A transcriptomic analysis in mice following a single dose of ibogaine identifies new potential therapeutic targets.

Ibogaine (IBO) is an atypical psychedelic with a complex mechanism of action. To date, the mechanisms that may underlie its anti-addictive effects are still not defined. This study aims to identify changes in gene expression induced by a single oral dose of IBO in the cortex of mice by means of a transcriptomic analysis for the first time. Our results showed significant alterations in gene expression in mouse frontal cortex samples 4 h after a single oral dose of IBO. Specifically, genes involved in hormonal pathways and synaptogenesis exhibited upregulation, while genes associated with apoptotic processes and endosomal transports showed downregulation. The findings were further corroborated through quantitative polymerase chain reaction (qPCR) analysis. However, the validation of gene expression related to hormonal pathways did not entirely align with the transcriptomic analysis results, possibly due to the brain region from which tissue was collected. Sex differences were observed, with female mice displaying more pronounced alterations in gene expression after IBO treatment. High variability was observed across individual animals. However, this study represents a significant advancement in comprehending IBO's molecular actions. The findings highlight the influence of IBO on gene expression, particularly on hormonal pathways, synaptogenesis, apoptotic processes, and endosomal transports. The identification of sex differences underscores the importance of considering sex as a potential factor influencing IBO's effects. Further research to assess different time points after IBO exposure is warranted.

Do classic psychedelics increase the risk of seizures? A scoping review.

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.

Validation of the Spanish version of the multifaceted empathy test: comparison between cannabis use effects and controls in social cognition.

OBJECTIVE: While social cognition is shown to be impaired in several mental disorders, the effects of cannabis on social cognition are still not clear. Past studies have used the multifaceted empathy test (MET) to study social cognition. This study aims to test the validity of the MET Spanish version and to evaluate the effects of cannabis use on social cognition. METHODS: In total 116 participants from a Cannabis Social Club (CSC) completed the MET and the reading the mind in the eyes test (RMET) under the effects of cannabis and were compared to 86 university students (control group). Internal consistency and convergent validity were assessed. Cognitive empathy (CE) and emotional empathy (EE) were tested in both groups. RESULTS: The MET CE scale shows low internal consistency, while the EE scale shows high internal consistency. Items showed similar difficulty for both groups. Cannabis users showed deficient overall emotional recognition, with reduced scores associated with positive stimuli. Overall scores for EE were similar for both groups, but the experimental group scored lower with negative stimuli when compared to controls. CONCLUSION: This study validates the MET Spanish version for its use in future studies. Results confirmed deficient emotional recognition in cannabis users and a dampened reaction to negative stimuli for the first time.

Ayahuasca-induced personal death experiences: prevalence, characteristics, and impact on attitudes toward death, life, and the environment.

Introduction: Despite an emerging understanding regarding the pivotal mechanistic role of subjective experiences that unfold during acute psychedelic states, very little has been done in the direction of better characterizing such experiences and determining their long-term impact. The present paper utilizes two cross-sectional studies for spotlighting - for the first time in the literature - the characteristics and outcomes of self-reported past experiences related to one's subjective sense of death during ayahuasca ceremonies, termed here Ayahuasca-induced Personal Death (APD) experiences. Methods: Study 1 (n = 54) reports the prevalence, demographics, intensity, and impact of APDs on attitudes toward death, explores whether APDs are related with psychopathology, and reveals their impact on environmental concerns. Study 2 is a larger study (n = 306) aiming at generalizing the basic study 1 results regarding APD experience, and in addition, examining whether APDs is associated with self-reported coping strategies and values in life. Results: Our results indicate that APDs occur to more than half of those participating in ayahuasca ceremonies, typically manifest as strong and transformative experiences, and are associated with an increased sense of transcending death (study 1), as well as the certainty in the continuation of consciousness after death (study 2). No associations were found between having undergone APD experiences and participants' demographics, personality type, and psychopathology. However, APDs were associated with increased self-reported environmental concern (study 1). These experiences also impact life in profound ways. APDs were found to be associated with increases in one's self-reported ability to cope with distress-causing life problems and the sense of fulfillment in life (study 2). Discussion: The study's findings highlight the prevalence, safety and potency of death experiences that occur during ayahuasca ceremonies, marking them as possible mechanisms for psychedelics' long-term salutatory effects in non-clinical populations. Thus, the present results join other efforts of tracking and characterizing the profound subjective experiences that occur during acute psychedelic states.