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Can a Pill Make You Lose Weight, Fall in Love, Stop Smoking?
Exploring the future of psychopharmaceuticals
Susannah Cahalan/ Source: NY Post
Need to lose weight, win friends and influence people? There's a pill for that.
Or at least there will be one in the not-so-distant future, says a new pop-neuroscience book, "The Compass of Pleasure: How Our Brains Make Fatty Foods, Orgasm, Exercise, Marijuana, Generosity, Vodka, Learning, and Gambling Feel So Good," which discusses the future of psychopharmaceuticals -- drugs that can, by adjusting brain chemistry, safely help adjust behaviors believed to be hardwired or a function of poor willpower.
Although there are plenty of chemicals that can help control behavior, the mystery that scientists struggle with is how to create a conduct-controlling drug that is both effective and harmless. This discovery is the pharmaceutical world's holy grail, says author and Johns Hopkins University neuroscience professor David Linden.
What scientists hope to do is to manipulate the brain's natural pleasure centers and make destructive but pleasurable activities -- such as excessive eating, alcohol consumption and drug use -- and blunt or suppress the neural kick you get from engaging in the activity.
This is no easy feat, since activating the pleasure center sends dopamine to several parts of the brain, including the pre-frontal cortex (responsible for judgment and planning), the hippocampus (important in memory), dorsal striatum (involved in habit-forming) and the amygdala (part of the brain's emotional center).
So when we engage repeatedly in satisfying activities, like trips to the fast-food counter, our brain connects that action with reasoning, emotion and long-term memory.
A milkshake is not just a milkshake — it's a braingasm.
However, it's important to know that the pleasure circuit isn't merely stimulated by bad behavior. Physical exercise, love, learning new facts, even paying taxes has been shown to activate the pleasure circuit in a similar way to drugs and fatty foods.
There are already several drugs available on the market to deal with nicotine, cocaine, alcohol and heroin addictions. Some are more primitive than others (for example, nicotine patches or methadone, which simply replace one addiction with another).
But one drug, called Naltrexone, actually blocks the brain's opioid receptors for drugs like heroin and alcohol, thereby curtailing the course of the pleasure circuit. Linden feels that this drug may be underused in treating addiction, partially because it takes a long time to adopt new therapies and also because of the "moral component to it."
"People are told they need to deal with it in a 12-step program. My view is if you can help yourself out in addition to a program and blunt your cravings, then it's only a benefit," Linden says.
When you move past addiction, brain-altering drugs are even more controversial.
One of the few products currently marketed, called "Liquid Trust," is a spray that claims to "give a boost to dating and relationship areas of your life" and even to help promote trust in business relationships. Although the statements appear too good to be true, there is at least some basis in science. The spray contains oxytocin, a natural hormone released post-orgasm and during breast-feeding that is involved in pair-bonding. When oxytocin nasal sprays were tested in labs, researchers showed that a quick spray made people more trusting and helped those with social phobias.
It's unclear (and highly unlikely, says Linden) that a perfume would have the same effect as a nasal spray. But it does open the door to using certain hormones, such as oxytocin and vasopressin (which, among other things, plays a role in social bonding) to make someone like you, or manipulate "cheaters" into faithful spouses.
"There's a big ethical problem there," Linden says. "Do you honestly think that the FDA will approve a drug to keep men from cheating? I don't think so. I think it's too ethically problematic. Even if a drug had no side effects, if it was the perfect drug, I don't think society is going there."
Pills that force you to diet and exercise
Still, the FDA sees no ethical issues with appetite-suppressant drugs. There are plenty on the market now (some legal, others illegal), but the problem is that in most cases the side effects far outweigh the benefits.
"The thing with weight-loss drugs is that the standard for safe has to be extraordinarily high, unlike, say a cancer-fighting drug," explains Linden. "Weight loss for many is not directly and immediately life-threatening."
It's also an unfortunate fact of nature: Our feeding circuits make it nearly impossible for many to lose a lot of weight and keep it off. Eating initiates a pleasure circuit, or a neuronal burst of activity that is highest when you begin eating, and tapers off as the meal continues.
Between and during meals, a complicated cascade of proteins and biochemicals, stemming from our gut and extending to our brain, alters metabolism and hunger drive, depending on what, when and how much we're putting in our bellies.
As weight drops, fat mass may decrease, but this decline instigates a stronger desire to eat and a slower metabolic rate.
"This is a sad but unavoidable truth that the multibillion-dollar-a-year diet industry doesn't want you to know," Linden writes.
Obese people seem to have an even more convoluted relationship with food. According to a recent study conducted by the University of Oregon, when obese and lean people are fed chocolate milkshakes, their brain responses differed dramatically. Heavy volunteers showed considerably less neural activation in the dorsal striatum than their thinner counterparts. Yet, strangely enough, obese people showed a greater activation of the pleasure reward circuit just before receiving the shake. In other words, obese people are rewarded more by cravings, and less by actual consumption.
Scientists are trying to crack this very conundrum. It may not be solved before your next high school reunion, but it certainly may be accomplished in our lifetime, Linden believes. Right now, drugs that deal with the pleasure circuit are being tested on mice and even, in some cases, humans.
One such candidate includes a set of drugs that enhance "fullness" signals from the gut to the brain. The drug, called SR146131, targets activation of specific receptors in gut hormones, thereby promoting a overall feeling of satiety.
Another set of drugs is designed to target pleasure circuits directly in the hypothalamus and the medial forebrain by deactivating certain receptors that create feelings of hunger.
There is even a "exercise pill" in development at Salk Institute for Biological Studies in California that triggers natural chemicals activated by physical activity, creating greater endurance and muscle tone in lab mice.
Researchers are finding that by administering drugs that activate certain enzymes in mice — specifically the AMPK (found in the brain and muscle tissue) and the PPAR(delta) (found in the brain body fat) — they can turn normal mice into long-distance ultra-runners, who do not gain weight even when supplied with high-fat foods.
Although this exercise drug is heading into clinical trials, it is still not cause for couch potatoes to rejoice.
"There is some encouraging research in animals," Linden says. "Is it safe and effective in humans? That's still unclear."
Quite possibly the most entertaining class of weight-loss drugs was inspired by stoners. Believe it or not, our own brain contains THC-like molecules called endocannabinoids that are involved with a variety of factors including pain, mood, memory — and, yes, the munchies.
Scientists noted that smoking cannabis stimulates appetite, so they thought, perhaps, that blocking the actions of endocannabinoids would do the converse. Indeed it did. In clinical trials, patients receiving the drug lost around 16 pounds in a year, compared to four with a placebo.
The endocannabinnoid-blocking drug called Rimonabant, with trade names Slimona and Acomplia, was at one point approved for the treatment of obesity in 56 countries in 2008, including in the European Union.
However, when the side effects, such as depression and suicidal thoughts, were uncovered, the EU withdrew it from the market.
Now scientists are exploring whether it is possible to create a drug with the same blocking capabilities without the serious side effects, although the chances of this are "low," says Linden. He thinks it's more likely that effective and safe weight loss will be accomplished via combination therapy, not just one type of drug. This, he says, might even be a possibility in the next 20 years.
"It turns out that appetite isn't just controlled by one biochemical system, it's controlled by at least six different biochemical signaling pathways that we know," Linden says. "It may be that a combination of drugs is optimal."
The hazy future of psychopharmacology seems like the plot of a sci-fi movie script.
For instance, pills will be obsolete, Linden says. Instead, scientists will be able to stimulate particular parts of the brain, perhaps with an implant, and control or create different behaviors as an outgrowth of that stimulation.
There are regions of rat brains that when stimulated with an electrode make them either eat like crazy or stop eating altogether. So if it became possible to electrically charge part of the brain (most likely in the hypothalamus) responsible for eating, then you could control hunger without drugs.
"Once we have that, our lives with change drastically," Linden says. "Psychoactive drugs, virtual reality, it all will be delivered directly to our brain. It's going to change things utterly."
The Smell of Trust?
It's trust in a bottle — or so it claims.
Body spray Liquid Trust will give you "the power of trust," all for only $30 per 1/4 of an ounce.
Liquid Trust contains oxytocin, called the "cuddle hormone," that occurs naturally in the brain and is released post-orgasm and during breast-feeding to help bond mother and child.
Studies have shown that when oxytocin is administered via a nasal spray it creates an increase in trusting behavior.
It's one of the first commercially available "psychopharmaceuticals," which promise to alter brain chemistry in hopes of a better life.
But scientists say it's impossible that a body spray, which contains lower amounts of oxytocin than the nasal sprays, is able to gain access to the brain in the same way.
"Spray it around like air-freshener so everyone will like you," neurologist and author David Linden scoffs. "This is nonsense."
The Post tested it out on a Midtown Starbucks. We ordered a coffee but when it arrived said that we didn't have the cash but would come back with it. "Do you mind if I take it?"
"Sure, go ahead," the barista, Quinna Satterwhite, said without batting a lash.
Had we discovered a new spray that would change our lives? Not exactly.
"I had a feeling you'd come back," Satterwhite said, after The Post explained that she'd just passed the "trust" test. "But I just let a lady last week walk away with a coffee and I don't think she was wearing that spray."
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