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Research Square

ISSN 2693-5015

196 papers in the library · 84 citations · publishing 2020-2026

Papers

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Inhaled N,N-Dimethyltryptamine Diminishes Connectivity between the Ventral Tegmental Area and the Nucleus Accumbens : relevance to pathologies of mesolimbic and mesocortical pathways

Research Square September 17, 2025 Gisela Lima, Carla Soares, Marta Teixeira et al.

Abstract Reward processing is a broad psychological construct that can be parsed into distinct components known as “reinforcement learning” (learning), “reward responsiveness” (liking), and “motivation to obtain a reward” (wanting). Dysfunctions in reward processing in mesolimbic and mesocortical pathways, are a core feature of many pathologies. Psychedelics have been proposed as a treatment...

Mindset Over Molecule: Comparing Self-Transcendent and Mystical Experiences Across Recreational Psilocybin, MDMA, and Cannabis Use

Research Square September 12, 2025 Christina Chwyl, Angelica Spata, Will Lucas et al.

Abstract Background Self-transcendent and mystical experiences may be key mechanisms underlying psychedelics’ therapeutic effects, yet how these experiences differ across substances remains unclear. This study compared mystical and self-transcendent experiences across psilocybin, 3,4-Methylenedioxymethamphetamine (MDMA), and cannabis in a diverse, community-based sample, while accounting for...

Psychedelic Therapy, Positive Emotional Experiences, and the Central Role of Self-Compassion

Research Square August 22, 2025 Richard J. Zeifman, George Danias, Gabrielle Agin-Liebes et al. 2 citations

Abstract Background: Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional...

The experience of recalled trauma during psychedelic experiences and perceived links to subsequent extended difficulties: A mixed-methods study

Research Square August 21, 2025 Guy Simon, Nir Tadmor, Michael Skragge et al. 2 citations

Abstract This mixed-methods study investigated the relationship between recalled childhood trauma during psychedelic experiences and subsequent extended psychological difficulties. While psychedelics can facilitate emotional processing of autobiographical material, a minority experience adverse effects or re-traumatization when trauma resurfaces. Phase 1 surveyed 608 individuals who experienced...

Cannabinoid use generalizes stress responses by altering the astrocyte plasticity through extracellular matrix signaling in the nucleus accumbens core.

Research Square August 21, 2025 Ritchy Hodebourg, Lillian Duncan, Eric Dereschewitz et al.

The rising legal acceptance of cannabis and the high comorbidity between cannabis use disorder (CUD) and post-traumatic stress disorder (PTSD) highlight the importance of understanding how stress and cannabis influence the brain. We recently discovered that cannabis use promotes two PTSD-like symptoms: avoidance coping behaviors and the generalization of stress-coping responses to a neutral...

Attitudes Toward Psychedelic-Assisted Therapies for Cancer-Related Psychosocial Symptoms: A Multi- Stakeholder Analysis

Research Square August 19, 2025

Abstract Background Psychedelic-assisted therapy (PAT) is gaining attention as a potential treatment for cancer-related psychosocial symptoms. While growing evidence highlights its promise, little is known about how different stakeholder groups perceive its use in oncology and palliative care. Objectives This study aimed to assess stakeholder-specific perspectives on PAT, including attitudes,...

Beyond the Journey: A Qualitative Analysis of Therapists’ Perspectives on Psychedelic Integration Challenges

Research Square August 5, 2025 Christina Chwyl, Odin S. Elvenes, Andrew S. R. Kleven et al. 2 citations

Abstract Background Psychedelic integration is widely acknowledged as essential, yet limited empirical data exists on challenges faced during integration. Objective To explore therapists' perspectives on post-psychedelic integration challenges and their approaches to supporting clients. Methods Online interviews were conducted with a purposive sample of licensed mental health professionals who...

Global Increases in Brain Glucose Metabolism Following Acute N,N-Dimethyltryptamine and Harmine Administration in Healthy Volunteers: An [¹⁸F]FDG-PET Study

Research Square July 27, 2025 Klemens Egger, Robert Bozsak, Helena Aicher et al. 1 citation

Global Increases in Brain Glucose Metabolism Following Acute N,N-Dimethyltryptamine and Harmine Administration in Healthy Volunteers: An [¹⁸F]FDG-PET Study

Ayahuasca prevents the reinstatement of cocaine-induced rewarding effects in C57Bl/6 mice

Research Square July 25, 2025 Vítor Bruno, Lídia Emmanuela Wiazowski Spelta, Matheus Lujan Pereira et al.

Abstract Ayahuasca is a psychedelic brew used for centuries in religious rituals by indigenous cultures. Recent studies suggest its potential to reduce depression and anxiety and as an alternative for treating ethanol and tobacco use disorders. However, research on its impact on cocaine use disorder remains limited. We investigated the effects of ayahuasca on the reinstatement of...

AI Discovery of Mechanisms of Consciousness, Its Disorders, and Their Treatment

Research Square July 8, 2025

Abstract Understanding disorders of consciousness (DOC) remains one of the most challenging problems in neuroscience, hindered by the lack of experimental models for probing mechanisms or testing interventions. To address this, we introduce a generative adversarial AI framework that pits deep neural networks—trained to detect consciousness across over 680,000 neuroelectrophysiology samples and...

To Turn Inward or Outward? Examining the Reciprocal Relationships Between Mindfulness, Interpersonal Emotion Regulation, and Aggression Over Time.

Research Square July 4, 2025 Erika Blair, David Chester

People frequently turn to others to help regulate their emotions in what is referred to as inter personal emotion regulation (IER). Mindfulness entails an intra personal strategy of turning inward to facilitate emotion regulation. Yet little research has examined the relationships between these distinct regulation strategies and their consequences for aggression. The current study aims to...

Minding the Body: A Meta-analysis of the Effects of Mindfulness Meditation Training on Self-reported Interoception.

Research Square June 4, 2025 Isaac N Treves, Ya-Yun Chen, Caitlyn L Wilson et al.

Mindfulness meditation training may cultivate interoceptive awareness and provide therapeutic benefit when implemented within mental and physical health interventions. This pre-registered meta-analysis evaluated the impact of mindfulness interventions on self-reported interoception measures and associated relationships with psychological outcomes. Twenty-nine randomized controlled trials with...

Practitioner perspectives on extended difficulties and optimal support strategies following psychedelic experiences: A qualitative analysis

Research Square May 13, 2025 Eirini K. Argyri, Joy Krecké, Oliver Robinson et al. 2 citations

Abstract Background As the use of psychedelics increases in both therapeutic and non-clinical settings, reports of extended post-experience difficulties have also emerged. While many individuals integrate their experiences effectively, others face persistent challenges. Despite growing recognition of these issues, there is limited research on best practices for mitigating and addressing...

Psilocybin Mitigates Behavioral Despair and Cognitive Impairment in Treatment-resistant Depression Model using Wistar Kyoto Rats

Research Square May 6, 2025 Zitong Wang, Brett Robbins, Ryan Zhuang et al.

Abstract Major depressive disorder (MDD) is a leading cause of disability that affects over 300 million people globally. Despite multiple antidepressant trials, approximately one-third of MDD patients remain symptomatic, progressing to treatment-resistant depression (TRD). This persistence possibly is due to the multifaceted etiology of TRD, encompassing biological, psychological, and...

Vigilance state dissociation induced by 5-MeO DMT in mice

Research Square May 6, 2025 Benjamin J. B. Bréant, José Prius-Mengual, Alexander Andrews et al.

Abstract Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of arousal. Here, we performed chronic electrophysiological recordings from the neocortex concomitant with pupillometry in freely moving adult male mice following an injection of a...

Calcium Activation Mechanism of a Noncanonical Aromatic L-Amino Acid Decarboxylase from Psilocybin Mushroom

Research Square April 28, 2025 Yi Wang, Tianjie Li, Erin S. Reynolds et al.

Abstract PcncAAAD is a calcium-activatable noncanonical aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-binding sites. In this study, we establish an in silico RMSD-based evaluation model through molecular dynamics simulations, validated by in vitro enzyme assays, to decipher the enzyme’s calcium activation mechanism. Between the two...

Radiation Therapy Patients’ Interest in Psychedelic-assisted Therapy: A Prospective Survey Study

Research Square April 16, 2025 Jino Park, Rufus Banks, Akul Munjal et al.

Abstract Background Comorbid mental health symptoms impact 30–40% of cancer patients, significantly compromising treatment adherence and increasing mortality rates. Among patients undergoing radiation therapy, which is delivered with palliative intent in nearly half of all cases and for those nearing end-of-life, these rates may be even higher. Emerging research underscores the promising...

Learning from Boundlessness: Psychedelic induced awe and epistemic shifts towards a holistic worldview

Research Square March 31, 2025 Eirini K. Argyri, Flora Fraser, Stefan Schilling et al.

Abstract Psychedelic substances are increasingly recognized for their potential to catalyse transformative shifts in worldviews. Central to these transformations are states of awe, a self-transcendent, epistemic emotion. This mixed-methods study explored how awe during psychedelic trips relates to lasting changes in boundaries between self and world, and epistemic shifts that follow...

Ayahuasca Mitigates Morphological Cortical Alterations in Juvenile Non-human Primates Following Chronic Stress Exposure

Research Square March 5, 2025 Expedito Do Nascimento Júnior, Luiz Pereira, Wigínio Lira-Bandeira et al.

Abstract Depression remains a debilitating mental health disorder affecting millions worldwide, with growing prevalence among adolescents. Recent studies highlight the critical role of the somatosensory cortex in the neuropathology of depression, including structural alterations that impair cortical function. This study investigates the prophylactic effects of ayahuasca, a traditional...

Cultural Humility and Psychedelics: A Framework Analysis of Psychedelic-Assisted Therapy Manuals and Practice Guidelines

Research Square February 13, 2025 Ayanna K. Bell, Bianca R. Watt, Arturo S. Lopez Flores et al. 1 citation

Abstract Background Cultural biases within healthcare systems result in inequitable treatment, harms, and mistrust—particularly for individuals with marginalized identities. Cultural humility training is dynamic, reflective, and emphasizes person-centered care and mutual respect. Psychedelic-assisted therapy (PAT) is an emerging modality for treating psychiatric disorders. Practice manuals and...