Category:Psychostimulants: Difference between revisions

The psychostimulants are a class of medicines that increase activity in the nervous system, producing wakefulness, alertness, and a sense of energy. They range from the mild psychostimulants of everyday life, such as caffeine, to the diverse and powerful . Their history runs through exploration and commerce, and it returns repeatedly to a single difficulty: the properties that make a psychostimulant useful are also the properties that make it liable to misuse.

The oldest history of the psychostimulants belongs to the coca plant. For thousands of years, peoples of the South American Andes have chewed the leaves of Erythroxylon coca for endurance and to ease the effects of work at high altitude.^[1] European explorers encountered the practice from the time of the earliest voyages, and coca leaves were carried back to Europe.

In the mid-nineteenth century, chemists isolated the leaf's active alkaloid; the isolation is generally credited to the German chemist Albert Niemann around 1859–1860, who gave the compound the name cocaine.^[1] Interest grew quickly. In 1884 the ophthalmologist Karl Koller demonstrated that cocaine could serve as a local anesthetic — a genuine and lasting medical advance, and the foundation of a whole family of later anesthetics. In the same year Sigmund Freud published Über Coca, enthusiastically promoting cocaine as a remedy for a range of conditions, including, notably, morphine addiction.^[2] Freud's enthusiasm did not age well: the friend whose morphine dependence he had hoped to treat with cocaine developed a severe cocaine problem instead, and through the 1880s reports of addiction and of cardiac harm accumulated.^[2]

In the later nineteenth century cocaine and coca were sold very widely and with extravagant claims — in coca wines, in tonics, in patent medicines promising to cure almost any complaint, and in the original formulation of Coca-Cola.^[1] As with the opioids of the same era, this period of free availability was followed by regulation. Cocaine was removed from Coca-Cola in the early twentieth century, and in the United States the Harrison Narcotics Act of 1914 restricted cocaine to prescription use.^[2] For roughly half a century afterward cocaine receded from public view, returning to prominence only in the later twentieth century, when powdered cocaine and later crack cocaine drove successive waves of use.

The synthetic psychostimulants have a separate history. Amphetamine was first synthesized in 1887, by the chemist Lazăr Edeleanu, but its properties as a medicine went unexamined for four decades. It was only in the late 1920s that amphetamine was investigated pharmacologically — initially as a substitute for ephedrine, then in short supply — and developed as a medicine.^[3] It reached the United States market in 1933 in an over-the-counter inhaler, Benzedrine, sold for nasal congestion, and was soon promoted for low mood and as an appetite suppressant. Methamphetamine, synthesized somewhat later, was introduced for a similar range of uses.^[1]

A turning point for the medical use of psychostimulants came in 1937, when the psychiatrist Charles Bradley, treating children at a home in Rhode Island, gave Benzedrine to young patients — and observed, unexpectedly, that it improved their behaviour and schoolwork rather than exciting them.^[4] Bradley's observation was largely set aside for some twenty-five years, but it was the foundation of the modern psychostimulant treatment of what is now called attention-deficit/hyperactivity disorder. The related medicine methylphenidate was synthesized in 1944 and later marketed as Ritalin; from the 1950s onward psychostimulants became, and remain, a mainstay of ADHD treatment.^[4]

Amphetamine and methamphetamine were used very widely in the mid-twentieth century — including by militaries to counter fatigue, and by the public for weight loss and low mood — and a reaction followed. Recognition of dependence and of stimulant psychosis, together with mounting non-medical use, led in the United States to the placing of amphetamines and related psychostimulants under the Controlled Substances Act of 1970, which classes the prescription psychostimulants as having accepted medical use alongside a high potential for misuse.^[4]

In the twenty-first century, psychostimulants are a major component of drug-overdose mortality. Overdose deaths involving cocaine and those involving methamphetamine both rose sharply through the 2010s and into the 2020s; a large majority of these deaths also involve opioids, reflecting the combination of psychostimulants with illicitly manufactured fentanyl, though psychostimulant-involved deaths without opioids have risen as well.^[5] The prescription psychostimulants, by contrast, are rarely involved in fatal overdose, though they too can be misused.^[5]

The psychostimulants are understood to act chiefly by increasing signalling at monoamine neurotransmitters in the brain — particularly dopamine and noradrenaline — although they do so by different routes. Cocaine is understood to block the reuptake of these neurotransmitters; amphetamine is understood also to increase their release. The mild psychostimulant caffeine acts differently again, understood to work principally by blocking adenosine receptors. That these substances act on these systems is well established; the fuller relationship between that action and the range of effects — the therapeutic effects, the euphoria, and the development of dependence — is more complex and remains a subject of research. The observation that psychostimulants can both sharpen attention and, at higher doses, impair it has been attributed in part to dose: the effect depends heavily on how much is taken.

The psychostimulants include the plant-derived cocaine; the synthetic amphetamine, methamphetamine, and methylphenidate; and, among the milder members, caffeine, nicotine, and the plant psychostimulants ephedrine and cathinone (the active psychostimulant of khat). MDMA is sometimes grouped with the psychostimulants, though it has hallucinogenic properties as well. The list is not exhaustive, and the psychostimulants shade at their edges into other classes.

The psychostimulants share a characteristic difficulty: the alertness and elevation of mood they produce are accompanied by a liability to misuse and, with repeated use of the more powerful members, to dependence. Acutely, psychostimulants raise heart rate and blood pressure and can place significant strain on the cardiovascular system; high doses are associated with cardiac events, with agitation and overheating, and, with sustained heavy use, with a psychosis that can resemble schizophrenia. Effects vary considerably with the particular substance, the dose, and the route of use, and the figures reported are population estimates that vary between studies. The mild psychostimulants in everyday food and drink carry a much lower order of risk than the potent synthetic psychostimulants, although they are not free of effects of their own.