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Despite psychedelic microdosing being a growing practice, the research on the topic is still in its infancy. While several studies have described the characteristics, motivations and practices of microdosers, the differences between individuals that only microdose and those that use both micro and macrodoses of psychedelics remain unexplored. In an online survey, we collected data of 6193 psychedelic consumers of which 2488 were microdosers of up to 11 different classical and atypical psychedelics. In comparison to respondents that use both microdoses and macrodoses, exclusive microdosers were older in age (46.4 vs. 42.0 years), had a larger proportion of females (68.4% vs. 44.7%), were non-Caucasian (25.4% vs. 14.7%), urban residents (43.9% vs. 38.5%), and had a lower average lifetime use of non-psychedelic substances (3.8 vs. 4.7 substances). Most consumers (52.5%) microdosed psychedelics multiple times a month, commonly using psilocybin (74.5%), LSD (34.4%), and ketamine (15.8%), with most users (64.6%) not testing their substances. The most common reason for microdosing was improving general wellbeing (73.0%), and psychedelics were used for treating several physical and mental health conditions. Additional analyses examined spending habits of consumers. This study adds to the growing literature on the naturalistic use of psychedelic microdosers. [ABSTRACT FROM AUTHOR]

\nPlain Language SummaryResults from clinical trials show that serotonergic psychedelics have efficacy in treating psychiatric disorders, where currently approved pharmacotherapies are inadequate. Developing psychedelic medicines, however, comes with unique challenges, such as tempering heightened anxiety associated with the psychedelic experience. We conceived a new strategy to potentially mitigate psychedelic effects with defined electromagnetic signals (ES). We recorded the electromagnetic fields emitted by the serotonin 2 receptor (5-HT2R) agonist (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) and converted them to a playable WAV file. We then exposed the DOI WAV ES to mice to assess its effects on the DOI-elicited, 5-HT2AR dependent head-twitch response (HTR). The DOI WAV signal significantly attenuated the HTR in mice elicited by 0.1 and 0.3 mg/kg subcutaneous DOI (p < 0.05 and p < 0.01, respectively). A scrambled WAV signal did not affect the DOI-elicited HTR, suggesting specificity of the DOI WAV signal. These results provide evidence that defined ES could modulate the psychoactive effects of serotonergic psychedelics. We discuss putative explanations for the distinct effects of the DOI WAV signal in the context of previous studies that demonstrate ES’s efficacy for treating other conditions, including pain and cancer.Numerous clinical studies demonstrate that psychedelic drugs can treat psychiatric disorders. A challenge with psychedelic drugs is that they can elicit distressing experiences, which require psychological support in some patients. Recent developments have allowed for the recording of the electromagnetic shell or field of molecules in solution. These electromagnetic signals (ES) can be emitted (as a magnetic field) to emulate the effects of the recorded drug. By using ES, we have the potential to manage or mitigate the negative effects of a drug, simply by turning off the magnetic field. The main target of serotonergic psychedelic drugs is the serotonin receptor, 5-HT2A. A reliable and well-studied drug used in psychedelic research is (±)-2,5-dimethoxy-4-iodoamphetamine (DOI). DOI binds and activates the 5-HT2A receptor. DOI is known to elicit head twitching in mice (called the head-twitch response or HTR) that is indicative of 5-HT2A receptor activation. A recording of DOI was played to evaluate its effect on the head-twitch response in mice. Here we report that the DOI WAV signal decreased the head-twitch response observed after treating mice with the DOI drug. The effects were measurable, reproducible and demonstrated the ability of the DOI recording to dampen the head-twitch response. This WAV recording has the potential to interfere with the unwanted effects of psychedelics, making their use safer. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsCurrently, there are great hopes for psychedelic substances in treating psychiatric conditions and improving well-being. These substances are illegal in many countries, and we lack knowledge of how conflicting discourses shape psychedelic use in naturalistic settings. This study explores how psilocybin use is made meaningful by participants and staff at a retreat including psychedelic ceremonies aimed at personal growth.Ethnographic fieldwork was conducted at a psychedelic retreat with participants from Sweden. The material was organized using Zinberg’s model of drug, set, and setting. Theoretical work related to comparisons was utilized to elucidate how psilocybin use was distinguished from other illicit drug use.The participants’ desires to be fundamentally transformed, combined with the staff’s staging of the setting as a haven primed the participants to approach psilocybin as an inherently benevolent substance. Positive experiences during the ceremonies were attributed to the substance, and negative experiences to personal shortcomings.The staff and participants combined different discourses to define the meaning of psilocybin, all of which condemned using it for purely recreational purposes. The psilocybin use at the retreat was considered an improvement and wholly unrelated to illegal drug use, dissociating this practice from such use to establish legitimate transgression. [ABSTRACT FROM AUTHOR]

Background: The emergence of New Psychoactive Substances (NPS), including synthetic psilocybin, has raised concern among health experts due to the numerous health and socioeconomic consequences. The current trend is shifting to the hazardous use of synthetic psilocybin in vaping, and little is known about the prevalence of use, specifically among amphetamine-type stimulants (ATS) users. Methods: Interviewer-administered questionnaires were conducted in drug detention centers between March and October 2022. The study was conducted using ASSIST 3.0 and obtained information on the respondents' socio-demographic characteristics and clinical profiles. N = 355 ATS users were enrolled in this study. Results: The results show a high prevalence of psilocybin vaping among ATS users (182/355, 53.1%). Most of the respondents were males (85.1%) and unmarried (69.3%), with a mean age of 29.2 (SD = 7.3). Across all respondents, five factors were associated with psilocybin vaping: tobacco smoking, aOR =5.790 (95% CI: 1.723, 8.183); cannabis uses, aOR= 9.152 (95% CI: 2.693, 10.396); and alcohol use, aOR= 3.137 (95% CI: 1.461, 5.817). Respondents of the Malay race had higher odds of being involved in psilocybin vaping compared to other races, with aOR= 1.638 (0.043, 2.459). Meanwhile, a reduction in age by 1.9 will increase the likelihood of involvement in psilocybin vaping with aOR = 1.897 (95% CI: 0.857, 1.938). Conclusion: Psilocybin in vaping is growing among ATS users and across all populations. Unfortunately, knowledge regarding the long-term effects on health is limited. Further studies should highlight the harmful effects of psilocybin and the potential risk of psilocybin vaping among the younger population. [ABSTRACT FROM AUTHOR]

There are profound methodological challenges facing microdosing research. One way we can address some of these methodological issues is by understanding how psilocybin microdosing fits in the broader existential context of people’s lives. We recruited participants who underwent psilocybin microdosing on their own and consented to being monitored for harm mitigation purposes. We combined momentary ecological assessment and detailed retrospective interviews. Participants reported loosening of mental structures (i.e., less intense strength of thoughts, tangential stream of consciousness), increased salience of external stimuli (varyingly associated with greater interest in otherwise mundane activities, as well as sensory overload), an increase in flexible cognition, a decrease in stable cognition, and various ego-dystonic contents. Highly structured environments were conducive to positive appraisal of experiences and vice versa. Momentary ecological assessment and retrospective interviews yielded differing accounts of microdosing experience. We relate our findings to stable and flexible cognition, as well as the notion of salience. We point out the necessity for systematic mixed methods studies to better characterize the lived experience of taking low doses of psilocybin. [ABSTRACT FROM AUTHOR]

Psychedelic-assisted therapy (PAT) has shown preliminary efficacy for psychiatric and physical health conditions. Although some people report naturalistic psychedelic use with so-called “underground” practitioners, little is known about PAT that occurs outside of controlled clinical settings or perspectives of these practitioners. We conducted an anonymous online survey of individuals who reported providing psychedelic support services (e.g. trip sitting and/or preparatory/follow-up psychotherapy) in naturalistic settings. We investigated demographics, including education and licensing, details about services provided, and reported client outcomes. Among 107 participants, 40.2% held a full or in-progress license and 44.9% had not obtained a relevant graduate degree. Almost all participants reported pre-screening clients before treatment, offering preparation, integration, and trip-sitting services, and most employed a range of therapeutic modalities, centering primarily on non-directive approaches. Participants reported that clients most commonly consumed psilocybin, and treated numerous conditions, primarily aligning with indications targeted in psychedelic clinical research. Perceptions of clients’ symptom changes were largely positive, although a small proportion reported worsened personality disorder symptoms. Further research delineating client and practitioner perspectives of naturalistic PAT services is warranted, and such work may shed light on the benefits and risks specific to naturalistic PAT as well as inform best practices for practitioners. [ABSTRACT FROM AUTHOR]

Emerging legal frameworks in Oregon and Colorado license facilitators to support adults receiving psychedelic services. The current legal frameworks are silent regarding facilitators’ personal experience with psychedelics. An e-Delphi process recruited 36 experts with at least 5 years’ experience facilitating psilocybin experiences in ceremonial settings, indigenous practices, or clinical trials. Respondents completed in-depth, semi-structured qualitative interviews via secure web links. Interviews were recorded, transcribed, and analyzed using Thematic Analysis. Experts with a mean of 15.2 (SD 13.1) years’ experience providing psilocybin services expressed the importance of first-hand experience with psychedelics as a qualification for the emerging workforce. One participant questioned the necessity of personal psychedelic experience. Experts suggested that personal experience may indirectly support high-quality care because it enhances facilitators’ personal wellbeing, and may help facilitators understand the complexity and nature of their clients’ psychedelic experiences. Novel state-legal psychedelic paradigms create a real-world opportunity to assess associations between facilitators’ personal psychedelic experience and the safety and outcomes of psychedelic services. [ABSTRACT FROM AUTHOR]

We sought to identify patterns of psychedelic use among United States military veterans, compare demographic variables and perspectives of those who did and did not report use, and characterize benefits and adverse outcomes associated with use. Respondents (N = 426) were recruited to complete an online cross-sectional survey. Approximately one-half (51%) reported using psychedelics. Most did so for healing/treatment (70%) and/or spiritual purposes (48%), and most (85%) reported benefiting from use. Those who used psychedelics reported they would be more likely to use VA services (p < .001, d = 0.64) and to return to the VA for care (p < .001, d = 0.79) if psychedelic therapy was offered. Almost two-thirds (59%) reported adverse outcomes associated with use. Equivalent proportions rated their psychedelic experiences as beneficial among those who did (89%) and did not (81%) report adverse outcomes. Fewer adverse outcomes were associated with being older, using psilocybin, feeling prepared and confident in the reasons for use, being in a comfortable setting, and being able to “trust, let go, and be open” (Rc = 0.77; p < .001). Psychedelics may offer benefits but may also lead to adverse outcomes without proper preparation and support. Future research should examine the utility of psychedelic-based approaches for veteran mental health care. [ABSTRACT FROM AUTHOR]

Psilocybin, a major indole alkaloid found in magic mushrooms (Psilocybe cubensis), has recently drawn attention as a breakthrough therapy to treat major depressive disorder. This review aimed to summarize and identify knowledge gaps concerning their pharmacokinetic characteristics of psilocybin and its active metabolite, psilocin. Original studies related to pharmacokinetics of psilocybin conducted in vitro, animals, and humans were systematically collected from PubMed, Scopus, and ScienceDirect, from their inceptions to November 2023. Twenty articles were included in this work and assessed for study quality. A comprehensive review of the pharmacokinetics of psilocybin and psilocin in both animals and humans was performed. Psilocybin is considered a prodrug that is dephosphorylated to psilocin by alkaline phosphatase. Following ingestion, the peak psilocin plasma and brain levels were rapidly achieved in a dose-dependent manner. Psilocin is metabolized primarily through both Phase I and Phase II processes with the half-life of 2–3 hours. This review also identified lack of some pharmacokinetic related information and limitations of available research that may help direct future investigations to better understand the pharmacokinetics and improve study design including dose selection and dosage optimization. [ABSTRACT FROM AUTHOR]

There has been a resurgence of interest in the use of psychedelic therapies for several mental and substance use disorders. Psilocybin, a "classic" serotonergic psychedelic, has emerged as one of the primary compounds of interest in clinical research. While research on psilocybin's potential mental health benefits has grown, data on the safety and efficacy of other serotonergic psychedelics remain limited. A comprehensive scoping review on the use of mescaline, ibogaine, ayahuasca, N,N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD) in the treatment of mental and substance disorders was conducted. Independent reviewers screened titles, abstracts, and full texts and conducted data extraction. Seventy-seven studies met the inclusion criteria. There were 43 studies of LSD, 24 studies of ayahuasca, 5 studies of DMT, 5 studies of ibogaine, and 5 studies of mescaline. Commonly reported benefits included improved mood and anxiety symptoms, improved insight, reduced substance use, improved relationships, and decreased vegetative symptoms. Commonly reported adverse effects were psychological, neurological, physical, and gastrointestinal in nature. Serious adverse events (homicide and suicide) were reported in published studies of LSD. In conclusion, there is only low-level evidence to support the safety and efficacy of non-psilocybin serotonergic psychedelics in individuals with mental and substance use disorders. [ABSTRACT FROM AUTHOR]

Despite the recent and sharp rise in psychedelic research, few studies have investigated how classic psychedelic use relates to employees' work-related outcomes. This is surprising given that the increased use, decriminalization, and legalization of classic psychedelics in the United States (U.S.) has the potential to impact both employees and their organizations. Addressing this gap, the current study explores how employees' lifetime psilocybin use relates to the amount of overtime they work, thereby offering insight into what current trends in psilocybin use could mean for businesses. Using pooled, cross-sectional data from the National Survey on Drug Use and Health (2002–2014) on 217,963 adults employed in the U.S. full-time, this study tests whether lifetime psilocybin use is associated with employees' number of overtime hours worked in the past week. After adjusting for sociodemographics and other substance use, a significant negative association is found between employees' lifetime psilocybin use and the amount of overtime they reported working. Specifically, the findings suggest that lifetime psilocybin use in the U.S. full-time working population is associated with an estimated 44,348,400 fewer overtime hours worked per year and may help explain recent findings linking employees' lifetime psilocybin use to a reduction in sick leave taken. [ABSTRACT FROM AUTHOR]

Few epidemiological studies have focused on seasonal variation in the use of common psychedelics and party drugs among nightclub and festival attendees, typically those who attend electronic dance music (EDM) events. We sought to determine whether the use of different drug types varies seasonally within this population. Across 15 seasons from summer 2017 through fall 2022, we surveyed 3,935 adults entering randomly selected nightclubs and festivals in New York City regarding their past-month use of cocaine, MDMA (3,4-methylenedioxymethamphetamine, commonly known as ecstasy), lysergic acid diethylamide (LSD), psilocybin (shrooms), and ketamine. Multivariable models were used to compare adjusted odds ratios for drug use within each season with the grand mean of combined seasons. Summer was associated with higher odds for use of LSD (aOR 2.72; 95% CI, 1.88–3.93) and psilocybin (aOR 1.65; CI, 1.12–2.43), independent of increases in psilocybin use over time (p <.001). A significant increase in use of ketamine (p =.014) and significant decreases in use of cocaine (p =.002) and ecstasy (p =.002) were found across time, but multivariable models did not detect seasonal variations. Summer is a risk factor for use of common psychedelics among people who attend EDM events. Therefore, the summer months may be the best time to disseminate information about harm reduction for psychedelic drug users. [ABSTRACT FROM AUTHOR]

This study translated and tested the psychometric properties of acute psychedelic effects measures among Spanish-speaking people. The Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ) were translated before being incorporated into a web-based survey. We recruited native Spanish-speakers (N = 442; Mage = 30.8, SD = 10.9; Latino/Latina = 62%; Hispanic = 91.4%; male = 71.5%) to assess their previous experience with one of two psychedelics (LSD = 58.4%; Psilocybin = 41.6%) and their acute and enduring effects. Confirmatory factor analysis (confirming factor structure based on the English version) revealed a good fit for the MEQ, PIQ and the CEQ. Repeating our analysis in each drug subsample revealed consistency in factor structure for each assessment tool. Construct validity was supported by significant positive associations between the PIQ and MEQ, and between the PIQ and MEQ and changes in cognitive fusion and negative associations between changes in prosocial behaviors. As a signal of predictive validity, persisting effects (PEQ) were strongly related to scores on the MEQ and PIQ. Findings demonstrate that the Spanish versions of these measures can be reliably employed in studies of psychedelic use or administration in Spanish-speaking populations. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

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]

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]

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]

Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A 42-year-old man with treatment-resistant major depressive disorder took 1 g of Psilocybe cubensis mushrooms, while prescribed tranylcypromine, extended-release dextroamphetamine-amphetamine, and other medications. Approximately half an hour later, he developed severe hypertension with chest pain, palpitations, and headache. Upon hospital presentation, the electrocardiogram demonstrated ST-elevation. The patient was diagnosed with a myocardial infarction and treated with lorazepam, nitroglycerin, and aspirin. He subsequently underwent emergency cardiac catheterization, which revealed no significant cardiac abnormalities. Following overnight hospitalization, he was discharged home with no lasting physical sequelae. Though data are few, past studies suggest that classic serotonergic psychedelics (5HT-2A receptor agonists) such as dimethyltryptamine (DMT), lysergic acid (LSD), and synthetic psilocybin should not produce hypertensive emergency when combined with MAOIs. We suspect phenylethylamine, found in Psilocybe cubensis and other species of psilocybin mushrooms, interacted with tranylcypromine and dextroamphetamine-amphetamine to produce this hypertensive emergency. Patients prescribed MAOIs should be warned of the potential for hypertensive emergency when consuming psilocybin mushrooms, particularly when also prescribed norepinephrine releasers such as dextroamphetamine-amphetamine. [ABSTRACT FROM AUTHOR]

Isotretinoin is used to treat severe acne, treatment-resistant moderate acne, and acne that leads to scarring or psychological distress. It has many side effects and is also associated with depression, sleep apnea, and sleep disturbances. In this study, we aimed to evaluate the effects of isotretinoin on depression, sleep apnea, and sleep quality. A total of 42 patients diagnosed with acne and started isotretinoin treatment were included in the study. In order to compare the effects of isotretinoin, patients were asked to fill out a questionnaire containing the Beck Depression Inventory (BDI), the Berlin Questionnaire (BQ), and the Pittsburg Sleep Quality Index (PSQI) at baseline and third months of treatment. There was no statistically significant difference in BDI, BQ, and PSQI scores between the 1st and 3rd months of treatment (p =.53, p =.5, p =.35). This study showed that isotretinoin had no significant effects on depression and sleep quality. [ABSTRACT FROM AUTHOR]

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

Mushrooms are a source of primary and secondary metabolites. Little is known about the most suitable conditions for production of mushrooms by submerged fermentation. This article reports antioxidant and cytotoxic assays, in addition to quantitatively evaluating the content of proteases with fibrinolytic action in the crude extracts of two species of edible mushrooms produced in different formulations, as well as evaluating the recovery of these enzymes by aqueous two-phase systems (ATPS). The mushrooms Pleurotus ostreatus and Pleurotus eryngii, at concentration of 100 µg/mL, displayed inhibition of DPPH and ABTS radicals below 50%. In the cytotoxicity test, the cells human fibroblast cell lines (MRC-5) showed cell viability greater than 80%. Concerning fibrinolytic activity, P. eryngii presented 226.47 ± 7.26 U/mL, therefore being more efficient than P. ostreatus (71.5 ± 0.56 U/mL). In the recovery of the P. eryngii extract by ATPS, the fibrinolytic protease was partitioned in the salt phase (30.25 U/mL). The molecular mass of the proteases was between 75 and 100 kDa. These results prove the low cytotoxicity of the extracts produced and that fermentation in supplemented malt broth favored the excretion of fibrinolytic proteases compared to the other evaluated media. [ABSTRACT FROM AUTHOR]

In recent years, policymakers have proposed and implemented regulatory changes promoting the deprioritization, decriminalization, or state-level legalization of one or more psychedelic substances, usually referencing data from clinical trials as reasons to support liberalizing drug control policies. As psychedelic policies continue to be drafted, personal possession limits may be considered for inclusion in those regulations. If "allowable amount" limits are to be written into law to set personal possession limits, then such amounts should be more consistently related to psychedelic doses found to be safe and efficacious in clinical trials, existing data on moderate-high doses commonly used in various naturalistic settings, and the few studies that estimate psychedelic dose equivalence based on the intensity of subjective effects. In this commentary, we provide an evidence-informed table of typical moderate-high doses for seven commonly used psychedelic substances. These estimates of comparable moderate-high doses can be used to inform "allowable amount" values for psychedelic substances. When such limits are written into legislation, the adoption of evidence-informed comparable limits akin to those presented here would be an important first step toward ensuring greater parity and consistency in drug policy, relative to limits that have little or no scientific basis. [ABSTRACT FROM AUTHOR]

The global use of certain classical psychedelics has increased in recent years, but little is known about their spectrum of toxicity within Australia. We aim to describe calls to New South Wales Poisons Information Centre relating to exposures to classical psychedelics including lysergic acid diethylamide, psilocybin, N,N-dimethyltryptamine, ayahuasca, mescaline and ibogaine. This is a retrospective observational study of calls to New South Wales Poisons Information Centre between January 2014 and December 2022. We identified exposures to classical psychedelics within New South Wales Poisons Information Centre database and measured the annual number of exposures, source of call (hospital, health care worker, member of the public), co-ingested substances, clinical features and advice given. There were 737 calls related to relevant psychedelic exposures; 352 (47.8 per cent) to lysergic acid diethylamide, 347 (47.0 per cent) to psilocybin, 28 (3.8 per cent) to N,N-dimethyltryptamine, 4 (0.5 per cent) to ayahuasca, 4 (0.5 per cent) to mescaline and 2 (0.3 per cent) to ibogaine. Cases were predominantly male (77.2 per cent) and aged between 20 and 74 years (65.6 per cent). Psychedelic calls more than doubled from 45 in 2014 to 105 in 2022 and 625 (85 per cent) of all calls were either from or referred to hospital. Co-ingestion of psychedelics with another substance occurred in 249 (33.8 per cent) of calls and the most frequent clinical features related to single substance psychedelic exposures were hallucinations (27.6 per cent), gastrointestinal symptoms (21.7 per cent) and tachycardia (18.1 per cent). Seizures occurred in 2.9 per cent of single substance psychedelic exposures. Increasing incidence of psychedelic exposure calls, including those reporting significant toxicity, likely reflects increasing community use. This may in part be driven by increasing interest in psychedelic assisted psychotherapy trials subsequently increasing public awareness. Relatively high poisoning severity contrasts with safety within clinical trials of psychedelic assisted psychotherapy that may relate to the uncontrolled nature of community use which is mitigated within clinical trial environments. Education about safe use may be useful. [ABSTRACT FROM AUTHOR]

Despite common depictions in the media, there is little scientific evidence on microdosing psychedelic drugs. We assessed awareness, prevalence, and dosing practices of microdosing psychedelic drugs among young adults 18–22 years old from Southern California (2018–2019). We examined whether sociodemographic factors, personality traits, mental health, or other substance use behaviors were correlated with having ever microdosed. Among 2,396 participants, 293 (12%) had heard of microdosing and 74 (3%) ever microdosed. Among those who had heard of microdosing, 79% correctly defined microdosing as taking an amount of a psychedelic much lower than a standard dose, whereas 15% misperceived microdosing as a standard psychedelic dose. Psilocybin was the most common drug ever microdosed (70%), followed by lysergic acid diethylamide (LSD, 57%). Among those who ever microdosed, ~18% reported using psychoactive doses far higher than would be generally considered a microdose. White race, male/masculine gender identity, bisexual identity, past 6-month other drug use, greater attention deficit/hyperactivity disorder symptoms, mindfulness, and sensation-seeking were positively associated with having ever microdosed in multivariable models. Young adult microdosing merits further attention from scientific and public health professionals to help prevent misperceptions and potential adverse consequences as well as explore its potential therapeutic applications. [ABSTRACT FROM AUTHOR]

The urgent need for solutions to critical environmental challenges is well attested, but often environmental problems are understood as fundamentally collective action problems. However, to solve these problems, there is also a need to change individual behavior. Hence, there is a pressing need to inculcate in individuals the environmental virtues – virtues of character that relate to our environmental place in the world. We propose a way of meeting this need, by the judicious, safe, and controlled administration of "classic" psychedelic drugs as a form of moral bio-enhancement. Recent evidence shows that psychedelics can be given safely in controlled environments, and can induce vivid experiences of unity and connectedness. These experiences, in turn, can durably increase feelings of nature-relatedness and pro-environmental behaviors. Therefore, we argue that responsible psychedelic use can reliably catalyze the development of a key environmental virtue known as living in place. This is a "master environmental virtue" that subsumes the qualities of respect for nature, proper humility, and aesthetic wonder and awe. Our account advances the environmental virtues debate by introducing a relevant practical proposal, and advances the psychedelic moral enhancement debate by providing a much-needed conceptual framework. [ABSTRACT FROM AUTHOR]

Critique the available systematic review and de novo assessment of the role of psychedelics in the treatment of alcohol use disorder. A systematic literature search of PubMed was completed from 1960 to 9/9/2023. We pooled randomized controlled trials comparing psychedelics to control therapy for the treatment of alcohol use disorder. At the first recorded follow-up, LSD [n = 3, Odds Ratio (OR) 1.99 (95% Confidence interval (CI): 1.10 to 3.61)] and any psychedelic [n = 4, OR 2.16 (95%CI: 1.26 to 3.69)] enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol versus placebo in randomized, double-blind, placebo-controlled trials. When the inclusion criteria were relaxed to include controlled trials without double-blinding or placebo control, LSD [n = 5, OR 1.79 (95%CI: 1.36 to 2.34)] and any psychedelic therapy [n = 6, OR 1.89 (95%CI: 1.42 to 2.50)] still enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol. Four of 6 trials had high risk of bias and other methodological issues. One trial found an instance of suicidal ideation as well as transient increases in blood pressure that requires further exploration before the balance of benefits to harms can be determined. The use of psychedelics to treat alcohol use disorder is promising, but the weaknesses in the literature base preclude making definitive statements about its value. Future trials with greater methodological rigor are needed. Lysergic acid diethylamine (LSD) and psilocybin (hallucinogenic mushrooms) are psychedelics that have been studied in patients with alcohol use disorder (chronic issue with heavy or problem drinking). When all the studies are pooled together in a meta-analysis, the odds of being able to refrain from drinking alcohol or to substantially reduce the amount of alcohol consumed was enhanced by 89%. This is a promising finding that if bore out in additional studies, especially those with higher study quality, would be a major advance in patients with alcohol use disorder. We cannot make more definitive conclusions because all the LSD studies were published between 1966 and 1970 which may not reflect contemporary practice and most of the studies had methodological weaknesses that reduce confidence in the studies to prove the benefits. It is heartening that the single psilocybin trial from 2022 was of higher methodological quality, reflected contemporary practice, and still showed positive effects. [ABSTRACT FROM AUTHOR]

In psychedelic therapy, the importance of set and setting is a fundamental but under-researched assumption. The aim of this study is to correlate variables of set (psychedelic use motivation) and setting (psychedelic use location and type of companion) with psychopathology, wellbeing and personality variables. A sample of 1022 participants of the Spanish-speaking population was collected through an online survey. A novel instrument, the Psychedelic Use Scale (PUS), was developed to measure substance use variables of LSD, mescaline, psilocybin, DMT, 5-Meo-DMT, ketamine, Salvia divinorum, ibogaine and MDMA. Various personality, well-being and psychopathology instruments were implemented to measure outcome variables. Growth motivations, natural settings and presence of significant others predicted less psychopathology, greater wellbeing and meaningfulness of psychedelic experiences, whereas problematic motivations predicted greater psychopathology, lower wellbeing and did not predict meaningfulness of psychedelic experiences. Based on these results, we suggest experimental hypotheses for future clinical trials and longitudinal studies with potential clinical implications. [ABSTRACT FROM AUTHOR]

Research suggests positive changes in both well-being and psychiatric symptoms following a psychedelic experience. One explanation may be the ability of psychedelic compounds to occasion mystical-type experiences. The Revised Mystical Experiences Questionnaire (MEQ30) is designed to assess the intensity and quality of such experiences. We examined the validity, reliability, and factor structure of a Danish translation of the MEQ30 in one sample of healthy volunteers receiving psilocybin in a laboratory setting (N = 47) and two samples of recreative users of psychedelics, in which MEQ30 was reported retrospectively through an online survey based on their most recent experience with psilocybin (N = 834) or their most memorable experience with any psychedelic (N = 500). We conducted a confirmatory factor analysis of the previously suggested factor structures, calculated alpha and omega, and tested the associations between MEQ30 total score and setting, intention and dose. We found excellent internal reliability estimates across all samples, and confirmatory factor analysis showed that a four-factor structure, had the best, fair fit to the data. We further found that the MEQ30 total score was correlated with dose and a spiritual/religious intention, but not with setting. The Danish MEQ30 seems to be a valid tool for accessing mystical-type experiences among Danish-speaking individuals. [ABSTRACT FROM AUTHOR]

There has been little research on the effects of psychedelics on menstrual and reproductive function, though anecdotal evidence suggests that these compounds may have striking effects on menstrual function in at least a subset of users. Social media and word of mouth were used to seek out individuals who had a history of changes in menstrual function following psychedelic use. Case histories were elicited from three respondents following informed consent. A literature search on the effects of classic psychedelics and related compounds was completed. Three women ranging from 27 to 34 years of age were interviewed and reported three distinct phenomena following the use of classic psychedelics: 1) resumption of menses following amenorrhea, 2) early onset of menses, in particular when psychedelics were used in the mid to late luteal period, and 3) improved menstrual regularity in a woman with irregular cycles who was eventually diagnosed with polycystic ovarian syndrome. The mechanisms behind these effects remain unclear, though they may be mediated via direct or indirect effects of 5-HT2A agonism on the hypothalamic-pituitary-gonadal axis. Although phenomena related to menstrual and reproductive function have been largely overlooked in the psychedelic literature to date, these effects may have therapeutic utility and warrant further study. [ABSTRACT FROM AUTHOR]

Patient-perceived treatment credibility is linked to important outcome measures including symptom reduction, therapeutic alliance, patient satisfaction, and attrition rates. However, few studies have tested strategies to enhance treatment credibility. The present study investigates the effect of brief, written educational materials and the use of an image induction prime on perceptions of credibility for cognitive behavioral therapy and psilocybin-assisted therapy for depression. Participants (N = 493) rated the perceived credibility of depression treatments before and after reading brief educational materials. Half of the participants were asked an image induction question containing the construct of open-mindedness. Results indicate that brief educational materials of about 300 words significantly increased perceived treatment credibility for both therapies, with a large effect size (Cohen's d =.91). The use of an image induction prime further increased perceived credibility for psilocybin-assisted therapy for depression (Cohen's d =.38). These strategies offer an efficient and cost-effective way to enhance treatment credibility. Future studies testing variations of the image induction prime might prove fruitful for optimizing the technique. [ABSTRACT FROM AUTHOR]

A new era of treatment for adults with treatment-resistant depression (TRD), which involves psychedelic substances, is dawning. Emerging evidence indicates that psychedelics can exert antidepressant effects through multiple neurobiological and psychological mechanisms. However, it remains to be seen if these new treatments will revolutionize the treatment of TRD. The present review focuses on the efficacy of serotoninergic psychedelics psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ayahuasca, 5‐methoxy‐N,N‐dimethyltryptamine (5-MeO-DMT) and mescaline (3,4,5-trimethoxyphenethylamine), as well as 3,4-methylenedioxymethamphetamine (MDMA), for TRD. A systematic search was conducted for psilocybin in TRD as emerging trials had not yet been subject to review. A narrative review summarized findings on other psychedelics. Psychedelic therapy has created a paradigm shift in the treatment of TRD, as it can maximize therapeutic benefits and minimize potential risks. Psilocybin holds promise as a potential game-changer in the treatment of TRD, with initial evidence suggesting a rapid antidepressant effect sustained for some responders for at least 3 months. Nevertheless, further adequately powered, double-blind, comparator-controlled trials are required to explore and clarify the mechanisms of action and long-term effects of psychedelics in TRD. Psychedelics also hold promise for other psychiatric conditions, such as bipolar depression and post-traumatic stress disorder. [ABSTRACT FROM AUTHOR]

There is great interest in the use of psychedelic-assisted therapies to treat a range of mental health conditions and initial randomized controlled trials (RCTs) have generated positive results. However, the effect sizes reported in psychedelic RCTs are likely inflated due to expectancy effects due to the de-blinding of both participants and study personnel to treatment allocation caused by the distinctive psychoactive effects of psychedelic drugs. An introduction to causal inference for RCTs, the underlying assumptions, and potential confounders along with graphical illustrations is provided. It is proposed that causal mediation analysis using objectively measured mediating biomarkers could be used to identify causal pathways between treatment and outcome in psychedelic RCTs, even with de-blinding of participants and give greater confidence as to the mechanistic basis and efficacy of psychedelic therapies. It is argued that psychedelic therapies should not be approved as licensed medicines until causal pathways are clearly established between treatment and outcome. Potential downsides of doing so include, future indication expansion based on low quality clinical trial evidence, the approval of other therapies based on similarly low-quality evidence, and the potential for efficacy to change over time after approvals has been granted. [ABSTRACT FROM AUTHOR]

Hallucinogen Persisting Perception Disorder (HPPD) is considered rare in hallucinogen users although there are conflicting reports about its incidence and prevalence. HPPD may be more common in those with trait neuroticism. In this study, we invited hallucinogen and other drug users to complete an online questionnaire about their use of hallucinogens, their experience of HPPD symptoms, and their trait neuroticism and mental health symptoms. We received 802 responses with 415 of these containing adequate data for further analysis. 39.7% of responders reported symptoms corresponding to Type I HPPD, and 4.3% reported symptoms corresponding to Type II HPPD. We found no significant difference between neuroticism scores for participants with or without HPPD. Individuals with Type II HPPD were more likely to report mental health symptoms including anxiety, obsessional thoughts, paranoia, hypochondria and panic attacks (p < .05). We also found that individuals with Type II HPPD were more likely to report the use of 25I-NBOMe, dextromethorphan, nitrous oxide and benzodiazepines (p < .05). 47.3% of participants had never tested their drugs, making the attribution of HPPD severity to specific drugs difficult. Further work into the development of HPPD is required, particularly with the rise of hallucinogens as potential treatments for depression and other mental illnesses. [ABSTRACT FROM AUTHOR]

Analyzing online retrospective experience reports of psychedelic use can provide valuable insight into their acute subjective effects. Such reports are unexplored in relation to mystical states, which are thought to be a therapeutic mechanism within psychedelic-assisted psychotherapy. We created a set of words that, when encountered in an experience report, indicate the occurrence of mystical elements within the experience. We used the Shroomery.org website to retrieve 7317 publicly available retrospective psychedelic experience reports of psychedelic use, primarily of psilocybin, and have a designated experience intensity level self-assessed by the text authors during submission of the report. We counted the mystical language words using Linguistic Inquiry and Word Count (LIWC) software and additionally performed sentiment analysis of all reports. We found that the occurrence of mystical language grew with increased self-reported experience intensity. We also found that negative sentiment increased, and positive sentiment decreased as self-reported psychedelic experience intensity increased. These two findings raise the question of whether mystical experiences can co-exist with challenging elements within the psychedelic experience, a consideration for future qualitative studies. We present a new mystical language dictionary measure for further use and expansion, with some suggestions on how it can be used in future studies. [ABSTRACT FROM AUTHOR]

The global prevalence of substance abuse and mental disorders continues to challenge healthcare systems, with one in eight individuals affected. The therapeutic potential of psychedelics is recognized not only for treating mental disorders but also for enhancing well-being and promoting pro-social behaviors. Conventional biomedical research models fall short in addressing the broader health needs of populations and poorly suited for overcoming barriers to service delivery. This special issue includes six articles that explore alternative approaches to psychedelic research and practice, emphasizing collaboration with diverse actors, including indigenous communities, and incorporating traditional knowledge systems into contemporary psychedelic research. They underscore the need for innovative research methods that engage multidisciplinary approaches while promoting culturally relevant outcome measures. They emphasize the importance of shifting from punitive drug policies to those grounded in public health and human rights, allowing for multi-country studies and the development of evidence-based care models for community mental health. Incorporating traditional knowledge and community-based methodologies into psychedelic science is vital for its evolution beyond biomedical research for widespread dissemination, offering new avenues for improved health outcomes and promotion of human flourishing. [ABSTRACT FROM AUTHOR]

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

The pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components. [ABSTRACT FROM AUTHOR]

Cultural awareness of anosmia and microsmia has recently increased due to their association with COVID-19, though treatment for these conditions is limited. A growing body of online media claims that individuals have noticed improvement in anosmia and microsmia following classic psychedelic use. We report what we believe to be the first three cases recorded in the academic literature of improvement in olfactory impairment after psychedelic use. In the first case, a man who developed microsmia after a respiratory infection experienced improvement in smell after the use of 6 g of psilocybin containing mushrooms. In the second case, a woman with anosmia since childhood reported olfactory improvement after ingestion of 100 µg of lysergic acid diethylamide (LSD). In the third case, a woman with COVID-19-related anosmia reported olfactory improvement after microdosing 0.1 g of psilocybin mushrooms three times. Following a discussion of these cases, we explore potential mechanisms for psychedelic-facilitated improvement in olfactory impairment, including serotonergic effects, increased neuroplasticity, and anti-inflammatory effects. Given the need for novel treatments for olfactory dysfunction, increasing reports describing improvement in these conditions following psychedelic use and potential biological plausibility, we believe that the possible therapeutic benefits of psychedelics for these conditions deserve further investigation. [ABSTRACT FROM AUTHOR]

Legal, scientific, and social landscapes for psychedelics are changing rapidly. Differences of opinion exist among key stakeholders regarding regulatory control, models of provisioning psychedelic therapy, and medicalization, decriminalization, and/or legalization policies. We assessed the policy preferences of people using psychedelics naturalistically (N = 1221) to understand how they aligned and differed with institutional entities and existing psychedelic policies. Three quarters of participants would support decriminalization and legalization. On average, participants strongly supported individuals being legally able to grow and possess psychedelic plants and/or fungi for personal consumption. Trends included more support for natural over synthetic substances, self-production and consumption over gifting, gifting over sales, and administration of psychedelics with therapeutic support than without therapeutic support. Participants were concerned about pharmaceutical-like policy models, including patents of natural and synthetic psychedelic compounds. Participants were mostly from the State of Michigan, though geographical differences were minor. Those who identified as a psychedelic guide, educator, or therapist had small yet extensive differences from those who did not. As psychedelic liberalization continues to advance, it is critical for policymakers to consider these preferences to ensure laws provide safe and equitable access to these substances and appropriate medical support for their use. [ABSTRACT FROM AUTHOR]

There is a surge of interest in psychedelics, including new stakeholders and greater media attention. There is a need to examine the information-seeking behavior of people using psychedelics naturalistically, given the importance of preparation and harm-reduction. We examined sources of information for people using psychedelics naturalistically, and the degree to which they are trusted in a large, anonymous, online survey (N = 1221). The most common source of participants' information on psychedelics was their own experimentation and experiences (79.52%). Most also sought information from Internet websites (61.67%), friends (61.02%), Internet discussion forums (57.08%), books (57%), and articles in peer-reviewed scientific journals (54.55%). Few sought information from their primary health care provider (4.83%). Articles published in scientific journals, psychedelic nonprofits, and researchers based in colleges or universities were the most trusted sources of psychedelic information. Government agencies and pharmaceutical companies were the least trusted. Few participants thought that the popular media accurately stated the benefits and risks of psychedelics and most thought that the popular media failed to distinguish between different types of psychedelics. Our results indicate a high level of information seeking among psychedelic users, with a diverse array of information sources typically outside of mainstream health and medical care systems. [ABSTRACT FROM AUTHOR]

Renewed interest in psychedelic substances in the 21st century has seen the exploration of psychedelic treatments for various psychiatric disorders including substance use disorder (SUD). This review aimed to assess the effectiveness of psychedelic treatments for people with SUD and those falling below diagnostic thresholds (i.e. substance misuse). We systematically searched 11 databases, trial registries, and psychedelic organization websites for empirical studies examining adults undergoing psychedelic treatment for SUD or substance misuse, published in the English language, between 2000 and 2021. Seven studies investigating treatment using psilocybin, ibogaine, and ayahuasca, alone or adjunct with psychotherapy reported across 10 papers were included. Measures of abstinence, substance use, psychological and psychosocial outcomes, craving, and withdrawal reported positive results, however, this data was scarce among studies examining a wide range of addictions including opioid, nicotine, alcohol, cocaine and unspecified substance. The qualitative synthesis from three studies described subjective experience of psychedelic-assisted treatments enhanced self-awareness, insight, and confidence. At present, there is no sufficient research evidence to suggest effectiveness of any of the psychedelics on any specific substance use disorder or substance misuse. Further research using rigorous effectiveness evaluation methods with larger sample sizes and longer-term follow-up is required. [ABSTRACT FROM AUTHOR]

The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview of these drugs' clinical and pharmacological issues. The focus here was on: stimulants (e.g. amphetamines, methamphetamine, and pseudoephedrine; phenethylamines; synthetic cathinones; benzofurans; piperazines; aminoindanes; aminorex derivatives; phenmetrazine derivatives; phenidates); classical (e.g. ergolines; tryptamines; psychedelic phenethylamines), and atypical (e.g. PCP/ketamine-like dissociatives) psychedelics. Stimulant and psychedelics are associated with: a) increased central DA levels (psychedelic phenethylamines, synthetic cathinones and stimulants); b) 5-HT receptor subtypes' activation (psychedelic phenethylamines; recent tryptamine and lysergamide derivatives); and c) antagonist activity at NMDA receptors, (phencyclidine-like dissociatives). Clinicians should be regularly informed about the range of NPS and their medical, psychobiological and psychopathological risks both in the acute and long term. Future research should focus on an integrative model in which pro-drug websites' analyses are combined with advanced research approaches, including computational chemistry studies so that in vitro and in vivo preclinical studies of index novel psychoactives can be organized. The future of psychedelic research should focus on identifying robust study designs to convincingly assess the potential therapeutic benefits of psychedelics, molecules likely to present with limited dependence liability levels. [ABSTRACT FROM AUTHOR]

Abstract Background Methods Results Conclusion The global drug control landscape is undergoing remarkable change. Many jurisdictions around the world, including jurisdictions in the United States, have decriminalized the possession and use of plant- and fungus-based psychedelics, such as psilocybin-containing mushrooms (PCM). With ORS 475 A, Oregon has gone a step further by becoming the first US state to legalize and regulate the cultivation, supply, and use of PCM in designated service centers.This commentary examines recent developments and presents two arguments for an alternative strategy for legalizing PCM.First, a non-profit legal framework for the production, supply, and non-medical use of psilocybin may be more advantageous than a for-profit framework, especially for a naturally occurring mushroom that is typically not frequently used. Second, people who use drugs (PWUD) can demonstrate agency in the self-supply of drugs and in the adoption of responsible use and harm reduction practices.Community or peer-based structures may offer a viable approach to ensuring a controlled supply of PCM and a safe environment for their non-medical use. An outline of a public health-oriented regulatory approach for the non-profit, community-based cultivation, supply, and use of PCM is presented. This framework may provide a regulatory pathway for policymakers to consider. [ABSTRACT FROM AUTHOR]