Saturday, June 26, 2010

Turbocharging the Brain - A Checkered History

The notion that existing drugs might enhance cognition in the healthy dates back for the better part of a century and has produced ambiguous results. Chemist Gordon Alles introduced am phetamine for medical use in 1929, a synthetic drug chemically similar to the Chinese herb ephedrine. (Alles also devised the drug Ecstasy, another amphetamine.) Various forms were dispensed on both sides during World War II to keep soldiers awake and alert and to bolster courage. The Germans and Japanese ingested methamphetamine, while the British and Americans used Benzedrine, a similar drug to Adderall.

Scientists soon wanted to know whether the perceived benefit in performance was genuine. Psychological assessments by both British and Americans during the 1940s found that users self-rated their performance highly on tests that measured reading speed, multiplication and other factors. But their test scores, in most tasks, were no better than those earned by subjects who ingested caffeine. Performance, in fact, could decline on more complex tasks. “Because of their mood-elevating effects, amphetamines tend to make us feel we are performing especially well, when in fact we are not,” says Nicolas Rasmussen, a historian of science at University of New South Wales in Sydney and author of the book On Speed (New York University Press, 2008). “In simplistic lab tests assessing performance on boring tasks, they boost scores by increasing diligence, but that’s not the same as taking a law school exam or flying in combat.”

Methylphenidate, a close chemical relative of the amphetamines, emerged in 1956 as a supposedly milder and gentler form of stimulant (“the happy medium in psychomotor stimulation,” in the words of the drugmaker), but both its biochemical and psychological effects are similar when adjusted for dose. The halcyon era for amphetamines occurred nearly 40 years ago. U.S. consumption reached as much as 10 billion pills in the late 1960s before the Food and Drug Administration clamped down and labeled them as controlled substances that required a special prescription. Neuroscientist Michael S. Gazzaniga of the University of California, Santa Barbara, one of the authors of the Nature commentary, remembers his father sending him Benzedrine for studying when he was in college in the early 1960s.

In the mid-1990s the growing use of methylphenidate for treatment of ADHD prompted researchers to deploy novel brain-imaging techniques and sophisticated neuropsychological tests to examine effects of the drug in healthy subjects, supplying a baseline for comparison with patients with ADHD and other neuropsychiatric disorders. A 1997 paper in Psychopharmacology by Barbara Sahakian, Trevor Robbins and their colleagues at the University of Cambridge showed that methylphenidate improved cognitive performance on several measures (spatial working memory and planning, in particular) in a group of rested, healthy young males but not on others, including attention and verbal fluency. As testing progressed, the volunteers seemed to make more errors in their responses, perhaps because of impulsivity induced by effects of the drug.

The same researchers found little cognitive benefit in healthy elderly males. And in 2005 a group at the University of Florida Medical School at Gainesville could not turn up any cognitive boost from the drug among 20 sleepdeprived medical students. Another impediment to methylphenidate ever being placed alongside NoDoz and other caffeine pills is its potential for causing cardiac arrhythmias and for abuse as a recreational drug. Addiction is rare with normal dosing. But in the 1970s methylphenidate users routinely became addicted after inhaling or injecting the drug that they called “West Coast.”

Source of Information : Scientific American October 2009

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