Abstract
In this paper, I explore scientific attempts to articulate a unified theory of the serotonin system and to explain the effects of psychedelic substances. I consider how certain accounts of psychedelic action have focused primarily on cognitive states, and I propose some phenomenological insights to supplement these models and inform work on psychedelics as therapeutic agents. Specifically, I argue that considering “psychological transformation” to be a core desideratum of psychedelic therapy should lead us to investigate the role of affect in guiding significant psychological change. The phenomenological tradition offers resources for describing the relationship between knowledge and affect, and I argue that epistemically significant affective states such as fascination and revelation are more central to psychedelic experience than is commonly acknowledged. I propose that understanding the role of affect in psychedelic experiences is critical to developing a plausible account of the potential for using these substances therapeutically.
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Notes
A 2023 search on clincaltrials.gov for “psilocybin” returned 147 studies involving subjects with a range of conditions, including studies in healthy volunteers.
Receptors are protein structures embedded in neuron cell membranes that respond to neurotransmitters by, for instance, triggering further metabolic or electrochemical changes in the cell.
Berridge and Robinson acknowledge that this is a subtler, but more supportable, description of dopamine’s role in the body than the story that it is the “pleasure” or “liking” chemical.
“Decades of research have elucidated a widespread functional involvement in sensation, memory, and behaviour, though no normal or aberrant behaviour has its origin in a sole serotonergic process.” (Homburg 2015).
This difficulty was recently emphasized by Joanna Moncreiff’s debunking of the popular “low serotonin” theory of depression. Her systematic review, published in 2022, found that “[t]he main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations” (Moncrieff 2022).
In a recent paper in Nature, Feng and colleagues introduce the framework like this: “When choosing a class in college, should you exploit the Math class you are sure to ace, or explore the Photography class you know nothing about? Exploiting Math may be the way to a better grade, but exploring Photography—and finding that it scratches an itch you never knew you had—could be the path to a better life. As with all such ‘explore–exploit’ decisions, picking the optimal class is hard—explore too much and you’ll never finish your degree, exploit too much and, like us, you will do Math for the rest of your life” (Feng 2021).
And perhaps lower than that: “the phylogenetically ancient serotonergic feeding networks that arbitrate approach/avoidance decisions in invertebrates are thought to be precursors of the evermore complex foraging, explore-exploit behaviours of vertebrates” (Shine 2022).
"[C]hronic stress primes the serotonin (2A receptor) system for the elicitation of a PiMS: a hyper-plastic state in which prior assumptions are relaxed, enabling an enhanced sensitivity to potential new information, consistent with rapid and deep learning" (Brouwer 2021).
As Wiese and Metzinger describe this framework in “Vanilla PP for Philosophers”: “The brain uses these representations to predict current (and future) sensory input and the source of it, which is possible because estimates at different levels of the hierarchy are predictive of each other.... Mismatches between predictions and actual sensory input are not used passively to form percepts, but only to inform updates of representations which have already been created (thereby anticipating, to the extent possible, incoming sensory signals).” (Wiese 2017).
“A corollary of relaxing high-level priors or beliefs under psychedelics is that ascending prediction errors from lower levels of the system (that are ordinarily unable to update beliefs due to the top-down suppressive influence of heavily-weighted priors) can find freer register in conscious experience, by reaching and impressing on higher levels of the hierarchy” (Carhart-Harris et al., 2019).
This is theoretically distinguished from more everyday decisions like whether or not to eat breakfast or wear shoes to the office. While these choices will lead to different experiences of one’s day, the outcomes are generally predictable and unlikely to transform future preferences dramatically.
Likewise, states of depression might be characterized by an insurmountable aversion to discovery. Rather than engage with the world around them, the depressed person finds the world “bereft of possibilities with which it was once imbued.... The practical significance of things is somehow diminished; they no longer offer up the usual possibilities for activity” (Ratcliffe 2015).
Consider the traveler who becomes acquainted with these facts but effectively ignores them or files them away as simply “weird” or insignificant. Knowledge by acquaintance can be descriptive of epistemic experience without explaining why some experiences matter and others do not.
The broader phenomenology of ego-loss might be aptly described as involving both of these moments at once: attention to “outward” phenomena replaces experience of “inward” narratives.
This paper’s explicit focus is serotonergic psychedelics, as distinct from dissociative anesthetics like ketamine, an enantiomer of which has already been approved for major depressive disorder as Spravato. Ketamine is an NMDA antagonist principally active in the glutamate system, and is more closely related to drugs like phencyclidine (PCP) than to psilocybin or LSD. While the phenomenology of all of these drugs might be termed “hallucinogenic,” I would contend that this is imprecise language for the distinct types of experiences that each can produce. While the phenomenology of dissociative anesthetics might also be relevant to their antidepressant effects, I think that inquiry should be kept separate from treatment of the “classic” psychedelics, if only because these drugs seem to operate within distinct neurological pathways.
A counterexample to this might be our tendency to become preoccupied with aging and death, which is, of course, as natural as sleeping, but which we permit as a more normal fixation (at least culturally).
Like Miceli McMillan, I think “pre-intentional possibility” is an apt description of what goes missing in major depression and what therapy should attempt to restore to the sober subject. However, I think we need to be clear that the psychedelic state itself does not offer a sustainable level of pre-intentional possibility—it might be better characterized as a surplus of possibility for the duration of the trip. How this short-term surplus might translate to a better sober baseline is the subject of this paper’s conclusion, and I intend to return to it in future work.
This is supported by studies of associative learning in humans on LSD that have found increased exploratory tendencies and enhanced reward learning rates (Kanen et al., 2021).
We could posit more specifically that the stimulus-reward mechanics of associative learning are most directly influenced by the dopamine and endorphin systems, and attentional dynamics most directly influenced by the cholinergic system, with serotonin performing broader integrative functions between these and other systems.
On psychedelics, you can genuinely “discover” a screensaver and skillfully navigate it for hours. What you’ve found may be hard to communicate to others, but that doesn’t necessarily change the epistemic significance of the experience.
As Shine and colleagues suggest, psychedelics are “analogous to cognitive laxatives,” pushing everything through the system at once. An important extension of this analogy would be that they also make the subject uncontrollably hungry and less able to discriminate with regard to what they are eating.
I am focused in this paper on experiences within a certain range of intensity. My discussion is most relevant to the phenomenology of a “normal” dose of psilocybin or LSD, not a “microdose” or a heavy dose leading to profoundly dissociative states. For psilocybin, this is probably around 25 mg, which was the dose used in a recent comparison to escitalopram for the treatment of depression (Carhart-Harris et al., 2021).
Lucy summarizes: “It was neither a good nor bad experience on the whole, but a learning one.”.
E.g., “I feel badly when I see myself wearing this shirt; I revise my belief that it was a good idea to buy it.”.
Likewise, if the revelations come with ambivalent feelings, then one could just end up having a very weird and not particularly transformative afternoon.
I feel obligated to reiterate that psychological change is not inevitable or necessary for a good psychedelic experience. Especially as decriminalization and perhaps legalization of these substances proceeds, it is just as important to develop and understand practices for recreational use. If you’re trying to have a fun afternoon, you can choose to stop thinking about your problems and go for walk in the woods, even if you perceive that there might be further work to do.
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Kochevar, C. Psychedelic phenomenology and the role of affect in psychological transformation. Phenom Cogn Sci (2023). https://doi.org/10.1007/s11097-023-09943-w
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DOI: https://doi.org/10.1007/s11097-023-09943-w