Ian enjoyed several months of relief from his depression as well as a new perspective on his life—something no antidepressant had ever given him. “Like Google Earth, I had zoomed out,” he told Watts in his six-month interview. For several weeks after his session, “I was absolutely connected to myself, to every living thing, to the universe.” Eventually, Ian’s overview effect faded, however, and he ended up back on Zoloft.
“The sheen and shine that life and existence had regained immediately after the trial and for several weeks after gradually faded,” he wrote one year later. “The insights I gained during the trial have never left and will never leave me. But they now feel more like ideas,” he says. He says he’s doing better than before and has been able to hold down a job, but his depression has returned. He told me he wishes he could have another psilocybin session at Imperial. Because that’s currently not an option, he’ll sometimes meditate and listen to the playlist from his session. “That really does help put me back in that place.”
More than half of the Imperial volunteers saw the clouds of their depression eventually return, so it seems likely that psychedelic therapy for depression, should it prove useful and be approved, will not be a onetime intervention. But even the temporary respite the volunteers regarded as precious, because it reminded them there was another way to be that was worth working to recapture. Like electroconvulsive therapy for depression, which it in some ways resembles, psychedelic therapy is a shock to the system—a “reboot” or “defragging”—that may need to be repeated every so often. (Assuming the treatment works as well when repeated.) But the potential of the therapy has regulators and researchers and much of the mental health community feeling hopeful.
“I believe this could revolutionize mental health care,” Watts told me. Her conviction is shared by every other psychedelic researcher I interviewed.
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“IF MANY REMEDIES are prescribed for an illness,” wrote Anton Chekhov, who was a physician as well as a writer, “you may be certain that the illness has no cure.” But what about the reverse of Chekhov’s statement? What are we to make of a single remedy being prescribed for a great many illnesses? How could it be that psychedelic therapy might be helpful for disorders as different as depression, addiction, the anxiety of the cancer patient, not to mention obsessive-compulsive disorder (about which there has been one encouraging study) and eating disorders (which Hopkins now plans to study)?
We shouldn’t forget that irrational exuberance has afflicted psychedelic research since the beginning, and the belief that these molecules are a panacea for whatever ails us is at least as old as Timothy Leary. It could well be that the current enthusiasm will eventually give way to a more modest assessment of their potential. New treatments always look shiniest and most promising at the beginning. In early studies with small samples, the researchers, who are usually biased in favor of finding an effect, have the luxury of selecting the volunteers most likely to respond. Because their number is so small, these volunteers benefit from the care and attention of exceptionally well-trained and dedicated therapists, who are also biased in favor of success. Also, the placebo effect is usually strongest in a new medicine and tends to fade over time, as observed in the case of antidepressants; they don’t work nearly as well today as they did upon their introduction in the 1980s. None of these psychedelic therapies have yet proven themselves to work in large populations; what successes have been reported should be taken as promising signals standing out from the noise of data, rather than as definitive proofs of cure.
Yet the fact that psychedelics have produced such a signal across a range of indications can be interpreted in a more positive light. When a single remedy is prescribed for a great many illnesses, to paraphrase Chekhov, it could mean those illnesses are more alike than we’re accustomed to think. If a therapy contains an implicit theory of the disorder it purports to remedy, what might the fact that psychedelic therapy seems to address so many indications have to tell us about what those disorders might have in common? And about mental illness in general?
I put this question to Tom Insel, the former head of the National Institute of Mental Health. “It doesn’t surprise me at all” that the same treatment should show promise for so many indications. He points out that the DSM—the Diagnostic and Statistical Manual of Mental Disorders, now in its fifth edition—draws somewhat arbitrary lines between mental disorders, lines that shift with each new edition.
“The DSM categories we have don’t reflect reality,” Insel said; they exist for the convenience of the insurance industry as much as anything else. “There’s much more of a continuum between these disorders than the DSM recognizes.” He points to the fact that SSRIs, when they work, are useful for treating a range of conditions besides depression, including anxiety and obsessive-compulsive disorder, suggesting the existence of some common underlying mechanism.
Andrew Solomon, in his book The Noonday Demon: An Atlas of Depression, traces the links between addiction and depression, which frequently co-occur, as well as the intimate relationship between depression and anxiety. He quotes an expert on anxiety who suggests we should think of the two disorders as “fraternal twins”: “Depression is a response to past loss, and anxiety is a response to future loss.” Both reflect a mind mired in rumination, one dwelling on the past, the other worrying about the future. What mainly distinguishes the two disorders is their tense.
A handful of researchers in the mental health field seem to be groping toward a grand unified theory of mental illness, though they would not be so arrogant as to call it that. David Kessler, the physician and former head of the FDA, recently published a book called Capture: Unraveling the Mystery of Mental Suffering that makes the case for such an approach. “Capture” is his term for the common mechanism underlying addiction, depression, anxiety, mania, and obsession; in his view, all these disorders involve learned habits of negative thinking and behavior that hijack our attention and trap us in loops of self-reflection. “What started as a pleasure becomes a need; what was once a bad mood becomes continuous self-indictment; what was once an annoyance becomes persecution,” in a process he describes as a form of “inverse learning.” “Every time we respond [to a stimulus], we strengthen the neural circuitry that prompts us to repeat” the same destructive thoughts or behaviors.
Could it be that the science of psychedelics has a contribution to make to the development of a grand unified theory of mental illness—or at least of some mental illnesses? Most of the researchers in the field—from Robin Carhart-Harris to Roland Griffiths, Matthew Johnson, and Jeffrey Guss—have become convinced that psychedelics operate on some higher-order mechanisms in the brain and mind, mechanisms that may underlie, and help explain, a wide variety of mental and behavioral disorders, as well as, perhaps, garden-variety unhappiness.
It could be as straightforward as the notion of a “mental reboot”—Matt Johnson’s biological control-alt-delete key—that jolts the brain out of destructive patterns (such as Kessler’s “capture”), affording an opportunity for new patterns to take root. It could be that, as Franz Vollenweider has hypothesized, psychedelics enhance neuroplasticity. The myriad new connections that spring up in the brain during the psychedelic experience, as mapped by the neuroimaging done at Imperial College, and the disintegration of well-traveled old connections, may serve simply to “shake the snow globe,” in Robin Carhart-Harris’s phrase, a predicate for establishing new pathways.
Mendel Kaelen, a Dutch postdoc in the Imperial lab, proposes a more extended snow metaphor: “Think of the brain as a hill covered in snow, and thoughts as sleds gliding down that hill. As one sled after another goes down the hill, a small number of main trails will appear in the snow. And every time a new sled goes down, it will be drawn into the preexisting trails, almost like a magnet.” Those main trails represent the most well-traveled neural connections in your brain, many of them passing through t
he default mode network. “In time, it becomes more and more difficult to glide down the hill on any other path or in a different direction.
“Think of psychedelics as temporarily flattening the snow. The deeply worn trails disappear, and suddenly the sled can go in other directions, exploring new landscapes and, literally, creating new pathways.” When the snow is freshest, the mind is most impressionable, and the slightest nudge—whether from a song or an intention or a therapist’s suggestion—can powerfully influence its future course.
Robin Carhart-Harris’s theory of the entropic brain represents a promising elaboration on this general idea, and a first stab at a unified theory of mental illness that helps explain all three of the disorders we’ve examined in these pages. A happy brain is a supple and flexible brain, he believes; depression, anxiety, obsession, and the cravings of addiction are how it feels to have a brain that has become excessively rigid or fixed in its pathways and linkages—a brain with more order than is good for it. On the spectrum he lays out (in his entropic brain article) ranging from excessive order to excessive entropy, depression, addiction, and disorders of obsession all fall on the too-much-order end. (Psychosis is on the entropy end of the spectrum, which is why it probably doesn’t respond to psychedelic therapy.)
The therapeutic value of psychedelics, in Carhart-Harris’s view, lies in their ability to temporarily elevate entropy in the inflexible brain, jolting the system out of its default patterns. Carhart-Harris uses the metaphor of annealing from metallurgy: psychedelics introduce energy into the system, giving it the flexibility necessary for it to bend and so change. The Hopkins researchers use a similar metaphor to make the same point: psychedelic therapy creates an interval of maximum plasticity in which, with proper guidance, new patterns of thought and behavior can be learned.
All these metaphors for brain activity are just that—metaphors—and not the thing itself. Yet the neuroimaging of tripping brains that’s been done at Imperial College (and that has since been replicated in several other labs using not only psilocybin but also LSD and ayahuasca) has identified measurable changes in the brain that lend credence to these metaphors. In particular, the changes in activity and connectivity in the default mode network on psychedelics suggest it may be possible to link the felt experience of certain types of mental suffering with something observable—and alterable—in the brain. If the default mode network does what neuroscientists think it does, then an intervention that targets that network has the potential to help relieve several forms of mental illness, including the handful of disorders psychedelic researchers have trialed so far.
So many of the volunteers I spoke to, whether among the dying, the addicted, or the depressed, described feeling mentally “stuck,” captured in ruminative loops they felt powerless to break. They talked about “prisons of the self,” spirals of obsessive introspection that wall them off from other people, nature, their earlier selves, and the present moment. All these thoughts and feelings may be the products of an overactive default mode network, that tightly linked set of brain structures implicated in rumination, self-referential thought, and metacognition—thinking about thinking. It stands to reason that by quieting the brain network responsible for thinking about ourselves, and thinking about thinking about ourselves, we might be able to jump that track, or erase it from the snow.
The default mode network appears to be the seat not only of the ego, or self, but of the mental faculty of time travel as well. The two are of course closely related: without the ability to remember our past and imagine a future, the notion of a coherent self could hardly be said to exist; we define ourselves with reference to our personal history and future objectives. (As meditators eventually discover, if we can manage to stop thinking about the past or future and sink into the present, the self seems to disappear.) Mental time travel is constantly taking us off the frontier of the present moment. This can be highly adaptive; it allows us to learn from the past and plan for the future. But when time travel turns obsessive, it fosters the backward-looking gaze of depression and the forward pitch of anxiety. Addiction, too, seems to involve uncontrollable time travel. The addict uses his habit to organize time: When was the last hit, and when can I get the next?
To say the default mode network is the seat of the self is not a simple proposition, especially when you consider that the self may not be exactly real. Yet we can say there is a set of mental operations, time travel among them, that are associated with the self. Think of it simply as the locus of this particular set of mental activities, many of which appear to have their home in the structures of the default mode network.
Another type of mental activity that neuroimaging has located in the DMN (and specifically in the posterior cingulate cortex) is the work performed by the so-called autobiographical or experiential self: the mental operation responsible for the narratives that link our first person to the world, and so help define us. “This is who I am.” “I don’t deserve to be loved.” “I’m the kind of person without the willpower to break this addiction.” Getting overly attached to these narratives, taking them as fixed truths about ourselves rather than as stories subject to revision, contributes mightily to addiction, depression, and anxiety. Psychedelic therapy seems to weaken the grip of these narratives, perhaps by temporarily disintegrating the parts of the default mode network where they operate.
And then there is the ego, perhaps the most formidable creation of the default mode network, which strives to defend us from threats both internal and external. When all is working as it should be, the ego keeps the organism on track, helping it to realize its goals and provide for its needs, notably for survival and reproduction. It gets the job done. But it is also fundamentally conservative. “The ego keeps us in our grooves,” as Matt Johnson puts it. For better and, sometimes, for worse. For occasionally the ego can become tyrannical and turn its formidable powers on the rest of us.* Perhaps this is the link between the various forms of mental illness that psychedelic therapy seems to help most: all involve a disordered ego—overbearing, punishing, or misdirected.*
In a college commencement address he delivered three years before his suicide, David Foster Wallace asked his audience to “think of the old cliché about ‘the mind being an excellent servant but a terrible master.’ This, like many clichés, so lame and unexciting on the surface, actually expresses a great and terrible truth,” he said.
“It is not the least bit coincidental that adults who commit suicide with firearms almost always shoot themselves in the head. They shoot the terrible master.”
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OF ALL THE PHENOMENOLOGICAL EFFECTS that people on psychedelics report, the dissolution of the ego seems to me by far the most important and the most therapeutic. I found little consensus on terminology among the researchers I interviewed, but when I unpack their metaphors and vocabularies—whether spiritual, humanistic, psychoanalytic, or neurological—it is finally the loss of ego or self (what Jung called “psychic death”) they’re suggesting is the key psychological driver of the experience. It is this that gives us the mystical experience, the death rehearsal process, the overview effect, the notion of a mental reboot, the making of new meanings, and the experience of awe.
Consider the case of the mystical experience: the sense of transcendence, sacredness, unitive consciousness, infinitude, and blissfulness people report can all be explained as what it can feel like to a mind when its sense of being, or having, a separate self is suddenly no more.
Is it any wonder we would feel one with the universe when the boundaries between self and world that the ego patrols suddenly fall away? Because we are meaning-making creatures, our minds strive to come up with new stories to explain what is happening to them during the experience. Some of these stories are bound to be supernatural or “spiritual,” if only because the phenomena are so extraordinary they can’t be easily explained in terms of our usual conceptual categories. The
predictive brain is getting so many error signals that it is forced to develop extravagant new interpretations of an experience that transcends its capacity for understanding.
Whether the most magnificent of these stories represent a regression to magical thinking, as Freud believed, or access to transpersonal realms such as the “Mind at Large,” as Huxley believed, is itself a matter of interpretation. Who can say for certain? Yet it seems to me very likely that losing or shrinking the self would make anyone feel more “spiritual,” however you choose to define the word, and that this is apt to make one feel better.
The usual antonym for the word “spiritual” is “material.” That at least is what I believed when I began this inquiry—that the whole issue with spirituality turned on a question of metaphysics. Now I’m inclined to think a much better and certainly more useful antonym for “spiritual” might be “egotistical.” Self and Spirit define the opposite ends of a spectrum, but that spectrum needn’t reach clear to the heavens to have meaning for us. It can stay right here on earth. When the ego dissolves, so does a bounded conception not only of our self but of our self-interest. What emerges in its place is invariably a broader, more openhearted and altruistic—that is, more spiritual—idea of what matters in life. One in which a new sense of connection, or love, however defined, seems to figure prominently.
How to Change Your Mind Page 38