Manufacturing depression (23 page)

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”?

Hofmann proceeded the old-fashioned way used by Paul Ehrlich and William Perkin before him—tweaking the compound, mixing together this and that to make new molecules and then seeing if they did something promising in the test tube or to an animal. He eventually invented a way to assay ergot’s presence in animal tissue, discovered its active ingredient, and synthesized it and a series of variations, but no clinical applications emerged. In 1938, he thought he’d found a drug,
Lysergsaüre-diäthylamid
(lysergic acid diethylamide), or LSD, that would be a good stimulant, but the guys in pharmacology concluded that it had no clinical promise. Five years later, Hofmann wanted to take another crack at convincing them. He whipped up a batch and suddenly found himself feeling unsteady and weak. He thought he was coming down with a cold, so he went home and got into bed, whereupon, as he put it in his report to his boss,
he experienced “an uninterrupted stream
of fantastic images of extraordinary plasticity and vividness accompanied by an intense kaleidoscopic play of colors.”

That was on Friday. By Monday, Hofmann had determined a course of action. “
I decided to conduct some experiments
to find out what was the reason for that extraordinary condition I had experienced,” Hofmann told an interviewer fifty years later. Perhaps because it had been a “not-unpleasant” experience (certainly more pleasant than John Hunter’s self-inoculation with syphilis), he decided to run the experiment on himself.

At first, he suspected that he had inhaled the solvent he’d used at the end of the synthesis. But when he tried directly exposing himself to it, nothing happened. Then he turned to the LSD. “
I was open to the fact
that, maybe, some trace of the substance had in some way passed into my body. That, maybe, a drop of the solution
had come onto my fingertips and, when I rubbed my eyes, it got into the conjunctival sacs. But, if this compound was the reason for this strange experience I had, then it had to be very, very active.” He decided to proceed with “extreme caution” by taking what he thought was only a tiny dose—a quarter of a milligram.

Hofmann quickly discovered that he had underestimated LSD. Within forty minutes of swallowing it, he could no longer write in his notebook. (“
Beginning dizziness,
feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh” was the last entry he managed to make.) That’s when he decided to go home—by bicycle, because the war was restricting the use of cars. It was a terrifying trip—“Everything in my field of vision wavered and was distorted as if seen in a curved mirror. I also had the sensation of being unable to move from the spot. Nevertheless, my assistant later told me that we had traveled very rapidly”—but that was nothing compared to what happened when he arrived home.

Every exertion of my will,
every attempt to put an end to the disintegration of the outer world and the dissolution of my ego, seemed to be wasted effort. A demon had invaded me, had taken possession of my body, mind, and soul. I jumped up and screamed, trying to free myself from him, but then sank down again and lay helpless on the sofa. The substance, with which I had wanted to experiment, had vanquished me. It was the demon that scornfully triumphed over my will. I was seized by the dreadful fear of going insane. I was taken to another world, another place, another time. My body seemed to be without sensation, lifeless, strange. Was I dying? Was this the transition?

Hofmann didn’t die. Nor did he go insane, at least not permanently. He did call a doctor, but by the time he arrived, “the horror softened and gave way to a feeling of good fortune and gratitude,” and Hofmann began “to enjoy the unprecedented colors and plays
of shapes that persisted behind my closed eyes.” After a few hours, he fell asleep, and the next day awoke

refreshed, with a clear head, though still somewhat tired physically. A sensation of well-being and renewed life flowed through me. Breakfast tasted delicious and gave me extraordinary pleasure. When I later walked out into the garden, in which the sun shone now after a spring rain, everything glistened and sparkled in a fresh light. The world was as if newly created.