Cocaine and Amphetamines

The stimulant effects of ephedrine, an alkaloid of the shrub, Ephedra vulgaris, were described in China more than 5000 years ago. Local physicians typically used the plant, also known as ma huang, as a herbal remedy for asthmatic wheezing and other pulmonary problems. These disorders are caused by severe constriction of the bronchial tree, and ephedrine simply relaxes bronchial muscle to improve respiration. AlthoughWesternmedicine relied on intravenous epinephrine (adrenaline) to treat severe asthma, pharmaceutical firms recognized the value of developing an oral medication for bronchial congestion. By 1935, several ephedrine analogues were synthesized, some of which remain in use as nasal decongestants (e.g. pseudoephedrine). The amphetamines were developed as part of this effort. In fact, the first synthetic ephedrine analogue was a mixture of dand l-amphetamine. Marketed in 1932 as a decongestant, these amphetamine isomers were the active ingredient in the popular Benzedrine inhaler, which quickly became known for its stimulant properties. The addition of a second methyl group created an even more potent amphetamine variant, methamphetamine, sold as Methedrine. After the amphetamines became available in tablet form, they were used to treat both narcolepsy, a condition characterized by sleep attacks, and attention-deficit hyperactivity disorder (ADHD), an apparent paradoxical effect (see below). Amphetamine tablets also were used as appetite suppressants; d-amphetamine was marketed for this purpose as Dexedrine in 1945, but the anorexiant effect faded rapidly with repeated use. It was during World War II, however, that the stimulant properties of the amphetamines became widely recognized.ManyAmerican,Germanand Japanese soldiers relied on the activating effects of these drugs during prolonged military campaigns. The problem was especially severe in Japan, where civilians used methamphetamine to keep up factory production for thewar effort, and large stockpiles of the drug continued to be available after the war. By the 1960s, abuse of amphetamines had spread throughout the industrialized world, and governments placed tight restrictions on the production and distribution of these drugs; the now-infamous Benzedrine inhaler was banned in 1959 as part of this effort. Despite the crackdown, abuse of amphetamines continued, and to make matters worse, authorities were soon confronted with a drug problem they thought had been solved many years earlier: cocaine abuse. Cocaine occurs naturally in the leaves of a shrub, which thrives along the eastern slopes of theAndes (Erythroxylon coca) and other circumscribed regions of South America (Erythroxylon novogranatense). Although natives of the Andean highlands have been known for centuries to chew coca leaves to increase energy and elevate the spirit, it was not until the 1860s ]when cocaine could be extracted from the leaves and refined to a pure form ] that cocaine use spread to Europe and other continents. The coca extract first gained popularity as a ‘feel-good’ additive to wines and other beverages, though some physicians, including a young Sigmund Freud, wrong-headedly recommended intravenous cocaine to treat morphine addiction. The real medicinal value of cocaine resided in its local anaesthetic effects, which allowed it to be used for delicate eye and lung surgery (see below). By the end of the nineteenth century, cocaine’s easy availability and favourable advertising, which included many celebrity endorsements, led to widespread abuse. Laws were passed to control its use and distribution. Cocaine abuse did not resurface on a large scale until the 1970s when snorting cocaine powder became a way to get ‘high’ without needles or other dangerous paraphernalia. In the mid-1980s, the introduction of a cheap, smokable version of the drug known as ‘crack’ led to another surge in cocaine abuse, creating more than 3 million addicts in the United States alone. The amphetamines also experienced an illicit upgrade, resulting in still more dangerous variants, including a smokable and highly addictive form of methamphetamine known as ‘ice’. More than 100 years after the first widespread use of cocaine, stimulant abuse continues to be a major, worldwide problem. Article