Manufacturing depression

by Gary Greenberg

  Joseph Wortis didn’t bring any of this caution back with him when he returned to America from Vienna in 1935. Instead, he brought insulin therapy to Bellevue Hospital, from which it spread to the rest of the country. He made his own contribution to the method, perfecting a technique for keeping people in comas for up to twenty-four hours—the program was terminated in 1942 after a patient died—and eventually became the editor of the journal Biological Psychiatry. Manfred Sakel arrived in the United States shortly after Wortis’s return. He administered insulin treatments to his wealthy clientele in hospitals, hotel rooms, and private homes and acquired a reputation, at least with the New York Times, as the “Pasteur of psychiatry.” In 1937, a pair of Upper West Side doctors started treating depressed New Yorkers with Metrazol, and in 1940, just as Lothar Kalinowsky set sail for America, an epidemic of ECT spread to asylums in New York, Chicago, Philadelphia, and even Cincinnati. Headlines like “Insanity Treated by Electric Shock” began to appear in the Times, and by 1950 the age of biological psychiatry had begun in earnest.

  If anyone was worried about the irrationality of all this therapeutic exuberance—other than the analysts whose livings it threatened—they weren’t saying. But then again, the guinea pigs in this experiment were terribly sick, which made it easy to justify desperate measures taken on their behalf. Had the shock doctors’ methods been less extreme and unpretty, had they been, say, gaily colored pills with friendlier names than electroshock therapy, remedies that just tweaked consciousness a little bit, that could be taken in the privacy of one’s own home, that had only a few side effects, and that were held out to cure a disease afflicting 20 percent of the population, there might have been a little more worry. In this sense, the depression doctors are in infinite historical debt to the shock doctors. They softened up the market for them, getting people used to the idea that doctors could mess with their heads even if they didn’t know exactly what they were doing.

  They also got people ready for the idea that Freud warned Wortis about and that my clinical trial made a fetish of: that our discontents and their cure are in our brains. The shock doctors, starting with the observation that biological interventions relieved psychic suffering, began to build the case that mental illness is fundamentally a biological problem. They took Kraepelin’s brilliant, build-it-and-they-will-come strategy—claim scientific authority by speaking in scientific language—one giant step farther.

  Kraepelin had in effect issued a promissory note: eventually, he promised, an explanation would emerge that would validate his taxonomy; on that assurance, the taxonomy, which sounded scientific, should be accepted now. The shock doctors realized that so long as they did something dramatic to a patient’s body, so long as what they did was plausibly biological, and so long as they got results, they could further claim that they had proved what they were still only assuming. They could have the capital without even making the promise. They also identified the market: not schizophrenia, which often remained unaffected by their treatments, and which rendered its victims nearly inhuman, but depression.

  CHAPTER 8

  THE ACID AND THE ECSTASY

  My first depression lasted for a couple of years. When drugs made it go away, it was an accident. Not the taking drugs part—that I meant to do—but the depression-lifting, anxiety-erasing, total-revolution-in-my-head part. I’m not sure what I was expecting when I took Ecstasy for the first time—although the name should have been a clue—but what actually happened is the last thing I would have predicted.

  When it comes to taking drugs like Ecstasy—whose official name is MDMA, or methylenedioxymethamphetamine—I am an educated and careful consumer. Before my first LSD trip, when I was eighteen, I prepared myself like a Boy Scout. I read about other people’s experiences, learned about what made them good trips or bad trips, sat with friends through theirs. On the appointed day, I made sure I trusted the people I was with, that we were in a safe place, that our nutrition and hydration needs could be met. I did one last walkaround of my own psychic state (as much as one can when one is so young) before I popped that little piece of paper in my mouth. No one told me to do all this; it just seemed prudent, the same way that it is prudent to learn how to drive a car before you get on the expressway. I guess that when it comes to taking dangerous drugs, I have a self-preservation instinct.

  And MDMA can be a dangerous drug. At high doses—not too high, maybe four or five times the normal human dose—it’s neurotoxic.* Of course, so is Prozac, or for that matter Pepto-Bismol (bismuth causes brain damage), although in both cases you need more like a hundred times the normal dose to cause problems. But that’s not why I hadn’t taken it before 1990. My reluctance wasn’t about the drug itself, but about me. I was concerned that my emotional state was too fragile to risk any disruption. I had, in fact, declared a moratorium on psychedelic drugs when, not long after I first got depressed, I took a dose of psilocybin mushrooms and spent a few hours resisting the urge to dash my brains out on a rock.

  Like I said, educated and careful.

  On the other hand, my circumstances seemed in some ways perfectly suited to MDMA. Its reputation among psychotherapists, at least of a certain stripe, was stellar. They gave it rave reviews, so to speak, for its ability to foster open, fearless communication—a mainline from the heart to the mouth and the ears, they said. It could, they went on, accomplish in an afternoon what years of therapy could not and was especially effective for couples with relationship issues.

  And boy did we have some of those.

  Susan had moved across the country to be with me. She’d left behind a marriage to a man whom she had been with for fourteen years, and all the life that went with that—house, friends, money—to move to my little New England village, whose inhabitants’ Yankee reserve registers with anyone from outside as disdain. She arrived to find me in the midst of my first depression, so morose and sour that I couldn’t even give her a kiss with her Valentine’s Day gift.

  We’d agreed not to live together, but that didn’t stop me from feeling responsible for her, a feeling I responded to by keeping her at arm’s length, by being cold, by letting her know in every way that I wasn’t going to take care of her, that I’d had enough of that in my first marriage and in my life and it wasn’t going to happen again—speeches that, had I been able to think clearly about it, I would have realized were unnecessary because that was the last thing in the world she wanted.

  Susan was, and is, too humane and proud to pressure me (and maybe too clever; she wasn’t about to fulfill my prophecy), but after a year of my ambivalence, I knew that she was getting impatient. Which I helpfully responded to by being even more standoffish. And more depressed.

  My therapist at the time asked, “But in your core, in your heart of hearts, do you love her?” That’s one of the all-time stupidest questions a therapist has ever asked, but I couldn’t blame her. She was tired of my dithering too.

  “Love is beside the point,” I told her. “I’m too old for that.” I was thirty-two, but I felt ancient. “I’m just not sure I want to marry her.”

  “She’s wants you to marry her?”

  “Well, she hasn’t said that. But I’m pretty sure.”

  “I wouldn’t be so sure. If someone treated me the way you’ve been treating her, I’m not sure I’d want to marry you.”

  Which was one of the all-time smartest things a therapist has ever said. It didn’t do anything for my depression, at least not directly, but I did resolve to figure this out—if for no other reason than to spare further misery to someone whom, in my core, in my heart of hearts, I did love. I gave myself a deadline—six more months and then I’d have to call it quits.

  Around that time, a friend of mine sent me some MDMA in the mail. (I should acknowledge that various felonies were committed here, and unjust as this is, it’s not something I am recommending that you try at home.) Susan and I decided to take it with us when we traveled to a grimy Rust Belt city to see the Grateful Dead. We took
the capsules—125 milligrams each of pure, lab-certified MDMA—in our hotel the morning of the show.

  We lay down on our bed and waited. Even the best psychedelic drug experiences are an ordeal, especially at the beginning. So we’re lying on this bed in the Rust City Holiday Inn, looking up at the ceiling, close but not quite touching, talking about nothing in particular, certainly not about the fact that at this moment I’m remembering my last psilocybin trip and wondering why in the world I’ve done this to myself. I’m just about to resign myself to four or five hours of avoiding the rocks, and I turn to say something to Susan, maybe even something honest about how scared I am, and she just happens to turn toward me at the same time. Our faces are about a foot apart at the nose, and I look into her eyes, which are a perfect shade of violet, soft—limpid is the word that comes to mind, a word that has rarely, if ever, crossed my mind before—and inviting, so inviting, like a calm blue sea. I dive in. I am looking back and seeing me as she does—literally, viscerally, Vulcan-mind-meldedly. My God, she loves me. I can’t say that I understand this, but whatever: I am forty fathoms deep in love.

  Which is cool enough, but nowhere near so cool as what comes next. In one moment, a nanosecond maybe, the dread, the self-loathing, the sadness and despair and nausea, all the dark, twisted thoughts that have black-dogged me for two solid years, keeping me up nights, ruining days, driving away opportunity by the carload and hurting the people I care the most for, including especially the one right here next to me, the one who has so graciously lent me her eyes—it all drains away, every last polluted ounce. I feel it leave me, like dirt washed off in a shower. I don’t know where it has gone, and I don’t care. Because for the first time in two years, and maybe in my life, the world feels like a hospitable place, and more than hospitable: welcome, friendly, full to the brim with love. Whatever poison has been running through me, I believe I have found the antidote. Not the drug, of course, but this person next to me, this steadfast, patient, kind woman who, beyond all reason, loves me. Who is the channel through which all this ecstasy flows.

  I’ll spare you the rest. Well, no I won’t. I have to tell you about Grace and Angel.

  Susan and I are lying on the bed inside this numinous bubble, it’s been an hour or so and we must be positively glowing as we stare into each other’s eyes. By now, I’m on top of her, but our clothes are on—as we will find out later (and I really will spare you this), the kind of lovemaking that involves genitals is a dicey proposition on this drug, probably because it’s totally redundant—and we’re talking gently to each other about this newfound world, when there is a knock at the door, followed quickly (or maybe not so quickly, our sense of time not being all that it could be) by the turning of the key and the entry of the maid. Whose hotel is full of Deadheads, so this can’t possibly be the weirdest thing she’s walked in on today—not to mention she’s a chambermaid, a professional walker-in-upon—but she is nonplussed anyway. She backs out quickly, starts to close the door. We stop her, tell her to come on in.

  It turns out that the Ecstasy bubble expands, and Angel—I’m not making these names up—soon calls her fellow housekeeper Grace into the room. We love her too. We love the janitor they fetch, whose name is probably Gabriel, but I’m not asking. We love the Irish whisky that we toast them with—and so does Gabriel—and the salsa music they find on the radio, and the beige uniforms they wear, and especially the rolling carts they’ve left by the door. They are brimming with fresh white linens, tiny bottles of shampoo and lotions, clean cups and bars of soap and rolls and rolls of toilet paper, and all this stuff designed to cater to our needs seems like an embodiment of all the inexhaustible supply of love in the world. And as we dance—Gabriel all sinewy and loose (and I don’t think this is the first snort he’s had today), the women bemused and happy, the joy jumping out of our skins—I can’t imagine what in the world that depression could have been about. All I know is that it’s like someone has finally shut off a jackhammer outside my window, one that has been banging for so long that I’ve almost forgotten it is there, let alone what the world sounds like without it. And I resolve never to feel that way again. Because it seems so totally unnecessary.

  On the other hand, I also find myself saying—because the man on the radio mentioned something about the local team—that it might be fun to go to a hockey game someday, that hockey must be a wonderful sport, and even in my disbelief-suspended state, I realize that this might be a bit much, that whatever valve has closed, and whatever humor it has shut off, the one that tempers love with judgment, that I probably can’t get along without it forever. The world is too dark and mean. But for the moment, I’ve stood on the other side and looked back. I’ve lived in the warm embrace. I’ve seen worry and despair for the folly that they are. I am healed.

  Susan and I were married within eighteen months. We’re still married, and I am sure we always will be. Even more germane, it was years—years!—before I was ever again depressed.

  Now, that’s my idea of an antidepressant.

  It turns out that I’m not the only one with that idea. Or at least something like it.

  MDMA has a very powerful effect on the brain. It rouses the nerve cells in a part of the brainstem called the dentate gyrus into a frenzy. Those cells produce electrical signals that travel through axons—fibers that project from the cell body into the farther reaches of the brain and end at the axon terminal, in which serotonin is stored. When a signal reaches the end of the line, the axon releases its serotonin into a synapse, a gap between nerve cells. On the other side of that gap are receptors attached to fibers (dendrites) that lead to other cell bodies. The MDMA-enhanced signaling causes massive amounts of serotonin to be launched into the synapse, where it stimulates the hell out of those dendritic receptors. Meanwhile the drug also suppresses the enzymes that would normally whisk the serotonin out of the synapse, break it down into its constituent parts, and recycle it for further use, which means that the increased amount of serotonin stays in the synapse longer than it usually would.

  To a literary guy like me, the fact that all the time you are bathed in the MDMA lovelight, your synapses are being bathed in serotonin is irresistible. You can’t help but want to cite it as evidence that the universe is a benevolent place, or at least that there are pockets of benevolence in an otherwise merciless world. You want to write a panegyric to your neurotransmitters, send them a thank-you note for making your experience possible, gush about this unmistakable and beautiful isomorphism, use this brilliant conjunction of the inner and outer worlds for all its metaphorical worth. And you’d consider taking the drug again, maybe see if it can do for your writing or your musicianship or your tennis game what it has done for your mood and your love life.

  On the other hand, if you’re a scientist, let’s say a scientist interested in curing mental illnesses, this conjunction is irresistible for other reasons. The fact that changing serotonin metabolism has such profound and positive results on experience and behavior makes you wonder what would happen if you figured out other ways to accomplish that goal—maybe ways that wouldn’t involve an overnight at the Holiday Inn or the risk of brain damage or imprisonment or a sudden wish to go to a hockey game. Even harder to resist would be the conclusion that the alteration of serotonin activity is what causes the alteration in experience, that the ecstasy is somehow in the serotonin. Basking in the glow of these results, you might well forget the basic rule of science: correlation is not causation. To discover that two things happen together is not necessarily to discover the cause of a phenomenon.

  That’s what was wrong with Hippocratic medicine in the first place: if the fact that a syphilitic gets better shortly after taking mercury leads you to the conclusion that mercury cured him, you might unleash a few centuries of using a bad poison as a medicine. Maybe giving the patient mercury was what we call a necessary cause of his cure—perhaps for no other reason than the placebo effect created when a doctor offers a remedy to a sick and desperate person�
�but until you find the mechanism of the response, or at the very least you replicate that response many times under controlled conditions, you can’t conclude that mercury is also the sufficient cause of the remission or that syphilis was a mercury insufficiency in the first place. The “cure” could just be a coincidence.

  This is exactly what has happened with neurochemistry, especially the neurochemistry of serotonin and depression. Scientists have made too much of coincidence in fashioning depression as a brain disease to be treated with antidepressants. It’s an understandable mistake. The series of coincidences about serotonin with which they were confronted starting in the late 1940s were as compelling as, well, a drug trip.

  That’s how the serotonin story begins—with a bicycle ride taken in 1943 by a Swiss scientist who was high to the gills on a then-unknown drug.

  Albert Hofmann was a thirty-seven-year-old medicinal chemist working for Sandoz, a pharmaceutical firm. For seven years, he had been trying to figure out what was going on, pharmacologically speaking, with ergot, a purple fungus that grows on rye. Ergot was infamous as the cause of St. Anthony’s fire, an affliction that causes a burning pain in the extremities, followed by gangrene and, eventually, after the patient’s toes and fingers start to drop off, a very painful death. (Ergot also induces hallucinations, and some historians think that witchcraft epidemics began with bread made with contaminated flour.) Ergot also had a history of medical use—as a labor-inducing drug that, according to one nineteenth-century physician, “expedites lingering parturition and saves to the accoucheur a considerable portion of time.” Sandoz was hoping that Hofmann could find out why it hastened labor and use this knowledge to patent a derivative of ergot for medical purposes. What better way to sell a medicine than to promise a doctor that his schedule won’t be held hostage to a woman’s “lingering parturition”?