uniMIND Symposium: Metamorphosis in psychedelic science

Abstract

As the field of psychedelic research evolves, so too does our understanding of the therapeutic process surrounding these compounds. This presentation shares experiential insights from my role as a study clinician and therapist in the PSIKET_001 trial, a randomized, double blind, placebo controlled clinical study at the NIMH, Czech Republic, comparing the efficacy, safety and mechanisms of action of Psilocybin and Ketamine in individuals with treatment-resistant depression (TRD).

Beyond the (preliminary) quantitative outcomes, I focus on the human dimension of the trial — the challenges encountered, the unexpected moments, and the nuanced responses of participants navigating these altered states. Drawing from selected case vignettes, I will highlight diverse therapeutic trajectories, key considerations in preparing and supporting participants, and the emotional complexity of integration work.

These reflections aim to inform best practices for clinicians and therapists working in psychedelic-assisted treatment models, while contributing to a more grounded and compassionate framework for future studies.

Abstract

In recent decades, the use of serotonergic psychedelics among young adults has significantly increased worldwide, highlighting the need for an in-depth exploration of consumption motivations during this developmental stage. This mixed-methods study examines the motivations for using classic psychedelics and their relationship to coping with age-specific developmental tasks.

The theoretical framework builds on Prepeliczay’s (2016) distinction between hedonistic (e.g., enjoyment, pleasure) and heuristic (e.g., insight, self-therapy) motivations. Additionally, I integrate classical age-specific developmental tasks, such as establishing a household, starting a career, and forming a family (Seiffge-Krenke, 2015), alongside modern tasks such as self-realization and the search for a meaningful life (Mayseless & Keren, 2014).

To address the lack of research in this area, I conducted 52 semi-structured interviews with 19 female, 30 male, and 3 non-binary participants (aged 18–70) who used serotonergic psychedelics during young adulthood. Motivations and modern developmental tasks were analyzed using qualitative content analysis (Mayring, 2022), while the mastery of classical tasks was quantified using a self-developed scoring system. Additionally, I measured Meaning Fulfillment using the Sources of Meaning and Meaning in Life Questionnaire (Schnell, 2009).

The results highlight curiosity, social influences, and new experiences as primary motives for initial substance use. In contrast, continued use is driven by insight-seeking, self-therapy, and further experiential exploration. Kruskal-Wallis tests reveal that heuristic motivations are linked to higher Meaning Fulfillment, Self-Transcendence, and Self-Actualization, key aspects of modern developmental tasks. These findings could inform the development of targeted education and harm reduction programs for this age group.

Abstract

DMT and 5-MeO-DMT are psychedelics with short action but great therapeutic potential. Both induce profound alterations in consciousness, yet their neural mechanisms remain elusive. This talk presents EEG findings from three distinct settings: (1) a transformational festival where participants smoked DMT, (2) a naturalistic study with an underground therapist administering intramuscular 5-MeO-DMT, and (3) a facilitator assisting with vaporized DMT. By comparing spectral dynamics, signal complexity, and neural timescales across these contexts, we explore how DMT modulates brain activity and consciousness. Insights from these studies reveal commonalities and divergences in neural signatures, highlighting the interplay between set, setting, and pharmacology. Our findings contribute to understanding DMT’s neurophysiology and its potential therapeutic implications.

Abstract

At the National Institute of Mental Health (NUDZ), preclinical psychedelic research integrates advanced behavioral pharmacology with 20-channel cortical EEG in freely moving rats. Our group is developing a large EEG database from various psychoactive compounds, enabling predictive modeling of drug classification, action duration, and safety. Building on this, we recently initiated addiction-focused studies using intravenous self-administration (IVSA) paradigms in combination with psychedelic treatment. Using a novel dose-escalation protocol, we tested the effects of psilocybin and ibogaine on extinction and relapse behaviors in a cocaine model. Both treatments significantly reduced cocaine-seeking during extinction without altering locomotor activity or emotionality, suggesting enhancement of extinction learning. No significant differences were observed during reinstatement testing. Future directions involve identifying EEG and epigenetic biomarkers linked to addiction stages and therapeutic response. By integrating multimodal readouts—including behavioral and molecular signatures—we aim to develop translationally valid biomarkers to guide and improve clinical protocols for psychedelic-based addiction treatments.

Abstract

This paper examines how current research on psychedelics and profit-oriented investment affect how psychedelics and their potentials are framed in society and how they are socially rehabilitated (Elliker & Reichle 2021). On one hand, the growing influx of capital—marked by an increasing involvement from financial markets—drives the commodification and commercialization of psychedelics (Elliker & Reichle 2025). On the other hand, current research is primarily focused on psychedelics as therapeutic tools, with the effect of medicalizing psychedelics and suggesting their rehabilitation as potential remedies for mental illnesses.

These dynamics shape the dominant focus of research, broader societal perceptions, and regulatory frameworks. In the interplay between medicalized research and capital investment, psychedelics are legitimized as medical tools and are confined to a narrow set of uses. As political discourses and mass media adopt this perspective, a broad range of non-clinical uses in everyday life are neglected and marginalized.

Drawing on ethnographic insights from Switzerland and employing a critical sociological lens, the paper investigates how institutional frameworks and dominant discourses prioritize certain aspects of psychedelic use over others. It shows how psychedelics are socially constructed in limited ways, constituting a societal neglect of the full range of their potentials. Ultimately, it calls for a broader, more inclusive research agenda that investigates the diverse non-clinical uses prevalent in everyday life, considering the interplay of different sets and settings. Such research, primarily grounded in sociological inquiry, is crucial for addressing the current societal neglect in the transformation of psychedelics.

Abstract

Psychedelic experiences can transform how individuals understand the world. This presentation explores how psychedelic experiences act as ‘Ontologically Diversifying Experiences’—events that disrupt normative frameworks of selfhood, relationships, and reality, expanding cognitive, emotional, and existential repertoires. These disruptions challenge deeply held societal norms, transforming people’s perceptions of normality by questioning their ingrained assumptions about identity, relationships, and the boundaries of reality.

Ontological shock—the sudden disruption of fundamental assumptions about existence, can become a catalyst for personal growth as one engages in a process of transformative learning. This disruption, however, can also entail significant challenges for an individual, including persisting cognitive disorientation and existential distress while they struggle to integrate newfound insights into daily life.

Drawing on findings from three recent collaborative projects—including interviews and surveys with individuals who have undergone such experiences—this talk examines the epistemic metamorphosis that can follow ontological disruption. We will discuss common post-experience challenges and explore how individuals navigate these disruptions to develop new ways of understanding themselves, others, and reality.

In the broader context of psychedelic science, these findings underscore the need for ethical and practical frameworks that go beyond biomedical models to include existential, educational, and community-based approaches. By viewing psychedelic-induced metamorphosis as an epistemic rather than merely neurochemical process, this research contributes to a deeper understanding of how altered states can foster sustainable personal and societal transformation.

Abstract

Consciousness functions similarly to an operating system, managing bodily processes, guiding goal-directed behaviour, and maintaining stability, often even at the expense of dysfunctional or pathological patterns. Breaking free from these deeply ingrained systems requires a radical disruption, akin to rebooting an operating system. This presentation explores the transformative power of extreme states, particularly 5-MeO-DMT, a potent psychedelic extensively studied for its ability to induce profound psychological and somatic experiences, including somatic release. Indeed, 5-MeO-DMT stands out as a unique psychedelic, with reports suggesting that sensory contents and thoughts are greatly minimized while awareness remains intact, resembling so-called ‘minimal phenomenal experiences.’ a key component of this proposed rebooting mechanism and its associated psycho-somatic release. While catharsis is often linked to emotional outbursts, we propose that it may also reflect deeper, invisible internal processes and physiological shifts occurring beneath the surface. Although not always visible as emotional releases, these shifts are crucial in resetting the system, much like rebooting a malfunctioning operating system. The concept of Pivotal Physical States, newly coined by Uthaug & Allocca (in prep), suggests that these physiological changes facilitate deep biological reorganisation, offering a path to long-term therapeutic outcomes. Understanding and harnessing these pivotal states may unlock new avenues for therapeutic interventions, fostering holistic healing and profound personal transformation.

Abstract

Background: Psychedelics like psilocin alter sensory processing via 5-HT2A receptor activation, affecting cortical network dynamics. However, their dose-dependent impact on inter-trial phase coherence (ITPC) of 40 Hz auditory steady-state responses (ASSRs) remains unclear. This study examines how psilocin (1 mg/kg, 4 mg/kg) and the 5-HT2A antagonist MDL-100,907 (0.5 mg/kg) modulate ITPC in Long-Evans male rats using a crossover design and 40 Hz click stimuli.

Methods: Nine restrained male Long-Evans rats received saline, psilocin (1 mg/kg or 4 mg/kg), and MDL-100,907 (0.5 mg/kg) subcutaneously. EEG analysis focused on ITPC at electrodes temporal cortex A3 (left hemisphere) and A4 (right hemisphere) in the 35-45 Hz range.

Results & Interpretation: Significant effects were observed only at A4, suggesting hemispheric asymmetry in serotonergic modulation of auditory processing. In the 35-45 Hz band, low-dose psilocin increased ITPC compared to saline and 4 mg/kg, with a pattern resembling the effects of MDL-100,907. In contrast, 4 mg/kg psilocin led to reduced phase coherence, indicating a dose-dependent disruption of neural synchronization.

The nonlinear effects of psilocin suggest that low doses enhance synchronization, potentially through partial 5-HT2A receptor desensitization or engagement of inhibitory feedback circuits, mimicking the stabilizing effects of MDL-100,907. In contrast, high-dose psilocin may disrupt phase coherence due to excessive cortical excitation, glutamatergic dysregulation, or desynchronization of local circuits.

These findings provide novel insights into serotonergic modulation of auditory processing, highlighting dose- and frequency-dependent effects with potential implications for psychedelic-induced perceptual alterations and psychiatric treatments targeting cortical network synchrony.

Abstract

This presentation shares insights from Onaya Science’s six-month follow-up pilot study on the mental health impact of Shipibo-led ayahuasca ceremonies for military veterans with PTSD. Forty veterans participated in five ayahuasca ceremonies over ten days, with sustained reductions in PTSD symptoms, depression, and anxiety, as well as improvements in life satisfaction observed at the six-month follow-up. EEG data suggests enhanced brain flexibility post-treatment, with additional findings from ongoing microbiome and epigenetic analyses forthcoming.

Beyond the study, this talk explores the broader implications of integrating traditional psychedelic practices into modern mental health care. As interest in psychedelic therapy grows, psychiatry faces increasing pressure to adapt and develop more integrative approaches that align with the transformative nature of these treatments. This presentation examines the intersection of Indigenous knowledge systems and contemporary science, emphasising the potential for a paradigm shift in mental health care to effectively and ethically accommodate the integrative and holistic demands of psychedelic treatments in modern health care settings.

Abstract

With growing evidence on the utility of psychedelic-assisted therapies for psychiatric conditions such as major depression and substance use disorders, the field is now expanding its horizons to examine the potential impact of psychedelics for new indications. Our team is currently conducting several clinical studies that will be discussed in this presentation.

The first is examining the impact of psilocybin for depression in people with Mild Cognitive Impairment (MCI) or early-stage Alzheimer’s Disease (AD). Neurodegenerative illnesses like AD are often comorbid with neuropsychiatric symptoms such as apathy and depressed mood that can significantly detract from quality of life. Standard antidepressant medications are not always effective in these populations, highlighting the need for novel therapies.

Similarly, a second trial is currently underway exploring the use of psilocybin in patients with depression and amyotrophic lateral sclerosis (ALS), expanding the investigation of psychedelic therapies in palliative care. Finally, we will present results from a recently completed study on psilocybin in patients with chronic Lyme Disease, an inflammatory infectious disease characterized by persistent fatigue, pain, and cognitive difficulties. There is no known treatment for chronic Lyme Disease.

Clinical rationale and preliminary findings from these studies will be presented, followed by a broader discussion of new directions and opportunities for studying the therapeutic potentials of psychedelic-assisted treatments in other medical conditions and populations.