by Matt Samet
Christmas break 1992 was a nightmare, a nauseous, tortured, insomniatic nightmare. Not only hadn’t I been eating, now I had such a nervous stomach I barely could eat even when I wanted to. I canceled plans to spend two weeks bouldering at Hueco Tanks and tried to climb only once, a jaunt with a friend to Socorro only an hour away during which I had to bail midday as “it” came shimmering over again like toxic drizzle. I’d also come to associate exercise with the fear—with that StairMaster session and ER visit—and refused to get my heart rate up. I stopped jogging. On bad nights, in my peripheral vision, I’d see shadows shifting along the walls, creeping upward like spilled paint in some upside-down mirror world. My best friend, Sky, a nonclimber, was home from Georgetown, so I’d either hang out with him at his dad’s house or hole up in my room playing Super Mario Bros and trying to will away the terror. With Sky, I went out once to a record store and again to the movies, and felt “it” happen: In these confined spaces, breathing forced, heated air, I’d begin to “suffocate” and have to run outside to regroup. I had another huge panic attack one night coming back to my dad’s while he and my stepmother were out to dinner. Alone in the house, juicing with adrenaline, I called 911 again, my voice so reedy that the EMTs were shocked to find a scared, healthy young man and not an old woman having a myocardial infarction when they rang the doorbell.
Before winter break had ended, I’d agreed to visit my old psychologist in Albuquerque, “Dr. Smith.” He was an empathetic, low-key soul who’d counseled me during the Challenge Program years, hip enough that he kept Carlos Castaneda books in his office and would let me borrow them. Dr. Smith was a good listener and engaged in a dialogue of equals, the definition of a solid therapist: someone who cares about you—not just your diagnosis—and, without judgment, leads you through the tangled web of your broken thinking. Dr. Smith referred me to his mentor, a professor in CU’s psychology department, and I began to see this new therapist, Jack, twice a week. Jack in turn referred me to a psychiatrist, which is often how these things play out—two complementary therapies. Unlike psychologists or therapists, psychiatrists are medical doctors generally focused on a diagnosis and on medicating symptoms, who might see you for a quick, fifteen-minute med check-in every three months and tend not to tangle with sticky issues like feelings. This doctor had the standard-issue sleepy demeanor and Sigmund Freud beard. We began experimenting with different antidepressants. The notion was that to treat anxiety you must first address any underlying depression. I tried Pamelor, the name-brand version of nortriptyline, but couldn’t deal with the dry mouth, palpitations, and orthostatic hypertension. I quit after a week. We tried Trazodone, an atypical antidepressant, but it made me logy and glassy-eyed, as if I were taking horse tranquilizers; I stopped this drug after only two days. Finally we settled on a low dose (10mg) of Paxil, a selective serotonin-reuptake inhibitor or SSRI, in the same family as Prozac, Luvox, Lexapro, Celexa, and Zoloft. We’ve all heard of SSRIs, the supposedly cleaner second-generation antidepressants—since 2004 with an FDA black-box suicide warning for children and adolescents—that allegedly outperform the old pills. The party line is that, instead of barraging all the neurotransmitter systems, SSRIs are superior because they target only one—serotonin—and thus cause fewer side effects than the old tricyclics and MAOI inhibitors. (SSRIs are thought to increase the bioavailability of serotonin by inhibiting its removal from the synapses—that is, they inhibit the “reuptake” or re-absorption of serotonin by the presynaptic neuron such that more can bind with the postsnynaptic neuron.7 However, no demonstrable link between this specific chemical action and the treatment of depression has ever been established.) I took Paxil on and off for years, but could never go beyond 10mg without feeling “off”—sped-up, agitated, queasy, and effusive, which is against my nature. It also had undesirable side effects, including an emotional iciness if not a downright aggressive streak, difficulty reaching orgasm, and no longer being ticklish, all of which created issues in romantic relationships. Finally, in 2005, in the throes of benzo withdrawal, an updose in Paxil caused me to be labeled “bipolar” and nearly killed me. I have not taken an SSRI since.
In truth it was a person—Jack—who more than any drug helped restore me to sanity. Together, Jack and I worked through a panic-disorder workbook that tracked things like mood and anxiety levels, correlating them with time of day, food intake, situation, thought patterns, and so on. I also had to note the time of each panic attack, and what was going on in the hour precedent. Fortunately (or unfortunately), the attacks kept coming fast and furious, usually up on campus where I felt surrounded and trapped by my fellow students. As the weeks wore on, I began to see a pattern: low blood sugar, a hot, claustrophobic classroom or lecture hall, an elevation in hyperventilation, and then, finally, an attack. In seeing the pattern, I felt a renewed sense of control: If I could keep my blood sugar stable and learn to recognize and defuse escalating symptoms, then I could derail an episode. I could have my life back. I quickly learned to block catastrophic what-if thoughts and substitute in more sensible notions like, No, you’re not dying of dehydration again—look at how many times you’ve peed in the last hour. And No, you’re not having a heart attack. You’re young, your heart’s strong, and it’s just beating more quickly. I could also adjust my breathing by taking slow, circular breaths in through my nose and out through my mouth. I could place my hands over my belly to bring my attention there and ensure I drew air down deep using my diaphragm, instead of taking hiccupping, upper-chest anxiety breaths. And I could run through the toe-to-head muscular clench-and-release that promoted a sense of calm, even while sitting in class. Soon I even stopped monitoring my distal pulse.
And on days when things were really bad, I could take one of the one-milligram Ativan (lorazepam)* pills the psychiatrist had prescribed, tiny white disks barely larger than cupcake sprinkles or spider mites. Like Klonopin and Xanax, Ativan is a fast-acting benzodiazepine.
“These are strong, Matt,” the doctor told me. We sat in his office, a sunny, upper-floor space in a tony building downtown, the mouth of Boulder Canyon white with snow-frosted pines through the window. “So I’m only going to give you ten a month. They can be addictive, and I don’t want you taking them all at once.”
“Okay,” I said. “I’ll be careful.” I’d never been much into pills, so the idea scared me a little—this notion of their potency. “How, um … well, how do I know when to take one?”
“Just keep them with you, and if you have a strong panic attack take a half or a whole pill. Or perhaps on really bad nights if you think you won’t get to sleep, take a whole pill before bed.”
“Okay.”
I filled my prescription at the supermarket and brought home the bottle. It had a droopy-eye drowsiness sticker and a warning not to operate heavy machinery. The pills looked innocuous, so small you’d scarcely notice them going down. They didn’t seem dangerous. And yet, if taken too long and/or at too high a dose, and especially if stopped abruptly, benzos can be exactly that.
Benzodiazepines lie in the family of minor tranquilizers, a class of drugs with which America has a long, tangled, love/hate relationship going back to Miltown, the first of the genre, discovered in 1950 and FDA approved five years later.8 (Pre-Miltown, to squelch anxiety doctors might prescribe alcohol, barbiturates, or opiates. Despite being fundamentally useful and even lifesaving in measured doses, anxiety is also a condition man has long sought to eliminate, and many substance abusers are thought to be self-medicating against it.) Andrea Tone’s authoritative The Age of Anxiety: A History of America’s Turbulent Affair with Tranquilizers gives a great sociocultural recounting of tranquilizers’ history, benzos and non-benzos alike. My takeaway from it is that each new anxiolytic (anxiety-reducing) medicine undergoes a boom phase of lavish acclaim and widespread prescription, followed by revelations of addictive properties, and an inevitable backlash. Huzzah, we think. We’ve finally found the cure for fear. Then: Boom, backtrack. The cure, yet again,
is worse than the disease.…
Benzodiazepines came into being thanks to Dr. Leo Sternbach, a Polish chemist who developed Librium for the pharmaceutical giant Hoffman-La Roche; this proto-benzo hit the market in March 1960,9 and by October of that year doctors were writing 1.5 million new prescriptions a month for what was billed as the latest panacea against anxiety.10 Librium went on to become America’s most widely prescribed drug through 1968 and the dominance of its more potent sibling, Valium, another Sternbach creation and the world’s most infamous benzo.11 Valium, aka “Mother’s Little Helper” as per the eponymous Rolling Stones song, had hit the market in 1963. It was, writes Tone, “the most widely prescribed pill in the Western world from the late 1960s to the early 1980s”12 (1968 to 1981). In Valium’s banner year of 1973, sales in the United States held at $230 million, or $1 billion in today’s dollars,13 and in 1978 alone Roche sold 2.3 billion tablets.14
Over the years, however, it became clear that patients were becoming addicted to benzos (an estimated 10 million American Valium addicts in the 1970s15) and that poly-drug abusers were adding Valium to their quiver, and the pill slipped into disfavor. Then, in 1986, the heavily marketed Xanax (alprazolam), a fast-acting, high-potency benzo, took over as America’s most widely prescribed medicine.16 Never mind that the faster-acting strains are typically more addictive; today, worldwide benzo prescriptions number in the tens of millions. In 2007 in the United States alone, doctors wrote more than 82 million prescriptions for benzos,17 up from 69 million in 2002;18 and in 2010 alprazolam was America’s eleventh-most prescribed drug, with 46.3 million prescriptions.19 (After 2000, benzos still represent the leading class of drugs prescribed for anxiety disorders: 38 percent of the top ten drugs prescribed for anxiety, as opposed to SSRIs, which come in second at 21 percent.20) Benzos remain ubiquitous, often cited as the most commonly prescribed family of psychiatric medicine, though they do have other applications outside anxiety: for insomnia and seizure disorders, and as muscle relaxants. Physiologically, benzos have five main mechanisms of action: 1) As anxiolytics, for anxiety and panic disorders, and phobias; 2) As hypnotics, for promoting sleep; 3) As myorelaxants, for muscle spasms and spastic disorders; 4) As anticonvulsants, for fits due to epilepsy or drug poisoning (they are also administered to detoxifying alcoholics to prevent seizures, and given for acute psychosis with hyperexcitability and aggression); and 5) For amnesia—to block short-term memory during premedication for surgery or as sedation for minor procedures like wisdom-tooth extraction.21 In layman’s terms, they knock you flat on your backside. It’s precisely because of this potency that benzos can be perilous.
Like the other consummate downers—barbs, alcohol, and Miltown, with which they are cross-tolerant—benzos act on the receptors for gamma amino butyric acid (GABA). GABA, according to Tone, is the brain’s “chief and most prolific inhibitory neurotransmitter”22 and one to which, writes Dr. Heather Ashton, an emeritus professor of psychopharmacology at Newcastle University in the United Kingdom and the world’s leading benzodiazepine expert, about 40 percent of the brain’s neurons respond.23 Indeed GABA, found throughout countless systems in the body, is what our brain and nervous system use to calm themselves—it’s “inhibitory” in the sense that it decreases nerve-membrane excitability, reducing the rate of neuronal firing, or the “activating” messages that speed across the synapses like a crown fire through a parched aspen grove. (Restak writes that seizure and anxiety disorders alike are thought to result from too much of such overexcitation in the brain.24)
On a baseline chemical level, GABA inhibition begins when a nerve impulse releases the neurotransmitter from the presynaptic neuron; this GABA then crosses the synaptic cleft to bind with special GABA-receptor sites on the postsynaptic neuron.25 (GABA sites, writes Tone, “modulate the emotional states associated with anxiety”; the brain’s highest concentration of GABA receptors is in the amygdala, a limbic-system component key to emotional regulation.26) This transmission causes the receiving neuron to open and let a negatively charged chloride ion enter, while a positively charged potassium ion escapes. As Jack Hobson-Dupont puts it in The Benzo Book, “… the electrical potential of the membrane is [thus] increased, which then counteracts any electrical stimulation of the neural receptor.”27 Or as Dr. Ashton frames it, the negative chloride ions “supercharge” the postsynaptic neuron, “making it less responsive to other neurotransmitters—like noradrenalin and epinephrine—which would usually excite it.”28 In other words the activating neurotransmitters that trigger fight-or-flight, and hence panic attacks, are inhibited from spreading their message.
Benzodiazepines, however, are not synthetic GABA: They don’t work by binding directly to GABA receptors but instead ligate to benzo-specific subreceptors along the GABA sites, with each subreceptor doing a slightly different duty (e.g., alpha 1 subreceptors are responsible for sedation, alpha 2 for antianxiety effects, and alphas 1, 2, and 5 for anticonvulsant effects, etc.)—though all benzos synch up to varying degrees with the various subreceptors, and all, writes Ashton, “enhance GABA activity in the brain.”29 Taking a benzo can thus be said to potentiate GABA, increasing the strength with which the neurotransmitter binds to the GABA receptors. Benzos are therefore “GABA boosters,” allowing a greater number of chloride ions to enter the postsynaptic neuron and ultimately make it more excitation-proof. The pills aren’t putting anything in your brain that’s not already there, but are simply working with what you already have. (As Ashton phrased it in a phone interview, “All benzos do is enhance the action of GABA—they don’t work on their own.”) Do you recall the locus coeruleus, the little blue spot in the brain that initiates the fight-or-flight response? Well, as Restak writes, “Drugs that decrease the firing rate of the locus stop the panic.”30 And benzos, it turns out, are one of those drugs—by boosting GABA, they have a synergistic dampening effect on norepinephrine, which helps halt the panic response. That’s why taking a fast-acting benzo like Xanax or Ativan or Klonopin mid-attack will knock it out—in that sense, the drugs are effective.
At least, that is, until they stop working. The problem is that if you consistently take benzos for too long—more than two to four weeks is a commonly cited time frame—something called down-regulation of the GABA receptors can occur. In this process, because the benzos have come to do so much of the receptors’ work, the latter’s ability to attract GABA, or GABA affinity, diminishes. The GABA receptors become less responsive, “so that the inhibitory actions of GABA and benzodiazepines are decreased,” writes Ashton in a scholarly paper.31 In a conversation with me, Ashton framed it as GABA receptors essentially getting absorbed into the inside of the neuron so that they are no longer on the surface and accessible to the neurotransmitter. In essence, having been phased out by a robot down at the plant, they no longer show up for work and instead stay home to watch TV and eat Doritos. Meanwhile, the robot itself—benzos—needs more and more fuel to do its job.
You’re now strung out; you’re officially dependent. You “need more and more benzos to get this calming effect,” says Ashton. “Or, if you stay on the same dose you go into withdrawal while you still take the benzos”—a bleak phenomenon called tolerance withdrawal. In this closed feedback loop, doses climb and receptors invert until your baseline anxiety level is higher than ever, perhaps with thickening storms of panic attacks. You might see temporary relief at each dosage increase, but it’s short-lived as down-regulation continues apace. Neither can you keep upping your dose indefinitely, milligram by milligram, for the rest of your life—at a certain point you’ll become toxic. Meanwhile you might start to feel “interdose anxiety,” common to the fast-acting benzos like Ativan, Klonopin, Xanax, and Halcion. These pills bind more tightly to receptors and have a shorter half-life than, say, Librium and Valium—they’re metabolized much more rapidly, increasing anxiety symptoms between doses and inciting a “craving” for the next pill. (I say “craving” in quotes because, unlike pleasure-center drugs like cocaine and heroi
n, which flood the brain with serotonin and dopamine, benzos are what Ashton calls “depunishing drugs.” Through their GABA-ergic action they “protect against punishing stimuli”32—namely anxiety—but won’t necessarily get you high except if abused in large doses. They’re not really much fun to take.)
The first benzo I took was in February 1992, that spring semester back in Boulder. I’d gone over to some friends’ house to watch Blade Runner, buying a gallon jug of Carlo Rossi white for us all. Still edgy with free-floating anxiety and also a little bit curious about the pills, I popped one as we cued up the movie. It hit ten minutes later as we watched Harrison Ford track his Replicants, a warm, billowing fog that swelled to fill the room. The Ativan imparted a feeling of everything is fine. Not, everything is GREAT!, as you might feel after a rail of coke or a few Vicodin. Just, everything is fine, as in nothing is wrong, and everything always has been and always will be okay. For the first time in months, my connection to the bodily scrutiny and catastrophic thoughts had been severed. I could not have had a panic attack had someone held a gun to my head.
The Ativan was very seductive. In a way—and perhaps because of the alcohol—I did feel “high.” It reminded me of the first time I’d been stoned on marijuana, one July night down in Albuquerque, the summer after I’d graduated from the Challenge Program. Leaving The Big Apple, a few of us punks had snuck into a dirt lot across the way and hidden behind a berm. I’d been around weed before but never inhaled, though this night someone explained how I needed to take the smoke down into my lungs and hold it. I did so, coughed, and then did it again. A few minutes later as we walked back toward the club, the world began coming in frames, like overlaid snapshots of itself stitched back together. I felt happy and giddy—almost reassured by the hallucinations. This was a better, more interesting version of reality: the siren song of any psychoactive substance. As my feet crunched tangibly over the dirt, I could pick out every pebble and grain of sand, elucidated in crystalline whiteness by the security lights across the way.