Newton’s third law of motion states that for every action there is an equal and opposite reaction. In particle physics we learn that for all matter there can be antimatter of opposite charge. But what about drugs? Is there an anti-weed, an anti-heroin, or an anti-beer? Pharmacologically speaking, the answer is yes. Scientists can identify regions of the brain stimulated by a given drug and then create an anti-drug with the opposite mechanism of action. Substances that do the opposite of common recreational drugs are useful in overdoses but rarely become recreational drugs in their own right for the simple reason that they make you feel totally and completely miserable. I decided to systematically test three of the most powerful anti-highs over the course of one week. Here are my results:
Worst omelet ever. Thanks, rimonabant. Photo by Maggie Lee
DOSE: 60 MG
Pharmaceutical researchers have observed that smoking weed gives people the munchies, so logically it follows that deactivating the receptors in the brain responsible for getting high would give you anti-munchies. They tested a drug with just such an action and found that it was incredibly effective. The drug was approved in Europe and appeared to be one of the best weight-loss drugs in history. Rimonabant is inexpensive, effective, and totally nonaddictive. Unfortunately, in addition to giving users anti-munchies it was found to have a prominent side effect called anti-happiness, aka suicidal depression. In the months following the drug’s clinical trials, there were over 70 patients displaying signs of suicidality, two completed suicides, a host of seizures, precipitated multiple sclerosis, domestic abuse, and a man who strangled his daughter.
When you smoke weed, it stimulates the parts of your brain called cannabinoid receptors. It may seem obvious, but our brain has these receptors for reasons other than getting stoned. Our cannabinoid receptors have an array of crucial regulatory functions in the unstoned brain. We depend on a cocktail of natural weedlike chemicals called endocannabinoids to regulate inflammation, appetite, and emotional stability. When you take rimonabant, not only is it impossible for you to get stoned on weed, it’s also impossible for your body to utilize its natural endocannabinoids. I have heard more than one stoner speculate about a future where the government requires rimonabant implants at birth to prevent the population from “expanding their minds.” Unlikely, but one must wonder what it would feel like to live in such a world!
Since normal drugs are generally taken socially at night, I decide to do my anti-high experiments first thing in the morning and alone. But I’m curious about how my friend Sam would respond to rimonabant so I persuade him to try it with me. Sam has smoked weed all day, every day, for the last five years. When I suggest he take a pill that would make it impossible for him to get high for at least 24 hours, he is not too keen on the idea. But after asking about 50 or 60 times and offering to buy him weed in return, he cautiously accepts my offer.
Both Sam and I take a whopping dose of rimonabant three times higher than the maximum dose used for weight loss. After swallowing the pills, Sam goes out to meet his weed dealer in Manhattan. A half hour later, he texts me to say he’s having an attack of “explosive diarrhea.” I’m also feeling the onset as a subtle but persistent anxiety. Sam comes back to my apartment and shakily loads a pipe. He takes a deep hit, waits, and shakes his head, saying he feels “absolutely nothing.”
We decide to go out and get some food at a Polish diner. Upon walking into the restaurant we realize that our waiter is an incredibly slow guy we’ve had in the past who never refills the small water glasses. Both of us tense up. I order an egg-white omelet and Sam interrupts me to say, “What are you talking about? You want the whole egg. Why would you just want the whites?”
“I usually get egg whites. They’re good. Is there something wrong with that?”
Sam turns to the waiter. “He wants the whole egg.”
I look down and see that my hands are trembling. I remember reading studies that suggest rimonabant lowers the seizure threshold. I don’t mention this to Sam. My omelet arrives and I start to feel nauseated the moment I look at it. It’s made with sickeningly orange American cheese. I might actually vomit. Sam has a healthy appetite. In the past I have seen him eat a whole chicken down to the skeleton, but on rimonabant he picks at his omelet for a few minutes before loudly protesting, “If someone does not get this omelet away from me I’m going to vomit… I’m going to fucking vomit and then I’m going to die!”
We leave the diner and anxiously walk down St. Mark’s. I stop inside a bong store and touch my fingers to the glass like a peasant outside a department store on Christmas. I have never felt so un-high in my life. I must admit that my thinking is unusually clear and I could see a lower dose of rimonabant being helpful when studying for a test—well, it
if it didn’t make me feel like I was about to simultaneously cry, puke, and have a seizure. The fact that this is a widely prescribed drug is unbelievable. The idea of taking this daily is insane. It would be less than a week before I killed someone.
In the late afternoon I try smoking some weed. I take a deep hit, feel a transient sensation of threshold stonededness, and then whatever it was passes in less than five minutes. Sam is not willing to let the rimonabant win, and throughout the day he continuously attempts to get high, taking hit after hit after hit from an aluminum cigarette. Around midnight, I hear him take a deep toke, sigh, and scream, “Damn it!”
I am the least high person in the universe. Photo by Maggie Lee
DOSE: 4 MG
Psychedelics like LSD were used in many early models of psychosis. Even today, the majority of scientific literature refers to psychedelic drugs as “psychotomimetics,” meaning drugs that mimic psychosis. Much psychedelic research has to be done under the guise of studying schizophrenia or related disorders. There is obviously a difference between schizophrenia and tripping on LSD, but the idea is that if drugs could be developed that did the opposite of LSD, they would be effective treatments for psychotic disorders. Antipsychotic drugs work by blocking the stimulation of dopamine and serotonin receptors, which are responsible for practically every enjoyable drug in the world from methamphetamine to cocaine to LSD. When the serotonin and dopamine receptors are blocked it effectively turns you into a zombie. Maybe you know a girl who takes Seroquel or you took it yourself once. It’s not fun. Just keeping your eyes open is an enormous struggle. If you’re a paranoid schizophrenic, antipsychotics can chemically dull you enough to keep you from acting on violent impulses. They are also useful for aborting a “bad trip,” and unlike Xanax or Valium, which only calm you down but don’t actually stop you from tripping, antipsychotics stop the trip dead in its tracks.
Before getting out of bed I take 4 mg of risperidone, a dose high enough to make a 300-pound homicidal maniac slumber peacefully. I get up and go out to get some vegetable juice. I walk down to the East River and look out across the water. After ten minutes I’m starting to feel sedated. I lie down in the grass. It starts to rain so I get up again; this time my entire body feels leaden. I have to think about picking up each leg as I walk. Pick up leg. I’m getting really wet and I don’t know if I will make it home. Pick up leg. A cop car drives by and slows down as it passes me. I feel painfully awkward because I know that I’m walking in slow motion through the rain without an umbrella, but I can’t move any faster. The cop car speeds off.
Pick up leg. I’m a pharmaceutical masochist. Curiosity—the things you’ve made me do! I’m the least high person on the planet. In the history of humans no one has been less high than me. I take a Ritalin and it does nothing; I might as well have dropped it down the sewer. Pick up leg. A ten-year-old on Grand Street says that I’m “walking like a fag,” to which I respond, “What’s up.” I stumble into my apartment building and crawl up the stairs. I crawl to my door, crawl inside, and pass out on the floor into the deepest, blackest, most deathlike sleep I have ever experienced. I wake up eight hours later feeling like I just had a successful lobotomy.
At the Chinatown needle exchange, where I am apparently a regular. Photo by Jess Williamson
DOSE: 200 MG
There are drugs called opioid antagonists, which do the opposite of recreational opioids like heroin. When paramedics treat heroin overdoses, they inject an opioid antagonist called naloxone into the body. On a molecular level, naloxone races into your brain, jumps ahead of the heroin molecules occupying your opioid receptors, and pushes them aside. Once the naloxone molecule is in place, heroin is unable to suppress your breathing and the overdoser rapidly regains consciousness. Naloxone has saved countless lives.
Researchers realized they could use a similar opioid antagonist called naltrexone to stop junkies from feeling the effects of heroin. A device was developed that is surgically implanted under the skin and releases a continuous supply of naltrexone into the body for several months at a time. Although some addicts have benefited from naltrexone implants, the results are usually disastrous. When you give a junkie naltrexone it not only prevents them from feeling heroin, it causes them to go into instantaneous accelerated withdrawal, exponentially worse than natural opiate withdrawal. Some people have killed themselves to escape the pain after getting naltrexone implants; others perform home surgery and cut the implants out of their body.
In the same way that rimonabant blocks endocannabinoids, naltrexone blocks natural opioids called endorphins. Endorphins are pleasure chemicals commonly associated with sex and exercise, but they’re also important regulatory factors in our daily mood and immune function. Even if you’re not a junkie, taking an opioid antagonist has a profound effect on your neurochemistry. For that reason, naltrexone has been shown to be an effective treatment for pedophilia and kleptomania. The natural opioid rush from acting on these compulsions is blocked, so fondling a child or stealing an iPod loses its euphoric rush.
I decide to take a dose of naltrexone four times higher than the daily dose used to treat opioid dependence. After taking the pills, I get on the train to Manhattan. I’m sort of giddy. I can’t quite describe the feeling but it’s not necessarily bad. The best anti-high thus far. I get off at Canal Street and I’m filled with tension amid all the shouting, sweaty, glistening tourists. At the same time I have this strange sensory enhancement that is not totally unpleasant. Vaguely erotic. I can feel each and every hair on my scrotum moving as I walk. Since I went to the bong store on rimonabant, I think it would only be appropriate for me to go to the needle exchange today. I walk inside and I’m immediately depressed and confused by my decision. As I’m filling out forms to get my needles, the woman looks at me and says my name is already in the computer—what? This twilight-zone moment makes me incredibly tense and paranoid. Why am I in the computer at the needle exchange? Why am I at the needle exchange? Why am I on naltrexone? I walk outside holding a paper bag full of needles and bleach and feel like I’m about to cry.
I’m totally absorbed in frantic and confused thoughts. I wish I understood addiction. I have read so many books, known so many addicts, but nothing makes sense to me. I don’t want to say addiction is a disease, because diseases are excuses. Diseases are permission slips for being sick. If I’m addicted to Valium, that’s a conscious choice I make each time I swallow a Valium tablet. But how can I say that? I feel guilty. I’m so confused. Thomas Szasz said, “If the desire to read
cannot be cured with an anti-
pill, then neither can the desire to use alcohol, heroin, or any other drug or food be cured by counterdrugs.” But is he right? My trance is broken when someone offers me a flyer for “mad mojitos.”
I get on the train to Union Square and find myself spontaneously breaking into song, then running full speed until I lose my breath. After running, my body is assaulted with sharp aches and pains. Is this what it feels like to be old? I almost step on a sparrow pecking at a muffin crumb and scream at the top of my lungs. Wow, am I on edge! When you meet new people, instead of shaking hands, both parties should scream at the top of their lungs. That would be the custom in a naltrexone alternate universe. As the day wears on, my muscles are starting to freeze up into terrible wooden knots. All my internal organs have been replaced with beef jerky. I have to keep stretching—continuously—to avoid hardening into a solid block of wood. I can’t wait for this sensation to pass. O sobriety, how I long for thee!
There are so many anti-highs I have neglected to experience, but some are seriously dangerous. Drugs with the opposite action of ketamine are potent neurotoxins, and drugs that do the opposite of alcohol and benzodiazepines are known to cause seizures. Scientists are still mapping the gelatinous landscape of our brains, and as new drugs are discovered, new anti-drugs will also be found. Who knows what kind of chemical misery the future might hold! Although I must admit, after a week of enduring these anti-highs I feel incredible. The neurochemical floodgates have opened and there is unimaginable rebound euphoria. All night I walk down the street, peaceful and optimistic, ready to high-five strangers. Ready to high-five the moon! Hey moon, what up!
All that is loved is loved by contrast. We love intoxication because we know sobriety; to love sobriety we should know anti-intoxication. We can’t know the high without the low, and after a week of getting low I’m feeling pretty high. I think the only thing we have to fear is the middle.