America’s First Amphetamine Epidemic 1929–1971€¦ · and course of the first, mainly...

PUBLIC HEALTH THEN AND NOW

American Journal of Public Health | June 2008, Vol 98, No. 6974 | Public Health Then and Now | Peer Reviewed | Rasmussen

Using historical research that draws on new primary sources, I review the causesand course of the first, mainly iatrogenic amphetamine epidemic in the UnitedStates from the 1940s through the 1960s. Retrospective epidemiology indicatesthat the absolute prevalence of both nonmedical stimulant use and stimulant de-pendence or abuse have reached nearly the same levels today as at the epi-demic’s peak around 1969. Further parallels between epidemics past and pres-ent, including evidence that consumption of prescribed amphetamines has alsoreached the same absolute levels today as at the original epidemic’s peak, sug-gest that stricter limits on pharmaceutical stimulants must be considered in anyefforts to reduce amphetamine abuse today. (Am J Public Health.2008;98:974–985. doi: 10.2105/AJPH.2007.110593)

THE UNITED STATES ISexperiencing an outbreak of am-phetamine abuse. The latest na-tional surveys show that about 3million Americans used ampheta-mine-type stimulants nonmed-ically in the past year, 600000 inthe past week, and that 250000to 350000 are addicted.1 Al-though survey data indicate thatthe number of nonmedical usersof amphetamine-type stimulantsmay have stabilized, the numberof heavy users with addictionproblems doubled between 2002and 2004.2 Thus, the publichealth problem presented by

| Nicolas Rasmussen, PhD, MPhil, MPH

A Quantitative and Qualitative Retrospective With Implications for the Present

America’s First AmphetamineEpidemic 1929–1971

the Philadelphia firm Smith,Kline and French (SKF) investi-gated the base form of ampheta-mine and patented it in 1933.SKF marketed it as the Ben-zedrine Inhaler, a capped tubecontaining 325 mg of oily am-phetamine base and little else.For congestion, one was meant toinhale amphetamine vapor everyhour as needed.6 Although nolegal category of prescription-only drugs existed in the 1930s,7

the Benzedrine Inhaler was ad-vertised for over-the-counter saleupon its introduction in 1933and 1934 and for the next 15years.8

At the end of 1934, Alles trans-ferred his patent on amphetaminesalts to SKF, and the firm spon-sored the drug’s further clinicaldevelopment.9 In 1937, the Amer-ican Medical Association (AMA)approved advertising of SKF’s“Benzedrine Sulfate” racemic am-phetamine tablets for narcolepsy,postencephalitic Parkinsonism,and minor depression.10 (The vol-untary AMA “Seal of Approval”system, in which mainly academicmedical experts evaluated datasubmitted by manufacturers before

amphetamines may still be in-creasing in severity; in many waysit surpasses that of heroin.3 Al-though all of this is widely appre-ciated, the history of an evenlarger amphetamine epidemic 4decades ago is less well-known.

ORIGINS OF THEEPIDEMIC, 1929–1945

The original amphetamine epi-demic was generated by the phar-maceutical industry and medicalprofession as a byproduct of rou-tine commercial drug develop-ment and competition. Searchingfor a decongestant and bron-chodilator to substitute forephedrine, in 1929, biochemistGordon Alles discovered the phys-iological activity of beta-phenyl-isopropylamine (soon to beknown as amphetamine). Allespublished his first clinical resultswith the compound in 1929,4

began amphetamine’s clinical de-velopment in collaboration withpharmacologists and clinicians atthe University of California, andreceived a patent on its orally ac-tive salts in 1932.5 Meanwhile,possibly inspired by Alles’s work,


supplied methamphetamine.17 Ofcourse, not all amphetamine sup-plied by the military was ingestedby servicemen, nor did users in-gest it ad libitum; there were ruleslimiting the drug’s use.18 However,these were not well observed. Forinstance, in a 1945 army surveyof fighter pilots, of the 15% (13 of85) who regularly used ampheta-mine in combat, the majority“made their own rules” and tookBenzedrine whenever they “feltlike it” rather than as directed.19

Along with growth in amphet-amine use for psychiatric indica-tions, the war years also saw anexplosion of amphetamine con-sumption for weight loss, al-though this medical usage wasnot yet approved by AMA andnot advertised by SKF. Off-brandpills manufactured by smallercompanies dominated this mar-ket. In 1943, SKF filed suit forpatent infringement against oneof these manufacturers, a NewJersey concern named Clark &Clark, producer of both 10-mgBenzedrine look-alike tabletsand colorful diet pills containingmetabolism-boosting thyroid hor-mone and 5 mg of amphetamine.The company’s output was amatter of dispute, but on the basisof sworn testimony from bothsides, combined amphetamineproduction for civilian use bySKF and Clark & Clark in late1945 must have stood between13 million and 55 million tabletsmonthly and may be conserva-tively estimated at about 30million tablets monthly, eachcontaining 5 to 10 mg of am-phetamine salts.20 This national(civilian) consumption rate forthe United States in 1945 wassufficient to supply half a millionAmericans with 2 tablets daily,the standard dosage schedule fordepression and weight loss. Past-year use in 1946 would have

almost certainly been higher, be-cause many were only occasionalusers.

Unsurprisingly, given such wide-spread availability of so inherentlyattractive a drug, significant abuseof amphetamine quickly developed.One noteworthy 1947 publicationhinted at its dimensions. Psychia-trists Russell Monroe and HymanDrell, stationed at a military prison

in 1945, encountered large num-bers of agitated, hallucinating pa-tients. A survey revealed that onequarter of the imprisoned person-nel were eating the contents ofBenzedrine Inhalers, which thencontained 250 mg of ampheta-mine base. Almost one third of the

June 2008, Vol 98, No. 6 | American Journal of Public Health Rasmussen | Peer Reviewed | Public Health Then and Now | 975

allowing advertising in cooperat-ing journals, was the only drug ef-ficacy regulation at the time.11)Amphetamine therapy for minor(“neurotic”) depression quicklyfound acceptance among psychia-trists and neurologists in the late1930s. SKF-funded Harvard psy-chiatrist Abraham Myerson playeda particularly influential role, theo-rizing that amphetamine adjustedhormonal balance in the centralnervous system by creating or am-plifying adrenergic stimulation soas to promote activity and extra-version. Because Meyerson under-stood minor depression as anhe-donia caused by suppression ofnatural drives to action, ampheta-mine represented an ideal depres-sion therapy to him.12

Fueled by advertising and mar-keting urging general practitionersto prescribe the drug for depres-sion, and at the same time promot-ing Myerson’s rationale for thatuse, annual sales of Benzedrinetablets (mainly 10 mg) grewsteadily to about $500000 in1941, over 4% of SKF’s totalsales.13 Thus, by World War II,amphetamine in tablet form wasfinding commercial success andgaining credibility as a prescriptionpsychiatric medication (the first“antidepressant”), despite sporadicreports of misuse.14 The war yearsdid nothing to diminish the drug’sgrowth in popularity; by 1945,SKF’s civilian amphetamine tabletsales had quadrupled to $2 mil-lion, including $650000 in salesof the firm’s new “Dexedrine” dex-troamphetamine tablets.15

The US military also suppliedBenzedrine to servicemen duringthe war, mainly as 5-mg tablets,for routine use in aviation, as ageneral medical supply, and inemergency kits.16 The British mili-tary also supplied Benzedrinetablets during the war, and theGerman and Japanese military

Amphetamine was successfully mar-keted as the first antidepressant inthe late 1930s and 1940s, togetherwith a particular understanding of de-pression as anhedonia.

Source. California Western Medicine 62(April 1945): 33 (advertising section) andAmerican Journal of Psychiatry 101(March 1945): xiii (advertising section).


abusers (8% of the prison popula-tion) had begun this practice inthe military before imprisonment.Only 11% of the inhaler abusers(3% of the prison population) hadused some form of amphetaminenonmedically before the war.Twenty-seven percent of abusershad been given amphetamine dur-ing military service, mainly by anofficer and in tablet form, com-pared with 5% of nonabusers—anodds ratio of 7.0. There is thusstrong evidence that Benzedrine

abuse, although an existing prac-tice, was multiplied many times bymilitary exposure, at least amongvulnerable subpopulations. Andalthough these prisoners were nottypical of military personnel, nei-ther, in the judgment of the psy-chiatrists, were most of them par-ticularly abnormal young men.21

To sum up, by the end of WorldWar II in 1945, less than a dec-ade after amphetamine tabletswere introduced to medicine, overhalf a million civilians were usingthe drug psychiatrically or forweight loss, and the consumptionrate in the United States wasgreater than 2 tablets per personper year on a total-population (allages) basis.22 Up to 16 millionyoung Americans had been ex-posed to Benzedrine Sulfate dur-ing military service, in which thedrug was not treated as dangerousnor was its use effectively con-trolled, helping normalize anddisseminate nonmedical ampheta-mine use. Misuse and abuse, espe-cially of the cheap nonprescriptionBenzedrine Inhaler but also oftablets, were not uncommon.However, as often occurs in thefirst flush of enthusiasm for newpharmaceuticals, abuse, adverseeffects, and other drawbacks hadnot yet attracted much notice.

GROWTH OF THEEPIDEMIC, 1945–1960

In 1945 and 1946, the courtsupheld Alles’s patent on ampheta-mine salts, affirming SKF’s mo-nopoly control of oral ampheta-mine until late 1949.23 Withrecouped business from infringingfirms, SKF’s annual sales of am-phetamine tablets (Benzedrineand Dexedrine Sulfate) doubled,from $2.9 million in 1946 to $5.7million in 1947.24 With AMA ap-proval to advertise amphetaminefor weight loss that year, sales

climbed further to $7.3 million in1949, despite competition frommethamphetamine-based weightloss and antidepressant productssuch as Abbot’s Desoxyn andWellcome’s Methedrine.25 Follow-ing expiration of Alles’s patent inlate 1949, consumption of phar-maceutical amphetamines in theUnited States surged. On the basisof voluntary manufacturer sur-veys, the Food and Drug Adminis-tration (FDA) placed 1952 pro-duction of amphetamine andmethamphetamine salts at nearlyquadruple the agency’s 1949 esti-mate by similar methods.26 Giventhat SKF amphetamine sales inthe period did not grow signifi-cantly, virtually all this expansionin amphetamine supply wasdriven by the marketing efforts ofcompetitors.27

During the 1950s, fierce com-mercial competition helped driveamphetamine consumption higherstill. In a particularly innovative ef-fort to expand medical usages forthe drug, in late 1950, SKF intro-duced a product called Dexamyl,a blend of dextroamphetamineand the barbiturate sedative amo-barbital.28 Intended to overcomethe unpleasant agitation that manyusers experienced with ampheta-mine and to quell anxiety withoutdrowsiness, Dexamyl was mar-keted with great success for every-day “mental and emotional dis-tress” in general practice and alsoas a weight-loss remedy striking atthe emotional causes of overeat-ing.29 Competing firms answeredwith their own sedative–amphetamine combinations, suchas Abbot’s Desbutal and Robins’sAmbar, blends of methampheta-mine and pentobarbital or pheno-barbital, respectively.30 Creativeamphetamine combination prod-ucts from both SKF and its com-petitors proliferated throughoutthe 1950s.31

American Journal of Public Health | June 2008, Vol 98, No. 6976 | Public Health Then and Now | Peer Reviewed | Rasmussen”“By the end of World War II in 1945, less than a

decade after amphetamine tablets were introducedto 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.

In the 1950s, competition amongpharmaceutical firms boosted am-phetamine consumption dramatically,after expiration of the Alles andSmith, Kline and French patent in1949.

Source. Journal of the American MedicalAssociation 147 (1951): 19 (advertisingsection).


According to FDA manufac-turer surveys, by 1962, US pro-duction reached an estimated80000 kg of amphetamine salts,corresponding to consumption of43 standard 10-mg doses per per-son per year on a total-populationbasis.32 Thus, in amphetaminealone, the United States in theearly 1960s was using nearly asmuch psychotropic medication asthe 65 doses per person per yearin the present decade that socialcritics today find so extraordi-nary.33 And the 1960s are rightlyremembered for excessive minortranquilizer consumption, around14 standard doses per person peryear on the basis of retail prescrip-tion sales.34 It is rarely appreciatedthat in the early 1960s, ampheta-mines were actually consumed ata higher rate than tranquilizers.This oversight may be caused byexcessive reliance on retail pre-scription audits (inappropriate foramphetamines when billions weredispensed directly; see the nextsection) and neglect of the fact thatamphetamine obesity medicationswere just as psychotropic as am-phetamine-based antidepressants.Through the rest of the 1960s,FDA estimates of amphetamineproduction would grow little be-yond 8 billion 10-mg doses, imply-ing that consumption of the drughad already reached saturationlevels in 1962. This conclusion,based on voluntary FDA produc-tion surveys, draws independentsupport from flat retail prescriptionsales from 1964 to 1970.35

The best published evidence ofthe nature and prevalence of med-ical amphetamine consumptionaround 1960 comes from studiesin the United Kingdom, thanks tothe National Health System, whichfacilitates comprehensive prescrip-tion monitoring and correlation ofphysicians with base populations.A study of retail prescriptions

filled in the Newcastle area during1960 found that about 3% werefor amphetamines, consistent bothwith UK national prescribing fig-ures and with contemporary pre-scribing in the United States ac-cording to commercial audits.36

Given similarities in culture andmedical practices, the British find-ings therefore shed light on am-phetamine use in America around1960, at least for drugs dispensedat pharmacies.37

In the Newcastle study, quanti-ties dispensed were sufficient tosupply more than 1% of the totalpopulation with 60 tablets permonth; two 5-mg doses of dextro-amphetamine daily was the mostcommon prescription, accordingto a 1961 companion study thataudited family practitioners in thesame area.38 Dexamyl—in Britaincalled Drinamyl—was the mostcommonly prescribed ampheta-mine product. About one third ofamphetamine prescriptions werefor weight loss, one third forclear-cut psychiatric disorders (de-pression, anxiety), and the remain-ing third for ambiguous, mostlypsychiatric and psychosomaticcomplaints (tiredness, nonspecificpain). The largest age groupamong the medical users werethose aged 36 to 45 years, and85% of all amphetamine patientswere women.39 Even making thesimplifying assumption thatweight loss prescriptions were en-tirely for women and taking intoaccount that women seek medicalattention more often than men,these figures indicate that perdoctor visit around 1960, awoman was twice as likely as aman to receive an amphetamineprescription to adjust her mentalstate—much like minor tranquiliz-ers in the same period.40

By about 1960, widespreadconsumption had begun to makeamphetamine’s negative health

consequences more evident. Am-phetamine psychosis had alreadybeen observed in the 1930samong long-term narcolepticusers of the drug, and individualcase reports mounted during the1940s and early 1950s.41 Ini-tially, psychotic episodes were at-tributed to latent schizophrenia“unmasked” by the drug or tosome other preexisting psychiat-ric pathology in the user.42 InPhilip Connell’s definitive 1958study of 40 cases, however, theBritish psychiatrist persuasivelyshowed that amphetamine psy-chosis could happen to anyone,and eventually would, givenenough of the drug.43 The highlyuniform set of paranoid symp-toms—sinister voices emanatingfrom toilet bowls, spies followingone’s every move—in a wide vari-ety of personality types arguedagainst any shared constitutionalfeature of the patients’ mentalityor neurology. Also, the psychosisgenerally took time to develop,suggesting a dosage-dependentcumulative effect. And althoughalmost all of Connell’s patientshad engaged in nonmedical usebefore their crises, a large propor-tion had first taken ampheta-mines by prescription, so theycould not be dismissed as deviantthrill-seekers. Finally, patients re-covered fully a week or two afterthey ceased amphetamine use,essentially proving they had notbeen schizophrenic.44

Evidence was also emergingaround 1960 that amphetamine istruly addictive, instead of merely“habituating” like caffeine, as lead-ing pharmacologists had assertedwhen the drug was first intro-duced.45 Postwar changes in think-ing about addiction, promotedparticularly by the World HealthOrganization, facilitated this newperspective on amphetamine bymoving the concept away from an




opiate model, defined by acutephysiological withdrawal, toward apsychosocial model of “drug de-pendency” defined by compulsivebehavior and erosion of function.46

Indeed, the previously mentionedBritish research uncovered evi-dence of significant dependencyon prescribed amphetamines. InNewcastle in 1961, 0.8% of a verylarge study population receivedamphetamine prescriptions duringa 3-month audit period; accordingto their physicians, between onefifth and one quarter of these am-phetamine patients were “habitu-ated or addicted” or dependent tosome extent.47 Taking the samplein these studies as representative(as the investigators intended),between 2% and 3% of the totalpopulation must have receivedamphetamines by prescription inthe course of a year.48 This, to-gether with the 0.2% of the gen-eral population identified as “ha-bituated or addicted,” implies adependency rate among past-yearmedical amphetamine users of6.7% to 10%.49

To distinguish between the ha-bituation and addiction reportedby Newcastle physicians, anothernorthern British study of the early1960s enrolled family practition-ers to dispense Dexamyl tablets,identical-looking placebos, or plainwhite tablets containing Dexamyl’sactive ingredients to their appar-ently amphetamine-dependentpatients on a double-blind basis.The study found that about onethird of “habituated or addicted”medical Dexamyl users were infact physically dependent.50 Takentogether with the prevalence esti-mates in the previous paragraph,this outcome implies extensiveiatrogenic amphetamine addictionin the early 1960s—that is, 2.2%to 3.3% of all patients receivingamphetamine prescriptions in agiven year.51

At the end of the 1950s, themonoamine oxidase inhibitor andtricyclic antidepressants were intro-duced and quickly acclaimed bypsychiatrists as superior to amphet-amines for depression. In theUnited States, however, prescribingrates for amphetamines did notdecline significantly in the1960s,52 despite the availability ofalternatives and increasing aware-ness of amphetamine’s defects.At that time, the vast majority ofpsychiatric medications were pre-scribed in primary care, muchmore so than today.53 Why, then,did family practitioners continueto prescribe mental health drugsthat psychiatric specialists judgedinferior?

The answer lies in the type ofpatient for whom amphetamine-based prescriptions had becometypical in the 1950s and thetrends and exigencies of primarycare. At least one third of primarycare office visits are motivated bycomplaints for which the physiciancan find no organic explanation, alongstanding fact of life for gen-eral practitioners that received of-ficial recognition in the 1950s.54

“Psychosomatic medicine” enjoyeda postwar vogue, and as a substi-tute for the archaic bromides andnerve tonics then still commonlyprescribed, primary care authori-ties in the 1950s began advocat-ing barbiturates, amphetamine,and amphetamine–barbituratecombinations for the mild depres-sions and other emotional distur-bances presumed to be drivingsuch mysterious complaints.55 Psy-chiatric specialists writing on gen-eral practice also endorsed theseprescribing approaches, althoughthey understood sympathy, reas-surance, and time as the maintherapeutic agents for all neuroticailments.56 Assisted by such trendsin medical thought, along withpharmaceutical marketing that

reinforced them, amphetaminesbecame first-line treatments foremotional distress and psychoso-matic complaints in the 1950s.

In the 1960s, the continuingpreference of family doctors foramphetamines caused psychia-trists some consternation. Evi-dently, the newer drugs did notwork as well for the typical dis-tressed amphetamine patient,even though they worked betteron bona fide depressives in con-trolled clinical trials. As one spe-cialist lamented in 1965, generalpractitioners had tried newer an-tidepressants, but they prescribedthem in subtherapeutic doses toavoid toxicity (in the case ofmonoamine oxidase inhibitors)and unpleasant side effects (inthe case of tricyclics). Used asplacebos to tide patients overtheir difficulties, amphetamineswere superior because they weremore agreeable and improvedcompliance. After a brief experi-ment, many primary care physi-cians therefore went “back to theold standbys, amphetamine andamphetamine-barbiturate combi-nations.”57 As one general practi-tioner explained in 1970, onlyamphetamine kept certain pa-tients “capable of performing oreven enjoying their duties”58—that is, of managing their prob-lems of living. In the UnitedStates, medical amphetamine usedeclined only after 1970, whennew laws restricted prescribing.In Britain, however, there was aclamor for physicians to show re-straint with such dangerous andaddictive medicines by the mid-1960s,59 leading to voluntarymoratoriums around 1968 thatapparently succeeded in reducingnational amphetamine prescrib-ing rates.60 This difference mightbe explained by a public healthinsurance framework in theUnited Kingdom that reduced

of amphetamine tablets consumedannually via this channel at 2 bil-lion.66 Finally, according to theFDA, of the roughly 8 billion to10 billion 10-mg amphetaminetablets manufactured by drug firmsannually in the United States bythe late 1960s, up to one half were“diverted” from medical channelsaltogether.67 As CBS television re-vealed in 1964, with a few hun-dred dollars and a fake companyletterhead, anyone could purchasemillions of tablets direct frommanufacturers by mail, notwith-standing pharmaceutical industrypretensions to self-regulation.68

When tighter regulation made thistactic more difficult in the later1960s, wholesale quantities wereshipped from manufacturers toMexico (even to addresses like theTijuana Golf Course’s 11th hole)and immediately reimported.69

The FDA’s crude population-level amphetamine consumptionestimates based on manufacturingsurveys (80000–100000 kg ofamphetamine salts produced for atotal population of around 200million in 1969, or up to 5010-mg doses per person) weresupplemented with prevalence es-timates from the first modern druguse surveys. A national surveyconducted in late 1970 and early1971 found past-year usage ofamphetamine-type drugs by 5%of American adults. This studywas designed exclusively to mea-sure medical, prescribed druguse.70 A more thorough, roughlysimultaneous survey in New YorkState explored both nonmedicaland medical amphetamine use. Itfound that 6.5% of the state’s13.8 million residents older than14 years had used amphetaminesin the past 6 months. If onecounts only those using oral am-phetamines made by pharmaceuti-cal firms (the great majority) in thepast 6 months, 39% sometimes

used them nonmedically and22% “abused” the drugs, definedas both obtaining drugs withoutprescription and using them on so-cial occasions.71

Because the New York survey’spast-6-month medical ampheta-mine usage rates were lower than,and consistent with, the nationalsurvey’s past-year prevalence fig-ures, we might reasonably (indeed,with conservative bias) extrapolatethe New York study’s combinedmedical and nonmedical usagerates to all 149.4 million Ameri-cans older than 14 years. By thisextrapolation, at least 9.7 millionAmericans were past-year users ofamphetamines in 1970. If we mayalso extrapolate the New Yorkmisuse rates, 3.8 million tookamphetamines nonmedically and2.1 million abused the drugs bythe New York criteria.72

To the extent that amphetamineaddiction is determined biologi-cally by active compound, dosageform, and dosage schedule oravailability, we may safely (again,with conservative bias) apply de-pendency rates derived from theearly-1960s British studies ofmedical users to the United Statesof the late 1960s, because thesame pills were being distributedon the same prescriptions. If weapply the higher range of theBritish medical amphetamine de-pendency rate (reflecting freersupply, predictably higher depend-ency rates among recreationalthan medical users, and the moreplausible past-year Newcastle pre-scription rate of 2%) to the in-ferred national population of past-year medical and nonmedicalamphetamine users combined,the United States in 1970 had970000 amphetamine usersmeeting some criteria of depend-ence and about 320000 ad-dicts.73 These should be regardedas minimal figures given the


incentives to overprescribe drugspopular with patients.

THE EPIDEMIC’S CRISIS IN THE 1960s

In the early 1960s, ampheta-mines were still widely acceptedas innocuous medications. Apartfrom vast numbers of middle-aged, middle-class patients receiv-ing low-dose prescriptions fromfamily doctors to help them copewith their daily “duties,” in muchthe same way that their doctorsprescribed minor tranquilizers,61 asignificant quasi-medical gray mar-ket in amphetamines had devel-oped. For instance, for his painfulwar injuries and also to help main-tain his image of youthful vigor,President John F. Kennedy re-ceived regular injections contain-ing around 15 mg of methamphet-amine, together with vitamins andhormones, from a German-trainedphysician named Max Jacobson.62

Known as a doctor to the starsand nicknamed “Dr Feelgood,” Ja-cobson also treated Cecil B. De-Mille, Alan Jay Lerner, TrumanCapote, Tennessee Williams, theRolling Stones, and ironically,Congressman Claude Pepper ofFlorida, a noted antidrug cam-paigner.63 Jacobson’s concoctionswere peculiar, but he was far fromunique in his readiness to pre-scribe or dispense amphetaminesfor the price of a consultation.64

Large quantities of ampheta-mines were also dispensed in the1960s directly by diet doctors andweight loss clinics, many of whichwere essentially subsidiaries of off-brand diet pill manufacturers.Huge profits could be made whenthe pharmacist was cut out in thisfashion; one dispensing diet doc-tor paid $71 for 100000 amphet-amine-containing tablets and soldthem for $12000.65 One widelycited estimate placed the number




multiple sources of conservativebias in our national past-year am-phetamine usage estimates for1970 and 1971. Furthermore,1970 to 1971 prevalence presum-ably underestimates amphetamineuse at the epidemic’s peak around1969, because consumption in theUnited States was already decliningwhen the surveys were conducted.74

As noted, in the United States,large-scale diversion from med-ical channels was widely ac-knowledged early in the 1960s,and amphetamine control mea-sures were discussed in Congressthroughout the decade. The leg-islation that in 1965 becamethe Drug Abuse Control Amend-ments was originally intendedto restrict the manufacture ofamphetamines, along with barbi-turates. However, the versionpassed into law stressed penaltiesfor the unauthorized distributionof these drugs and the “counter-feiting” of any name-brand phar-maceuticals, no matter howsafe.75 The manufacture of suchpotentially dangerous pharma-ceuticals remained “an areawhere guidance has to be pro-vided without enforcement,” asthe drug industry’s spokesmenurged.76 National consumption ofamphetamines showed no sign ofdecline following the legislation’simplementation.

Drug abuse in general becamean increasingly exigent politicaltopic during the later 1960s, aspopular concern mounted aboutwidespread amphetamine abuseeverywhere from leafy suburbs toVietnam to hippie enclaves likeHaight-Ashbury.77 In 1969, an-other congressional hearing wasdevoted to the theme “Crime inAmerica—Why 8 Billion Amphet-amines?”78 The legislation thatemerged, the 1970 Comprehen-sive Drug Abuse Preventionand Control Act, established the

modern set of controlled sub-stance “schedules” in harmonywith new international agreementsand enabled federal narcotics au-thorities to establish and enforceproduction quotas on drugs in themost strictly controlled SchedulesI and II. However, reflecting in-dustry interests, only a handful ofrarely prescribed injectablemethamphetamine products wereplaced in Schedule II, while some6000 oral amphetamine productson the US drug market wereclassed in Schedule III, meaningthey were subject to no manufac-turing quotas and to looserrecordkeeping and their prescrip-tions could be refilled 5 times.79

The impact on amphetamine con-sumption was not dramatic, withreported legal production drop-ping only 17% between 1969 and1970.80

Although congressional focuson a comparatively small butfrightening population ofmethamphetamine-injecting“speed freaks” spared industry anymajor inconvenience in 1970,81

law enforcement authorities hadnot forgotten that 80% or 90% ofamphetamines seized on the streetwere pills manufactured by USpharmaceutical firms.82 Civil ser-vants now stepped forward whereelected representatives feared totread. In mid-1971, the Bureau ofNarcotics and Dangerous Drugs(BNDD; forerunner to today’sDrug Enforcement Administration[DEA]) exercised administrativeauthority gained under the 1970act by shifting all amphetamineproducts to Schedule II, includingmethylphenidate (Ritalin) and thediet drug phenmetrazine (Pre-ludin), both of which had provedattractive to high-dose injectionabusers. Drugs in Schedule II re-quired a fresh prescription eachtime they were filled, and doctorsand pharmacists had to keep strict

records or face prosecution. Pre-scription sales of amphetaminesand related drugs shot up whenthe new restrictions were an-nounced and then plummeted60% below their original levelwhen they came into effect.83

Large numbers of doctors and pa-tients obviously realized that their“medical” usage was difficult tojustify.

The move to Schedule II em-powered federal narcotics authori-ties, in consultation with the FDA,to set quotas limiting the produc-tion of amphetamines to quantitiesrequired by medicine. Meanwhile,the FDA was narrowing legitimateuses of the amphetamines, retro-actively declaring the drugs to beof unproven efficacy in obesityand depression. Manufacturerswere invited to submit applica-tions demonstrating efficacy, butin general these submissions werebased on older trials and werefound wanting by modern stan-dards of clinical research. Onlynarcolepsy and “hyperkinetic dis-order of childhood” (today’s atten-tion deficit disorder, then rare) re-mained approved usages.84

While the FDA pursued itsreevaluation of amphetamine effi-cacy, in 1971, the BNDD took ap-plications from firms wishing tomanufacture Schedule II drugs, aprocedure that required reportingof past production. According tothis reporting, US firms applyingfor 1971 quotas manufactured17000 kg of amphetamine baseand 8000 kg of methampheta-mine base in 1969. (In terms ofthe units used in prior voluntaryFDA surveys, this figure equalsabout 3 billion 10-mg ampheta-mine sulfate tablets and 1 billion10-mg methamphetamine hy-drochloride tablets—altogether, 4billion doses, a fair estimate of ac-tual medical consumption in 1969given the context of reporting).85


The BNDD originally set 1971quotas to allow the manufactureof about 15000 kg of ampheta-mine and methamphetamine basecombined, 40% less than re-ported 1969 levels. Another 40%cut in the quantity of ampheta-mines manufactured in the UnitedStates was slated for 1972. Giventhe prescribing slump that fol-lowed Schedule II listing, how-ever, the BNDD, with FDA agree-ment, instead set production levelsfor 1972 at one fifth of 1971 lev-els and at one tenth of reportedmedical production (or about onetwentieth of actual production) in1969.86 Under the supply controlsimposed by the 2 agencies, am-phetamines became relativelyminor drugs of abuse by the late1970s, while illicit cocaine useexploded.87

RECENT TRENDS IN THELIGHT OF HISTORY

The first amphetamine epi-demic was iatrogenic, created bythe pharmaceutical industry and(mostly) well-meaning prescribers.The current amphetamine resur-gence began through a combina-tion of recreational drug fashioncycles and increased illicit supplysince the late 1980s.88 On thebasis of treatment admissionsdata, methamphetamine abusedoubled in the United States from1983 to 1988, doubled again be-tween 1988 and 1992, and thenquintupled from 1992 to 2002.89

According to usage surveys, dur-ing 2004, some 3 million Ameri-cans consumed amphetamine-typestimulants of all kinds nonmed-ically, twice the number of a dec-ade earlier. As noted, 250000 to350000 of them were addicted.90

Thus, in terms of absolute num-bers, the current epidemic hasnow reached approximately thesame extent and severity as that of

the original epidemic at its peak in1970, when there were roughly3.8 million past-year nonmedicalamphetamine users, about320 000 of whom were addicted(Table 1). (Of course, the nationalpopulation then was about 200million compared with 300 mil-lion today, meaning that in rela-tive terms today’s epidemic is onlytwo thirds as extensive.)

Another striking similarity be-tween present and past epidemicsrelates to the role of pharmaceuti-cal amphetamines. Although illic-itly manufactured methampheta-mine launched the currentepidemic, in step with rising am-phetamine abuse in recent years,the United States has seen a surgein the legal supply and use of am-phetamine-type attention deficitmedications, such as Ritalin(methylphenidate) and Adderall(amphetamine). American physi-cians, much more than those inother countries, apparently areagain finding it difficult to resistprescribing stimulants that patientsand parents consider necessary, orat least helpful, in their strugglewith everyday duties.91 Accordingto DEA production data, since1995, medical consumption ofthese drugs has more than quintu-pled, and in 2005, for the firsttime exceeded amphetamineconsumption for medical use at

the epidemic’s original peak: 2.5billion 10-mg amphetamine baseunits in 1969 vs 2.6 billion com-parable units in 2005.92 Thus,just as the absolute prevalence ofamphetamine abuse and depend-ency have now reached levelsmatching the original epidemic’speak, so has the supply of medicalamphetamines (Figure 1).

Might the recent increases inboth medical and nonmedicalamphetamine use be related, andif so, how? Childhood stimulanttreatment for attention deficit dis-order as a cause of later nonmed-ical amphetamine consumption isone possible connection that hasreceived considerable attention.Although controversy remains,the weight of evidence suggeststhat medication prescribed for at-tention deficit disorder does notpredispose individuals to stimu-lant abuse or dependence.93

Moreover, if there is a statisticalassociation, it may link stimulantmisuse to attention deficit disor-der per se (rather than to medica-tion),94 as one would expect ifsome nonmedical amphetamineuse is in fact self-medication. Nev-ertheless, this line of inquiry doesnot eliminate any possible rela-tionship between prescribing forattention deficit disorder andrates of stimulant abuse. Even ifthere is no connection at the


Table 1—Estimated Prevalence of Amphetamine Misuse and Dependency in the United States at Peak ofFirst and in Current Epidemics, Expressed as Numbers of Individuals and Percentage of Total Population

Past Year Nonmedical Physical Dependency or Total USYear Amphetamine Use, Millions (%) Addiction, Thousands (%) Population, Millions

1970 3.8a (1.9) 320b (0.16) 203c

2002 3.2d (1.1) 303d (0.10) 291c

Source. For references to footnotes, see endnote 91.aDerived by taking past-6-month New York State usage prevalence figures as indicators of national past-year usage.bDerived by applying upper-range medical dependency and addiction rates from early 1960s in northern Britain to total US medical andnonmedical amphetamine-using population in 1970. Note that the informal but relatively stringent “physical addiction” of the 1960s is notidentical to “dependence” as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.cFrom the Bureau of the Census.dData for 2002 are consistent with more recent household drug use survey data.



Americans used psychiatric stim-ulants other than methampheta-mine nonmedically in the pastmonth.96 Thus, legally manufac-tured attention deficit medica-tions like Adderall and Ritalinappear to be supplying frequent,and not just casual, misusers.A detailed analysis of stimulantabuse in recent national house-hold drug surveys found not onlythat 1.6 million of the 3.2 millionpast-year nonmedical users ofstimulants in the United Statesused strictly nonmethampheta-mine psychiatric stimulants in thepast year, but that over 750 000of them had never used anystimulants except attention deficitpharmaceuticals in their entirelives. In that study, those whoabused only nonmethampheta-mine (i.e., pharmaceutical) stimu-lants in the past year accountedfor one third of the approxi-mately 300 000 Americans esti-mated to be amphetamine ad-dicted (reflecting the fact thatnonmethamphetamine users

have a somewhat lower rate offrank addiction than metham-phetamine users.97 On this evi-dence alone, one can fairly de-scribe the high production andprescription rates of these med-ications as a public health men-ace of great significance.

Besides iatrogenic dependenceand diversion to nonmedical users,there is another way that wide-spread prescription of amphetamine-type stimulants can contribute toan amphetamine epidemic. Whena drug is treated not only as a legalmedicine but as a virtually harm-less one, it is difficult to make aconvincing case that the same drugis terribly harmful if used nonmed-ically. This is what happened inthe 1960s and is presumably hap-pening today. Thus, to end theirrampant abuse, amphetamines hadto be made strictly controlled sub-stances and their prescriptionsharply curtailed. Today, ampheta-mines are widely accepted as safeeven for small children, and thisreturn of medical normalization in-

evitably undermines public healthefforts to limit amphetamine abuse.We have not yet reached the pointwhere up to 90% of the ampheta-mines sold on the street are prod-ucts of US pharmaceutical firms, asthe federal narcotics chief reluc-tantly admitted before Congress in1970.98 But with half the nation’snonmedical users evidently con-suming pharmaceutical ampheta-mines only, the comments madeby Senator Thomas Dodd in thosehearings echo strongly today.America’s drug problems were noaccidental development, Dodd ob-served; the pharmaceutical indus-try’s “multihundred million dollaradvertising budgets, frequently themost costly ingredient in the priceof a pill, have pill by pill, led, coaxedand seduced post–World War IIgenerations into the ‘freaked out’drug culture” plaguing the nation.99

Any effort to deal harshly withmethamphetamine users today inthe name of epidemic control,without touching medical stimu-lant production and prescription, isas impossible practically as in1970—and given historical experi-ence, even more hypocritical.

About the AuthorThe author is with the School of History andPhilosophy and the National Drug and Al-cohol Research Centre, University of NewSouth Wales, Sydney, Australia.

Requests for reprints should be sent toNicolas Rasmussen, PhD, MPhil, MPH,History & Philosophy of Science, Room 314Morven Brown, University of New SouthWales, Sydney NSW 2052 Australia(e-mail: [email protected]).

This article was accepted August 4,2007.

AcknowledgmentsThis research has been supported byfunding from the University of NewSouth Wales and the Australian ResearchCouncil (Discovery Project grantDP0449467), as well as small grantsfrom the California Institute of Technol-ogy Archives, the Chemical HeritageFoundation, and the American Instituteof the History of Pharmacy.

FIGURE 1—US medical consumptionof amphetamine and methylphenidate,expressed as common dosage units(10-mg amphetamine and 30-mgmethylphenidate, anhydrous base),based on Drug EnforcementAdministration production quota figures.92

individual level, there may beone at the population level.

Other than converting atten-tion deficit disorder patients intoabusers, prescribed ampheta-mines can contribute to the na-tional stimulant epidemic in atleast 2 other ways. For one, themere distribution of so manystimulant tablets in the popula-tion creates a hazard. Diversionfrom students with attentiondeficit prescriptions to thosewithout is known to occur inhigh schools, and at Americanuniversities, both diversion andnonmedical use by those withprescriptions are commonplace.95

In 2005, some 600 000



This article has benefited from the re-search assistance of Larissa Johnson; fromhelp by archivists at the California Instituteof Technology, the Library of the Collegeof Physicians in Philadelphia, HarvardUniversity’s Countway Library of Medi-cine, the Rockefeller Archive Center, theUniversity of California at San Francisco,the University of Pennsylvania, the USNational Academy of Sciences, several USNational Archives and Records Adminis-tration facilities, and the UK NationalArchives at Kew; and from the commentsof anonymous reviewers and many friends.

Endnotes1. Substance Abuse and Mental HealthServices Administration (SAMHSA),Methamphetamine Use, Abuse, and Depen-dence: 2002, 2003 and 2004 (Rockville,Md: US Dept of Health and Human Ser-vices, September 16, 2005), available at:www.oas.samhsa.gov/2k5/meth/meth.htm, accessed September 15, 2006;SAMHSA, Results From the 2005 Na-tional Survey on Drug Use and Health: Na-tional Findings (Rockville, Md: US Dept ofHealth and Human Services, 2006),available at: http://oas.samhsa.gov/NSDUH/2k5NSDUH/2k5results.htm, ac-cessed September 15, 2006.

2. SAMHSA, Methamphetamine Use,Abuse, and Dependence.

3. SAMHSA, Results From the 2005National Survey on Drug Use and Health.

4. G. Piness, H. Miller, and G. Alles,“Clinical Observations onPhenylethanolamine Sulfate,” Journal ofthe American Medical Association 94(1930): 790–791.

5. N. Rasmussen, Making the FirstAnti-Depressant: Amphetamine in Ameri-can Medicine, 1929–1950,” Journal ofthe History of Medicine and Allied Sciences61 (2006): 288–323.

6. AMA Council on Pharmacy andChemistry, “Benzedrine,” Journal of theAmerican Medical Association 101(1933): 1315.

7. J. Swann, “FDA and the Practice ofPharmacy: Prescription Drug RegulationBefore the Durham-Humphrey Amend-ment of 1951,” Pharmacy in History 36(1994): 55–70; H. Marks, “Revisiting‘The Origins of Compulsory Drug Pre-scriptions,’ ” American Journal of PublicHealth 85 (1995): 109–115.

8. C. O. Jackson, The Amphetamine In-haler: A Case Study of Medical Abuse,”Journal of the History of Medicine 26(1971): 187–196.

9. Rasmussen, “Making the First Anti-Depressant.”

10. AMA Council on Pharmacy andChemistry, “Present Status of Benzedrine

Sulfate,” Journal of the American MedicalAssociation 109 (1937): 2064–2069.

11. H. Marks, The Progress of Experi-ment: Science and Therapeutic Reform inthe United States, 1900–1990 (Cam-bridge, England: Cambridge UniversityPress, 1997).

12. Rasmussen, “Making the First Anti-Depressant”; A. Myerson, “Effect of Ben-zedrine Sulfate on Mood and Fatigue inNormal and Neurotic Persons,” Archivesof Neurology and Psychiatry 36 (1936):816–822.

13. Smith, Kline & French, “For Depres-sive States [Benzedrine Sulfate advertise-ment],” New England Journal of Medicine222 (1939): unpaginated; Smith, Kline &French, “The Patient With Mild Depres-sion [Benzedrine Sulfate advertisement],”New England Journal of Medicine 223(1940): unpaginated; Rasmussen, “Mak-ing the First Anti-Depressant”; Anony-mous, “Untitled Quarterly Royalty Re-ports,” in Gordon Alles Papers, CaliforniaInstitute of Technology Archives, box 6,folder “1941–1945 SKF Accounting toAlles, Alles Accounting to Piness.”

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20. “Untitled Quarterly Royalty Re-ports”; Rasmussen, On Speed, chap 4;SKF v Clark & Clark, Records of Case No.C-2311 (1943), US District Court, NewJersey, US National Archives Administra-tion. For further information, see theMethodological Appendix, Part 1, avail-able as a supplement to the online ver-sion of this article at http://www.ajph.org.

21. R. Monroe and H. Drell, “Oral Useof Stimulants Obtained From Inhalers,”Journal of the American Medical Associa-tion 135 (1947): 909–915.

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23. Opinion of Judge Forman, Smith,Kline & French Laboratories v Clark &Clark, 62 F Supp 971 (D NJ 1945);Opinion of Judge Biggs, Smith, Kline &French Laboratories v Clark & Clark, 157F 2d 725 (3rd Cir 1946).

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26. Jackson, “Before the Drug Culture.”

27. Rasmussen, On Speed, chap 4–5;“Sales Record of 1-Phenyl-2-AminopropaneSulfate in Tablets.” Journal of the AmericanMedical Association 147 (1951):19 (adver-tising section).

28. Rasmussen, On Speed, chap 5.

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80. Statement of Ingersoll in Diet Pill(Amphetamines) Traffic.

81. Graham, “Amphetamine Politics onCapitol Hill.”

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