Category:Psychostimulants: Difference between revisions

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]].<ref name="cns"/> 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.<ref name="basicmed">Gorelick DA, Baumann MH. The pharmacology of cocaine, amphetamines, and other stimulants. In: Ries SK, Fiellin DA, Miller SC, Saitz R, eds. ''The ASAM Principles of Addiction Medicine.'' 5th ed. Wolters Kluwer; 2014, Ch. 10.</ref> 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.<ref name="basicmed"/>

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.<ref name="cns"/> 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.<ref name="basicmed"/> 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.<ref name="rasmussen">Rasmussen N. Amphetamine-type stimulants: the early history of their medical and non-medical uses. ''Int Rev Neurobiol.'' 2015;120:9–25. PMID 26070751.</ref> 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.<ref name="cns"/>

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.<ref name="adhd-rev">Connolly JJ, Glessner JT, Elia J, Hakonarson H. ADHD & pharmacotherapy: past, present and future: a review of the changing landscape of drug therapy for attention deficit hyperactivity disorder. ''Ther Innov Regul Sci.'' 2015;49(5):632–642. PMID 26366330.</ref> 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.<ref name="adhd-rev"/>

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.<ref name="adhd-rev"/>

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.<ref name="cdc-mmwr">Tanz LJ, Miller KD, Dinwiddie AT, Gladden RM. Drug overdose deaths involving stimulants — United States, January 2018–June 2024. ''MMWR Morb Mortal Wkly Rep.'' 2025;74(32):491–499. PMID 40875496.</ref> The prescription psychostimulants, by contrast, are rarely involved in fatal overdose, though they too can be misused.<ref name="cdc-mmwr"/>

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.