Manufacturing depression (25 page)

So, theoretically anyway, one man can use MDMA to save his relationship and fix his depression and not be guilty of substance abuse, while another can take it so much that he ends up with a
diagnosis. In real life, of course, things aren’t quite so simple. Sometimes doctors have to convince patients that the reason they keep getting fired or divorced or going broke is because they are drinking too much, and that their failure to comprehend this is denial. I myself have done this, and I think I’ve been correct in most cases. But under this logic, it remains easy to diagnose away disagreement, to call behavior sick when it merely fails to conform to standards that have little or nothing to do with what we consider health.

For instance, among the clinical impairments listed in the DSM are
legal issues,
which means that after 1986, when it was made illegal, MDMA use could earn a diagnosis in a way that it previously could not. The DSM, committed to neutrality, can’t comment on the political or social dimensions of this symptom. Instead, it can only refer to a patient’s run-in with the law as a health problem—as if the only reason to break the drug laws is that you are mentally ill. Similarly, if you get arrested for drunk driving, the DSM is going to diagnose your difficulty as substance abuse rather than the misfortune of living in a country where mass transit barely exists and where the focus on individual responsibility is so great that lawmakers don’t even bother trying to require cars to be impossible to start if a driver is intoxicated.

Driving, in fact, is what led Papakostas to tell me that I was a substance abuser. He was following the script of the Structured Clinical Interview for the DSM-IV (SCID), asking me about my history of substance use. As I listed the drugs I had taken, he blinked rapidly, maybe even blanched a little. But he refrained from comment until I answered his question about whether or not I’d had impairment or distress because of my drug use.

“Not really,” I said. “Oh, I suppose there have been times when I’m high that I wish I wasn’t, but I’m pretty careful about the circumstances. I only went to school stoned once. Seemed to me a waste of my time, a stupid place to be high. Same with work. I’ve never been arrested or fired or any of that. I’ve never operated heavy machinery under the influence.”

Papakostas was silent.

“Except once,” I added. “The first time I took LSD. I was eighteen. I tried to drive the half mile home from my friend’s house. I got about three blocks. The road was converging ahead of me, like railroad tracks do when you look into the distance, only it was happening just a few feet in front of me. I was sure I was going to get squeezed into a single atom if I kept going, and that’s when I realized that driving was not such a good idea. So I parked and walked the rest of the way and fetched the car in the morning.”

“Well, you know, that’s drug abuse,” he said.

“It is?”

“Yes. You used in a way that was dangerous.”

It was, in fact, a textbook case. Substance abuse, the DSM says, includes
“recurrent substance use
in situations in which it is physically hazardous (e.g., driving an automobile…when impaired by substance use).” Well, nearly a textbook case. It did only happen once.

But I didn’t remember the “recurrent” part at the time. I was too hot with shame to think clearly. Looking back at myself through Papakostas’s eyes I did not like what I saw, and I wanted to set the record straight. I wanted to tell him that I thought I had done a hell of a job being a responsible citizen, especially for an eighteen-year-old kid, that given the fact that I’d just spent six hours on the beach watching the gulls and waves and boats consort under a pulsating winter sky, that I had seen myself—indeed I could right now, more than thirty years later, see exactly what I looked like, what my friends and I were wearing; I could smell the day like a madeleine—dancing with them toward the threshold of my adult life, that for maybe the first time it had felt not like the edge of a cliff but a portal to a better world, that maybe, just maybe, I was going to get up and fly away, that given all this, I thought leaving the car showed good judgment, was a sign of incipient mental health even.

“But it was more than thirty years ago,” I squeaked out. “And it was only
three blocks,
” and when I heard myself pleading my case,
my shame only deepened. I’d never been called a substance abuser before, and certainly not by a Harvard doctor. It was one thing to get pigeonholed the way I’d been prepared for—as a depressive—and quite another to be told that something I considered to be an important and mostly positive part of my life, something that I thought I handled pretty well, was a problem. And not just a problem but a mental disorder.

But even if I’d had the presence of mind to cite the DSM, or, for that matter, to remind Papakostas that one of the greatest neuroscientists of the twentieth century had taken LSD, and chased it with amphetamine to boot, there was no explaining my way out of it. Partly that was because Papakostas wasn’t really trying to cast judgment on my drug habits. He was just trying to make sure that I was diagnostically pure, that I didn’t have a disease that would add an unwelcome variable to his statistics, and the way to prove that surely wasn’t to convince him that I was a
responsible
substance abuser.

At the time, it seemed as if we were standing on opposite sides of an ontological divide that would swallow up any attempt at conversation. On the other hand, maybe our worldviews weren’t all that different. Freud wrote in
Civilization and Its Discontents,
“It is precisely those communities
that occupy contiguous territories and are otherwise closely related to each other that indulge in feuding and mutual mockery. I [call] this phenomenon the ‘narcissism of minor differences.’” Freud had in mind the traditional warring cousins: the Spaniards and the Portuguese, the Scots and the Brits. But he could as easily have been writing about the Prozackers and the Potsmokers or whatever you want to call the communities to which Papakostas and I belong, which occupy territories that are not only contiguous but often overlapping: the domain of consciousness-altering drugs. Antidepressants (which, interestingly, are not listed as possible drugs of abuse in the DSM, despite the fact that they cause both withdrawal syndromes and dependence) are not only, chemically speaking, the spawn of LSD, one of the most notorious recreational drugs ever to come down the pike. They also, as you’ll
see shortly, owe their entire existence to the fact that people taking drugs for conditions other than depression—tuberculosis, allergies, schizophrenia—suddenly and unexpectedly felt a whole lot better. Or, as we drug abusers say, they got high. Maybe not as high as John Gaddum or Albert Hofmann got, but high enough.

If you’re a psychiatrist or a drug company, this uncomfortable closeness places a great premium on dividing up the territory, on separating your chemicals from theirs, on making sure that yours are medicine and theirs are drugs, that you are treating illnesses while they are abusing substances. You have to disown your embarrassing cousins, even if it means buying an escutcheon from a different family and claiming a scientific pedigree that you don’t really deserve.

This brings me to the third conversation that I had with Papakostas about psychedelic drugs. A few weeks after my clinical trial got underway,
Carlos Zarate
, a National Institutes of Health scientist, released the results of his own trial. Zarate had given one intravenous dose of the anesthetic drug ketamine to seventeen depressed people who had not responded to antidepressants. Within a couple of hours of the injection, most of the patients felt much better; a day later twelve of them were significantly improved, and five of those met the criteria for remission. Half of the responders continued to feel better after a week.

These numbers were remarkable for two reasons: first, that the response was so strong—71 percent, a number that SSRIs can only dream of—and second that it was so rapid. The ten-day to three-week lag between starting to take SSRIs and when they kick in is not only inconvenient, it’s also the period during which patients seem to be at most risk of becoming suicidal. Not surprisingly, Zarate’s study was hailed as a breakthrough in the national media.

In his report, published in
Archives of General Psychiatry,
Zarate took credit not only for solving the biggest problems of the SSRIs—their weak performance in clinical trials and the lag period before they take effect—but for running a study that, unlike most antidepressant
research, was based on a secure theoretical foundation. Like Ladislas von Meduna, who argued that the theoretical nature of Metrazol therapy made it superior to Sakel’s empirical insulin therapy, Zarate informed his readers that all our current antidepressants owed their existence to
“serendipitous discovery,”
while his treatment was anything but accidental.

Zarate built his case on two lines of evidence. First, he cited the psychological research. Normally, subjecting animals to inescapable stressors leads to behavioral despair. But, Zarate wrote,
“a single dose [of ketamine]
interferes with the induction of behavioral despair for up to 10 days”—which means, presumably, that the animals won’t go on strike no matter how bad you make their working conditions. Employers of the world, take notice!

And then there is the data from the biochemists. Zarate recounted the evidence that the glutamates, a group of neurotransmitters affected by ketamine, “
play an important role
in the pathophysiology of depression.” The glutamate theory is a state-of-the art account that states that glutamates, and especially N-methyl-D-aspartate (NMDA), are the ultimate beneficiaries of antidepressants, which means that changing serotonin metabolism is only the indirect means to changing NMDA metabolism. Zarate didn’t consider what this means for all those patients who thought that the reason they had to take antidepressants for the rest of their lives is that they have a serotonin imbalance, but then again, among neuroscientists the serotonin-imbalance theory has long been a thing of the past. Besides, Zarate’s point was more parochial: ketamine is precision manufactured, a bullet designed for a specific target rather than a shot in the neurochemical dark. Unlike what has come before, his was a truly scientific approach to depression.

But speaking of the narcissism of minor differences, the distinction between ketamine and its accidentally discovered cousins is not all that Zarate cracks it up to be. Indeed, there is a “serendipitous discovery” in Zarate’s closet:
anesthesiologists and pain doctors have long noted
that depressed people given the drug for surgery or pain
management—its usual uses—just happen to get less depressed. All that stuff about NMDA and pathophysiology may well be true, but the reason doctors like Zarate were looking there in the first place and spinning these elaborate stories is exactly the reason that, as we will see in a moment, doctors were looking at serotonin: that a drug that unexpectedly made people feel better was found to have an effect on certain neurochemicals.

That’s not the only embarrassment. Zarate also fails to mention that people who come out from under ketamine anesthesia sometimes have an emergence reaction. They experience themselves as awake and aware and yet disembodied, a “consciousness without an I,” as one person told me, pure energy traveling freely through the cosmos. This may be an unwanted side effect to doctors, but to psychedelic warriors it’s a glimpse of the universe in all its glory and indifference—which is why
they’ve been using the drug therapeutically
, mostly underground, for forty years. (Naturally, ketamine has also found its way into the recreational drug scene, something else Zarate left out.) Zarate did mention that his patients suffered certain adverse events, including
“perceptual disturbances, confusion…
increased libido…euphoria [and] derealization.” But just as he erased this part of ketamine’s history, he never, not once, mentioned what the experience was actually like for his patients. Perhaps he figured that if he didn’t ask them, he wouldn’t have to tell the world whether or not they got high.

Or maybe Zarate just thinks that inner life is entirely a side effect. That was what I really wanted to talk to Papakostas about when I brought up Zarate’s research—my increasing sense that I was only the middleman, the guy he had to go through to get to the truth of the matter, which lay not in my thoughts and feelings but in my biochemistry, not in my spirit but in my meat. It was one thing to ask questions about my subjectivity that seemed designed to erase it. It was quite another to study the effect of a psychedelic drug on consciousness without ever talking about consciousness itself. I wanted to know, do depression doctors really think that subjectivity,
especially the experience of transformation, is irrelevant? And if so, then aren’t they making an enormous and controversial claim about the mind: that it is merely the biggest side effect of all?

Our conversation was short. Papakostas knew about Zarate’s research, he told me. But he didn’t seem to know that ketamine was a consciousness-altering drug. I explained what I knew to him. “Sort of like ECT,” he said. “The way it’s supposed to reset your neurotransmitters.”

“But isn’t there a difference between ECT and ketamine?”

“Well, of course ketamine works mostly on glutamate pathways…”

“No. I mean that you’re conscious when you take ketamine and unconscious when you get ECT.”

The distinction seemed lost on Papakostas. He looked at his watch, said we were out of time. For a second I thought I caught a whiff of regret, as if maybe he wanted to talk about the nature of consciousness and its relationship to what we were doing. But I might have been making that up. Mostly what I felt was an immense frustration, a version of the same frustration I felt when he told me I was a substance abuser: that when it came to
Homo sapiens,
we simply weren’t talking about the same animal.

But then again, I was the depressed person and he was the doctor, and maybe he knew something I didn’t. Maybe the insuperable indeterminacy of consciousness is really not a supreme mystery that will always beg for and elude solution in nearly equal measure, but rather the sign that the question isn’t worth asking, that if you want to feel better the last thing in the world you should do is inquire into your inner life. Unless by that you mean the amino-acid-rich neurochemical soup that roils in dumb silence inside your head.