Search

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.

BACKGROUND: Access to psychedelic drugs is liberalizing, yet responses are highly unpredictable. It is therefore imperative that we improve our ability to predict the nature of the acute psychedelic experience to improve safety and optimize potential therapeutic outcomes. This study sought to validate the Imperial Psychedelic Predictor Scale (IPPS), a short, widely applicable, prospective measure intended to be predictive of salient dimensions of the psychedelic experience. METHODS: Using four independent datasets in which the IPPS was completed prospectively - two online surveys of naturalistic use (N = 741, N = 836) and two controlled administration datasets (N = 30, N = 28) - we conducted factor analysis, regression, and correlation analyses to assess the construct, predictive, and convergent validity of the IPPS. RESULTS: Our approach produced a 9-item scale with good internal consistency (Cronbachs α = 0.8) containing three factors: set, rapport, and intention. The IPPS was significantly predictive of mystical, challenging, and emotional breakthrough experiences. In a controlled administration dataset (N = 28), multiple regression found set and rapport explaining 40% of variance in mystical experience, and simple regression found set explained 16% of variance in challenging experience. In another (N = 30), rapport was related to emotional breakthrough explaining 9% of variance. CONCLUSIONS: Together, these data suggest that the IPPS is predictive of relevant acute features of the psychedelic experience in a broad range of contexts. We hope that this brief 9-item scale will be widely adopted for improved knowledge of psychedelic preparedness in controlled settings and beyond.

OBJECTIVE: Affective symptoms such as anxiety, low mood, and loneliness are prevalent and highly debilitating symptoms among older adults (OA). Serotonergic psychedelics are currently investigated as novel interventions for affective disorders, yet little is known regarding their effects in OA. We investigated the mental health effects and psychological mechanisms of guided psychedelic group experiences in OA and a matched sample of younger adults (YA). METHODS: Using a prospective observational cohort design, we identified 62 OA (age ≥60 years) and 62 matched YA who completed surveys two weeks before, a day, two weeks, four weeks, and six months after a psychedelic group session. Mixed linear regression analyses were used to investigate longitudinal well-being changes, as well as baseline, acute, and post-acute predictors of change. RESULTS: OA showed post-psychedelic well-being improvements similar to matched YA. Among baseline predictors, presence of a lifetime psychiatric diagnosis was associated with greater well-being increases in OA (B = 6.72, p = .016 at the four-week key-endpoint). Compared to YA, acute subjective psychedelic effects were less intense in OA and did not significantly predict prospective well-being changes. However, relational experiences before and after psychedelic sessions emerged as predictors in OA (r(36) = .37,p = 0.025). CONCLUSIONS: Guided psychedelic group sessions enhance well-being in OA in line with prior naturalistic and controlled studies in YA. Interestingly, acute psychedelic effects in OA are attenuated and less predictive of well-being improvements, with relational experiences related to the group setting playing a more prominent role. Our present findings call for further research on the effects of psychedelics in OA.

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.

This study demonstrates that changes in mindfulness predict subsequent changes in well-being in a data set including individuals who recently engaged in psychedelic use.

AIM: Psychedelics have recently gained attention as potential therapeutic agents for various psychiatric disorders. Previous research has highlighted that a diminished sense of self, commonly termed ego-dissolution is a pivotal feature of the psychedelic-induced state. While the Ego-Dissolution Inventory (EDI) is a widely acknowledged instrument for measuring this phenomenon, no Japanese version has been available. This study aimed to develop a Japanese version of the EDI. METHODS: We adhered to the Guidelines for Best Practices in the Translation and Cultural Modification Process for Patient-Reported Outcomes Instruments: Document from the ISPOR Committee on Translation and Cultural Modification during our translation approach. Two Japanese psychiatrists independently conducted initial translations, and a consolidated version was achieved via mutual agreement. This version was then back-translated to English and assessed by the original authors for consistency. The repetitive modification process was conducted in continuous dialogues with the original authors until they accepted the concluding back-translated version. RESULTS: The finalized, approved back-translated version of the EDI is presented in the accompanying figure. In addition, the authorized Japanese version of the EDI is included in the Appendix. CONCLUSIONS: In this study, we successfully developed the Japanese version of the EDI. This instrument will assist in assessing ego-dissolution experiences associated with psychedelic-assisted therapy among Japanese speakers. Additional studies are necessary to evaluate the reliability and validity of this newly translated instrument.

BACKGROUND: Resurgent psychedelic research has largely supported the safety and efficacy of psychedelic therapy for the treatment of various psychiatric disorders. As psychedelic use and therapy increase in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem to be rare; however, studies are limited by biases and small sample sizes. The current analytical approach was motivated by the question of whether rare but significant adverse effects have been under-sampled in psychedelic research studies. METHODS: A bottom margin analysis approach was taken to focus on negative responders to psychedelic use in a pool of naturalistic, observational prospective studies (N = 807). We define negative response by a clinically meaningful decline in a generic index of mental health, that is, one standard error from the mean decrease in psychological well-being 4 weeks post-psychedelic use (vs pre-use baseline). We then assessed whether a history of diagnosed mental illness can predict negative responses. RESULTS: We find that 16% of the cohort falls into the negative responder subset. Parsing the sample by self-reported history of psychiatric diagnoses, results revealed a disproportionate prevalence of negative responses among those reporting a prior personality disorder diagnosis (31%). One multivariate regression model indicated a greater than four-fold elevated risk of adverse psychological responses to psychedelics in the personality disorder subsample (b = 1.425, p

Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes, such as personality changes. These findings are particularly intriguing, given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g., from wakefulness to sleep). However, little is known about how context impacts the entropy-enhancing effect of psychedelics, which carries important implications for how it can be exploited in, for example, psychedelic psychotherapy. This article investigates how brain entropy is modulated by stimulus manipulation during a psychedelic experience by studying participants under the effects of lysergic acid diethylamide (LSD) or placebo, either with gross state changes (eyes closed vs open) or different stimuli (no stimulus vs music vs video). Results show that while brain entropy increases with LSD under all of the experimental conditions, it exhibits the largest changes when subjects have their eyes closed. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing a video─potentially due to a competition between external stimuli and endogenous LSD-induced imagery. Taken together, our findings provide strong quantitative evidence of the role of context in modulating neural dynamics during a psychedelic experience, underlining the importance of performing psychedelic psychotherapy in a suitable environment.

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.

BACKGROUND: Refugees and immigrants can experience complex stressors from the process of immigration that can have lasting and severe long-term mental health consequences. Experiences after ayahuasca ingestion are shown to produce positive effects on psychological wellbeing and mental health, including anecdotal reports of improved symptoms of trauma and related disorders. However, data on the longitudinal health impact of naturalistic ayahuasca use in Middle Eastern and North African (MENA) immigrant and refugee populations is limited. AIMS: The current longitudinal online survey study was conducted to gather prospective data on ceremonial ayahuasca use in a group (N = 15) of primarily female MENA immigrants and refugees and to provide further insight into the patterns and outcomes surrounding that use. The study sought to assess self-reported changes in physical and mental health, well-being, and psychological functioning, examine relationships between aspects of individual mindset (e.g., psychedelic preparedness) prior to ayahuasca use and observed outcomes during (e.g., subjective drug effects) and afterwards (i.e., persisting effects), characterize risks and negative experiences, and describe trauma exposure and personal history. RESULTS/OUTCOMES: Our findings revealed ceremonial use of ayahuasca is associated with significant improvements in mental health, well-being, and psychological functioning, including reductions in depression, anxiety, and shame, and increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced notable positive behavioral changes persisting months after ingestion. CONCLUSION/INTERPRETATION: While preliminary, results suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during the process of migration.

N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that induces a rapid and transient altered state of consciousness when inhaled or injected via bolus administration. Its marked and novel subjective effects make DMT a powerful tool for the neuroscientific study of consciousness and preliminary results show its potential role in treating mental health conditions. In a within-subjects, placebo-controlled study, we investigated a novel method of DMT administration involving a bolus injection paired with a constant-rate infusion, with the goal of extending the DMT experience. Pharmacokinetic parameters of DMT estimated from plasma data of a previous study of bolus intravenous DMT were used to derive dose regimens necessary to keep subjects in steady levels of immersion into the DMT experience over an extended period of 30 min, and four dose regimens consisting of a bolus loading dose and a slow-rate infusion were tested in eleven healthy volunteers (seven male, four female, mean age ± SD = 37.09 ± 8.93 years). The present method is effective for extending the DMT experience in a stable and tolerable fashion. While subjective effects were maintained over the period of active infusion, anxiety ratings remained low and heart rate habituated within 15 min, indicating psychological and physiological safety of extended DMT. Plasma DMT concentrations increased consistently starting 10 min into DMT administration, whereas psychological effects plateaued into the desired steady state, suggesting the development of acute psychological tolerance to DMT. Taken together, these findings demonstrate the safety and effectiveness of continuous IV DMT administration, laying the groundwork for the further development of this method of administration for basic and clinical research.

BACKGROUND: The ability of psychedelic compounds to profoundly alter mental function has been long known, but the underlying changes in cellular-level information encoding remain poorly understood. METHODS: We used two-photon microscopy to record from the retrosplenial cortex in head-fixed mice running on a treadmill before and after injection of the nonclassic psychedelic ibogaine (40 mg/kg intraperitoneally). RESULTS: We found that the cognitive map, formed by the representation of position encoded by ensembles of individual neurons in the retrosplenial cortex, was destabilized by ibogaine when mice had to infer position between tactile landmarks. This corresponded with increased neural activity rates, loss of correlation structure, and increased responses to cues. Ibogaine had surprisingly little effect on the size-frequency distribution of network activity events, suggesting that signal propagation within the retrosplenial cortex was largely unaffected. CONCLUSIONS: Taken together, these data support proposals that compounds with psychedelic properties disrupt representations that are important for constraining neocortical activity, thereby increasing the entropy of neural signaling. Furthermore, the loss of expected position encoding between landmarks recapitulated effects of hippocampal impairment, suggesting that disruption of cognitive maps or other hippocampal processing may be a contributing mechanism of discoordinated neocortical activity in psychedelic states.

Emerging evidence indicates that ayahuasca consumption may have beneficial mental health effects. This study undertakes the largest analysis to date of associations between naturalistic ayahuasca use and current mental health status via an online cross-sectional survey. The sample included 7,576 participants (average age 41, 47% female) who had consumed ayahuasca in religious, traditional, or non-traditional settings in over 50 countries. Bivariate analysis, multivariate linear regressions and generalized structural equation modeling were used to explore associations between ayahuasca use variables, current mental health (K10, SF-12 MCS), and psychological well-being change (PWG). The number of ayahuasca uses was found to be positively associated with current mental health status (all measures), and this remained highly significant in multivariate models, with little evidence of associations diminishing over time. Variables such as the strength of the mystical experience, self-insights, and community/social variables were also positively associated with current mental health and PWG, while acute extreme fear and integration difficulties were negatively associated. Findings suggest that naturalistic ayahuasca use is associated with better current mental health status and enhanced psychological wellbeing for individuals with and without a history of mental illness, independent of community effects, with certain variables contributing positively or negatively to these effects. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Aim/Question Method Results Discussion Limitations Implications Recommendations Psychedelic science is re‐emerging to address mental health conditions, of which certain populations in the United States experience disparities. However, the perspectives of registered nurses (RNs), who have important roles within mental health care, towards psychedelics are largely unknown.To assess attitudes, knowledge, and beliefs of a large, state‐wide sample of RNs towards psychedelics in healthcare settings.RNs were randomly selected from a statewide directory to participate in a cross‐sectional, multi‐method online survey.793 RNs completed all items, with generally positive attitudes towards psychedelics but mixed opinions regarding the legal landscape, including decriminalisation. Few (12.7%) reported psychedelic content in their training, and most expressed low confidence in their knowledge.Findings generally align with previous research regarding provider attitudes towards psychedelics. Participants in this study had slightly more favourable attitudes and higher knowledge scores.The study has potential selection bias, lacks a priori power analysis, and is limited to one state.As psychedelic science emerges as a potential treatment option for several mental health conditions, RNs must be prepared to support individuals and communities.Additional education in this emerging area of mental health nursing is warranted to ensure RN competence and confidence. [ABSTRACT FROM AUTHOR]

Deep Reinforcement Learning is a branch of artificial intelligence that uses artificial neural networks to model reward-based learning as it occurs in biological agents. Here we modify a Deep Reinforcement Learning approach by imposing a suppressive effect on the connections between neurons in the artificial network—simulating the effect of dendritic spine loss as observed in major depressive disorder (MDD). Surprisingly, this simulated spine loss is sufficient to induce a variety of MDD-like behaviors in the artificially intelligent agent, including anhedonia, increased temporal discounting, avoidance, and an altered exploration/exploitation balance. Furthermore, simulating alternative and longstanding reward-processing-centric conceptions of MDD (dysfunction of the dopamine system, altered reward discounting, context-dependent learning rates, increased exploration) does not produce the same range of MDD-like behaviors. These results support a conceptual model of MDD as a reduction of brain connectivity (and thus information-processing capacity) rather than an imbalance in monoamines—though the computational model suggests a possible explanation for the dysfunction of dopamine systems in MDD. Reversing the spine-loss effect in our computational MDD model can lead to rescue of rewarding behavior under some conditions. This supports the search for treatments that increase plasticity and synaptogenesis, and the model suggests some implications for their effective administration. [ABSTRACT FROM AUTHOR]

This study presents a comprehensive multimodal analytical study of an Egyptian ritual Bes-vase, of the 2nd century BCE employing cutting-edge proteomics, metabolomics, genetics techniques, and synchrotron radiation-based Fourier Transformed Infrared microSpectroscopy (SR µ-FTIR) to characterize organic residues of its content. We successfully identified the presence of various functional, bioactive, psychotropic, and medicinal substances, shedding light on the diverse components of a liquid concoction used for ritual practices in Ptolemaic Egypt. Using LC-MS/MS with a new methodological approach, we identified key proteins and metabolites, enabling the identification of botanical sources, confirmed by genetic sequences. Our analyses revealed traces of Peganum harmala, Nimphaea nouchali var. caerulea, and a plant of the Cleome genus, all of which are traditionally proven to have psychotropic and medicinal properties. Additionally, the identification of human fluids suggests their direct involvement in these rituals. Furthermore, metabolomics and SR µ-FTIR analyses also revealed the presence of fermented fruit-based liquid and other ingredients such as honey or royal jelly. The identification of specific chemical compounds, such as alkaloids and flavonoids, provides insight into the psychoactive and therapeutic uses of these in ancient ritual practices. This multidisciplinary study highlights the complexity of ancient cultures and their interactions with psychoactive, medicinal, and bioactive substances. These findings contribute to our understanding of ancient belief systems, cultural practices, and the utilization of natural resources, ultimately enhancing our knowledge of past societies and their connection to the natural world. [ABSTRACT FROM AUTHOR]

Psychedelic drugs have profound effects on perception, cognition and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head‐fixed mice navigating on a treadmill. The place specificity of neurons to distinct locations along the belt was reduced by psilocybin. Moreover, the stability of place‐related activity across trials decreased. Psilocybin also reduced the functional correlation among simultaneously recorded neurons. The 5‐HT2AR (serotonin 2A receptor) antagonist ketanserin blocked these effects. These data are consistent with proposals that psychedelics increase the entropy of neural signaling and provide a potential neural mechanism contributing to disorientation frequently reported by humans after taking psychedelics. [ABSTRACT FROM AUTHOR]

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]

AbstractPsychedelic compounds continue gaining scientific and regulatory traction as potential new treatments for psychiatric disorders. While most psychiatrists will likely not work directly with these compounds, psychedelic research practices provide insights that may improve conventional psychiatric care. Through its emphasis on ‘set and setting’ (mindset and environment, respectively), psychedelic research highlights the importance of non-pharmacologic factors maximizing therapeutic outcomes. While psychedelics and serotonergic antidepressants are distinctly different in their subjective experience, new findings suggest mechanistic overlap between them. Both have been found to modulate neurotrophins, enhance neuroplasticity, and reopen critical periods of learning, molded by the environmental context in which they are administered.This paper will argue that by integrating insights from psychedelic research (particularly set and setting), depression treatment outcomes in traditional psychiatric settings can improve by optimizing non-pharmacological factors in treatment, including the provision of high-quality psychotherapy. [ABSTRACT FROM AUTHOR]

AbstractPsychedelics have shown early evidence for a range of benefits and low harm profiles in extant research. However, adverse effects (AEs) research in psychedelics has been limited, leading to underspecified AE profiles, inconsistent measurement, and potential undercounting of AEs. The development of safe, effective psychedelic therapies and treatments for AEs when they occur requires a thorough assessment of psychedelic-related AEs, their phenomenology, risk factors, and longitudinal duration. This article proposes that research on meditation-related AEs, which overlap in important ways with the phenomenological and contextual characteristics of psychedelic-related AEs, has engaged many methodological challenges present in the study of psychedelic-related AEs. Thus, meditation-related AE research offers thematic and methodological insights that are valuable to psychedelic AE research. An integrative review of extant AE research in both psychedelics and meditation is provided, and an agenda for leveraging meditation research to advance the investigation of psychedelic AEs is recommended. This includes the utility of meditation-related AEs as a comparator condition for psychedelic-related AEs, as well as recommendations for the adoption of (1) detailed and comprehensive, (2) user-informed, (3) impact-based, (4) standardized, (5) unbiased, and (6) representative measures of AEs and (7) examining factors that influence their impacts and trajectories. [ABSTRACT FROM AUTHOR]

The modulation of social cognition is suggested as a possible mechanism contributing to the potential clinical efficacy of psychedelics in disorders involving socio-emotional and reward processing deficits. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) can be used to detect changes in brain connectivity during psychedelic-induced states. Thus, this pharmacoimaging study investigates the effects of N,N-Dimethyltryptamine (DMT) on functional connectivity in brain areas relevant to social cognition, using a within-subject design in eleven healthy experienced users. The study included both an active and a control condition, conducted at different time points. The active condition involved DMT inhalation, while the control condition did not. Seed-based connectivity was measured for the two core regions involved in theory of mind and emotional processing, respectively, the posterior supramarginal gyrus and the amygdala. DMT increased supramarginal gyrus connectivity with the precuneus, posterior cingulate gyrus, amygdala, and orbitofrontal cortex. Additionally, increased connectivity emerged between the amygdala and orbitofrontal cortex. These results demonstrate that DMT modulates brain connectivity in socio-emotional and affective-value circuits, advancing our understanding of the neural mechanisms underlying the psychedelic experience and its potential therapeutic action. [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]

The aim of this study was to explore the perception of psychedelics within the medical population. Participants were asked by questionnaire about the potential of abuse, the somatic and psychiatric complications, and the risks of self-harm and aggression associated with the use of psychedelics using Likert Scales. A total of 407 participants were included. In our sample, the following means were found: 3.05 for general risk (<.001), 2.68 for self-harm risk (<.001), 2.47 for aggression (<.001), 2.71 for addictive risk (< .001), 2.76 for psychiatric disorder risk (<.001), and 2.11 for somatic disorder(< .001). Physicians from the lower mean of age were significantly more supportive of therapeutic potential, while general practitioners were significantly less likely to consider psychedelics as a treatment than specialists (<.001). By the term therapeutic potential, we meant the therapeutic value attributable to psychedelics and the risks expressed the possibility of damage caused by the use of the drug. Clinicians who considered psychedelics as a potential treatment were less likely to associate these with risks than their counterparts (<.001). The results of this study show that the perception of the danger of psychedelic use was important in the medical community in France. [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]

In the Netherlands, scientific interest in psychedelics and their subjective effects has been increasing. The present study examined the reliability, construct and predictive validity of the Dutch 30-item Revised Mystical Experience Questionnaire (MEQ30), a self-report measure that has been used to assess subjective and mystical experiences occasioned by psychedelics. In an online survey, 322 Dutch-speaking adults retrospectively reported on profound experiences with psychedelics. Confirmatory factor analyses demonstrated that both a four-factor structure and the same model extended with the MEQ30-total score as a second-order latent variable fit the data. Factor scores showed good internal reliability (α = between.81 and.94) and were significantly higher in participants that beforehand endorsed having had a mystical experience compared to those that did not, providing evidence for the construct validity of the questionnaire as a measure for self-reported mystical experiences. Additionally, MEQ30 scores significantly predicted the meaningfulness and spiritual significance of the psychedelic experience, as well as self-reported positive changes in well-being, life satisfaction and behavior, providing preliminary evidence for the predictive validity of the Dutch MEQ30. Findings suggest the reliability and validity of the Dutch MEQ30 and support the use of the scale in future studies on the subjective effects of psychedelics. [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]

BACKGROUND: Neurorehabilitation in military populations is complicated by higher rates of PTSD and unique characteristics of military institutions. These factors can adversely impact the patient-therapist therapeutic alliance and engagement with the rehabilitation process leading to poorer outcomes. MDMA is a non-classical psychedelic with pro-social and fear regulating properties. MDMA-assisted therapy is being explored as a novel treatment for PTSD that potentially offers rapid symptom improvement and enhances therapeutic alliance. OBJECTIVE: A review of MDMA-assisted therapy for PTSD is provided in the context of neurorehabilitation in military populations. The molecular mechanism of MDMA is outlined and a novel application of MDMA for neurorehabilitation is proposed. METHODS: This is an expert review and synthesis of the literature. RESULTS: Results from late-stage clinical trials suggest MDMA-assisted therapy for PTSD would be of particular benefit for military populations with PTSD. The unique pro-social properties of MDMA could be leveraged to enhance the therapeutic alliance and patient engagement during neurorehabilitation. CONCLUSION: The unique qualities and benefits of MDMA and MDMA-assisted therapy for PTSD suggest relevant application in military personnel undergoing neurorehabilitation. There are many similarities in patient-therapist dynamics in PTSD treatment and neurorehabilitation. The properties of MDMA which enhance therapeutic alliance, downregulate fear, and increase cognitive flexibility would potentially benefit both military personnel with and without PTSD undergoing neurorehabilitation. [ABSTRACT FROM AUTHOR]

The serotonin 2A (5-HT2A) receptor is an important target for drug development and the main receptor through which classical psychedelics elucidate their hallucinogenic effects. The 5-HT2A receptor antagonist ketanserin has frequently been used as a tool to block the receptor. Here, we establish the dose-occupancy relation of ketanserin and the cerebral 5-HT2A receptor in healthy participants by conducting a positron emission tomography (PET) study. 120-min PET scans using the 5-HT2A receptor agonist radiotracer [11C]Cimbi-36 were conducted at baseline and after oral doses of either 10, 20, or 40 mg of ketanserin; each participant underwent one or two scans after ketanserin administration. Occupancy was defined as the percent change in neocortex binding potential (BP ND), estimated using the simplified reference tissue model (SRTM) with the cerebellum as reference region. Peroral ketanserin intake resulted in a plasma concentration-related increase in cerebral 5-HT2A receptor occupancy with the highest plasma ketanserin concentrations measured after ∼2 h. The relation between mean plasma ketanserin concentrations and 5-HT2A receptor occupancy conformed to a single-site binding model with an estimated EC 50 (95 % CI) of 2.52 (0.75; 8.1) ng/mL, which corresponds to a peroral dose of ketanserin of approximately 10 mg. These data elucidate for the first time in humans the cerebral pharmacodynamics of ketanserin, both benefitting its use as a pharmacological tool for probing brain function and adding to its potential for therapeutic use in rescuing a bad psychedelic experience. [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]

Social cognitive deficits and social behavior impairments are common in major depressive disorder (MDD) and affect the quality of life and recovery of patients. This review summarizes the impact of standard and novel treatments on social functioning in MDD and highlights the potential of combining different approaches to enhance their effectiveness. Standard treatments, such as antidepressants, psychotherapies, and brain stimulation, have shown mixed results in improving social functioning, with some limitations and side effects. Newer treatments, such as intranasal oxytocin, mindfulness-based cognitive therapy, and psychedelic-assisted psychotherapy, have demonstrated positive effects on social cognition and behavior by modulating self-referential processing, empathy, and emotion regulation and through enhancement of neuroplasticity. Animal models have provided insights into the neurobiological mechanisms underlying these treatments, such as the role of neuroplasticity. Future research should explore the synergistic effects of combining different treatments and investigate the long-term outcomes and individual differences in response to these promising interventions. [ABSTRACT FROM AUTHOR]

Recent trials have shown promising results for the use of psychedelic-assisted therapies in treating severe refractory psychiatric illnesses, and there has been growing interest in examining the effectiveness of these therapies in treating eating disorders. To move forward in a safe, ethically sound, and scientifically rigorous manner, the field must address critical considerations. In this Comment article, we outline important risks and ethical considerations, along with methodological aspects that require careful consideration in the design of psychedelic-assisted therapy trials. We conclude by providing provisional guidelines for clinical research trials to help shape the future of this work, with the aim of investigating and employing the use of psychedelics for treating eating disorders in a manner that protects clients and research participants while maximizing methodological rigour. [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]

Increased psychological flexibility (PF) may underlie the lasting positive effects of psychedelic experiences on mental well-being. The associations between different components of PF, psychological inflexibility (PI), and well-being with psychedelic use are not well understood. We conducted a cross-sectional internet survey of participants (N = 629) with experience of classical psychedelics. Using network analysis, we examined how aspects of a single psychedelic experience (mystical-type features and psychological insights) and the frequency of past psychedelic use, were associated with current PF and PI components, as well as with mental well-being and ill-being. Mediation analyses explored whether PF mediated the relationship between past psychedelic use and well-being or ill-being. The network analysis linked psychological insight to the PF component Acceptance, with no association found between the frequency of past use and PF. Mediation analyses showed PF mediates the association between past psychedelic use and well-being and ill-being. These results suggest that the quality and depth of the psychedelic experience, rather than the frequency of use, are primarily linked to psychological flexibility, particularly Acceptance, and overall well-being. This underscores the importance of treating PF as a multidimensional construct to better understand the long-term mental health benefits of psychedelics. [ABSTRACT FROM AUTHOR]

Despite increasing interest in psychedelics and their potential therapeutic effects, research on inhaled N,N-Dimethyltryptamine (DMT) remains limited. Inhaled DMT has a reputation for rapid, dramatic onset and a brief duration, but correlates of use frequency remain poorly understood. A sample recruited from relevant internet sites, including nearly 400 people who had inhaled DMT, reported substance use histories, motivations for use, DMT sources, risk perceptions, and other variables. Generally, participants reported initiation motivated by curiosity about DMT’s effects, interest in psychedelics more broadly, and potential spiritual benefits. Those who had used other psychoactive substances (especially ayahuasca) and who had extracted DMT themselves reported inhaled DMT more frequently. Most (>60%) reported obtaining DMT from a friend and claimed it was “slightly difficult” to procure. Participants most commonly inhaled DMT from a glass pipe, in private homes, frequently alone or in small groups. Salient positives associated with inhaling DMT included psychologically cleansing or cathartic experiences. Associated challenges concerned difficult integration, aversive experiences, or “bad trips.” Participants rated DMT as very or slightly safe. These data underscore the need for continued work on this topic to inform education and harm reduction efforts, particularly as the molecule’s reputation for ameliorative effects receives media coverage. [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: 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]

AbstractThe renewed interest in psychedelics as treatments for mental health disorders is often referred to as the “Psychedelic Renaissance.” This article assesses whether this resurgence truly constitutes a paradigm shift in psychiatry, as some proponents claim, or if it should be viewed as an integration of existing therapeutic approaches. We explore historical contexts, noting that psychedelics were extensively researched in the mid-20th century and argue that many of the current claims about their novelty overlook prior knowledge and research from that period. While psychedelics do introduce novel aspects, such as rapid therapeutic effects and unique modes of action, we challenge the idea of a full paradigm shift, suggesting that these developments are better understood as enhancements to existing frameworks rather than a wholesale replacement. We emphasize the importance of integrating psychedelics within a broader bio-psycho-social model of psychiatry, combining pharmacological, psychological, and contextual factors. The therapeutic potential of psychedelics in psychotherapy has previously been described as working as “nonspecific amplifiers” of psychological processes, rather than introducing entirely new mechanisms. We suggest a balanced, integrative approach that incorporates psychedelics into existing mental health care models, cautioning against “psychedelic exceptionalism” and the risk of overselling their potential as a revolutionary treatment. [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]