AUTHOR=Swanson Link R. TITLE=Unifying Theories of Psychedelic Drug Effects JOURNAL=Frontiers in Pharmacology VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00172 DOI=10.3389/fphar.2018.00172 ISSN=1663-9812 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 scientific theories of psychedelic drug effects and highlight key theoretical features 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 empirical data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared theoretical features. I then briefly review recent neuropharmacological and neurophysiological findings. Finally, I describe some recent theories of psychedelic drug effects that leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—highlighting their shared theoretical features and pointing out how they link back to earlier theories. From this analysis a key theoretical concept is identified which cuts across many theories past and present: psychedelic drugs perturb specific brain processes which normally sustain constraints on perceptual, affective, cognitive, and self-related neural systems. While a truly unifying theory has yet to emerge, I suggest that the enduring theoretical features and formalized frameworks highlighted in this article could form a groundwork for future unifying theories of psychedelic drug effects.