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      Unifying Theories of Psychedelic Drug Effects

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          Abstract

          How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories— model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks— entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function.

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          The brain's default network: anatomy, function, and relevance to disease.

          Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
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            The free-energy principle: a unified brain theory?

            A free-energy principle has been proposed recently that accounts for action, perception and learning. This Review looks at some key brain theories in the biological (for example, neural Darwinism) and physical (for example, information theory and optimal control theory) sciences from the free-energy perspective. Crucially, one key theme runs through each of these theories - optimization. Furthermore, if we look closely at what is optimized, the same quantity keeps emerging, namely value (expected reward, expected utility) or its complement, surprise (prediction error, expected cost). This is the quantity that is optimized under the free-energy principle, which suggests that several global brain theories might be unified within a free-energy framework.
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              Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging.

              The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                02 March 2018
                2018
                : 9
                : 172
                Affiliations
                [1] 1Center for Cognitive Sciences, University of Minnesota , Minneapolis, MN, United States
                [2] 2Department of Philosophy, University of Minnesota , Minneapolis, MN, United States
                [3] 3Minnesota Center for Philosophy of Science, University of Minnesota , Minneapolis, MN, United States
                Author notes

                Edited by: Andrew Robert Gallimore, Okinawa Institute of Science and Technology, Japan

                Reviewed by: Milan Scheidegger, ETH Zürich, Switzerland; Cristiano Chiamulera, University of Verona, Italy

                *Correspondence: Link R. Swanson, link@ 123456umn.edu

                This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.00172
                5853825
                29568270
                6b1aafb0-84c5-4528-b43c-77e71b7ca8ae
                Copyright © 2018 Swanson.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 December 2017
                : 15 February 2018
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 276, Pages: 23, Words: 0
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                psychedelic drugs,lsd,psilocybin,ego dissolution,cognitive flexibility,entropic brain theory,integrated information theory,predictive processing

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