Why Psychedelics Don’t Fit The “Drug” Paradigm
The decision in August by the FDA to reject Lykos Therapeutics’ application for MDMA-assisted psychotherapy has engendered a wave of hand-wringing and finger-pointing, a surprising volta after half a decade of steady psychedelic hype. To best understand how a regulatory agency’s routine vote on whether to approve a novel psychiatric treatment could cause such consternation, we must return, in psychedelic parlance, to our set and setting.
Just as Lykos entered the ninth inning of its campaign for the approval of MDMA-assisted psychotherapy, I was hard at work in the home stretch of my doctoral dissertation research, focused on the question of why taking psychedelics affects different people in such remarkably different ways, and the factors that help predict a person’s response to a psychedelic compound. In the span of just a few weeks in June, both projects were scrutinized by committees with the stamp of institutional credibility: Lykos’ by the FDA’s Advisory Committee, and mine by one convened at Columbia’s Department of Clinical Psychology. While the results were starkly opposite (my dissertation passed), to me, this pair of hearings, unimaginable a decade ago, seemed to represent the “psychedelic renaissance” in its full flower.
This institutionally-backed, bipartisan-friendly psychedelic renaissance owes much of its mainstream success to broad-based concerns over an unprecedented mental health crisis—one that’s been subject to reams of speculative essaying, and special after primetime special. At the time of this writing, we are at such an advanced stage of discourse around “the mental health crisis” that credible voices are beginning to argue that too much discourse about mental health is in fact one of the things fueling this crisis—by teaching people to reify patterns of suffering that might otherwise be related to differently, and to even take them on as identities.
Regardless of how much this is the case, we would do well to remember that how we talk about suffering and stuckness has the potential to shape our experience in dramatic ways—and that we should choose our words accordingly, with great care.
Similarly, the choice of which frames to use in talking about psychedelics carries great ethical implications that go far beyond the lab. Is psilocybin the next Prozac? Is 5-MeO-DMT a ten-minute path to certain enlightenment? Readers of headlines and recipients of targeted Facebook ads, whether motivated by hope, despair, or simple curiosity, could be forgiven for jumping to such conclusions. And the expectations generated in the process may be setting people up for disappointment in their pursuit of psychedelic healing.
The Current Landscape
For proponents of a primarily biological model of mental health dysfunction, the recent surge in reported rates of depression, anxiety, and suicidality, as well as in utilization of mental health counseling services and antidepressant prescriptions, presents a serious problem. Namely: to the best of our knowledge, people’s genetic predispositions and neurochemical baseline do not appear to have changed radically in the span of a decade or two – by all accounts, this would be impossible.
What has changed – rapidly, profoundly, and rather mercilessly – is our environment. As famously documented at a much less advanced stage in Bowling Alone (2000), participation in longstanding institutions of civic culture and group-level belonging, such as churches, service clubs, and unions, has plummeted dramatically. Meanwhile, far beyond the 1960s split between the establishment and the counterculture, the last few decades have witnessed an almost omnidirectional splintering of the social narrative – leading to a profound collapse of consensus trust in institutions, and even of the sense of a “consensus reality”.
Even though “objective” measures of overall material well being have mostly continued to trend upward, especially across the developing world, popular discourse has become fuller and fuller each year with the sense that we are “in a crisis” – one that, whatever its root causes, is experienced as something primarily psychospiritual. And while it’s no wonder that some online social critics have taken to new coinages such as “the polycrisis” and “the metacrisis,” I recommend sticking with John Vervaeke’s phrasing: “the meaning crisis“.
Not only is the consensus around what is meaningful in shambles – but, on a more elemental level, people are increasingly losing access to the capacity to make meaning, even in the midst of dizzying novelty and technological miracles. It is of note that against this backdrop, psychedelics are experiencing a surge of interest not seen since the 1960s.
Psychedelics As A Tool For Enchantment
Owing to the fact that psychedelics are a class of drugs, it is understandable that pharmacologically-minded parties tend to think of psychedelics as representing a neurochemical fix for the mental health crisis – in other words, the latest and greatest in pharmacotherapeutic psychiatry. But psychedelics – which unlike SSRIs, benzodiazepines, and mood stabilizers create dramatic, complex changes in quality of consciousness – are a poor fit for this paradigm, and are likely to disappoint clinicians, patients, and investors if slotted into it.
Rather, the power of psychedelics to treat mental health ailments makes the most sense when understood in terms of their role in helping people to address contemporary culture’s crisis of meaning and sense-making.
Put another way, psychedelics enchant – a word which literally means, to put under a spell or song. Psychedelics enable a state of consciousness where things experienced as ordinary in “default consciousness” become deeply resonant with meaning – the process of poetic enchantment by which Whitman’s “leaf of grass” becomes “no less than the journey-work of the stars.” In The Doors of Perception, Huxley describes his experience of enchantment under mescaline, beholding a vase of flowers:
One useful theory chalks this tendency toward enchantment up to psychedelics’ nature as “non-specific amplifiers” of all conscious content, pleasant or otherwise – and argues that psychedelics in essence make people more suggestible. Meanwhile, as part of their “relaxed beliefs under psychedelics” (REBUS) model, Carhart-Harris and Friston (2019), working within the framework of predictive processing, speculate that psychedelics tend to dampen “top-down” priors about what things “should mean.” This allows people to be more responsive to “bottom-up” sensory data, more easily surprised and awed.
“The vase contained only three flowers — a full-blown Belle of Portugal rose, shell pink with a hint at every petal’s base of a hotter, flamier hue; a large magenta and cream-coloured carnation; and, pale purple at the end of its broken stalk, the bold heraldic blossom of an iris … I was not looking now at an unusual flower arrangement. I was seeing what Adam had seen on the morning of his creation — the miracle, moment by moment, of naked existence.”
It is easy to argue why depressed and even run-of-the-mill anxious people would tend to benefit from experiences that cast the world as pregnant with meaning, possibility, and play. Many different ways of theorizing depression circle around the idea of depression as a state of constriction, in which people get stuck in pessimistic beliefs about the self and the future, become disconnected from sources of positivity and surprise, and become fixated on the self-narrative at the expense of engaging with the wider world, from the microscopic to the macroscopic.
When the world and all its objects become enchanted under the lens of psychedelics, it becomes untenable to stay cooped up inside the small self. Even if the “macro” level offers plenty of reasons to be pessimistic, the psychedelic brain finds a way to revel in the delights of the “micro” – showing depressed people that the possibility of meaning is always there.
We should also ask: is more enchantment always the answer? My analyses of mystical and psychedelic experience in the general population suggest that the answer might be no. While data suggest a link between mystical experience and positive post-psychedelic outcomes, I also found evidence that depending on other factors, mystical experience may be linked to either improvements or declines in socioemotional functioning.
Meanwhile, for people coming to psychedelics with an already high baseline level of enchantment, whether entrained through spiritual practice or hard-wired in the form of high trait absorption (i.e. a person’s baseline tendency to get fully absorbed in things), making the world even more resonant with meanings might actually prove to be counterproductive, even harmful. And while depression may be framed as a problem of too little meaning-making – one amenable to treatment with psychedelics – there exists an opposite condition, where people detect significance and see patterns too easily for their own good, developing elaborate stories to explain the constant sense of surprisal. In other words, psychosis.
It must also be emphasized that not all encounters with psychedelics are experienced as enchanting or mystical. They may, for example, bring about experiences in which the world of perception becomes brighter and more striking for five or ten hours – but without this translating into a deeper, more pervasive sense of enchantment with the world as it is, after the initial ecstasy. My analyses of 379 trippers’ responses to the Altered States of Consciousness Questionnaire as part of a 2017 data collection by Imperial College London revealed the following: people may or may not experience dramatic alterations of perception on psychedelics; they may or may not be dazzled by such alterations; they may or may not interpret being dazzled as profoundly meaningful; and they may or may not channel a sense of profound meaningfulness into changes in mood and way of life.
Psychedelics As “Nondeterministic Medicine”
At the end of my dissertation project, which focused on the heterogeneity of psychedelics’ effects, I found myself asking: does psychedelic experience even have a minimum universal definition? That is to say, is there something that we can be sure defines all experiences people have when they ingest psychedelics? Or does the lens of careful empirical scrutiny force us to jettison the notion of “psychedelic experience” entirely in the interest of precision, especially when both empirical evidence and field anecdotes suggest a highly imperfect correlation between ingesting serotonergic psychedelics, and having distinctive alterations in consciousness?
One of Ram Dass’s best-known stories, widely considered apocryphal in psychedelic circles, describes the unexpected non-reaction of Hindu guru Neem Karoli Baba when given a massive dose of LSD. Charged with evangelical zeal about the singular power of LSD to produce spiritually-significant radical alterations in consciousness, the former Harvard psychologist gave his “psychedelic-naïve” spiritual teacher several active doses’ worth of the psychedelic drug – expecting it to dazzle and astound. To Ram Dass’ surprise, the holy man rode out his dose day unfazed, with no significant changes to his baseline consciousness – leading the former to believe that some advanced spiritual practitioners may already be living in a “psychedelic” default state, thanks to hard-earned, gradual spiritual discipline, rather than to chemical agents.
The radically non-deterministic nature of psychedelics is another reason it would be a grave mistake to treat psychedelics as the latest, most advanced class of pharmacotherapeutic for depression, anxiety, addiction, and eating disorders. Even if psychedelics might commonly produce an experience that is unitive-mystical in nature, and an average clinical response that is positive in quality, my review of the research shows that no two sampled groups of people show quite the same distribution of experiences and outcomes.
Preparation and integration practices focused on bolstering social connectedness, mindfulness, and spiritual connection – a “relational triad” I’ve identified as important in shaping the relationship between mystical experiences and mental health – may go a long way toward promoting more mystical and positively-valenced experiences. They may also result in greater improvements in mood, psychological insight, and existential well being. But despite our best efforts, guaranteeing one kind of experience or another is all but impossible. This is a crucial point.
Evidence suggests that a wide range of psychiatric drugs and interventions in physical medicine are subject to expectancy and framing. But no currently indicated treatment approved by the FDA and offered by medical doctors is so widely variegated in its effects, and so elementally shaped by set, setting, and expectancy. As far as regulators and insurers are concerned, replicable impact is essential. No matter the organism’s particular quirks and life story, the drug atorvastatin inhibits the synthesis of cholesterol; sertraline inhibits reuptake of serotonin from the synaptic cleft.
Psychedelics meet an individual where he or she is, and instantiate experiences that only he or she could have. For this reason as well, attempts to categorize psychedelics in Western biomedical terms as drugs first and foremost are doomed to miss the point, at best, and cause harm, at worst. Healing work with psychedelics is not deterministic medicine; it’s the art of working with a concentrated, hormetic dose of entropy, temporarily reopening a critical learning window, and channeling it for good. And entropy is, by its nature, neither good nor bad – but rather, nonspecific.
Viewed in this light, my finding that people lower in baseline mood and well being may gain more from psychedelics, and vice versa, stands in clearer relief. For people stuck in an unsatisfying place, the expected value of shuffling the psychic deck, of resetting brain-wide functional connectivity, or of re-annealing the brain’s energy landscape, is basically high. On the other hand, for people who are fundamentally satisfied with their present homeostatic baseline, rolling the dice is far less likely to lead to a new, improved mental health set point – even in a situation where downside risk is unlikely to be large in magnitude.
It’s important to note, however, that not all psychedelic use is motivated by the desire to feel better. Individuals who choose to take psychedelics for spiritual, creative, or consciousness exploration purposes may indeed experience benefits in these realms – even if they do not register in the form of reduced depression and anxiety quotients. Meanwhile, to the extent that psychedelic research can offer insights into brain functioning and the phenomenology of consciousness, pursuits epitomized by the work of the Emergent Phenomena Research Consortium and the Qualia Research Institute, a risk-benefit analysis focused exclusively on improvements in mood may not fully capture the true, multidimensional risk-benefit profile of psychedelics.
Psychedelics And The Power of the Frame
Taking a step back, psychedelics may offer us a lesson that transcends psychiatry – one which they embody in concentrated microcosm – namely, that the frames we choose matter profoundly. This may seem like a trivial point. To be sure, nothing in the world can be known by human minds in an unmediated way. We are storytelling creatures who, in Lakoff and Johnson’s phrasing, “live by” metaphor. What is unique about psychedelics is that they appear to tap into the very machinery of meaning-making and salience-ascription, allowing humans to experience anything as utterly resonant or utterly hollow.
In the same vein, psychedelics seem to directly activate our capacity for suggestibility, making these serotonergic drugs’ individual and societal-level effects especially subject to framing. Not only must individual clinicians and psychedelic users be thoughtful about how they frame and pre-program an individual psychedelic experience – but we, as researchers, should take care to remember that the stories we tell about psychedelics at this critical juncture will play a role in shaping millions of individual experiences. These stories could also impact the collective experience of how psychedelics get metabolized by our warp speed culture.
Having scoured the literature, I offer two simple axioms for framing the discussion of psychedelics: 1) that they are nondeterministic (“nonspecific”), and 2) that they are serious stuff (“amplifiers”). In other words, when we talk about psychedelics, we would do best to be not too sure and not too flip. In the language of values, we could speak of humility about the limits of our rational understanding, and reverence for compounds astonishing in both their power and subtlety. Against a zeitgeist defined by hyper-rationalism, consumerism, and cynicism about all structures and limits, this stance might seem a tall order.
Fortunately, there is already a longstanding mode of speaking about psychedelics available to us, one which by its very definition incorporates these considerations: the sacred. Treating something as sacred – or “set apart”, as both the Hebrew and Latin roots for the concept connote – is a move cultures have made since time immemorial, as a way to more safely engage with powerful, unpredictable forces, and make them tractable. Paradoxically, this act of “setting apart” is what allows cultures to integrate and make space for forces that are otherwise impossible to make total rational sense of. Psychedelics, as extraordinarily potent, inexpensive agents with the power to heal, enchant, connect people to God, or otherwise, misdirect and destabilize, stand the best chance of being integrated in a meaningful, healing way if “set apart” as something sacred – something to be talked about with humility, if not a bit quakingly.