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Introduction: Clinical high risk for psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution through enhanced awareness. A potential compensatory strategy is to use estimates of individual pretest risk as a 'gatekeeper' for specialized assessment. We aimed to test a risk stratification model previously developed in London, UK (OASIS) and to train a new predictive model for the Swiss population., Method: The sample was composed of 513 individuals referred for CHR assessment from six Swiss early psychosis detection services. Sociodemographic variables available at referral were used as predictors whereas the outcome variable was transition to psychosis., Results: Replication of the risk stratification model developed in OASIS resulted in poor performance (Harrel's c=0.51). Retraining resulted in moderate discrimination (Harrel's c=0.67) which significantly differentiated between different risk groups. The lowest risk group had a cumulative transition incidence of 6.4% (CI: 0-23.1%) over two years., Conclusion: Failure to replicate the OASIS risk stratification model might reflect differences in the public health care systems and referral structures between Switzerland and London. Retraining resulted in a model with adequate discrimination performance. The developed model in combination with CHR assessment result, might be useful for identifying individuals with high pretest risk, who might benefit most from specialized intervention., (Copyright © 2024 The Author(s). Published by Elsevier España S.L.U. All rights reserved.)

The pharmacodynamic effects of lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by non-pharmacological factors such as personality traits and mood states. The aim of this study was to determine pharmacological and psychological predictors of the LSD effects in healthy human subjects. This analysis is based on nine double-blind, placebo-controlled, cross-over studies with a total of 213 healthy subjects receiving between 25-200 µg LSD. The influence of sex, age, dose, body weight, pharmacogenetic, drug experience, personality, setting, and mood before drug intake on the peak autonomic and total subjective responses to LSD was investigated using multiple linear mixed effects models and Least Absolute Shrinkage and Selection Operator regression. Results were adjusted for LSD dose and corrected for multiple testing. LSD dose emerged as the most influential predictor, exhibiting a positive correlation with most response variables. Pre-drug mental states such as "Well-Being", "Emotional Excitability", and "Anxiety" were also important predictor for a range of subjective effects but also heart rate and body temperature. The trait "Openness to Experiences" was positively correlated with elevated ratings in "Oceanic Boundlessness" and mystical-type effects. Previous experiences with hallucinogens have been negatively associated with the overall altered state of consciousness and particularly with "Anxious Ego Dissolution". Acute anxiety negatively correlated with the genetically determined functionality of the Cytochrome 2D6 enzyme. In summary, besides the amount of drug consumed, non-pharmacological factors such as personal traits and current mood also significantly predicted the subjective drug experience. Sex and body weight were not significant factors in influencing the drug experience., (© 2024. The Author(s).)

MDMA is a recreational drug commonly used to enhance euphoria, but it is also used in non-party settings with self-insight or social connection intentions. Yet, little is known about whether distinct consumer groups are formed based on consumption setting and intention. We aimed to characterize different types of recreational MDMA users based on consumption setting and intentions, and to examine their differences in perceptions of long-term social-emotional effects of MDMA use. We analyzed self-reports of 766 individuals (ages 18-61, mostly from Western countries), reporting on their MDMA consumption habits and perceived effects. We used a K-medoids clustering algorithm to identify distinct types of consumption settings and intentions. We identified three setting types - party settings with friends (N = 388), private home settings (N = 132), mixed settings (N = 246) - and three intention types - euphoria and energy (N = 302), self-insight (N = 219), mixed intentions (N = 245). Members of the self-insight and mixed intentions clusters reported considerably more long-term socio-emotional benefits than members of the euphoria and energy cluster. No differences were observed between the setting clusters. In this particular sample, more long-term benefits than harms were reported. Our findings suggest that the long-term social-emotional benefits of MDMA are associated with whether users seek self-insight or have mixed intentions., (© 2024. The Author(s).)

Aims: Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome., Methods: Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale., Results: During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome., Conclusions: These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder., (© 2023 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

To investigate the longitudinal latent state-trait structure of the different dimensions of psychosis symptoms in clinical high-risk state (CHRS) and first episode psychosis (FEP) individuals over a one year time-span. This paper examines if the symptom clusters Positive Symptoms, Negative Symptoms, Affectivity, Resistance, Activation, and Excitement according to the Brief Psychiatric Rating Scale (BPRS) differ in their trait and state characters in 196 CHRS and 131 FEP individuals. Statistical analysis was performed using latent state-trait analysis. On average, trait differences accounted for 72.2% of Positive Symptoms, 81.1% of Negative Symptoms, 57.0% of Affectivity, and 69.2% of Activation, whereas 15.0% of the variance of Resistance and 13.2% of the variance of Excitement were explained by trait differences. Explorative analyses showed a trait components' increase of 0.408 in Positive Symptoms from baseline up to the 9th month and an increase of 0.521 in Affectivity from baseline up to the 6th month. Negative Symptoms had the highest trait component levels of all subscales between baseline and 6 months. The finding that an increasing proportion of psychosis symptoms is persisting over time underlines the importance of early intervention programs in individuals with psychotic disorders., (© 2022. The Author(s).)