The Trippy Science of Psychedelic Studies
After I signed up for one, I started to dig into their data. That’s when things got weird.
I've never been the kind of person to gush about mind-altering drugs. In fact, it takes only the slightest whiff of woo-woo to send me rolling my eyes — hard, with gleeful abandon. But when I tell people I’ll be taking a not-insignificant dose of psychedelics as part of a research study to treat depression, no shock ensues.
We live in a psychedelic renaissance where tripping for divine revelation or high productivity is fast becoming a trend. But what really interests me is the scientists — in particular, those who talk about treating depression and dissolving the ego, all in the same breath.
The research team I’ve picked at Imperial College London (ICL) is one of a few exploring the potential for psychedelics to treat intractable mental illnesses. The results of their work so far have been impressive. For instance, in a 2016 study, all 12 of the volunteers (all of whom struggled with treatment-resistant depression) saw relief. Eight were depression-free after just one week, five of those stayed in remission, and two others sustained a significant reduction in symptoms at the three-month follow-up. Other psychedelic studies have shown similar promise in helping people with alcohol addiction, smoking, obsessive-compulsive disorder, and cancer-related anxiety — and all it often takes is a single hit of the drug.
While participating in the study, I’ll make seven visits to the lab. Each will be between two and eight hours long and I’ll undergo two MRI scans, 90 minutes each. By the end of the study, I’ll have taken two doses of psilocybin (either high or low), the active ingredient in magic mushrooms, and six weeks of pills — placebos or antidepressants (escitalopram) — in between.
For some reason, I find myself completely untroubled by the high substance dose — 25mg, enough to produce a full-blown, out-of-control, out-of-body experience for someone of my weight. What bothers me more is the idea of being trapped for 90 minutes inside the noisy sarcophagus of the MRI machine. Not because of claustrophobia, mind you, but because of boredom. This is the thing I’ll later look back on and regret the most: that careless shrug, the almost leap-of-faith decision to turn my psyche over to the scientists and their drugs.
If you’re a child of the ’80s, the recent comeback of psychedelics may appear surprising. I didn’t know that in the 1950s and ’60s, classic psychedelic drugs such as LSD, psilocybin, and mescaline enjoyed great popularity among a wide variety of researchers and health professionals. During this period, scientists published over 1,000 papers and held six international conferences on LSD; some 40,000 people were treated with the drug.
Psychotherapists gave it to clients to surface repressed material; psychiatrists used it to invoke and study psychotic symptoms in their patients.
Eventually, as psychedelics spread to the general public and gained rapid adoption among the hippie movement, they became increasingly politicized. Florid, often exaggerated stories of abuse appeared in the media spawning fears and criticism, and the government cracked down on the drugs. By the early 1970s, the research had dried up; the party was over.
After decades of hiatus, the pendulum again began to swing in the ’90s, as more rigorous studies uncovered new evidence about the medical potential of psychedelics. Over the past 15 years, this evidence has only grown in size and promise. For example, a 2016 study of cancer patientswith anxiety and depression found that five weeks after taking a high psilocybin dose, 92% of subjects showed a reduction in their depressive symptoms by at least 50% and 60% of the subjects were nearly depression-free. (Remarkably, the number of depression-free subjects even rose slightly after six months.) Other psilocybin studies have reached similarly compelling outcomes.
In one, 15 heavy, chronic tobacco smokers received up to three moderate to high doses of the drug. In six months, 80% of participants were abstinent — an impressive number if you compare it to the less than 35% quit rate attributed to nicotine replacement therapies and other pharmacological interventions. In the context of such rapid and enduring positive changes, the mounting public interest in mind-altering drugs comes as no surprise.
Some scientists, however, are cautious of the hype. What we have now, they say, is only a handful of small, preliminary studies showing psychedelics to be well tolerated, nonaddictive, and safe to use in a therapeutic setting.
We can’t yet draw definitive conclusions about the drugs’ clinical efficacy or practical use. Most existing studies still lack the placebo controls, too, plus the blinding procedures and adequate sample sizes that would be expected from trials of new drugs to ensure that the observed effects are not a fluke.
As far as I can tell from their testimonies, posttrial participants spend less time holed up in front of the TV and more time outdoors… They speak of being “saturated in the majesty of existence.”
For this reason, Guy Goodwin at the psychiatry department of the University of Oxford sums up his position on psychedelics as “upbeat pessimism.” Somewhat more cheerfully, Robin Carhart-Harris, who heads ICL’s Psychedelic Research Group (and my study), describes his own stance as “tempered optimism.”
I’m optimistic, like Carhart-Harris. And for a while, my optimism is through the roof. I learn that subjects of psychedelic studies on mental health don’t simply feel better and do better after the treatment — they also seem to become better humans. Pouring over follow-up interviews with participants, I can’t help but wonder: Are these people for real?
As far as I can tell from their testimonies, posttrial participants spend less time holed up in front of the TV and more time outdoors. They don’t waste precious energy on petty fights and they don’t sweat the small stuff. They’ve let go of resentment, released past hurt, and forgiven old grudges. They’ve owned their vulnerability, reconnected with their values, and transformed their relationships. They speak of being “saturated in the majesty of existence.” And though the language of these reports makes me cringe, I have no real reason to doubt their truthfulness, or to brush their comments off as the vacuous babble of pseudo-enlightened spiritual gurus.
Except. There’s a small detail I stumble upon in the smokers’ study. It’s barely visible under reams of ecstatic accounts and I nearly miss it: As it turns out, five of the 12 participants that agreed to be interviewed “reported not wanting to experience psilocybin again.” A sixth one had mixed feelings.
One of the ICL researchers wants to assess my suitability as a subject. Her voice has the strained breeziness of someone caught in an awkward situation and in my compulsion to comfort her, I worry that I’m not coming across as properly distressed. At the end of the call, I ask about something that’s been eating at me ever since a friend shared his harrowing mushroom experiment: the odds of having a bad trip. There’s no such thing, the researcher tells me.
That’s not to say the psychedelic experience is easy or wholly euphoric. In fact, a quarter to over half of participants report negative emotions during a trip , like sadness, fear, despair, confusion, and even paranoia. Usually, though, these feelings pass quickly. And many participants and researchers believe a degree of struggle bears therapeutic benefits. In one survey of nearly 2,000 people, subjects explained their bad trip. Over half said it was among the most difficult experiences in their lives, yet a whopping 84% still felt their trip had helped them.
In the 1950s, psychedelics were often used as mind-manifesting agents. For the Freudian psychiatrists at the time, the drugs seemed to reveal the inner workings of the subconscious. Patients ingested small doses to help them retrieve suppressed memories and feelings, which could then be worked out in therapy. In modern clinical trials, subjects typically confront their demons on a single, emotionally intense trip (though the procedure is sometimes repeated once or twice). Alexander Belser, a founding member of the psychedelic research program at New York University who currently works at Yale, talks about “an arc of experience or a necessary sequence” that resembles the rising action, climax, and resolution of the hero’s journey in stories. The twist of the psychedelic trip is that in order to triumph, the hero must actually surrender. Surrendering to struggle in the drug-altered state has emerged as key to attaining emotional catharsis and resolving your inner conflicts.
In one study, subjects were instructed to “trust, let go, and be open.” This mantra comes in handy when hard emotions bubble up and the instinct to resist them begins to take over. Because it’s this resistance to uncomfortable feelings, rather than the feelings themselves, that’s believed to turn a trip bad.
Emotional catharsis may be one way in which psychedelics can improve mental health. Another possible mechanism is the mystical or spiritual experience that accompanies high-dose trips.
Mystical experiences often occur when the boundary between self and surroundings falls away and a blissful sense of merging takes place, a sense of oneness with nature, God, the Universe, “the family of things,” as poet Mary Oliver put it. One participant in a trial of psilocybin-assisted psychotherapy described the feeling as “being inside a drop of water, being inside of a butterfly wing.”
But there’s a paradox lurking in the mystical experience: To become one with the world, you must give up what appears to connect you most intimately to it — your self. In spiritual and science circles alike, this is called ego dissolution. Michael Pollan, author of the bestselling book How To Change Your Mind, described his own drug-induced ego dissolution as “a pile of Post-its being scattered to the wind.”
For Pollan, the ego is the enemy. Ego is the voice in your head that won’t stop talking, won’t stop spinning loops of self-loathing, and brooding rumination. Only when you let it go, can you see through the ego’s maddening chatter. In a dramatic way, ego dissolution reveals to us that there’s nothing necessary or immutable about our identities, nothing that ties us to who we are right now — and this opens up the possibility of a new, better self to emerge.
During a trip, one subject in the smoking cessation study saw herself turning into a purple vine of such lush grandeur that cigarettes began to look silly and trivial to her in comparison. Having found a more compelling self in her vision, she easily kicked her habit. It’s a simple realization : “I’m not defined by my past” or “I can change.” What psychedelics seem to do is turn this abstract idea into embodied knowledge.
Intellectually, you know you can and do change, and yet people tend to cling to who they already are, treating themselves as fixed objects. In contrast, the knowing that occurs during a mystical trip is not that of reasoned thought. You don’t arrive at it so much as it possesses you. You don’t learn something; rather you become something. It’s this enactment of insight that allows you to make it your own. And there, perhaps, lies psychedelics’ power : the way they transform received wisdom into personal, skin-deep truth.
But there’s a problem with this picture. Are the drugs giving us a glimpse into higher, hidden realms? A peek at who we really are? Or is the mystical experience just a powerful hallucination that feels eerily real?
📷In2014, Carhart-Harris coined the term “the entropic brain” to explain how psychedelics exert their remarkable effects on mental health. From physics, he borrowed the concept of entropy — the degree of randomness, or uncertainty, in a system — and applied it to the human brain, together with evidence from neurobiology and elements of psychoanalysis. Brain states, Carhart-Harris proposed, occupy a continuum between order (low entropy) and chaos (high entropy). High-entropy states are when thoughts run wild and free, like in deep sleep, early psychosis, and infancy. This mode of consciousness is flexible and creative but also irrational and anarchic. On the other end of the spectrum are low-entropy brain states like in rigid thinking, that feed on logic, rules, and structure, and favor control over creativity.
Normal consciousness sits somewhere in the middle of those two extremes, tipping slightly toward order. But order comes at the expense of flexibility and too much of it can become pathological. Depression, addiction, and OCD show how an errant thought can turn into a rigid, monolithic structure: Everything seems bleak, nothing can get you through the day except a bottle of Smirnoff, you have to count every object in sight or something bad will happen. It’s as if the mind, grasping for certainty, traps itself in a rut, unable to adapt to changing situations or transcend them.
Psychedelics let in chaos, blast mental grooves, and shatter stiff structures, prying loose all manner of thoughts, perspectives, and states of mind. In neurobiological terms, the default mode network (DMN) relaxes its hold on the sensory, more primitive regions of the brain. In the ensuing anarchy brought on by the drugs, the brain is freed to make creative leaps, to bend time and space and self. Ideas, cut off before, now collide and combine into new perspectives, altering our moods and expanding our universe of attainable mental states.
In this way, Carhart-Harris says, psychedelics may actually normalize a brain that’s tipped too far into order by making it more random and therefore more flexible. Increased flexibility, in turn, gives us a wider range of responses and coping mechanisms to choose from rather than being locked into a few dysfunctional ones.
Evidence supporting this view comes from a study in which subjects dosed with psilocybin were more open-minded 14 months later — a remarkable outcome given how stubborn our personalities tend to be. And yet to think of psychedelics simply as perspective shifters that make people more open, nimble, and resourceful misses a key nuance in their mechanism. The drugs don’t merely facilitate neural connections and insight; instead, they seem to engineer and deliver a certain type of insight. It’s this seemingly small detail that casts doubt on the ethics of their therapeutic effects.
Psychedelics users have long known that the quality of their trips depends on the environment in which they occur. Ido Hartogsohn, a researcher who studies the social and cultural aspects of these substances, writes that “the same drug can create anxiety or relaxation, fear or joy, cognitive enhancement or retardation, suspiciousness or intimacy, depending on how it is used.” This can help explain the contradictory outcomes of early psychedelic studies:
To hospital patients dosed with LSD against their will, the compounds were “anxiety-producing agents,” whereas people who experimented freely and in positive settings found in the drugs a font of “new sanity.”
According to Harvard psychologist Timothy Leary, a key and controversial figure in the early psychedelics movement, these drugs magnify what’s already present in the mind. Leary argued that the two most crucial elements of the psychedelic trip are its “set and setting” — a term he coined in 1963 that’s still in use today. Set refers to the user’s personality, preparation, intention, and expectations (including wishes and fears) and setting consists of the surrounding physical, social, and cultural environments.
Set and setting are more than background — they also supply the inputs for the psychedelic experience. And just like you can tinker with your ingredients to create a dish the way you like it, so can you manipulate the set and setting of your psychedelic trip. This is exactly what happens in modern clinical trials, and the implications get murkier the more you ponder them.
Consider Johnson’s study of long-term smokers: Prior to taking their first psilocybin dose, subjects received instruction in mindfulness as well as four counseling sessions with two trained study guides. Their preparation also included a personal mantra, guided imagery, and scented oils to lock in positive suggestions. On the day of the experiment, participants arrived in a cozy room fitted with a sofa, should they want to lie down during the trip. A face mask blinked the world away as they journeyed inward. Evocative music seeped through earphones while the study guides stood by and encouraged the subjects to “trust, let go, and be open.”
In other words, by the time they took the psilocybin, the participants were already primed for a positive experience. The deliberate setting provided the raw materials — sounds, sights, and smells. The thorough preparation — from the strong bonds forged with the guides to the sense of ritual and profundity evoked by the oils, mantras, and visualizations – supplied key emotional cues.
The trouble is, this harkens back to an idea Timothy Leary had back in the ’60s: To get set and setting down to a science would allow people to optimize and preprogram the precise psychedelic experiences they want to have. Could this be an extreme version of what happens now in psychedelic trials? Are people being manipulated into better mental health? In a recent NPR interview, Michael Pollan addressed the question of whether the drugs create illusions in people. “I got a variety of answers to that question from the researchers. One was, who cares, if it helps them? And I can see the point of that.”
I can, too. But I can also see the dangers.
The brain on psychedelics is not only susceptible to cues, but it also exaggerates their meanings. And here’s the problem with that: We can debate what’s real and what is an illusion, but we can’t ignore the power of the drugs, or the power of the people who administer them to us, and we can’t ignore our own vulnerability to both. This is what chills me.
And so it comes as a relief, rather than a disappointment, when at the end of our second conversation, the ICL researcher informs me that I’m not sufficiently depressed enough for their study.