with positive outcomes. This new model, the ACE (Accept, Connect, Embody) model presents the six psychological flexibility processes, renamed and rearranged in an acceptance triad (defusion, present moment focus, willingness) and a connection triad (self as context, values, committed action). This paper describes the ACE model and how it is being used in an ongoing trial of psilocybin treatment for major depression. It also describes qualitative evidence supportive of the idea that psychological flexibility may be key to characterizing the processes of change involved in psilocybin assisted therapy for depression. These and other results suggest that psilocybin may be specifically increasing psychological flexibility and point to the possibility that psychotherapy approaches incorporating the PFM may serve as a means to deepen and extend the benefits of psilocybin treatment, thus bridging the experiential gap between a potent inner experience and an outer life better lived. • The psychological flexibility model can be used to guide psychedelic assisted therapy. • A new model, the ACE (Accept, Connect, Embody) model, is outlined. • The paper describes how this new model is being used in a psilocybin trial. • Qualitative data is re-analyzed in terms of psychological flexibility processes. [ABSTRACT FROM AUTHOR]

Attention Deficit Hyperactivity Disorder (ADHD) is a complex neurological disorder with a lack of an official scientific understanding of its genetic nature and the potential causes. However, there are practical research data that points to certain directions. In this paper, we examine the possible external causes of the disorder and specifically ones whose influence is related to pregnancy and (early) childhood years. Children born prematurely and/or with low birth weight are at high risk of developing ADHD. Maternal smoking, alcohol consumption and psychological disorders during pregnancy were proven to play a part as well. Some special social and economic situations raised the risk of appearance in the minors experiencing them. Electronics are a factor of distraction to children and were found to exacerbate symptoms. Most importantly, parenting choices can be determinant for a child with the disorder. A solution often proposed for symptoms of this nature is medication. Nonetheless, there were many defects and risks found within the psychostimulants used for the disorder. Alternative treatments are proposed before reaching for medication, two very effective ones being brain training and meditation. [ABSTRACT FROM AUTHOR]

Entomopathogenic fungi routinely kill their hosts before releasing infectious spores, but a few species keep insects alive while sporulating, which enhances dispersal. Transcriptomics- and metabolomics-based studies of entomopathogens with post-mortem dissemination from their parasitized hosts have unraveled infection processes and host responses. However, the mechanisms underlying active spore transmission by Entomophthoralean fungi in living insects remain elusive. Here we report the discovery, through metabolomics, of the plant-associated amphetamine, cathinone, in four Massospora cicadina -infected periodical cicada populations, and the mushroom-associated tryptamine, psilocybin, in annual cicadas infected with Massospora platypediae or Massospora levispora , which likely represent a single fungal species. The absence of some fungal enzymes necessary for cathinone and psilocybin biosynthesis along with the inability to detect intermediate metabolites or gene orthologs are consistent with possibly novel biosynthesis pathways in Massospora. The neurogenic activities of these compounds suggest the extended phenotype of Massospora that modifies cicada behavior to maximize dissemination is chemically-induced. [ABSTRACT FROM AUTHOR]

Mushrooms possess therapeutic attributes such as anti-cancer, immunomodulation, antioxidant, hypolipidaemic, antiviral, antibacterial, hepatoprotection, and antidiabetic effects. In the family Pleurotaceae , Pleurotus spp. is the second most important commercial mushroom. The most widely cultivated Pleurotus spp. is Pleurotus ostreatus , followed by Pleurotus pulmonarius. Several bioactive compounds of Pleurotus spp., such as carbohydrates, glycoproteins, lipids, or secondary metabolites, could be attributed to its health properties. However, in most studies focusing on the therapeutic effects of Pleurotus spp., traditional extraction methods were used to obtain its extracts. Most conventional extraction methods, such as maceration, hot water extraction, and Soxhlet extraction, can be time-consuming and require a larger volume of solvents. Alternative extraction methods often have shorter extraction times, decreased solvent volume, and sometimes allow for the extraction of thermolabile constituents. This review discusses the bioactive compounds of Pleurotus mushrooms, highlights important considerations for extraction processes, explores both conventional and alternative extraction techniques to obtain bioactive compounds from Pleurotus spp., discusses their advantages and limitations, as well as evaluates their impact on extract bioactivities and therapeutic properties. [Display omitted] • Pleurotus spp. are among the most widely cultivated and consumed mushrooms. • Bioactive compounds in Pleurotus are mostly extracted by conventional methods. • Alternative methods using reduced extraction time, temperature and solvent is key. • These efficient and eco-friendly methods can target selected compounds. [ABSTRACT FROM AUTHOR]

Dissociative symptoms can occur in prevalent psychiatric illnesses, and they are particularly frequent in Functional Neurological Disorders which belong to Dissociative Disorders in international classifications. Although the pathophysiology of these disorders remains partially unknown, it has been related to the impairment of cognitive control abilities. Evidence suggest that psilocybin is likely to enhance cognitive control, but no clinical trial has evaluated the value of psilocybin in Dissociative Disorders. We believe that functional/dissociative seizures (previously named psychogenic non-epileptic seizures) constitute a good model for studying the effect of therapeutic interventions on dissociative phenomena. To investigate the effect of psilocybin on cerebral networks, we propose to focus on the circuits associated with cognitive control and their interactions with the processing of emotional information by quantifying changes in the activity of the cognitive control network assessed with functional brain MRI during an emotional Go-No Go task. [ABSTRACT FROM AUTHOR]

E-learning is a powerful educational tool nowadays. Particularly, it could activate classrooms and enhance the understanding of educational content taught by teachers. However, teachers often have various difficulties for using e-learning. One problem is for them to produce educational tools on their own. Some teachers need support for this type of activity. From the viewpoint, it is very important for us to know the various types of support that teachers need. In this study, we focused on teachers' mental situations when they produce educational materials for their classrooms. We aimed to establish a model, so that the data of eye blinking could be analyzed and applied to evaluate teachers' psychological and mental situations. Using a commercial glass-type sensor to observe eye blinking behaviors, we measured them for three teachers (as examinees), while they were producing their own presentation files. The data for the blinking behaviors were compared with the concentration power index and analyzed. And we discussed the possibility of applying the model to determine how teachers could be supported technically. [ABSTRACT FROM AUTHOR]

In the last years, the debate on the use of psychedelics in psychotherapeutic settings has intensified, attracting a lot of interest and attention from the scholarly community as well as from clinicians and paving the way for new therapeutic paradigms. Besides classical addictions and addictive behaviors, there exist forms of addictions, the so-called new addictions or behavioral addictions, whose characterization is not linked so much to substances but to widespread and socially accepted activities such as games, shopping, internet use, sex, love relationships, work and exercises, physical activities or sports. Among the various addictions, the gambling disorder is the first form of behavioral addictions officially recognized by the DSM-V, in accordance with a wealth of neurobiological and clinical data showing the activation in patients of the gratification systems (especially dopamine). Orthos, as intensive residential intervention program envisaging a non-moralistic approach to gambling, can be combined with the administration of psilocybin, a substance characterized by a very low potential for abuse, modulating brain areas and networks affected by addictive behaviors. Therefore, our proposal would be to start treating behavioral addictions combining psilocybin administration with existential-humanistic psychotherapy, like Orthos. [ABSTRACT FROM AUTHOR]

The present paper reports a meta-analysis of published evidence on the effects of temperature in school classrooms on children's performance in school. The data from 18 studies were used to construct a relationship between thermal conditions in classrooms and children's performance in school. Psychological tests measuring cognitive abilities and skills, school tasks including mathematical and language-based tasks, rating schemes, and tests used to assess progress in learning including end-of-year grades and the examination results were considered as indicators of children's performance Due to the lack of complete measurements, thermal conditions were characterized by measured classroom temperatures. To create the relationship, the fractional change in performance of psychological tests and school tasks was regressed against the average temperature at which the change was recorded; all published data were used regardless of whether the change in learning outcome changed significantly with temperature. For other learning outcomes, no relationship was created because the data were insufficient. The relationship derived in the analysis shows that the performance of psychological tests and school tasks can be expected to increase on average by 20% if classroom temperatures are lowered from 30 °C to 20 °C and that the temperature for optimal performance is lower than 22 °C. The relationship is valid only for temperate climates. It requires verification for other climates and extensions to temperatures lower than 20 °C and higher than 30 °C. • A relationship was developed between temperature and various indicators of learning outcomes. • It is based on data collected mainly in temperate climates concerning performance of psychological tests and school tasks. • Reducing temperature by 10 K from 30 °C to 20 °C is expected to increase performance of tasks relevant for learning by 20%. • The effects of temperature on schoolwork seems to be greater in magnitude than has been found for office work. • The optimal temperature for the performance of schoolwork seems to be lower than for office work. [ABSTRACT FROM AUTHOR]

An accumulation of CO 2 in occupied indoor spaces is correlated to negative impacts on concentration, sleepiness and aspects of cognitive performance. However, factors such as: (a) the relative effect of CO 2 itself compared to other pollutants; (b) the minimum necessary exposure time for cognitive performance to be affected; and (c) the physiological drivers of cognitive performance reductions due to increased indoor CO 2 concentrations are not yet clear. A within-subjects counterbalanced study design was used to test cognitive performance, subjective and physiological parameters of 31 volunteers during short (< 60 min) exposures to normal CO 2 (830 ppm) and high CO 2 (2700 ppm, raised by introducing pure CO 2 alongside the occupant generated CO 2). The study was conducted in a small naturally ventilated office and EEG was used as an objective indicator of sleepiness. The addition of pure CO 2 to the room resulted in the absence of an expected learning effect in two cognitive performance test battery components which could not be explained by any of the physiological, psychological, or reported comfort, sick building syndrome and health variables measured. However, participants who had slept less the previous night appeared more susceptible to becoming sleepier as a result of the increased CO 2. The results suggest (1) the addition of pure CO 2 may influence aspects of cognitive performance after only short exposures (2) these changes occur in the absence of clear physiological drivers, (3) lack of sleep may mediate people's response to higher CO 2 concentration. • Elevated CO 2 concentration may influence aspects of cognitive performance after only short exposures. • Short duration exposure to elevated CO 2 increases heart rate but not respiration rate. • EEG is a suitable method for the objective measurement of drowsiness. • Lack of sleep may mediate people's response to elevatedr CO 2 concentration. [ABSTRACT FROM AUTHOR]

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Psychedelic substances have regained interest as therapeutic agents in the treatment of stress-related disorders. The effects seem to be of persisting nature even after a single dose. Also in lower than 'regular' recreational doses, so-called micro-doses, without the typical effects on consciousness, users report beneficial effects on cognitive processes and well-being. The exact neurobiological mechanism underlying these persisting effects is not clear. While previous research has mainly focused on the central nervous system including the immune system and the neuroendocrine system, I propose a central role for sleep and the microbiome in the effects of regular and low doses of psychedelics respectively. It will be explained why this is hypothesized and studies to test this idea proposed. It is concluded that while these studies are needed to understand the biology underlying psychedelic medicine, it is also important to approach it in a holistic way, including all the above mentioned biological processes psychedelics are known to affect, and explore the role of other substance-related factors like route of administration and form, and factors like diet and lifestyle which are part of the psychedelic experience. [ABSTRACT FROM AUTHOR]

Importance: Reports of a recent increase in US outpatient mental health care raise questions about whether it has been driven by rising rates of psychological distress and whether mental health treatment has become either more or less focused on people with higher levels of distress.Objective: To characterize national trends in serious psychological distress and trends in outpatient mental health service use by adults with and without serious psychological distress.Design, Setting, and Participants: The 2004-2005, 2009-2010, and 2014-2015 Medical Expenditure Panel Surveys (MEPS) were nationally representative surveys taken in US households. The analysis was limited to participants 18 years or older. Dates of this analysis were February 2018 to April 2018.Main Outcomes and Measures: Annual national trends in the percentages of adults with serious psychological distress (Kessler 6 scale score ≥13), outpatient mental health service use (outpatient visit with a mental disorder diagnosis, psychotherapy visit, or psychotropic medication), and type of psychotropic medication use (antidepressants, anxiolytics/sedatives, antipsychotics, mood stabilizers, and stimulants). Age- and sex-adjusted odds ratios of the associations of survey period with the odds of serious psychological distress, outpatient mental health service use, and outpatient mental health service use were stratified by level of psychological distress.Results: The analysis involved 139 862 adult participants from the 2004-2005, 2009-2010, and 2014-2015 MEPS, including 51.67% women, 48.33% men, 67.11% white adults, and 32.89% nonwhite adults, with an overall mean (SE) age of 46.41 (0.14) years. Serious psychological distress declined overall from 4.82% (2004-2005) to 3.71% (2014-2015), including significant declines among young (3.94% to 3.07%), middle-aged (5.52% to 4.36%), and older adults (5.24% to 3.79%); men (3.94% to 3.09%) and women (5.64% to 4.29%); and major racial/ethnic groups (white, 4.52% to 3.82%; African American, 5.12% to 3.64%; Hispanic, 6.03% to 3.55%; and other, 5.22% to 3.26%). Overall, the percentage of adults receiving any outpatient mental health service increased from 19.08% (2004-2005) to 23.00% (2014-2015) (adjusted odds ratio, 1.25; 95% CI, 1.17-1.34). Although the proportionate increase in outpatient mental health service use for adults with serious psychological distress (54.17% to 68.40%) was larger than that for adults with less serious or no psychological distress (17.26% to 21.08%), the absolute increase in outpatient mental health service use was almost completely the result of growth in outpatient mental health service use by individuals with less serious or no psychological distress.Conclusions and Relevance: The recent increase in outpatient mental health service use occurred during a period of decline in serious psychological distress. Adults with less serious psychological distress accounted for most of the absolute increase in outpatient mental health service use, while adults with serious psychological distress experienced a greater relative increase in outpatient mental health service use. [ABSTRACT FROM AUTHOR]

Exposure to arsenic, a widespread environmental toxin, produces multiple organ toxicity, including gastrointestinal toxicity. Nigella sativa (NS) has long been revered for its numerous health benefits under normal and pathological states. In view of this, the present study attempts to evaluate the protective efficacy of orally administered Nigella sativa oil (NSO) against arsenic-induced cytotoxic and genotoxic alterations in rat intestine and elucidate the underlying mechanism of its action. Rats were categorized into the control, NaAs, NSO, and NaAs+NSO groups. After pre-treatment of rats in the NaAs+NSO and NSO groups daily with NSO (2 ml/kg bwt, orally) for 14 days, NSO treatment was further continued for 30 days, with and without NaAs treatment (5 mg/kg bwt, orally), respectively. Various biochemical parameters, such as enzymatic and non-enzymatic antioxidants, carbohydrate metabolic and brush border membrane marker enzyme activities were evaluated in the mucosal homogenates of all the groups. Intestinal brush border membrane vesicles (BBMV) were isolated, and the activities of membrane marker enzyme viz. ALP, GGTase, LAP, and sucrase were determined. Further, the effect on kinetic parameters viz K M (Michaelis-Menten constant) and V max of these enzymes was assessed. Integrity of enterocyte DNA was examined using the comet assay. Histopathology of the intestines was performed to evaluate the histoarchitectural alterations induced by chronic arsenic exposure and/or NSO supplementation. Arsenic accumulation in the intestine was studied by inductively coupled plasma-mass spectroscopy (ICP-MS). NaAs treatment caused substantial changes in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in the intestinal mucosal homogenates. The isolated BBM vesicles (BBMV) also showed marked suppression in the marker enzyme activities. Severe DNA damage and mucosal arsenic accumulation were observed in rats treated with NaAs alone. In contrast, oral NSO supplementation significantly alleviated all the adverse alterations induced by NaAs treatment. Histopathological examination supported the biochemical findings. NSO, by improving the antioxidant status and energy metabolism, could significantly alter the ability of the intestine to protect against free radical-mediated arsenic toxicity in intestine. Thus, NSO may have an excellent scope in managing gastrointestinal distress in arsenic intoxication. [ABSTRACT FROM AUTHOR]

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