Sandeep Nayak reviews Philosophy of Psychedelics (Oxford University Press, 2021) by Chris Letheby.
This is Part Four of a Book Forum on Philosophy of Psychedelics. The Forum consists of four reviews and a reflection from the author.
For Part One by Nathan Emmerich and Bryce Humphries, click here.
For Part Two by Evgenia Fotiou, click here.
For Part Three by Nicolas Langlitz, click here.
For Part Five by Chris Letheby, click here.
Philosophy of Psychedelics is the first comprehensive philosophical treatment of psychedelics that I have seen, and provides a set of concepts that I suspect will become increasingly useful the more we learn from psychedelic research. In the book, Chris Letheby makes a spirited defense of the notion that the psychedelic experience is intelligible under naturalism, which Letheby describes as the notion that “mind and consciousness are not fundamental in the universe”—roughly the opposite of religious or spiritual kinds of beliefs (p.2). Assuming, as Letheby does, that naturalism is true, psychedelics can produce experiences and beliefs that are false – consider telepathy, benevolent spirits, or life after death. Such experiences constitute an “epistemic risk” according to Letheby. However, he holds that psychedelics can also produce genuinely valid knowledge (such as useful psychological insights) whose therapeutic effects are not necessarily grounded in non-naturalistic falsehoods. He also contends that the fruits of psychedelic experiences, including therapeutic benefits and spirituality, can be reconciled with naturalism.
As a psychiatrist and researcher at the Johns Hopkins Center for Psychedelic and Consciousness Research, I read this book with great interest and an eye towards therapeutic implications. While psychedelics are interesting and important far beyond their therapeutic value, even a rigid fixation on therapeutic utility quickly leads to broader questions about how they are similar to, and different from, conventional psychiatric treatments. A wide variety of stakeholders (scientists, new drug companies, neo-shamans, retreat leaders) are invested in the notion that psychedelics are novel, groundbreaking psychological treatments that form a rupture not only with existing treatments, but perhaps also with an atomized, individualistic, capitalist society. The oft-discussed finding that therapeutic effects of psychedelics correlate with mystical experiences, such as experiences of selflessness, eternity, rapture, etc. (1–4) certainly seems novel. However, such psychedelic exceptionalism risks overlooking the more conventional ways that psychedelics may be therapeutically useful.
Psychedelics are therapeutic by altering the self
The book offers one of the best descriptive accounts of the powerful acute subjective effects of psychedelics available. While some researchers take the contrarian view that these are an epiphenomenal sideshow, and that the enduring psychological effects (therapeutic or otherwise) of psychedelics are brought about by some experience-independent drug action, the majority view is probably that these acute subjective experiences are responsible in large part for subsequent enduring effects. Letheby adopts this majority position yet argues that this does not mean psychedelics work therapeutically by proffering metaphysically “comforting delusions”.
He suggests that a range of subjective effects can be therapeutically beneficial apart from mystical experience — those of psychological insight, emotional breakthrough, enhanced connectedness, expanded emotional range, and so forth. The underlying active therapeutic ingredient, Letheby argues, is an altered experience of the self. In particular, psychedelics perturb normally invisible, or “transparent”, aspects of the self, rendering them “opaque” constructions that can be experienced as mutable and separable from oneself (p. 140).
In addition, he expounds on his ‘predictive self-binding’ account of psychedelic action. This account draws heavily on the REBUS (RElaxed Beliefs Under pSychedelics) model (5) and predictive processing (which posit that under psychedelics, high level beliefs are “relaxed” to allow more flexible revision with lower level information) and applies these more specifically to beliefs about the self. Here Letheby states his overall thesis:
“By experiencing radically different forms of self-modelling, we come to see vividly that the previously unquestioned sense of who I am is just a story, and can be told otherwise; it is not given, but constructed by a malleable modelling process” (p.183).
He argues that many of the subjective measures predictive of enduring benefit—mystical experience, psychological insight, emotional breakthrough, increased psychological flexibility and mindfulness capacities—can be described as altering one or more domains of the self.

The predictive self-binding model is a useful, coherent, and flexible frame for therapeutic psychedelic effects. I am reminded of a participant I worked with in a psychedelic clinical trial who described experiencing their usual negative self-talk as a “fun house mirror” that distorts their view of themself. This realization came with the sense that these thoughts were not facts, and that they had the freedom to step around the mirror. In this way, they were able to viscerally realize something already known. This was a self-related psychological insight attached to a practicable skill. Letheby’s account very comfortably accommodates this individual’s experience in a way that the mystical framework does not. More generally, Letheby’s account comports with my feeling that there are a variety of ways that psychedelics are likely to be therapeutically useful, and that these will differ across people.
Though the claim that psychedelics work by altering self-representations is compelling on its own terms, Letheby leans heavily (and in my view prematurely and unnecessarily) on results from resting state fMRI studies to support it. In particular, he suggests using perturbations in certain brain networks (such as decreased Default Mode Network (DMN) connectivity) as a measure of effects on the self and predictor for subsequent benefits. As my colleague at Johns Hopkins, the cognitive neuropsychopharmacologist Manoj Doss summarizes, “The small samples, short scan times, numerous reports based on single datasets, underreporting of comparable or larger effects on other brain networks, and inconsistency across studies between brain measures and ego dissolution undermine the strength of reverse inferential claims regarding the specificity of DMN effects to ego dissolution,” (6). Not only does decreased DMN connectivity not always correlate with ego-dissolution (7), it is not specific to psychedelic drugs alone, and occurs following short-term antidepressants (8), alcohol (9,10), stimulants (11,12), and salvinorin A (6).
At times, the predictive self-binding account may overreach, and risks explaining too much. For example, “the noetic quality—the feeling of certainty or direct knowledge—might also result from a weakening of the sense of separate selfhood. The idea here is that the sense of being an entity distinct from the object of knowledge is a prerequisite for conceiving of the possibility of error: With no sense of a distinct knowing subject, there is no sense of a fallible epistemic connection between that subject and a distinct object of potential knowledge; hence, doubt is inconceivable,” (p. 119-120). This strikes me as a stretch and would require noetic experiences to be selfless experiences. Nonetheless, this model goes a long way in explaining therapeutic effects of psychedelics that does not require recourse to mystical or transcendent explanations.
Forms of knowledge
A clinical mentor of mine once dismissed psychedelic-derived insights as “drug drivel”. This remains a common view that Letheby argues against. He states there are a variety of ways that psychedelics can be said to produce valid knowledge. Perhaps the two most defensible are “knowledge how”, and “new knowledge of old facts”. The former refers to a variety of skills that may be cultivated during psychedelic use, such as attentional or emotional skills akin to those cultivated in mindfulness meditation or exposure therapy. The latter is related to the oft described experience of participants in psychedelic studies “remembering what they already know”. For example, a participant in a Johns Hopkins smoking cessation trial stated:
“I don’t know if I really learned – it was more like letting back in stuff that I had blocked out?… I don’t think I changed my values, just remembered more of them. Or just remembered to honour them more, or…allow them more.” (13).

However, Letheby holds that psychedelics can also produce genuinely useful knowledge in the form of psychodynamic insights into one’s own mind. “Assuming that such [psychodynamic insights] do contribute causally to symptom reduction, a simple explanation is that the putative insights are genuine” (p. 167). While this is possible, a complicating factor is the psychotherapeutic truism that beliefs are useful if they are believed and guide action. As psychiatrist and psychedelic researcher during the ‘first wave’ of scientific inquiry in the 1960s Sydney Cohen wrote, “Any explanation of the patient’s problems, if firmly believed by both the therapist and the patient, constitutes insight or is as useful as insight. It is the faith, not the validity that counts” (14). Perhaps not only is there “no general formula” for distinguishing “genuine insights and placebo insights”—maybe there is no fundamental distinction between them (p. 171). While this may muddy the water in terms of identifying whether psychedelic insights are “valid”, sober evaluation of any new knowledge is probably the best judge.
Naturalizing psychedelia
Letheby’s project of naturalizing psychedelic spirituality in many ways mirrors the project of Buddhist Modernism, that positioned meditation as a rational, empirical endeavor fully in compliance with a secular, naturalist worldview (15). This disenchanted and rationalized Buddhism, shorn of metaphysical commitments has been very successful and is probably the dominant form of meditation engaged with in the West. For meditation and psychedelics, this may be a necessary step in adaptation to a secular culture.
Nonetheless, there remains a buried tension here. While psychedelic effects (or Buddhist meditation) may be theorized and experienced in an entirely naturalistic framework, the non-naturalistic aspects and interpretations remain a potent draw for meaning-making. Also, and particularly in the United States where demonized cultural practices (meditation, cannabis) often gain legitimacy through medicalization, the naturalization project risks sweeping less assimilable aspects under the rug. For example, Buddhist meditation is traditionally “aimed at exiting the world, rather than a means to a happier, more fulfilling life within it,” (16), and this disjuncture can lead to hard-to-reconcile adverse psychological experiences. Willoughby Britton, a psychologist who studies such adverse experiences resulting from meditation, recalls being chastised by a meditation teacher “Why are you therapists always trying to make meditation a relaxation technique? That’s not what it’s there for” (17). A study from her group summarizes, “Some of the ‘adverse’ responses to meditation experiences can be attributed to a lack of fit between practitioner goals and expectations and the normative frameworks of self-transformation found within the tradition” (18).
Similarly, we risk minimizing or overlooking the “less naturalizable” aspects of psychedelics. I am unsure that it is always clear what is baby and what is bathwater when it comes to the project of naturalizing psychedelics. While I fully agree with Letheby that the fruits of psychedelic use can be naturalized, I am less sure about the extent to which they will be by those who take these drugs. And whether or not psychedelic therapy primarily works by inducing non-naturalistic metaphysical beliefs, it does often appear to induce such beliefs.
Lastly, recent research suggests that taking a psychedelic appears to change one’s metaphysical beliefs in particular, non-naturalistic directions (19), yet Letheby’s account does not clearly get at this seeming directionality in belief change. Chapter 7 does offer a fascinating description of why psychedelics might lead to idealistic beliefs that elevate mind over matter. Namely, by inducing “global opacity” of mental representations—“the profound and existentially destabilizing insight that one’s entire experienced world is a purely mental construction” (p. 143). However, it’s hard to reconcile this idea of “global opacity”, that all is mutable mental representation, with the noetic sense of felt certainty typical of psychedelic experiences. Moreover, this account would not seem to generalize to other beliefs. In general, these beliefs mirror non-naturalistic beliefs found all over the world, and it is plausible that the cognitive tendencies that give rise to these beliefs around the world without psychedelics may also be at play in the psychedelic experience. In other words, non-naturalistic beliefs are far and away the human norm. Perhaps it’s the same universal psychological processes that give rise to non-naturalism with or without psychedelics, rather than idiosyncratic effects of New Age culture?
References
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- Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: A randomized controlled trial. Journal of Psychopharmacology. 2016 Dec;30(12):1165–80.
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- Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, et al. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021;
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- Doss MK, May DG, Johnson MW, Clifton JM, Hedrick SL, Prisinzano TE, et al. The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain. Scientific Reports. 2020 Oct;10(1):16392.
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Sandeep Nayak MD is a psychiatrist and postdoctoral research fellow at the Johns Hopkins Center for Psychedelic and Consciousness Research. His research focuses on the application of psychedelics to various psychiatric conditions, including mood and substance use disorders. He is also interested in how to understand psychedelic therapy as psychotherapy more broadly, and in psychedelics’ effects on belief formation. Follow Sandeep on Twitter @sdpnayak.