Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.03.28.587237

Trauma Under Psychedelics: MDMA Shows Protective Effects During the Peritraumatic Period

Netzer, O.·Magal, N.·Stern, Y.·Polinsky, T.·Gross, R.·Admon, R.·Salomon, R.
View original source ↗Export metadata ↓

Abstract

Traumatic events play a causal role in the etiology of stress-related psychopathologies such as depression and posttraumatic stress disorder (PTSD). Recent research highlighted the therapeutic potential of psychoactive substances in alleviating trauma symptoms among chronic stress-related patients. This study is the first to investigate the impact of psychoactive substances consumed during actual trauma exposure. Our cohort includes 772 adult survivors (487 males, Mean{+/-}SD Age: 26.96{+/-}6.55) of the high-casualty attack that occurred at the Supernova festival in Israel on October 7th, 2023. Survivors completed the study during the peritraumatic period of one to four months following the attack. Primary outcomes include the PTSD Checklist for DSM-5 (PCL-5), the Kessler Psychological Distress Scale (K6), and a self-reported rating of feeling overwhelmed. Secondary outcomes include subjective experiences during the attack and reports on social interactions and sleep quality. All survivors reported being in direct danger of death during the attack. Approximately two-thirds of the sampled survivors were under the influence of psychoactive substances at the time of the attack, including LSD, MDMA, Ketamine, Cannabis, and Alcohol, creating a tragic and unique natural experiment to study the impact of psychoactive compounds on trauma processing. Analysis revealed that participants that were under the influence of MDMA during the attack (n=99) reported feeling less overwhelmed, having more social interactions, improved sleep quality, and reduced psychological distress compared to those not under the influence of any substance during the attack (n=216). In contrast, those consuming Cannabis and/or Alcohol during the attack (n=68) showed higher psychological distress, more PTSD symptoms, and worse sleep quality compared to those not under the influence of any substance during the attack. Together, these novel findings suggest that trauma exposure under the influence of MDMA is associated with reduced psychological distress and higher sociality, possibly mediated through MDMAs known effects of reducing negative emotions and elevating prosociality, while Cannabis and/or Alcohol consumption produces deleterious effects. Further research is needed to explore the cognitive and physiological mechanisms linking psychoactive substances to trauma recovery and establish the putative protective role of MDMA.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Netzer, O., Magal, N., Stern, Y., Polinsky, T., Gross, R., Admon, R., Salomon, R.. 2024-03-31. Trauma Under Psychedelics: MDMA Shows Protective Effects During the Peritraumatic Period. https://doi.org/10.1101/2024.03.28.587237

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗
bioRxiv2026

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗
bioRxiv2026

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗