Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.

In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently established approach, based on the Mapper algorithm from topological data analysis. After generating subject-specific maps for two groups (psilocybin vs. placebo, 18 subjects/group) of experienced meditators, organizational principles were uncovered using graph topological tools, including the optimal transport (OT) distance, a geometrically rich measure of similarity between brain activity patterns. This revealed characteristics of the topology (i.e. shape) in space (i.e. abstract space of voxels) and time dimension of whole-brain activity patterns during different styles of meditation and psilocybin-induced alterations. Most interestingly, we found that (psilocybin-induced) positive derealization, which fosters insightfulness specifically when accompanied by enhanced open-monitoring meditation, was linked to the OT distance between open-monitoring and resting state. Our findings suggest that enhanced meta-awareness through meditation practice in experienced meditators combined with potential psilocybin-induced positive alterations in perception mediate insightfulness. Together, these findings provide a novel perspective on meditation and psychedelics that may reveal potential novel brain markers for positive synergistic effects between mindfulness practices and psilocybin.

Not in the drug, not in the brain: Causality in psychedelic experiences from an enactive perspective.

Psychedelics are psychoactive substances that receive renewed interest from science and society. Increasing empirical evidence shows that the effects of psychedelics are associated with alterations in biochemical processes, brain activity, and lived experience. Still, how these different levels relate remains subject to debate. The current literature presents two influential views on the relationship between the psychedelic molecule, neural events, and experience: The integration view and the pluralistic view. The main aim of this article is to contribute a promising complementary view by re-evaluating the psychedelic molecule-brain-experience relationship from an enactive perspective. We approach this aim via the following main research questions: (1) What is the causal relationship between the psychedelic drug and brain activity? (2) What is the causal relationship between brain activity and the psychedelic experience? In exploring the first research question, we apply the concept of autonomy to the psychedelic molecule-brain relationship. In exploring the second research question, we apply the concept of dynamic co-emergence to the psychedelic brain-experience relationship. Addressing these two research questions from an enactive position offers a perspective that emphasizes interdependence and circular causality on multiple levels. This enactive perspective not only supports the pluralistic view but enriches it through a principled account of how multi-layered processes come to interact. This renders the enactive view a promising contribution to questions around causality in the therapeutic effects of psychedelics with important implications for psychedelic therapy and psychedelic research.

Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects.

Background: There is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic "ayahuasca" for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspired by ayahuasca, which contain specific and standardized active components, are a potential remedy. Methods: We investigated subjective acute and persisting effects of a novel formulation containing the reversible monoamine oxidase inhibitor harmine (orodispersible tablet containing 100 mg MAO-I) and N,N-dimethyltryptamine (incremental intranasal dosing of up to 100 mg DMT), compared with two other conditions, namely harmine alone and placebo, in a crossover RCT in 31 healthy male subjects. Results: DMT + harmine, but not harmine alone, induced a psychedelic experience assessed with the 5D-ASC rating scale [global score: F(2,60) = 80.21, p < 0.001] and acute experience sampling items over time, characterized by psychological insights [PIQ, F(2,58.5) = 28.514, p < 0.001], emotional breakthroughs [EBI, F(2,60) = 26.509, p < 0.001], and low scores on the challenging experience questionnaire [CEQ, F(2,60) = 12.84, p < 0.001]. Participants attributed personal and spiritual significance to the experience (GSR) with mainly positive persisting effects (PEQ) at 1- and 4-months follow-up. Acute drug effects correlated positively with persisting effects. We found no changes in trait measures of personality, psychological flexibility, or general well-being, and no increases in psychopathology (SCL-90-R) were reported. Discussion and Conclusion: Our results suggest that the experience induced by the standardized DMT + harmine formulation induces a phenomenologically rich psychedelic experience, demonstrates good psychological safety and tolerability, is well tolerated, and induces beneficial psychological processes that could possibly support psychotherapy. Further studies are required to investigate the psychotherapeutic potential in patients.

Knowing the Knowing. Non-dual Meditative Practice From an Enactive Perspective.

Within a variety of contemplative traditions, non-dual-oriented practices were developed to evoke an experiential shift into a mode of experiencing in which the cognitive structures of self-other and subject-object subside. These practices serve to de-reify the enactment of an observing witness which is usually experienced as separate from the objects of awareness. While several contemplative traditions, such as Zen, Mahamudra, Dzogchen, and Advaita Vedanta emphasize the importance of such a non-dual insight for the cultivation of genuine wellbeing, only very few attempts in contemplative science have turned toward the study of non-dual-oriented practices. This article starts from a recently developed theoretical cognitive science framework that models the requirements of a temporary experiential shift into a mode of experiencing free from cognitive subject-object structure. This model inspired by the enactive approach contributes theoretically grounded hypotheses for the much-needed rigorous study of non-dual practices and non-dual experiences. To do so, three steps are taken: first, common elements of non-dual-oriented practices are outlined. Second, the main ideas of enactive cognitive science are presented including a principled theoretical model of what is required for a shift to a pure non-dual experience, that is, an experiential mode that is unbound by subject-object duality. Third, this synthesized theoretical model of the requirements for the recognition of the non-dual is then compared with a specific non-dual style of meditation practice, namely, Mahamudra practice from Tibetan Buddhism. This third step represents a heuristic for evaluating the external coherence of the presented model. With this, the aim is to point toward a principled enactive view of non-dual meditative practice. In drawing the implications of the presented model, this article ends with an outlook toward next steps for further developing a research agenda that may fully address the concrete elements of non-dual practices.

Towards new concepts for a biological neuroscience of consciousness.

In the search for a sound model of consciousness, we aim at introducing new concepts: closure, compositionality, biobranes and autobranes. This is important to overcome reductionism and to bring life back into the neuroscience of consciousness. Using these definitions, we conjecture that consciousness co-arises with the non-trivial composition of biological closure in the form of biobranes and autobranes: conscious processes generate closed activity at various levels and are, in turn, themselves, supported by biobranes and autobranes. This approach leads to a non-reductionist biological and simultaneously phenomenological theory of conscious experience, giving new perspectives for a science of consciousness. Future works will implement experimental definitions and computational simulations to characterize these dynamical biobranes interacting.

Knowing Groundlessness: An Enactive Approach to a Shift From Cognition to Non-Dual Awareness.

The enactive approach has become an influential paradigm in cognitive science. One of its most important claims is that cognition is sense-making: to cognize is to enact a world of meaning. Thus, a world is not pregiven but enacted through sense-making. Most importantly, sense-making is not a fixed process or thing. It does not have substantial existence. Instead, it is groundless: it springs from a dynamic of relations, without substantial ground. Thereby, as all cognition is groundless, this groundlessness is considered the central underlying principle of cognition. This article takes that key concept of the enactive approach and argues that it is not only a theoretical statement. Rather, groundlessness is directly accessible in lived experience. The two guiding questions of this article concern that lived experience of groundlessness: (1) What is it to know groundlessness? (2) How can one know groundlessness? Accordingly, it elaborates (1) how this knowing of groundlessness fits into the theoretical framework of the enactive approach. Also, it describes (2) how it can be directly experienced when certain requirements are met. In an additional reflexive analysis, the context-dependency and observer-relativity of those statements themselves is highlighted. Through those steps, this article exhibits the importance of knowing groundlessness for a cognitive science discourse: this underlying groundlessness is not only the "ground" of cognition, but it also can be investigated empirically through lived experience. However, it requires a methodology that is radically different from classical cognitive science. This article ends with envisioning a future praxis of cognitive science which enables researchers to investigate not only theoretically but empirically the "foundationless foundation" of cognition: groundlessness.