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Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these real-world patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.

There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders. Many of these compounds are known to produce prosocial effects, but how these effects relate to therapeutic efficacy and the extent to which prosocial effects are unique to a particular drug class is unknown. In this article, we present a narrative overview and compare evidence for the prosocial effects of MDMA and serotonergic psychedelics to elucidate shared mechanisms that may underlie the therapeutic process. We discuss 4 categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. While both categories of drugs alter self-perception, MDMA may do so in a way that is less related to the experience of mystical-type states than serotonergic psychedelics. In the case of social reward, evidence supports the ability of MDMA to enhance responses and suggests that serotonergic psychedelics may also do so, but more research is needed in this area. Both drug classes consistently dampen reactivity to negative social stimuli. Finally, preclinical evidence supports the ability of both drug classes to induce social neuroplasticity, promoting adaptive rewiring of neural circuits, which may be helpful in trauma processing. While both MDMA and serotonergic psychedelics produce prosocial effects, they differ in the mechanisms through which they do this. These differences affect the types of psychosocial interventions that may work best with each compound.

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

Studies of psychedelic-assisted therapy with LSD, psilocybin, MDMA, and related substances show clinical promise but inadequately assess side effects. Measuring side effects is challenging because they are not always easily differentiated from treatment effects or disease symptoms and show high heterogeneity, variable duration and impact, and sensitivity to context. A systematic questionnaire describing important characteristics of side effects of psychedelics and MDMA would greatly improve on previous methods. We aimed to create a standardized tool for recording clinically relevant side effects of psychedelics and MDMA, including their severity, duration, impact, and treatment-relatedness. We constructed the Swiss Psychedelic Side Effects Inventory (SPSI) based on insights from previous research. It was pilot tested in 145 participants from three studies. Structured feedback from an expert panel was used to improve validity and feasibility. The final SPSI contains 32 side effects and standardized follow-up questions about their severity, impact, treatment-relatedness, and duration. It is compatible with any study design and can be administered as an interview or self-report at any timepoint after treatment with psychedelics or MDMA. The SPSI omits relatively unimportant side effects for brevity's sake, though space for additional symptoms is given. Future studies are needed to confirm its validity in different contexts. The SPSI is available in English and German for collecting systematic data on side effects from psychedelics and MDMA. This information is vital for improving clinical decisions, informed consent, and patient safety. • Psychedelics and MDMA can cause a unique profile of side effects which are not well-captured by the methods used in previous studies. • Psychedelic side effects vary in their severity, duration, and subjective impact. • Using previous studies, pilot data, and expert feedback, we developed the Swiss Psychedelic Side Effects Inventory (SPSI). • The SPSI contains 32 side effects and assesses their severity, impact, duration, and treatment-relatedness. • The SPSI can be used at any timepoint after psychedelic administration in any study of psychedelics or MDMA. [ABSTRACT FROM AUTHOR]

Psychedelic use has been increasingly accepted socially and legally. However, there is a gap in understanding how religion can influence the relationship between psychedelics and mental health. This study aims to explore this relationship by examining the impact of lifetime classic psychedelic use (LCPU), religious attendance, and religious salience on monthly psychological distress, using the K6 scale. The data for this project is sourced from the National Survey of Drug Use and Health (NSDUH) from 2008 to 2019, with a sample size of 458,372. The analysis utilizes several Ordinary Least Square regression models conducted in Stata 17. The results indicate that both religion and psychedelic use are associated with lower levels of psychological distress. While increased religious salience is linked to reduced distress, this effect is weakened by psychedelic use, as higher salience is associated with higher levels of distress among individuals who have used psychedelics. However, a three-way interaction analysis reveals that individuals with high religious salience and attendance experience the lowest levels of distress. [ABSTRACT FROM AUTHOR]

Psychedelic-assisted therapy is becoming increasingly acknowledged as an effective therapeutic intervention for various psychiatric illnesses. However, the evaluation of masking success is rarely reported in trials. The objective of the present systematic review was to evaluate placebo-control and masking in studies exploring psychedelic-assisted therapy. Nine (k = 9) studies dating between January 2010 and March 2023 were retrieved using six databases, following strict inclusion and exclusion criteria. The results show that almost 78% of the studies had, at best, “poor” masking success. At the same time, 60% of active placebo and 75% of inactive placebo studies showed large effect sizes. In other words, masking influences, including benign unmasking, cannot be excluded. We therefore conclude that efficacy of psilocybin, Ayahuasca, or LSD is only one of the possible interpretations of large, positive changes in symptomatology for patients suffering from, for example, alcohol use disorder, anxiety with or without life-threatening disease, anxiety and/or depression with life-threatening cancer, treatment-resistant depression or major depressive disorder. We recommend care be taken to increase successful masking procedures and discuss alternative treatment designs to better control for potential masking influences. [ABSTRACT FROM AUTHOR]

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]

Introduction Methods Results Discussion and Conclusions This study explores the attitudes of psychologists towards psychedelics and psychedelic‐assisted therapy (PAT) following the world‐first regulatory changes in 2023 in Australia which permitted psilocybin and 3,4‐methylenedioxy‐methamphetamine (MDMA) to be used in clinical services.A purposive sample of 20 Australian psychologists was recruited using snowball sampling. Semi‐structured interviews were conducted which explored participants' attitudes, knowledge and concerns about PAT. Data were coded and analysed to identify and develop theme categories.Most psychologists exhibited positive attitudes towards psychedelics and their therapeutic potential, viewing them as promising for addressing chronic mental health conditions like depression. However, there was a notable concern regarding the limited evidence on efficacy and potential adverse experiences, as well as the complexity of the individualised treatment protocol. Despite enthusiasm, many psychologists had limited detailed knowledge about the interventions themselves. The need for comprehensive education and training programs, including exposure to psychedelic experiences and credible higher education institutions, was emphasised to ensure competence in administering PAT.Psychologists displayed notably positive attitudes towards PAT, likely reflecting both shifting perceptions of psychedelics and self‐selection bias within the sample. Despite this optimism, concerns were raised about psychiatric risks and the necessity for comprehensive and reputable training and supervision. The cohort showed openness to both novel treatments and innovative training methods, underscoring the importance of enhancing educational frameworks to ensure effective implementation of PAT. [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 use of psilocybin to treat alcohol use disorder is very promising, but its mechanisms of action remain poorly understood. We combined behavioural, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time, when injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing the effect of intraperitoneal psilocybin or directly within the nucleus accumbens core or the ventral tegmental area. Transcripts from the dopaminergic system were quantified in the nucleus accumbens and prefrontal cortex. Psilocybin significantly reduced (by 50%) ethanol self-administration when injected 4 h before the session either intraperitoneally (1 mg/kg) or directly within the left nucleus accumbens (0.15 μg) but not the right nucleus accumbens or the left ventral tegmental area. The effect of intraperitoneal injection of psilocybin was prevented by intra-left nucleus accumbens injection of 0.3 μg of the 5-HT2A receptor antagonist ketanserin. In rats that self-administered ethanol but not in those self-administering saccharin, dopamine D2 receptor (D2R) mRNA was increased in both the nucleus accumbens and the prefrontal cortex by psilocybin, while dopamine D1 receptor mRNA was increased only in the prefrontal cortex. As in humans, psilocybin reduced ethanol self-administration in rats through the 5-HT2A receptor within the left nucleus accumbens, possibly through increased D2R expression. Our results open unexpected perspectives regarding the hemispheric lateralization of psychedelic effects. [ABSTRACT FROM AUTHOR]

Background: Short‐lasting unilateral neuralgiform headache attacks (SUNHA) are trigeminal autonomic cephalalgias that feature intense and recurrent paroxysms of pain and autonomic symptoms. Many patients are left with debilitating symptoms despite best‐available treatment. Psychedelics, such as the serotonin 2A partial agonist psilocybin, have shown promise in related disorders such as migraine and cluster headache. In this open‐label phase Ib ascending dose study, we aimed to assess the effects of low‐dose oral psilocybin with psychological support in six to 12 patients with chronic SUNHA. Study objectives were to determine effects on cognition, as well as safety, tolerability, and effects on headache severity and frequency. Methods: Oral psilocybin in ascending doses of 5, 7.5, and 10 mg (one dose per session; three dosing sessions in total) were administered. Cognition was assessed via the Cambridge Neuropsychological Tests Automated Battery. Headache attacks were assessed via headache diaries and the six‐item Headache Impact Test (HIT‐6). Subjective dose intensity was assessed via the five‐Dimensional Altered States of Consciousness Questionnaire (5D‐ASC). The study was terminated early due to recruitment difficulties; four patients were enrolled, three of whom were study completers. Post hoc, we undertook a thematic analysis of the applicable free‐text clinical trial notes from the dosing and subsequent visits (n = 22). An inductive method was employed to establish emergent themes. Results: No significant adverse events were recorded. We were unable to collect data as planned on cognitive function during the acute experience due to high ratings of subjective dose intensity (mean 5D‐ASC scores 37.8–45.7). The impact of the headaches remained severe throughout the duration of the trial (HIT‐6 mean scores 64.3–65.7). There were limited effects on headache duration and severity based on the diaries; however, mean daily attack frequency decreased by >50% in two participants at final follow‐up (22.9 to 11.0 and 56.4 to 28.0, respectively). Completing participants and their clinicians recorded "much" (two participants) or "minimal" improvements (one participant) at final follow‐up via the Clinical Global Impression rating scale. Thematic analysis indicated that psychological insights were key features of participants' experience; these insights included re‐configured relationships to their headache pain. Conclusion: The study met with recruitment difficulties and cognition could not be assessed during the acute experience due to subjective dose intensity, likely mediated in part by expectancy effects. The clinical results provide no conclusive evidence for the use of psilocybin in SUNHA. We suggest that accounting for psychological factors in chronic SUNHA may be an important facet of treatment. Plain Language Summary: Short‐lasting unilateral neuralgiform headache attacks (SUNHA) are intensely painful headaches that cannot always be treated with conventional medical therapy. This was the first medical trial to administer the psychedelic drug psilocybin with psychological support to patients with SUNHA. Unfortunately, we had difficulty recruiting patients for the trial; only three patients were able to complete it, and so we are not able to make any definitive conclusions about whether psilocybin might be useful for treating SUNHA. [ABSTRACT FROM AUTHOR]

The recreational use of psilocybin or psilocin-containing products, a chemical found naturally in certain mushroom species, is on the rise across the United States. Several cases of serious clinical effects related to mushroom-containing products have recently been reported to the Food and Drug Administration (FDA). The emergence of these new products and their health consequences are not yet well understood. This case series aims to characterize exposures to mushroom-containing chocolate products, including patient characteristics, clinical effects, treatment(s), and clinical outcome severity, reported to a poison center network. This was a retrospective case series conducted in patients exposed to mushroom-containing chocolate products across three poison centers between January 2023 to August 2024. Patients were identified via a database search of ToxSentry®. Patients were included if they were exposed to a mushroom-containing chocolate product. Patients were excluded if they ingested an unrelated product or if there was insufficient information documented within ToxSentry®. The primary endpoint was to describe clinical outcome severity after exposure to mushroom-containing chocolate products. A query of ToxSentry® identified 164 cases; 36 cases met study criteria. The median age of patients in this case series was 17 years old. For most patients (23, 64 %), the reason for the exposure was intentional, with 20 reporting intentional abuse or misuse of the product. Common clinical effects reported included mental status changes (26, 76 %), paranoia/hallucinations (10, 28 %), dysrhythmias (7, 19 %) and gastrointestinal discomfort (6, 17 %). There was one report of seizure. Most clinical effects lasted between 3 and 24 h after ingestion (29, 81 %). Intravenous fluids (18, 50 %) and benzodiazepines (7, 19 %) were the most common treatments given. No fatalities were reported. While most patients in this series experienced minor clinical effects, some developed serious effects after ingestion of a mushroom-containing chocolate product. Findings from this study further characterize the limited patient demographics, clinical effects, and outcomes published thus far. Further characterization in a larger cohort of patients could expand on our initial findings and is needed to better identify factors that may influence clinical outcomes. [ABSTRACT FROM AUTHOR]

As clinical trials for psychedelics move into phase III in the USA, Europe must address its lag in integrating professional education around psychedelic-assisted therapy (PAT) and supporting psychedelic drug research. This paper evaluates the necessary frameworks for implementing PAT in Germany, emphasizing the nation's potential leadership role within the European Union. With Australia having already approved MDMA and psilocybin for mental health indications, the Ukrainian government exploring MDMA treatment for war-related PTSD, and initial clinical trials involving MDMA and LSD with patients in Switzerland which restarted the restricted medical use of these substances around 2014, the medical authorization of psychedelics in these countries establishes precedent showcasing both the promise and challenges of researching and implementing PAT in nations where the substances were formally scheduled as illicit substances. Key challenges include establishing rigorous standards for practitioner training, accessibility, and defining regulatory oversight. This paper focuses on the development of robust infrastructure in Germany, which will support the roll out of PAT, and details ethical considerations, training protocols, and governmental roles in the formulation of treatment frameworks. This approach aims not only to guide Germany in adopting PAT but also to influence broader European policy, ensuring that patients receive ethically sound and proficient care. The findings suggest pathways for Europe to reclaim its historical lead in psychiatric and therapeutic innovation. [ABSTRACT FROM AUTHOR]

Psychedelics have a complex history marked by traditional use among indigenous cultures, early scientific interest, and subsequent prohibition. Despite their classification as controlled substances, recent decades have witnessed a resurgence of research into their therapeutic potential for various mental health conditions. However, most studies have focused on controlled clinical settings, leaving a significant gap in understanding how these substances are used in naturalistic contexts, particularly in Latin America. This study investigates the regular use of macrodoses of psychedelics among Latin American adults. We aimed to characterize the sociodemographic profiles, consumption practices, and subjective effects experienced by individuals who use psychedelics regularly. Data were collected via an online survey from 4,270 participants across several Latin American countries. Results indicated a diverse user base with varied motivations, predominantly psychological and spiritual well-being. The most frequently used substance was psilocybin mushrooms, with significant associations found between demographic variables and specific psychedelics used. The study provides new insights into the naturalistic use of psychedelics in Latin America, highlighting the need for informed, safe, and legal use frameworks. [ABSTRACT FROM AUTHOR]

Psychedelic therapies are an emerging class of treatments in psychiatry with great potential, however relatively little is known about their interactions with other commonly used psychiatric medications. As psychedelic therapies become more widespread and move closer to the clinic, they likely will need to be integrated into existing treatment models which may include one or more traditional pharmacological therapies, meaning an awareness of potential drug-drug interactions will become vital. This commentary outlines some of the issues surrounding the study of drug-drug interactions of this type, provides a summary of some of the relevant key results to date, and charts a way forward which relies crucially on multimodal neuroimaging investigations. Studies in humans which combine Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI), plus ancillary measures, are likely to provide the most comprehensive assessment of drug-drug interactions involving psychedelics and the relevant effects at multiple levels of the drug response (molecular, functional, and clinical). [ABSTRACT FROM AUTHOR]

Background: Psychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT. Aims: This study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers. For the patients, it also investigated the relationship between antidepressant effects and six measures of acute drug effects. Methods: We compared data on acute psychedelic drug effects between 28 PAT patients with data from 28 healthy participants who participated in a randomized, double-blind crossover trial. All participants received varying doses of psilocybin and LSD. Subjective effects were assessed on an hourly basis during the acute drug effects, and the Mystical Experience Questionnaire (MEQ) was completed retrospectively. For patients, depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Results: Ratings of overall drug effect and mystical experience were similar across groups. Compared with healthy controls, patients reported lower ratings of ego dissolution. Patients showed a significant decrease in MADRS scores, and the greatest predictor of antidepressant outcome was relaxation during the PAT session. We did not observe a relationship between mystical-type experiences and antidepressant effects. Most patients experienced mild adverse effects which resolved within 48 h. Conclusion: PAT reduced depressive symptoms in this heterogeneous patient group. Patients may experience more challenging psychedelic effects and reduced ego dissolution. Hourly assessment of drug effects may predict clinical outcomes better than retrospectively assessed mystical experiences, and the impact of relaxation during PAT should be investigated further. [ABSTRACT FROM AUTHOR]

Background: Non-ordinary states of consciousness induced by psychedelics can be accompanied by so-called "peak experiences," characterized at the emotional level by their intensity and positive valence. These experiences are strong predictors of positive outcomes following psychedelic-assisted therapy, and it is therefore important to better understand their biology. Despite growing evidence that the autonomic nervous system (ANS) plays an important role in mediating emotional experiences, its involvement in the psychedelic experience is poorly understood. The aim of this study was to investigate to what extent changes in the relative influence of the sympathetic (SNS) and parasympathetic nervous systems (PNS) over cardiac activity may reflect the subjective experience induced by the short-acting psychedelic N,N-Dimethyltryptamine (DMT). Methods: We derived measures of SNS and PNS activity from the electrocardiograms of 17 participants (11 males, mean age = 33.8 years, SD = 8.3) while they received either DMT or placebo. Results: Results show that the joint influence of SNS and PNS ("sympathovagal coactivation") over cardiac activity was positively related to participants' ratings of "Spiritual Experience" and "Insightfulness" during the DMT experience, while also being related to improved well-being scores 2 weeks after the session. In addition, we found that the state of balance between the two ANS branches ("sympathovagal balance") before DMT injection predicted scores of "Insightfulness" during the DMT experience, as well as subsequent sympathovagal coactivation. Conclusion: These findings demonstrate the involvement of the ANS in psychedelic-induced peak experiences and may pave the way to the development of biofeedback-based tools to enhance psychedelic therapy. [ABSTRACT FROM AUTHOR]

Background: The applications of psilocybin, derived from 'magic mushrooms,' are vast, including a burgeoning practice known as microdosing, which refers to the administration of sub-hallucinogenic doses of psychedelic substances to obtain benefits without experiencing significant cognitive and perceptual distortion. However, current research is fairly new with several limitations and gaps that hinder adequate conclusions on its efficacy. Aims: This semi-structured review aimed to identify and highlight research gaps in the field of psilocybin microdosing for future research. Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses based strategy was employed, utilizing a chain of keywords and key phrases across multiple databases, augmented by a cross-sectional Google search for relevant grey literature in the form of the top 10 search results. A total of 40 studies and 8 unique websites were identified, summarized and tabulated into four distinct categories, namely non-clinical, clinical, observational and anecdotal evidence. Results: The majority of available evidence originates from observational studies, while non-clinical and clinical study findings remain comparatively sparse and inconsistent. Web-based findings were consistent with current research findings. Key research gaps were highlighted: the imperative for more randomized placebo-controlled trials, exploration of dose-response ranges, psychological and personality testing of participants, utilization of active placebos, greater diversity in study populations, an increase in psilocybin-exclusive microdosing studies and the refinement of animal models. Conclusion: Definitive conclusions regarding the efficacy of psilocybin microdosing remain elusive, emphasizing the need for further study. Numerous research gaps necessitate consideration for future investigations. [ABSTRACT FROM AUTHOR]

Background: Psychedelic substances reliably induce marked altered states of consciousness (ASC), which may be important for lasting effects and clinical outcomes of psychedelic intervention. Several instruments are available to measure the acute psychedelic experience, of which the Five Dimensional Altered States of Consciousness Questionnaire (5D-ASC) is commonly used. The questionnaire can be scored and analyzed as having five dimensions or 11 subscales, but the two have not been evaluated with comparable factor analysis methods. Methods: The Danish translation of the 5D-ASC was completed by one sample of healthy volunteers receiving psilocybin in a laboratory setting (N = 47) and one sample of recreative users5D-ASC of psychedelics (N = 550), who reported retrospectively through an online survey based on their most recent experience with psilocybin. We calculated internal consistency measures of Cronbach's alpha and McDonald's omega, conducted a confirmatory factor analysis of the previously suggested factor structures, and tested for possible associations between the 5D-ASC total scores and dose, setting, and intention. For the 11 subscales, we reported omega-sem (composite reliability) using the parameters of the fitted confirmatory factor analyses model. Results: Confirmatory factor analysis showed that the 11 subscales had a good fit to data and showed a better fit compared to the originally proposed five-dimensional solution and good internal consistencies. We further found that the 5D-ASC total scores correlated positively with the dose in the recreative sample. We found no correlations between 5D-ASC total scores and intention or setting. Discussion: We find the Danish 5D-ASC to be a valid tool for measuring ASC among Danish-speaking individuals. [ABSTRACT FROM AUTHOR]

Psilocybin is a classic psychedelic with demonstrated preliminary clinical efficacy in a range of psychiatric disorders. Evaluating the impact of psilocybin on cognitive function is essential to unravel its potential benefits and risks. In this systematic review, we assessed psilocybin's effect on cognitive function through a comprehensive search of electronic databases from inception to January 2024, identifying 20 articles involving 2,959 participants. While 85% of studies were conducted in healthy volunteers, most of these studies (85%) used macrodoses, ranging from 45 μg/kg to 30 mg/70 kg. Various cognitive aspects were evaluated and yielded mixed results. Global cognitive function, and processing speed remained mostly unchanged in healthy individuals; However, a limited number of studies reported improvements in certain areas such as sustained attention, working memory, and executive function especially in patients with treatment‐resistant depression (TRD). Emotional processing was positively modified, particularly in TRD patients. Psilocybin was observed to enhance emotional empathy without significantly altering cognitive empathy and social cognition. Cognitive flexibility and creative cognition were noted to initially decline but could potentially improve over time. Additionally, with respect to learning and memory skills, psilocybin showed promise in improving specific memory types such as semantic associations and associative learning, while its effects on episodic and verbal memory have been less pronounced compared to other cognitive enhancers. The observed mixed findings underscore the complexity of psilocybin's cognitive influence. Further research is essential to provide a clearer understanding of psilocybin's impact on cognitive domains and to guide the development of safe and effective interventions. [ABSTRACT FROM AUTHOR]

Objective: Despite rapid advances in psychedelic sciences and the increasing number of countries legalizing psychedelics for the treatment of mental illnesses, the attitudes, knowledge and readiness of both mental health consumers and the general population remain largely unknown. Methods: A cross-sectional survey was conducted among Australians, targeting individuals with mental illness as potential mental health service users. A sub-sample of individuals free of mental illness was also surveyed to assess attitudes in the general population. Participants completed the Attitudes on Psychedelics Questionnaire, the Basic Knowledge of Psychedelics Test and a questionnaire by Corrigan et al. to capture attitudes toward psychedelic therapy by mental health service users. Results: Of the 502 respondents, 64.5% self-identified as having a mental illness. A significant proportion favored legalizing psychedelics for medical use (43%) and were open to their use (52.4%), yet fewer viewed their effects positively (24%) or considered them safe (33%). Most participants reported to be psychedelic naive (61%). Participants with mental illness had significantly more experience with psychedelics than participant free of mental illness (44.1% vs 29.7%). Experience, perceived knowledge and actual knowledge significantly predicted attitudes toward legalization, effects, risks and openness to psychedelics. Conclusions: While a large proportion of Australians are in favor of legalizing psychedelics for medical purposes, concerns about safety remain. People with self-identified mental illness, those with previous recreational psychedelic experience and those with greater knowledge of psychedelics were more likely to have positive attitudes toward psychedelics and psychedelic-assisted therapy. [ABSTRACT FROM AUTHOR]

This document is a compilation of summaries of four different articles from various medical journals. The first article discusses the use of a two-bag N-acetylcysteine (NAC) system for acetaminophen poisoning, comparing its effectiveness and safety to the FDA-approved three-bag system. The second article examines the use of physostigmine in the treatment of anticholinergic toxicity, finding that patients treated with physostigmine alone were less likely to be intubated. The third article explores the use of dexmedetomidine in non-intubated patients, concluding that it is a safe and useful adjunct in the care of agitated toxicological patients. The fourth article compares the acute effects of mescaline, lysergic acid diethylamide (LSD), and psilocybin in a randomized, double-blind, placebo-controlled study, finding that the subjective experiences were similar at the studied doses. These articles provide valuable insights for toxicologists and poison centers in the treatment of various toxicological conditions. [Extracted from the article]

Psychedelic medicine is currently being evaluated for numerous mental health indications, and there is significant interest in applying these models of care to eating disorders (EDs) given the limited efficacy of available treatment models, especially for those living with anorexia nervosa. Preliminary findings across a number of studies suggest promise. In this commentary, researchers with experience in psychedelics and EDs present a rationale and considerations for the application of psychedelic medicine, including psychedelic-assisted therapy (PAT) for EDs. These contributions are informed by those with lived experience as well as the authors' experiences in the field. By addressing underlying psychological and transpersonal factors and improving treatment engagement, psychedelic medicine, though not without risks, may offer a valuable adjunct to existing treatments, enhancing overall outcomes for some living with an ED. This commentary also aims to provide a multi-dimensional perspective to inform the field, including with respect to the etiology of these illnesses, as psychedelic medicine becomes more accessible in naturalistic, research and clinical settings. [ABSTRACT FROM AUTHOR]

Background Aim and Objectives Method Findings Conclusions Research on psychedelics centres on two key areas: the action of psychedelics on the brain and the protocol for delivering therapy. There is little research that considers the implications of this novel therapy on the therapist delivering the treatment. This research study sought to explore this.The aim of this research was to explore the considerations for psychotherapists interested in delivering psychedelic therapy. Objectives were to examine the therapeutic conditions needed for effective outcomes, to explore the perceived differences between the practice of standard psychotherapy and psychedelic therapy and to determine the challenges for therapists working in the field.Six semi‐structured interviews were conducted with therapists who work in clinical or retreat settings. Interview transcripts were analysed using qualitative thematic analysis.Three themes emerged that highlight the importance of preparation for effective clinical outcomes, the differences in standard and psychedelic practice and the personal and professional implications for therapists.The results highlighted challenges and revealed the need for clear protocols for integrating psychedelics into psychotherapy practice. [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]

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]

Key Clinical Message: Psilocybin shows promise as a treatment for CRPS, offering significant pain relief and functional improvement in a patient with refractory symptoms. This case highlights the need for further research into psilocybin's efficacy and optimal dosing for chronic pain management. [ABSTRACT FROM AUTHOR]

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Abstract As clinical trials for psychedelics move into phase III in the USA, Europe must address its lag in integrating professional education around psychedelic-assisted therapy (PAT) and supporting psychedelic drug research. This paper evaluates the necessary frameworks for implementing PAT in Germany, emphasizing the nation’s potential leadership role within the European Union. With Australia having already approved MDMA and psilocybin for mental health indications, the Ukrainian government exploring MDMA treatment for war-related PTSD, and initial clinical trials involving MDMA and LSD with patients in Switzerland which restarted the restricted medical use of these substances around 2014, the medical authorization of psychedelics in these countries establishes precedent showcasing both the promise and challenges of researching and implementing PAT in nations where the substances were formally scheduled as illicit substances. Key challenges include establishing rigorous standards for practitioner training, accessibility, and defining regulatory oversight. This paper focuses on the development of robust infrastructure in Germany, which will support the roll out of PAT, and details ethical considerations, training protocols, and governmental roles in the formulation of treatment frameworks. This approach aims not only to guide Germany in adopting PAT but also to influence broader European policy, ensuring that patients receive ethically sound and proficient care. The findings suggest pathways for Europe to reclaim its historical lead in psychiatric and therapeutic innovation.

Abstract Psychedelics have a complex history marked by traditional use among indigenous cultures, early scientific interest, and subsequent prohibition. Despite their classification as controlled substances, recent decades have witnessed a resurgence of research into their therapeutic potential for various mental health conditions. However, most studies have focused on controlled clinical settings, leaving a significant gap in understanding how these substances are used in naturalistic contexts, particularly in Latin America. This study investigates the regular use of macrodoses of psychedelics among Latin American adults. We aimed to characterize the sociodemographic profiles, consumption practices, and subjective effects experienced by individuals who use psychedelics regularly. Data were collected via an online survey from 4,270 participants across several Latin American countries. Results indicated a diverse user base with varied motivations, predominantly psychological and spiritual well-being. The most frequently used substance was psilocybin mushrooms, with significant associations found between demographic variables and specific psychedelics used. The study provides new insights into the naturalistic use of psychedelics in Latin America, highlighting the need for informed, safe, and legal use frameworks.

Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique leveraging neuroplasticity, to improve executive functions (EFs). Thirty-seven eligible participants were randomized into an experimental group (n = 18) and a passive control group (n = 19). The experimental group underwent three microdose sessions and then three psilocybin-assisted NF sessions, without requiring psychological support, demonstrating the approach's feasibility. NF learning showed a statistical trend for increases in frontal-midline theta from session to session with a large effect size and non-significant but medium effect size dynamical changes within sessions. Placebo effects were consistent across groups, with no tasks-based EF improvements, but significant self-reported gains in daily EFs—working memory, shifting, monitoring and inhibition—showing medium and high effect sizes. The experimental group's significant gains in their key training goals underscored the approach's external relevance. A thorough study with regular sessions and an active control group is crucial to evaluate EFs improvement and their specificity in future. Psilocybin-enhanced NF could offer significant, lasting benefits across diagnoses, improving daily functioning. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'. [ABSTRACT FROM AUTHOR]

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

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

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]

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

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

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

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

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

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

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

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

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

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]

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

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