The amphetamine that was once considered harmless

Before psychostimulants found their place in modern medicine, patients were inhaling pure Benzedrine vapour to clear their sinuses.

For decades, one of medicine’s most powerful stimulants was considered suitable for everything from sinus congestion to low mood.

In mid-20th-century pharmaceutical advertising, Benzedrine (amphetamine), was promoted as a remedy for ‘mild depression’ and narcolepsy.^1,2  While prescribing amphetamines for a minor case of the Mondays is unthinkable today, specially formulated Benzedrine ‘pep pills’ were once accepted as harmless pick-me-ups.¹ They persisted as a treatment for low mood, weight loss and fatigue until the early 1970s.²

An accidental discovery

The chemical roots of Benzedrine trace back to 1887, when Romanian chemist Lazăr Edeleanu synthesised beta-phenyl-isopropylamine. The compound sat forgotten for more than 40 years after being dismissed as pharmaceutically useless.¹

That changed in 1929 when Los Angeles chemist Gordon Alles, searching for a synthetic asthma remedy, had himself injected with 50 milligrams of the drug. Within minutes, his nasal passages were bone dry.¹ Soon after, his heart raced, his blood pressure climbed and he experienced an overwhelming ‘feeling of well being’.¹

Recognising the drug’s commercial potential, Smith, Kline & French (SKF) patented an alternate base form of amphetamine and launched the Benzedrine Inhaler in 1933 as an over-the-counter decongestant inhaler.²

The amphetamine boom

The early Benzedrine Inhaler was simple: a plastic tube housing 325 mg of an oily amphetamine base.² By 1937, SKF had introduced Benzedrine Sulfate tablets,² encouraging physicians to prescribe it for conditions ranging from mild depression and fatigue to hypochondria.¹

Combination formulations soon followed in the 1950s, most notably Dexamyl – a blend of dextroamphetamine and the sedative amobarbital – designed to temper stimulant-related anxiety while maintaining alertness.² In 1937, American psychiatrist Charles Bradley stumbled upon a new use for the drug.³

While administering Benzedrine to children in an attempt to relieve headaches, Bradley observed an unexpected transformation: instead of becoming hyperactive, the children became remarkably calm, focused and cooperative. Teachers and observers reported dramatic improvements in classroom performance and an unprecedented drive to accomplish schoolwork.³

Over the following two decades, as child psychiatry formalised diagnoses like ‘hyperkinetic impulse disorder’ (a precursor to ADHD), Benzedrine became one of the first psychostimulants to manage hyperactivity and inattentiveness in children.^3,4

The fallout

As enthusiasm for Benzedrine spread, its uses extended beyond treating medical conditions. During World War II, military commanders issued Benzedrine tablets to keep combat pilots awake on long missions.¹ By the 1950s, housewives, truck drivers, and students were consuming billions of Benzedrine pills annually to manage their daily workloads.¹

However, the dark side of Benzedrine soon became apparent. In 1958, British psychiatrist Philip Connell published a landmark study finding that high doses of Benzedrine triggered severe, paranoid psychosis, along with auditory hallucinations and sinister delusions, even in patients with no underlying mental illness.²

Evidence continued to emerge in 1960 that amphetamine was truly addictive and not just ‘habitual’ like coffee.²

Benzedrine’s legacy

In 1971, federal authorities placed Benzedrine and related psychostimulants under strict controls, capping factory production and restricting prescriptions.² As understanding of ADHD evolved, classic Benzedrine gradually disappeared from clinical use.⁴ It was replaced by more refined stimulant medications including methylphenidate (Ritalin, Artige, Rinidate) and lisdexamfetamine (Vyvanse), which offered more predictable effects and a lower risk of misuse.

References

1. Hicks J. Fast times: the life, death, and rebirth of amphetamine. Science History Institute. 2012. At: sciencehistory.org/stories/magazine/fast-times-the-life-death-and-rebirth-of-amphetamine/
2. Rasmussen N. America’s first amphetamine epidemic 1929–1971: a quantitative and qualitative retrospective with implications for the present. Am J Public Health 2008;98(6):974–85.
3. Strohl MP. Bradley’s Benzedrine studies on children with behavioral disorders. Yale J Biol Med 2011;84(1):27–33.
4. Lange KW, Reichl S, Lange KM, et al. The history of attention deficit hyperactivity disorder. ADHD Atten Def Hyp Disord 2010;2(4):241–55.
5. Heal DJ, Smith SL, Gosden J, et al. Amphetamine, past and present: a pharmacological and clinical perspective. J Psychopharmacol 2013;27(6):479–96.