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Using historical research that draws on new primary sources, I review the causes and course of the first, mainly iatrogenic amphetamine epidemic in the United States from the s through the s.

The latest national surveys show that about 3 million Americans used amphetamine-type stimulants nonmedically in the past year, in the past week, and that to are addicted. The original amphetamine epidemic was generated by the pharmaceutical industry and medical profession as a byproduct of routine commercial drug development and competition. Searching for a decongestant and bronchodilator to substitute for ephedrine, in , biochemist Gordon Alles discovered the physiological activity of beta-phenyl-isopropylamine soon to be known as amphetamine.

SKF marketed it as the Benzedrine Inhaler, a capped tube containing mg of oily amphetamine base and little else. For congestion, one was meant to inhale amphetamine vapor every hour as needed. SKF-funded Harvard psychiatrist Abraham Myerson played a particularly influential role, theorizing that amphetamine adjusted hormonal balance in the central nervous system by creating or amplifying adrenergic stimulation so as to promote activity and extra-version.

Because Meyerson understood minor depression as anhedonia caused by suppression of natural drives to action, amphetamine represented an ideal depression therapy to him.

The US military also supplied Benzedrine to servicemen during the war, mainly as 5-mg tablets, for routine use in aviation, as a general medical supply, and in emergency kits. Along with growth in amphetamine use for psychiatric indications, the war years also saw an explosion of amphetamine consumption for weight loss, although this medical usage was not yet approved by AMA and not advertised by SKF.

Off-brand pills manufactured by smaller companies dominated this market. Past-year use in would have almost certainly been higher, because many were only occasional users. Unsurprisingly, given such widespread availability of so inherently attractive a drug, significant abuse of amphetamine quickly developed. One noteworthy publication hinted at its dimensions.

Psychiatrists Russell Monroe and Hyman Drell, stationed at a military prison in , encountered large numbers of agitated, hallucinating patients. A survey revealed that one quarter of the imprisoned personnel were eating the contents of Benzedrine Inhalers, which then contained mg of amphetamine base. There is thus strong evidence that Benzedrine abuse, although an existing practice, was multiplied many times by military exposure, at least among vulnerable subpopulations.

And although these prisoners were not typical of military personnel, neither, in the judgment of the psychiatrists, were most of them particularly abnormal young men. Amphetamine was successfully marketed as the first antidepressant in the late s and s, together with a particular understanding of depression as anhedonia. California Western Medicine 62 April In the s, competition among pharmaceutical firms boosted amphetamine consumption dramatically, after expiration of the Alles and Smith, Kline and French patent in Journal of the American Medical Association To sum up, by the end of World War II in , less than a decade after amphetamine tablets were introduced to medicine, over half a million civilians were using the drug psychiatrically or for weight loss, and the consumption rate in the United States was greater than 2 tablets per person per year on a total-population all ages basis.

Misuse and abuse, especially of the cheap nonprescription Benzedrine Inhaler but also of tablets, were not uncommon. However, as often occurs in the first flush of enthusiasm for new pharmaceuticals, abuse, adverse effects, and other drawbacks had not yet attracted much notice. During the s, fierce commercial competition helped drive amphetamine consumption higher still. In a particularly innovative effort to expand medical usages for the drug, in late , SKF introduced a product called Dexamyl, a blend of dextroamphetamine and the barbiturate sedative amobarbital.

According to FDA manufacturer surveys, by , US production reached an estimated kg of amphetamine salts, corresponding to consumption of 43 standard mg doses per person per year on a total-population basis. This oversight may be caused by excessive reliance on retail prescription audits inappropriate for amphetamines when billions were dispensed directly; see the next section and neglect of the fact that amphetamine obesity medications were just as psychotropic as amphetamine-based antidepressants.

Through the rest of the s, FDA estimates of amphetamine production would grow little beyond 8 billion mg doses, implying that consumption of the drug had already reached saturation levels in This conclusion, based on voluntary FDA production surveys, draws independent support from flat retail prescription sales from to The best published evidence of the nature and prevalence of medical amphetamine consumption around comes from studies in the United Kingdom, thanks to the National Health System, which facilitates comprehensive prescription monitoring and correlation of physicians with base populations.

About one third of amphetamine prescriptions were for weight loss, one third for clear-cut psychiatric disorders depression, anxiety , and the remaining third for ambiguous, mostly psychiatric and psychosomatic complaints tiredness, nonspecific pain.

Amphetamine psychosis had already been observed in the s among long-term narcoleptic users of the drug, and individual case reports mounted during the s and early s.

Also, the psychosis generally took time to develop, suggesting a dosage-dependent cumulative effect. Finally, patients recovered fully a week or two after they ceased amphetamine use, essentially proving they had not been schizophrenic.

In Newcastle in , 0. At the end of the s, the monoamine oxidase inhibitor and tricyclic antidepressants were introduced and quickly acclaimed by psychiatrists as superior to amphetamines for depression. At that time, the vast majority of psychiatric medications were prescribed in primary care, much more so than today.

The answer lies in the type of patient for whom amphetamine-based prescriptions had become typical in the s and the trends and exigencies of primary care.

At least one third of primary care office visits are motivated by complaints for which the physician can find no organic explanation, a longstanding fact of life for general practitioners that received official recognition in the s.

In the s, the continuing preference of family doctors for amphetamines caused psychiatrists some consternation. Evidently, the newer drugs did not work as well for the typical distressed amphetamine patient, even though they worked better on bona fide depressives in controlled clinical trials. As one specialist lamented in , general practitioners had tried newer antidepressants, but they prescribed them in subtherapeutic doses to avoid toxicity in the case of monoamine oxidase inhibitors and unpleasant side effects in the case of tricyclics.

Used as placebos to tide patients over their difficulties, amphetamines were superior because they were more agreeable and improved compliance. In the United States, medical amphetamine use declined only after , when new laws restricted prescribing.

In Britain, however, there was a clamor for physicians to show restraint with such dangerous and addictive medicines by the mids, 59 leading to voluntary moratoriums around that apparently succeeded in reducing national amphetamine prescribing rates. In the early s, amphetamines were still widely accepted as innocuous medications. For instance, for his painful war injuries and also to help maintain his image of youthful vigor, President John F.

Kennedy received regular injections containing around 15 mg of methamphetamine, together with vitamins and hormones, from a German-trained physician named Max Jacobson. Large quantities of amphetamines were also dispensed in the s directly by diet doctors and weight loss clinics, many of which were essentially subsidiaries of off-brand diet pill manufacturers.

This study was designed exclusively to measure medical, prescribed drug use. It found that 6. By this extrapolation, at least 9. If we may also extrapolate the New York misuse rates, 3. To the extent that amphetamine addiction is determined biologically by active compound, dosage form, and dosage schedule or availability, we may safely again, with conservative bias apply dependency rates derived from the earlys British studies of medical users to the United States of the late s, because the same pills were being distributed on the same prescriptions.

As noted, in the United States, large-scale diversion from medical channels was widely acknowledged early in the s, and amphetamine control measures were discussed in Congress throughout the decade. The legislation that in became the Drug Abuse Control Amendments was originally intended to restrict the manufacture of amphetamines, along with barbiturates.

Drug abuse in general became an increasingly exigent political topic during the later s, as popular concern mounted about widespread amphetamine abuse everywhere from leafy suburbs to Vietnam to hippie enclaves like Haight-Ashbury. However, reflecting industry interests, only a handful of rarely prescribed injectable methamphetamine products were placed in Schedule II, while some oral amphetamine products on the US drug market were classed in Schedule III, meaning they were subject to no manufacturing quotas and to looser recordkeeping and their prescriptions could be refilled 5 times.

Drugs in Schedule II required a fresh prescription each time they were filled, and doctors and pharmacists had to keep strict records or face prosecution.

The move to Schedule II empowered federal narcotics authorities, in consultation with the FDA, to set quotas limiting the production of amphetamines to quantities required by medicine. Meanwhile, the FDA was narrowing legitimate uses of the amphetamines, retroactively declaring the drugs to be of unproven efficacy in obesity and depression. Manufacturers were invited to submit applications demonstrating efficacy, but in general these submissions were based on older trials and were found wanting by modern standards of clinical research.

While the FDA pursued its reevaluation of amphetamine efficacy, in , the BNDD took applications from firms wishing to manufacture Schedule II drugs, a procedure that required reporting of past production. According to this reporting, US firms applying for quotas manufactured kg of amphetamine base and kg of methamphetamine base in In terms of the units used in prior voluntary FDA surveys, this figure equals about 3 billion mg amphetamine sulfate tablets and 1 billion mg methamphetamine hydrochloride tablets—altogether, 4 billion doses, a fair estimate of actual medical consumption in given the context of reporting.

Given the prescribing slump that followed Schedule II listing, however, the BNDD, with FDA agreement, instead set production levels for at one fifth of levels and at one tenth of reported medical production or about one twentieth of actual production in The first amphetamine epidemic was iatrogenic, created by the pharmaceutical industry and mostly well-meaning prescribers.

The current amphetamine resurgence began through a combination of recreational drug fashion cycles and increased illicit supply since the late s. As noted, to of them were addicted. Another striking similarity between present and past epidemics relates to the role of pharmaceutical amphetamines. Although illicitly manufactured methamphetamine launched the current epidemic, in step with rising amphetamine abuse in recent years, the United States has seen a surge in the legal supply and use of amphetamine-type attention deficit medications, such as Ritalin methylphenidate and Adderall amphetamine.

American physicians, much more than those in other countries, apparently are again finding it difficult to resist prescribing stimulants that patients and parents consider necessary, or at least helpful, in their struggle with everyday duties. US medical consumption of amphetamine and methylphenidate, expressed as common dosage units mg amphetamine and mg methylphenidate, anhydrous base , based on Drug Enforcement Administration production quota figures.

Might the recent increases in both medical and nonmedical amphetamine use be related, and if so, how? Childhood stimulant treatment for attention deficit disorder as a cause of later nonmedical amphetamine consumption is one possible connection that has received considerable attention. Although controversy remains, the weight of evidence suggests that medication prescribed for attention deficit disorder does not predispose individuals to stimulant abuse or dependence.

Nevertheless, this line of inquiry does not eliminate any possible relationship between prescribing for attention deficit disorder and rates of stimulant abuse. Even if there is no connection at the individual level, there may be one at the population level.

Other than converting attention deficit disorder patients into abusers, prescribed amphetamines can contribute to the national stimulant epidemic in at least 2 other ways. For one, the mere distribution of so many stimulant tablets in the population creates a hazard. Diversion from students with attention deficit prescriptions to those without is known to occur in high schools, and at American universities, both diversion and nonmedical use by those with prescriptions are commonplace.

A detailed analysis of stimulant abuse in recent national household drug surveys found not only that 1. In that study, those who abused only nonmethamphetamine i. Besides iatrogenic dependence and diversion to nonmedical users, there is another way that widespread prescription of amphetamine-type stimulants can contribute to an amphetamine epidemic.

When a drug is treated not only as a legal medicine but as a virtually harmless one, it is difficult to make a convincing case that the same drug is terribly harmful if used nonmedically. This is what happened in the s and is presumably happening today. Thus, to end their rampant abuse, amphetamines had to be made strictly controlled substances and their prescription sharply curtailed. Today, amphetamines are widely accepted as safe even for small children, and this return of medical normalization inevitably undermines public health efforts to limit amphetamine abuse.

National Center for Biotechnology Information , U. Am J Public Health. Find articles by Nicolas Rasmussen. Accepted August 7, This article has been cited by other articles in PMC. Abstract Using historical research that draws on new primary sources, I review the causes and course of the first, mainly iatrogenic amphetamine epidemic in the United States from the s through the s. Open in a separate window. For references to footnotes, see endnote National Findings Rockville, Md:


America’s First Amphetamine Epidemic –

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