Brain/Memory enhancers, Time Magazine

Sunday, Jan. 08, 2006
Can You Find Concentration in a Bottle?
By Unmesh Kher

If you haven't already heard the term nootrope, better jot it down. Chances are you'll hear it a lot in the future. A marriage of the Greek words noos, for "mind," and tropein, for "toward," it refers to drugs that enhance mental performance—popularly known as smart drugs. Nootropes aren't new. Amphetamines, first synthesized by a German chemist in 1887 and used in over-the-counter inhalers by the 1920s, were doled out generously during World War II to Allied and German troops to keep them alert. Military pilots still take dextroamphetamine, or go pills, to stay in fighting form on long missions. But in the post-Viagra era, many neurologists believe—and ethicists fear—that scientific advances and social changes may have set the stage for a new age of cosmetic nootropy.

Indeed, some argue that the era is well under way. There's already a lively market for brain boosters. Herbs and supplements with names like Focusfactor and Brain Quicken clutter health-store shelves and the Internet, often with little scientific basis for their claims. Pill popping in some circles has become as American as SAT-prep classes. Students and professionals in growing numbers are taking potentially addictive stimulants like Ritalin to focus their minds and bolster their memory.

The latest addition to that budding pharmacopoeia is a narcolepsy drug called modafinil that was approved two years ago to help shift workers stay alert. And there's a lot more in the pipeline. Neurologists have made rapid progress unraveling the molecular underpinnings of memory and attention, and drug companies are testing dozens of compounds derived from those discoveries to treat cognitive ailments like Alzheimer's disease and schizophrenia.

Memory Pharmaceuticals in Montvale, N.J., for instance, is developing drugs that boost the expression of genes essential to shoring up the connections among neurons—the physical process that is thought to turn immediate experiences into long-term memories. Cortex Pharmaceuticals in Irvine, Calif., meanwhile, is testing compounds that accomplish something similar more indirectly. Those molecules amplify the response of brain chemicals called AMPA receptors, among the first players in a long biochemical cascade that takes place in the neuron as it encodes memory. The first of those ampakine molecules has been shown in a recent study to boost the attention and mental performance of healthy, sleep-deprived men. The more powerful compounds in Cortex's untested arsenal, says CEO Roger Stoll, may bolster long-term memory without inducing the jittery side effects of drugs like Ritalin and caffeine.

Drugs already on the market, notably those that treat Alzheimer's disease, have been shown in small studies to improve the performance of healthy brains, though not by much. (Most of the research to date has been carried out on patients suffering from cognitive deficits.) "It's not like you start out with an IQ of 100 and get an IQ of 140 after taking these drugs," says Dr. Anjan Chatterjee, a neurologist at the University of Pennsylvania.

Ritalin-type drugs, which have a broadly stimulating effect on the nervous system, clearly improve attention and memory. According to a 2002 study of helicopter pilots operating flight simulators, so does donepezil, a drug that raises levels of the neurotransmitter acetylcholine. In another study, men on 200 mg of modafinil did better at mentally challenging games than subjects taking a placebo. But those results must be kept in perspective. Research at the Walter Reed Army Institute of Research in Silver Spring, Md., found that neither modafinil nor the military pilots' go pills were any better than several cups of coffee at restoring the attention and performance of sleep-deprived people.

If the effects are that mild, what are ethicists so worried about? Almost everything. "As our society becomes more competitive and specialized," says Chatterjee, "even the perception that these medicines provide a slight advantage can drive demand." If new and more effective drugs have few immediately discernible side effects, patients will probably pressure doctors to prescribe them. And as their usage spreads, people may feel forced to take them just to keep up. Would the means to pay for them determine who gets them? Would the rich get smarter and the poor fall further behind? What effects would such drugs have on the personality and mental health of users in the long run? The tendency to forget some things, for example, may be a big part of emotional stability and efficient problem solving.

Those issues don't seem to bother the Americans who pop pills and snap up supplements touted as brain enhancers. The latter are often a waste of money. Studies examining the cognitive benefits of supplements have either proved inconclusive or shown only modest effects. There's some evidence that the popular herb ginkgo biloba boosts cerebral blood flow and improves mental functioning, particularly when taken with ginseng. But there's also evidence that it doesn't.

Some of the most popular brain supplements, including deanol, are stimulants, but they have not been shown to improve cognition. "Americans like to have the five-Starbucks-triple-latte effect," says complementary-medicine guru Dharma Singh Khalsa, who sells his own line of "brain longevity" supplements. He recommends a regimen of antioxidants like vitamins E and C and co-enzyme Q10 to keep the brain healthy. Beyond that, one of his favorite nootropic formulations is a combination of ginkgo, phosphatidylserine (a molecule essential to the health of neural-cell membranes) and omega-3 fats (found in fish oils). But Khalsa emphasizes that nine-tenths of the mental boost people seek can be had by eating well, staying mentally and physically active and keeping stress at bay.

And if that doesn't help, you can always try a cup of joe.

SCHOOLYARD DRUGS Adderall and Ritalin, two drugs widely used to treat attention-deficit disorders, can focus healthy minds as well. These potentially addictive stimulants are increasingly abused by students and professionals—so much so that the U.S. government now considers them "drugs of concern"

Provigil, otherwise known as modafinil, was approved to help narcoleptics and shift workers stay awake. Lately it has joined the ranks of Ritalin as a popular performance aid. Some recent studies suggest it may indeed boost attention and mental acuity

NEW BRAIN BOOSTERS Some drugs for treating Alzheimer's disease increase the levels of the neurotransmitter acetylcholine, which plays a key role in attention and memory. One of the drugs, donepezil, was shown in a study of helicopter pilots to enhance mental performance. These drugs, however, are not widely abused

MEANWHILE, IN HEALTH STORES... ...the shelves are filled with herbs and supplements advertised as brain boosters. Few, if any, clinical trials have assessed their efficacy, but here's what we know about some of the more popular ingredients in these concoctions

Some studies suggest ginkgo biloba, especially in combination with panax ginseng, can boost mental performance

Found in plants like the common snowdrop, galantamine is approved by the FDA as the Alzheimer's drug Razadyne. It's marketed to healthy people as a memory enhancer, but no reliable studies support the claim

Derived from a chemical found in the periwinkle, vinpocetine increases blood circulation in the brain. Will taking it make you smarter or more attentive? No one really knows

Derived from the Chinese club moss, huperzine A works like donepezil and galantamine. But there is no evidence it helps young, healthy brains work better

Many swear by the memory-boosting power of phosphatidylserine, and studies suggest it may aid those with age-related problems

Bacopa monniera, or brahmi, has not yet been proved to make anyone any smarter

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Taping Kinesio Physical Therapy

August 19, 2008, 7:46 am

A Quirky Athletic Tape Gets Its Olympic Moment
By Tara Parker-Pope
Beach volleyball champion Kerri Walsh wearing a new type of athletic tape. (Natacha Pisarenko/The Associated Press)
Watching Olympian Kerri Walsh compete in beach volleyball last week, many viewers were wondering the same thing: what is that black thing on her shoulder?

A tattoo? A bizarre fashion statement? No. Ms. Walsh was sporting a new type of athletic tape called Kinesio, touted by physical therapists as a better way to relieve pain and promote healing of injured muscles.

The appearance of Kinesio on the well-toned Ms. Walsh — she even wore it while meeting President Bush — has spurred international interest in the little-known brand. In black, pink, blue and beige, the tape has been spotted on a number of other Olympians, including the shoulder of U.S. water polo player Lauren Wenger and the elbows of Canadian Greco Roman wrestler Ari Taub. Members of Spain’s basketball team and Jamaica’s track team are wearing it.

Ms. Walsh and the other athletes don’t have endorsement deals with Kinesio USA; the company simply donated 50,000 rolls of the tape to 58 countries for use at the Olympic Games. But whether its appearance on the international athletic scene is a sign of its therapeutic benefit or just smart marketing remains to be seen.

Traditionally, white athletic tapes are wrapped around gauze to form a stiff bandage that immobilizes a joint or muscle. By comparison, the 100-percent cotton Kinesio tape is said to be modeled on the thickness and elasticity of real skin. The flexible tape is applied to the skin in specific patterns, depending on the injury, a technique designed to create support and guide injured muscles and joints without limiting the athlete’s range of motion.

“This tape moves with the body, so the biomechanics are still there,” said John Jarvis, director of Kinesio USA.

Both the tape and the new wrapping technique have spread mostly by word-of-mouth among athletes and trainers who swear by it. Cycling great Lance Armstrong reportedly dedicates a page to the tape in his latest book. Recently soccer superstar David Beckham traded jerseys after a game and was spotted with pink Kinesio tape on his back.

Some limited data suggest it may be effective. In July, the Journal of Orthopaedic & Sports Physical Therapy published a study of 42 people with shoulder injuries. Half of them were treated with Kinesio tape applied in a pattern designed to support the injured muscle. The other half were given a “sham” treatment in which two strips of tape were simply pressed across the arm. The study was conducted by physical therapists at Winn Army Community Hospital in Fort Stewart, Ga., who didn’t receive funding from the tape company. Notably, the study participants who received the real therapeutic tape treatment reported an immediate improvement in pain.

Last year, Research in Sports Medicine published a study from San Jose State University showing that in 30 healthy test subjects, use of the tape along the lower trunk area appeared to increase the range of motion.

Kinesio claims that in addition to supporting injured muscles and joints, the new taping method helps relieve pain by lifting the skin, allowing blood to flow more freely to the injured area. The tape is also widely used in pediatric physical therapy for muscle disorders like cerebral palsy.

Given Kinesio’s high profile at the Olympics, it seems likely that we will be seeing more and more of it. Mr. Jarvis said the tape already is used by many professional basketball, baseball and football teams. Before the Olympics, the company Web site received about 600 views a day. Since Ms. Walsh appeared with the spider-like Kinesio pattern on her shoulder, Web traffic has jumped to 345,000 views daily.

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Anxiety Medications

Medications for Anxiety Disorders
Medications prescribed to treat anxiety disorders fall into two main categories: antidepressants and antianxiety drugs. The latter term is a misnomer because they are no longer the only kinds of drugs that have antianxiety properties. In fact, antidepressants have become the first choice for many anxiety disorders. Other types of medications, such as beta blockers and sedatives, are also used for anxiety.
Selective Serotonin Reuptake Inhibitors (SSRIs)
Dual Reuptake Inhibitor
Tricyclic Antidepressants (TCAs)
Monoamine Oxidase (MAO) Inhibitors
Benzodiazepines
Buspirone (BuSpar), Beta Blockers, and Sedatives
Selective Serotonin Reuptake Inhibitors (SSRIs)
This class of antidepressants became a first-line treatment for many anxiety disorders during the 1990s. The serotonin system is active in many regions of the brain, affecting anxiety, mood, arousal, impulses, and aggression. SSRIs work by slowing the reuptake of serotonin, which means they prevent this neurotransmitter from being quickly reabsorbed by the neurons that released it. This prolongs the time that the serotonin can work at receptor sites. (See How SSRIs Work ).) SSRIs also appear to change the number and sensitivity of receptors and may indirectly influence other neurotransmitters that play a role in anxiety, including norepinephrine and dopamine. (See Brain Cell Communication.)

The main reason for the popularity of SSRIs is that they have fewer and less severe side effects than do older medications for anxiety. SSRIs are prescribed for generalized anxiety disorder, obsessive-compulsive disorder, social phobia, panic disorder, and post-traumatic stress disorder. There are several kinds of SSRIs, each having a slightly different mode of action.

Though they are usually well tolerated, SSRIs can have troublesome effects in some people. They can cause sexual dysfunction, weight gain, and insomnia. Sometimes they even temporarily heighten anxiety symptoms. Your doctor should monitor you closely for this reaction and, if necessary, switch your medication. SSRIs can also interact with certain antihistamines, anticonvulsants, or other antidepressants. Reactions to SSRIs vary. What induces side effects in one person may not cause any problems in another. Therefore, it may take some trial and error to determine which medication is right for you.

For more information, see the chart of Medications for Anxiety Disorders.
Dual Reuptake Inhibitor
Venlafaxine (Effexor) blocks the reuptake of both serotonin and norepinephrine, another neurotransmitter that plays a role in anxiety. To a lesser degree, the drug also blocks the reabsorption of a third neurotransmitter involved in mood, dopamine. Venlafaxine is prescribed for generalized anxiety disorder and post-traumatic stress disorder, either initially or when SSRIs aren’t effective or cause intolerable side effects. Like SSRIs, however, venlafaxine can exacerbate sleep problems and cause nausea and headache. Effexor XR, the extended-release form of the drug, has fewer side effects than the shorter-acting version. For example, it doesn’t cause nausea. And it is taken just once a day.

For more information, see the chart of Medications for Anxiety Disorders.

Tricyclic Antidepressants (TCAs)
Tricyclic antidepressants (TCAs) have been used since the 1970s to treat panic disorder and obsessive-compulsive disorder. Their name derives from their three-ring molecular structure. Medications of this class are thought to relieve anxiety and depression mainly by increasing the availability of norepinephrine and serotonin. TCAs do so by slowing the reabsorption of these neurotransmitters into the neurons that released them and by changing the sensitivity of the receptors.

But compared to venlafaxine or the SSRIs, TCAs can cause side effects that are more numerous and more severe, including dizziness, constipation, blurred vision, and trouble urinating. TCAs can also cause weight gain and disturbances in heart rhythm. Thus, people with heart disease should usually avoid these drugs unless they’ve tried other medications without a good response. Because of their side effects, TCAs are considered second-line treatments for generalized anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and panic disorder. They’re sometimes paired with an SSRI when such a drug doesn’t work well enough alone. TCAs are often prescribed as an alternative for people who can’t use or tolerate SSRIs. For some people, TCAs actually work better and cause fewer troublesome side effects than SSRIs. A period of trial and error can help determine which drug will work best.

For more information, see the chart of Medications for Anxiety Disorders.
Monoamine Oxidase (MAO) Inhibitors
The neurotransmitters norepinephrine and serotonin are members of a class of compounds called monoamines, which are normally broken down in the body by the enzyme monoamine oxidase. By blocking monoamine oxidase, these drugs raise the levels of norepinephrine and serotonin in the brain, thus decreasing anxiety and improving mood.

If SSRIs aren’t helpful, MAO inhibitors are used for social phobia and panic disorder. Among MAO inhibitors, phenelzine (Nardil) is most commonly prescribed for these disorders, but tranylcypromine (Parnate) and isocarboxazid (Marplan) are also used. Although MAO inhibitors don’t have many of the side effects of TCAs, they can cause dizziness and other serious side effects.

People who take MAO inhibitors must avoid certain foods and beverages, including yogurt, aged cheese, pickles, beer, red wine, and other foods containing tyramine. Combining tyramine, an amino acid, with MAO inhibitors can raise blood pressure to dangerously high levels, possibly resulting in a stroke.

For more information, see the chart of Medications for Anxiety Disorders.

Benzodiazepines
These tranquilizers were the first class of medications used specifically for anxiety. They induce mental and physical relaxation. They enter the brain quickly and bind to receptors for the neurotransmitter gamma-aminobutyric acid (GABA), which reduces brain activity. When they bind to GABA receptors, benzodiazepines enhance GABA’s calming effects. (See How Benzodiazepines Work ).)

The many benzodiazepines include diazepam (Valium), lorazepam (Ativan), and alprazolam (Xanax). These medications are used for generalized anxiety disorder, panic disorder, and specific phobias. They’re often paired with a longer-acting drug such as an SSRI, and the dose is gradually reduced once the SSRI starts working. Doctors try to limit the use of benzodiazepines because they can cause tolerance, that is, a need for greater amounts of the drug to produce the same effects. But because these medications are so helpful for generalized anxiety disorder, they’re sometimes used alone for extended periods. In such cases, patients should be monitored carefully for signs of tolerance. Benzodiazepines are also prescribed alone, as needed, to treat specific phobias. Someone with a fear of flying, for example, may take a benzodiazepine before getting on a plane to control anxiety immediately before and during the flight.

In addition to tolerance, benzodiazepines can cause drowsiness and cognitive impairment. Older adults, as well as people with a history of substance abuse, should avoid them whenever possible because such individuals may be particularly sensitive to their side effects.

For more information, see the chart of Medications for Anxiety Disorders.
Buspirone (BuSpar), Beta Blockers, and Sedatives for Anxiety
Buspirone (BuSpar): One of the newest drugs for anxiety, buspirone (BuSpar) binds to receptors for serotonin and dopamine. The effect is to increase serotonin activity and decrease dopamine activity in the brain. Like the SSRIs, buspirone is used for the long-term treatment of generalized anxiety disorder. But it begins to work faster, after about 2 weeks. Because it has few side effects and no serious drug interactions, it’s a good alternative to benzodiazepines in the treatment of generalized anxiety disorder in older individuals or those with a history of substance abuse. However, this medication isn’t effective for most other anxiety disorders.

Beta blockers: Though they’re mainly used to treat high blood pressure, beta blockers can also relieve performance anxiety, a specific social phobia that usually occurs when an individual needs to give a speech or perform in front of an audience. Because beta blockers slow the heart rate, they also help with the physical symptoms of social phobias and panic attacks, such as pounding of the heart and shaking of the hands.

Sedatives: These drugs are prescribed for insomnia, a common symptom in anxiety disorders. Benzodiazepines are sedatives used for short-term treatment of insomnia. Newer medications such as zaleplon (Sonata) and zolpidem (Ambien) have begun replacing the benzodiazepines because they are just as effective, but shorter-acting. This means that they’re less likely to cause side effects, such as tolerance or withdrawal symptoms. Some sedating antidepressants, such as tricyclic antidepressants and trazodone (Desyrel), are also used to improve sleep.

For more information, see the chart of Medications for Anxiety Disorders.

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