Unifying Theories of Psychedelic Drug Effects, Link R. Swanson, 2018

Unifying Theories of Psychedelic Drug Effects

Link R. Swanson

Frontiers in Pharmacology, 2018, Volume 9, Article 172, 1-23

www.frontiersin.org (2 March 2018)

doi: 10.3389/fphar.2018.00172



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.

Keywords : psychedelic drugs, LSD, psilocybin, ego dissolution, cognitive flexibility, entropic brain theory, integrated information theory, predictive processing



Lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), psilocybin, and mescaline— the ‘classic’ psychedelic drugs—can produce a broad range of effects in perception, emotion, cognition, and sense of self. How do they do this? Western science began its ‘first wave’ of systematic investigations into the unique effects of mescaline 125 years ago. By the 1950s, rising interest in mescaline research was expanded to include drugs like DMT, LSD, and psilocybin in a ‘second wave’ of psychedelic science. Because of their dramatic effect on the character and contents of subjective awareness, psychedelic drugs magnified the gaps in our scientific understanding of how brain chemistry relates to subjective experience (see Evarts, 1957; Purpura, 1968). Huxley (1991, p. 12) commented that our understanding circa 1954 was “absurdly inadequate” and amounted to a mere “clue” that he hoped would soon develop into a more robust understanding. “Meanwhile the clue is being systematically followed, the sleuths—biochemists, psychiatrists, psychologists— are on the trail” (Huxley, 1991, p. 12). A ‘third wave’ of psychedelic science has recently emerged with its own set of sleuths on the trail, sleuths who now wield an arsenal of 21stcentury scientific methodologies and are uncovering new sets of clues.

Existing theoretical hurdles span five major gaps in understanding. The first gap is that we do not have an account of how psychedelic drugs can produce such a broad diversity of subjective effects. LSD, for example, can produce subtle intensifications in perception—or it can completely dissolve all sense of space, time, and self. What accounts for this atypical diversity?

The second gap is that we do not understand how pharmacological interactions at neuronal receptors and resulting physiological changes in the neuron lead to large-scale changes in the activity of neural populations, or changes in brain network connectivity, or at the systems-level of global brain dynamics. What are the causal links in the multi-level pharmaconeurophysiological chain?

The third gap is that we do not know how psychedelic druginduced changes in brain activity—at any level of description— map onto the acute subjective phenomenological changes in perception, emotion, cognition, and sense of self. This kind of question is not unique to psychedelic drugs (i.e., Crick and Koch, 1998; Tononi and Edelman, 1998) but our current understanding of psychedelic drug effects clearly magnifies the disconnect between brain science and subjective experience.

Fourth, there is a gap in our understanding of the relationships between psychedelic effects and symptoms of psychoses, such as perceptual distortion, hallucination, or altered self-reference. What is the relationship between psychedelic effects and symptoms of chronic psychotic disorders?

Fifth and finally, there is a gap in our clinical understanding of the process by which psychedelic-assisted therapies improve mental health (Carhart-Harris and Goodwin, 2017). Which psychedelic drug effects (in the brain or in subjective experience) enable clinical improvement? How?

Scientific efforts to understand diverse natural phenomena aim to produce a single theory that can account for many phenomena using a minimal set of principles. Such theories are sometimes called unifying theories. Not everyone agrees on the meaning of ‘unification’ or ‘unifying theory’ in science.1 Morrison (2000) observed that, although theory unification is a messy process which may not have discernible universal characteristics, historically successful unifying scientific theories tend to have two common features: (1) a formalized framework (quantitative mathematical descriptions of the phenomena) and (2) unifying principles (abstract concepts that unite diverse phenomena). On this conception, then, a unifying theory of psychedelic drug effects would offer a single formalized (mathematical or computational) framework capable of describing diverse psychedelic phenomena using a minimal set of unifying principles. Unfortunately, the survey of literature in this review does not locate an existing unifying theory of psychedelic drug effects. It does, however, highlight enduring abstract principles that recur across more than a century of theoretical efforts. Furthermore, it reviews recent formalized frameworks which, although currently heterogeneous and divergent, hint at the possibility of a quantitative groundwork for a future unifying theory.

The field of cognitive neuroscience offers formalized frameworks and general principles designed to track and model the neural correlates of perception, emotion, cognition, and consciousness. These broad frameworks span major levels of description in the brain and attempt to map them onto behavioral and phenomenological data. Corlett et al. (2009, p. 516) argue that until this is done “our understanding of how the pharmacology links to the symptoms will remain incomplete.” Montague et al. (2012, p. 1) argue that ‘computational psychiatry’ can remedy the “lack of appropriate intermediate levels of description that bind ideas articulated at the molecular level to those expressed at the level of descriptive clinical entities.” Seth (2009, p. 50), has argued that “computational and theoretical approaches can facilitate a transition from correlation to explanation in consciousness science,” explains how a recent LSD, psilocybin, and ketamine study (Schartner et al., 2017) was motivated by a need to elucidate descriptions at intermediate levels somewhere between pharmacology and phenomenology. “We know there’s a pharmacological link, we know there’s a change in experience and we know there’s a clinical impact. But the middle bit if you like, what are these drugs doing to the global activity of the brain, that’s the gap we’re trying to fill with this study” (quoted in Osborne, 2017). Taken together, the above quotations point to an emerging sense that cognitive neuroscience frameworks can address gaps in our understanding of psychedelic drug effects.

In this article I review theories of psychedelic drug effects. First, making an effort to clearly define the target explananda, I review the acute subjective phenomenological properties of psychedelic effects as well as long-term clinical outcomes from psychedelic-assisted therapies. Second, I review theories from first-wave and second-wave psychedelic science— model psychoses theory, filtration theory, and psychoanalytic theory—and identify core features of these theories. Third, I review findings from recent neurophysiological research in humans under psychedelic drugs. Finally, I review select 21st-century theories of psychedelic effects that have been developed within cognitive neuroscience frameworks; namely, entropic brain theory, integrated information theory, and predictive processing. My analysis of recent theoretical efforts highlights certain features, first conceptualized in 19th- and 20th-century theories, which remain relevant in their ability to capture both the phenomenological and neuro-physiological dynamics of psychedelic effects. I describe how these enduring theoretical features are now being operationalized into formalized frameworks and could serve as potential unifying principles for describing diverse psychedelic phenomena.