*Exploring the future of psychopharmaceuticals*
*By 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
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
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
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
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
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
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
"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
Edited by: Lawyer Asad