Minnesota White Rabbit: One Pill Made You Larger, One Pill

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In April, the University of Minnesota’s Psychiatry Department Chairman stepped down and psychiatric drug studies were halted, in the wake of a state report criticizing the school’s role in the suicide of patient Dan Markingson. Against his mothers’ wishes, the 27-year-old Markingson had been enrolled in a 2004 clinical trial for antipsychotic drugs. This week the University approved sweeping changes to protect human subjects involved in medical trials. In retrospect, we wonder what took so long? We harken back to a surreal winter in 1936 when the U of M was doling out free breakfast and lunch amphetamines to its Psychology students -- in another very special trial.

A Wondrous Time to be a Gopher

Touted as the World’s Largest College Newspaper in 1936, the Minnesota Daily was immersed in coverage of the nation’s best college football team. Dwarfing Ohio State Buckeye mania, the Minnesota Gophers rode a historic 21-game winning streak spanning three seasons. Despite an upset at the hands of Northwestern, blowouts of Iowa (52-0) and Wisconsin (24-0) led the way to their third consecutive national championship. So great was demand for tickets that more than 350 students were called into the Dean’s office one by one, for questioning about illegal use of their fee statements. The statements were being used to purchase and scalp season tickets. The Daily produced a number of special football sections covering all aspects of the Gopher gridiron including accolades from sports columns across the nation. A representative example came from the sports editor of the Kansas City Journal who stated the Gopher winning streak record “may stand forever”. The Daily served as the social media of the day. In a typical week it tracked a frenzied schedule of ballroom dances being held by the Greeks as well as those run by the Dentists, the Military and even the YWCA. During Thanksgiving Week it followed five dances but had time to announce what debutantes were wearing: Eva Obermeyer would be in black taffeta while Ann Tschida would present in “gold hammered satin with a train”. Recognizing students’ hectic academic and social demands, the paper dedicated a column to student fatigue: Instead of Midnight Oil1. Their columnist lamented that “we become tired conveniently during a dull lecture or in the library”. And then he asserted that fatigue was a flimsy excuse in the same vein as fainting or “nervous breakdowns”. In short order, U of M students would learn about a new wonder drug that could make fatigue a thing of the past.
The Next Wonder Drug

Calif Western Medicine 1962 Benzedrine Photo

By the mid-1930s the pharmaceutical company Smith Klein and French had unveiled a successful amphetamine inhaler called Benzedrine. The inhaler was a potent, capped tube of 325mg of oily amphetamine base. Its initial value was to clear bronchial passages for cold sufferers. But in a matter of months, Benzedrine showed every sign of becoming the next wonder drug. It displayed startling results in battling narcolepsy and depression. Then, clinical tests showed effectiveness in relieving the symptoms of Parkinson’s Disease. Indeed, physicians were leapfrogging one another to run the next clinical trial for the drug. Dr. M. H. Nathanson was working at the University of Minnesota, Department of Medicine and was active in studying the effects of Benzedrine. The recent successes detailed in the Journal of the American Medical Association (JAMA) gave him pause. Could there be an even wider therapeutic benefit to the drug? He prepared an ambitious clinical trial for the winter of 1936, to measure the impact of Benzedrine on mental aptitude, performance and alertness. His choice of subjects, students and teaching assistants in the U of M Psychology Department—would prove historic. Foregoing inhalers, Dr. Nathanson prepared ‘pep pills’ of Benzedrine for his study. The ‘lucky’ control group of 40 students was given a pep pill at breakfast and a pep pill at lunch. Red Bull couldn’t hold a candle to the positive vibrations related by his participants2: “I have done things today I usually dislike, but which I rather enjoyed today.” “My spirits have been high all day and I have felt bubbly inside.” “I wanted to stop and talk to everybody I met.” 67% of students taking Benzedrine reported a feeling of exhilaration and a sense of well-being! 56% said they were much more talkative. More than half of participants cited increased energy and capacity for work. Can you imagine the ballroom buzz? The good doctor’s findings in the January 1937 JAMA, cautioned that more testing was needed but trumpeted: ‘wide therapeutic application’ for the drug. Students at the U of M didn’t need to read any stuffy medical journal. The word was out. Benzedrine was a student’s best friend. Clearly, the Psychology Department had discovered their own “midnight oil”. Students flocked to local drug stores to get the readily available, over-the-counter pills and it quickly became the drug du jour. Coffee was out. Benzedrine was in for ‘peppering up’. Spring 1937 at the U, became an extraordinary time for cramming, study hall or just about any mundane academic task. And the pills gave new meaning to the term ‘pep rally’.
Boynton Alarm Bells
Within 90 days, student health directors were alarmed by new cases of collapse, fainting and insomnia. What a surprise. Students were taking much bigger doses than the pill-for-breakfast, pill-for-lunch regimen. University medical pioneer Dr. Ruth Boynton was worried enough, that she published a warning in the Minnesota Daily:
“While we know the pills keep one awake, so little is actually known of their cumulative effects that we think it unwise for students to take them without a physician’s advice. No more than two of these pills should be taken in any 24-hour period.” She commented on the lack of controls: “Unfortunately at one of the university cities where the drug has been obtained, it has been principally from the drug store of a large national chain, whose owners are apparently more interested in the immediate profit than in the ultimate effects on the purchaser.”
Despite the overdoses, Benzedrine was not banned and continued to flourish over-the-counter for two more decades. In particular, Smith Klein and French (SKF) benefitted from its patent exclusivity. The company provided 5 mg tablets on a widespread basis to World War II military personnel. The pills were popular with pilots as a means to stay alert. By the end of the war there were one half million regular users and the company was producing enough tablets for each American to take two per day--for a whole year.
Influence on Culture

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The Minnesota discovery would make a lasting impact on culture and the great American novel. The drug was commemorated in the forties jazz song, “Who Put the Benzedrine in Mrs. Murphy’s Ovaltine” by ‘Harry the Hipster’ Gibson. In spring 1951, writer Jack Kerouac taped together 12 foot strips of drawing paper, and popped Benzedrine as a means for continuous frenetic typing. He finished the iconic On The Road in 20 days. Then quickened his pace and finished his fourth novel, The Subterraneans in just three days. Kerouac was addicted to Benzedrine much of his adult life. In the Sixties, he was ingesting so many inhalers, that friends reported that his hair was falling out and his legs were horribly swollen. Another famous user of Benzedrine was Ian Fleming’s James Bond. In periods of great stress Bond used the pills to clear his mind and enhance mental alertness. In the novel Live and Let Die Bond pops tablets to find his way through the treacherous coral reefs off the coast of Jamaica. By late 1959, the bloom was coming off the rose for Benzedrine. The FDA banned Benzedrine inhalers and all over-the-counter purchases. At the same time, researchers found that amphetamine psychosis was not just a rare schizophrenic side effect, but was common among long-term users. Symptoms included anxiety, paranoia and what physicians termed “hearing sinister voices”. Kerouac and his girlfriend frantically called police about an attempted murder in progress in the apartment below them. When police arrived they reported that no one was home in that apartment. At the same time, the industry was changing its view that amphetamines were mildly habit-forming like caffeine. New research by the British psychiatrist Philip Connell revealed user dependence characterized by compulsive behavior and degradation of function. Back at the U of M today, the National Institute on Drug Abuse estimates that 8.5% of arriving high school seniors uses the modern prescription stimulants of Adderall and Ritalin. These drugs have been prescribed extensively for treatment of attention deficit disorder (ADHD). Only half as potent as Benzedrine, it’s the new drug of choice for burning the midnight oil. For students facing a grueling schedule, Adderall or Ritalin garnered through illegal means are said to run $20 per pill. Students acquire them through friends with valid prescriptions or continue childhood prescriptions. We’ve come a long way since 1936 and one can only hope it’s a saner, safer world where in the words of the Jefferson Starship song, the pills “that mother gives you don't do anything at all”.   Sources: 1 Minnesota Daily November 21, 1936 2 Journal of American Medical Association January 1937   Retired after 31 years in marketing with United and Northwest Airlines, Tony has been published by MinnPost, Minnesota Connected, Air Cargo News, The Forward, CNS Air Cargo Focus, TC Daily Planet and the Rake. He has won a Silver Addy award in Advertising and launched United Cargo’s Friendly Skies ad campaign in 2014.   Photos courtesy of: Alexius Horatius -- University of Minnesota    

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