DocunrrMIME RD 099 708 CG 009 214

TITLT . Report Series 28, No. 1. INSTITUTION National Inst. on Drug Abuse (DHEN/PRS) , Rockville, 8d. National Clearinghouse for Drug Abuse Information. REPOPT NO DREW-ADM-74-52 PUB DATE reb 74 NOT? 17p.; Prepared jointly by the Clearinghouse and Donald R. Wesson Associates, San Francisco, California AVAILABLE PROMNational Clearinghouse for Drug Abuse Information, P.O. Box 1908, Rockville, Maryland 20850

EDRS PRICE Mr-$0.75 HC-S1.50 PLUS POSTAGE DESCRIPTORS *Drug Abuse; *Drug Education; *Information Dissemination; *Physical Health; *Psychological Needs; State of the Art Reviews

ABSTRACT This report, prepared by the National Clearinghouse for Drug Abuse Information, presents substantial information on the use and abuse of the drug *family" known asamphetamines. A brief history of the drug is given, along with its basic pharmacology. The current medical uses for include: (1) short-term treatment of obesity, (2) treatment of the hyperkineticsyndrome, (3) treatment of narcolepsy, and (4) treatment of mild . The sany nonmedical uses of these drugs arelisted, along with the treatment process for overdoses and the amphetaminewithdrawal syndrome. The legal status of those caught illicity using or selling these drugs is reviewed, along with other important issues and opinions on the topic. (Author/PC) BEST COPYAVAILAr3LE

SERIES 28, NO. 1 FEBRUARY 1974

The National Clearinghouse for Drug Abuse Information recognizes the need for clarifying some of the more complex issues in drug abuse by gathering the significant research findings on each subject and developing fact sheets on the problem. These fact sheets, which are part of the Clearinghouse Report Series, presentinformation about treatment modalities, the pharma- cology and chemistry of various drugs of abuse, ant opinions and practices of recognized authorities in the field. This publication was prepared by the Clearinghouse and Donald R. Wesson Associates, 527 Irving Street, San Francisco, California 94122, under Contract No. IISM 42-72-99.

.60 4 US DEPIIIITMENT OP MERLYN. EDUCATION & WELFARE RATICRMAL MIST ITUTE OP DuCATSON Tostb DoCumtnet14.46 BEEN REPRO DUCE!" EXACTLY M. RECEIVEDF RaVI ?ME PERIL* OR DROPIVIZAT ATrMG 10% I? PDow TS 0? V lEbV ORDiliaiIONS 4TATfD DO NOT NECESSAiittv REPRE Ili; Cl; ; PC likt RPM fflutAlit%posi loft OR pattlySt+tOrf Of

AMPliFTAMINE

ex. Amphetamine is part of a chemical "family" which includes rnethamphetamine, dextroarnphetamine, and other drugs. Its best known major effects include the dilation of the bronchial passages, appetite depression, the relief of , and a the stimulation of the central nervous system (CNS). Some of the undesirableside C) effects at high dose levels include insomnia, stomach disorders, cardiac , and, more rarely, paranoid psychosis. The beneficial properties have led to e':tensive medical use, both by prescription and over the counter. However, recreational use of amphetamine has created prob- lems in Japan and Sweden as well as in the , and although amphetamine

_ problems have partly abated in this country , they still exist. aua..sll.u-- AgASIABLi BEST COQ 1;riefI istory

Amplictaurne vls synthcsi zed in :hilt ;the first significant investigation into its ir t1 le possibilities. was performed in N27.At that time. t:,,rdon Alis alifrn.a phart-01C010!th-itprepared a number of phenylall:v1;4Mino t n1-t:nds in .in r:tort to find .t synthetic 1.e.hstitutu 1,ir ephedrine, a drili2 deriVt'd ,!:. :.:1;41;!.., ti,ed for tratilig asthma. All :: research led to his lie c.:1! o:11-. patEt the d:,, itt i'132.In exchange for royalties on sales. he the ;tent to .:-n-fith. tans and French Laboratories which used the drug, renicilrita,P inhaler aid in dilating the bronchial passages.

..f t?:;tit.'..v ere Oh-covered during the 19.30's.in . as 1 prescription tablet.It was used to treat discaie producing an uncontrollable urge to sleepand. paradoxi- iaiiv .:Ctilt'11.,-peractive syndrome of children. As clinical use continued. .,ht :fects as an appetitr suppressant and a became known.

rid ;r it 11in amphetamine was extcnsi..ely used 13oth by Japanese f':' ,t1...i mihtar.- to counteract battle fatigue, to maintain alertness. and to by the war. After the war. large stocks of 'i.e Itcan:e w:t1t:t tirscrintion. and the nunilJer of heavy users of incrtiasd that it -dical problems from its use developed.

! ;: IeNal control.s were steadily developed and tightened, along with ,eatr.ant ...,11.ities and sti-engthening of penal provisions. These rota entec: by public eclucati,n campaign. with the result the an,rile.:,!-Nit,f_, nuse oroblem in later years. v.ith ar.:iihetarine and stimulant abuse. Since the 1. 1.0;.:1 riedit. al restrictions on the distribution and use iter-;!- :Of 1 halt ti-.c illegal misti--le of the drugs.tej..7ally. st. rkstrictd to %cr.; ,electe..d medical cases by special license.

Tn S.. ates the recent nha., of intravenous injection of metham-- 1 :, tar: throi,::,hout :.catcountry from its bf.ginnings in the San Francisco in !he, and early 19tAs.Prescription of injectable amphetamine as an aitcir.ativ to opiate addiction, and unethical distribution of the drug by a few pi.ysicians, made the drug easily available to potential abusers as a liquid in am p.1es. Although closer legal controls then were placed on prescriptions, a black market developed. In 1970 and 1971, the amphetamines and methamphetamine were placed under ,:trict Federal controls. Continued Federal concern about the drugs refl,,.ctecl in Senate Clearings in 1971 and 1972, which focused on high- dose intra-.enous use, misuse of prescribed amphetamines, and diversion of legally- pr,Klured amphetamine into illegal channels. ilitZt'.1.1.4:t1141,'"V BEST COPY AVAILABLE

The Cot:11ris: three chLnnicallv related p:,i,r141:..I he` tern: inin: the chemical designationof disq 1,11e:14..111%.1- tht. three compounds are tpt.e:i! the s.ot.e.hi mica! formula, with the .r. :!..;.te f eoch and the third is a methylated ;r. r CI:o111;c:1! fc,rtulae for the corppounds Eire s n

'S tt H --t

it

ley are cht H.:71i!ar ti- epinephrine ;adrenaline). a secreted by the ,i,.:renal act- as a central nervous system (CNS) stimulant.

he a::!til,etir".!r.e., of the mc,:t po,...-erful of the CNS , may be injected, oi il.ren,2::, the nasal ilrecous nlembranes. Once in the body /1. taine 2 to ; t'at'ti to eliminate 10 to 20 milligrams (mg.)

. : ,t 0- li 1.1142 Ch1L`V:-) Wi thtlili thc' +:: (.1; r1-1411.4 Exceton rore rapid when the urine is acidic.

At: p} ,nee ilbsohed whtn taken orally,and with the usual therapeutic dose vi 10 tn.,. peak effects tiro found 2 to .3 hours after ingestion. Tolerance to the appetitc-deprossfint effect:; ut amphetamine occurs withinweeks. Tolerance effect., increased 1:eart rate, and elevated blood pressure. eili)div than tolerance to the central nervous system effects of et:ohoria. The ainphetamineS. major effects are thought to take place in two brain systems that rele..art tfl their cli.Ucal use as well as their misuse. One system is the reucular activating system. which is responsible for controlling the level of lctivariun of the 1..rain and is itself regulated by inputs from many areas of the ei: from the senses. The reticular :,ystem in turn arouses the i.repare it':.5 e and prOC.0 +5 the:-.. sensory inputs. The degree of arouLsal thi.;!; re'st'si to the degree of stimulus input and its meaning. Amphetamine is thought to cause a biochemical arousal of the reticular activating :--,ysten-, in the Al):.ence of sensory input. The activation is transmitted to all parts of

3 &SI Llitif AVAILAba,

Thir4 ti ir ; t!.e I lit 1.!:du Li is 14 ,,tlert, 1:rpersensitivc. :!,av ,though there is evidence that a continual high level of anon niav induce zinxietv.

he be::eved he s.triitw!v :,cted zrephetamines is the medial :orebrain bundle, the rem ad sv:itern.Increased activity in this system is experienced a: a fee:.ng o: pivasure. ticiubtlt:-. the for thi. euphoria experienced in en when ar:pheta:rinv:, aretal.en in lo close:;..1 he' "flash" or sudden feeling of intense p'easure experienced from an intravenous dust" probablyresults in part from the delH;ery of a very high bleoe! concentration of the drug to the reward areaof the bra:n.

Current Vedical Uses

Yi .amphetamines had been prescribed for a large -.umber of conditions d l:resiiicn, fatigue, and long- term weight reducforIn 1970, the Food ant: T.)t-Lig .V!-.Inklratior. restricted the le a? use of the amph:rifles to three types narceleviy, hyperkinetic heT....INicir, and short-..-in weight reduction pri;grams.

Shur wry; treatment of obesity

A;;Wi:t1:1:1.111C, ZS al+ a host of similar compounds, isprescribed for appetite ei,Ltrol !.iecau.,.e. it decreaseli . The drug dees this by a ,:ariety of mechanisms r,f,t cie:ir:y under:itoud a: this tittle.One theory is that aniphe.tamine acts to suppress the appi: tile center in the Ilypothalaniu.i .Its action of decreasing food intake without afiect,ng iiood sugar levels is the baNi:; for the Food and Drug Administration's tf atipLetan:ine f,ar use in some s. eight- loss programs.

In ...Tile of this advantage, factors argue against the widespread, prolonged use of. arEphetdmine for weight control. One i., that tolerance develops rapidly to the appetite depressant characteristics of the drug. Even with moderate dosage increases. 4 to 6 weeks seems to be the limit before tolerance develops to the anorectic effectof amphetamine. The second reason is that overeating seems to be controlled primarily by psycho- logcal and behavioral factors, not by the of the body. Overeating is regarded by many authorities as a habit, which must be changed if the individual is to lose weight after developing tolerance to the anorectic effect of the amphetamine drugs. Marked differences in opinion occur betwiien physicians involved in the treatment of obesity and those treating drug abuse.Signor B. Penick has stated (1969):

4 BEST COPYAVAILABLE

3) I i't ;4.:! 1111;:1"121e tilL"S`

; h. 11:11.,:1,1.tt ' 114 tt,t US NV lia-e tatient:: who have tolerate tl :...! 4..(1: .t pt.1,t: them or hecc)rniti ::-..re ,.-ert.v-te and liabituatii.,n are

; L t Accuratel estintating tilt' n 1,rest :in anThear,ino for an cbe:-..e pat:ti

t_A the "dree abuse" orientoticm:

-twist HIL.,v, ti t i 1 st,ppres.-.. and that subjects lose t'.77 pounds !::ero during an S to 12. week period suirect... . At the end of this time, the re:-.::-.;tant to the anorexic (appetite reducing) effect of ant? tiCriVt.< little nc further benefit. The cosmetic ati..antages ed from a 6.75 pound weight loss are quite tli.. reason; retiponsib!t. physicians are of the opinion that --hr,u'ad riot be prescribed for appetite suppression.

!_vndrotile childhood (minimal brain damn e) This di,order manifested by impulsive, hyperactive behavior. The child has an unu::ually short attention span, and in spite of normal or superior intelligence is t'reciuentlail ,1.-ifierachiever in school. Amphetamines have the paradoxical effect in .,uch acting as a tranquilizer, increasing attention span, and decreas- ing hyperactive behavior .Considra-ble professional controversy and widespread public iittenton have recently been focused on drug treatment for the hyperkinetic ,,yridrome. However, the main iris ue relates more to the prevalence of the syndrome and reliable diagnostic criteria than to the efficacy of amphetamine in its treatment. has been reported in recent studies to he as effective as amphetamine in treating hyperkinesis with less undesirable side effects.

Na rco I eps y This is a very rare disorder in which the individual experiences frequent episodes of sudden, uncontrollable desire for sleep, sometimes as many as a hundred times a day.Amphetamine was first used to treat narcolepsy in 1955, with the discovery three years later that acute paranoid psychosis was a side effect to be guarded against.

11111.1r1 depression

Stimulantsexcluding amphetamines - are still prescribed for the treatment of BEST WY WWII

1 Ilts'At."."Or their USe lti1;n1:1e't: because alet' Clown ' period usually !oIio.v ksphoria prodtik..ed 1.v the stimular.t, tending to increase the existini: depres!.ed mood rather than .111,v iatinc it.1.suallv,agitated depressions are aggravated by ampiictatrines rather than rlevcd: their use would thus be counter- nroductive.

ca,ion ally .vith 1: p,:v pari:insnisti. syndrome including nius- cu:ar:id. , tVIt,thy t'ace, and tren.,,rhave benetityd trn:n ?Inplietarrline trati:.k.::: 'A lienthk:r dr...L.,: tailed.11,11t'ever. iither drugs are considered the drugs tot c11:t`ttor trk.-atr.nt thesk disorders.

f it: I 1,11,11C tar nett

b"...eve that

The u: levels of airphetaiiiine use presented Belowa synthesi., of descr:ptl,,r,- by seVe1-2-1: ittItiltrittt't-7 .tk c1141:- tCrill "31JUSe" altogether, Arid covers rr,t,st sitt.at.,r,s 14.1:',Cil amphetamines are used beycnd initial experimentation.

; 11yr tia tient ,r)st".'LIS('

Many individuals uccasionally tal..e 5 to 20 mg. of amphetamines orally to allay fatigue, elevate raookl while doing an unpleasant task, produce prolonged wakefulness, help recover from a hangover. or to "get high." Often the pill.; are obtained from friends, who more than likely obtained them by prescription for weight reduction. Only rarely are they pur- chased on the black market. individuals may be any age and usually have little interest in amphetamine use as a "life style.'

2)Sustained low-dose use In this pattern, the individual obtains amphetamine pills from his doctor for weight control, but takes the pills 3 to 4 times a day for the stimula- timi and euphoria produced by the drug. He may develop a strong on the pills and feel that he cannot get along

6 BEST COIetc \lithilut 1:14.ti:.It lie sii!p.4.. daiiy amphetAmines, Withdrawal depres- sion ocLut-,. the de pressivn can be easily and tempor arily 'cured >y renewed dosage ot pills, the dependencebecomes difficult to break . Some individuals gradually increase their daily intake of amphetamines and becin faining sleenint pills or to relieve the insomnia which usually develops.:lie d,.elopment this "upper-downer" cycle is danverous cat:se it increases the probability of overdose.

3. di se intra%eneus E.ethamphetaine use

Th..; is tl:c wklelx public; 7CCI p "s Ire et" Amphetamine: abuse. Aithouii the pattern involves fewer individuals than does oral ampheta .the bizarre behavior and dress of the intravenous "speed ire , the hie!: inciclence of violent behavior and the resultant medical ci,r-plications have focused dispi -op ,rtionate public and professional ti-As pattern. A major motivation is the "flas.h or "rush, an intense fee:inp. p;easure immediately following the injection. During a speed binge. an individual may inject between 500 and 1,000 mg. of methamphetamine every 2 ur 3 hours; by contrast, the usual prescribed dose ranges between 2.5 and 15 mg. per day .The substance, called -crank" or "crystal,may consist of illegally produced methamphetamin or dissolved prescription tablets.

David E. Smith (:citio) described the "speed cycle" in terms of an 'action-reaction" phenomenon, illustrated in the accompanying diagram. With the onset of the drug effect, one sees the -action phase" or "high." During the action phase the inch- vidual is hyperactive and may continue to shoot niethamphetamine many times a day in order to Perpetuate his "high" when it begins to wear off.Because of the marked stimulation the individual is unable to sleep, and because of the anorexic effect may not eat.As the individual accumulates progressively larger amounts of metham- phtamine within his body,he frequently develops extreme suspiciousness which merges into an overt paranoid psychosis. The high energy level associated with paranoia results in unpredictable behavior and, sometimes, violent behavior.

For a variety of reasons - fatigue, paranoia, or simply the lack of the drugthe individual eventually stops injecting methamphetamine and the "reaction phase" begins. As the effects of the amphetamine wear off, the individual lapses into a period of exhaustion and may sleep continuously for I or 2 days. Following this exhaustion phase, the individual often has a prolonged and severe depression which may last days to weeks. THE SPEED CYCLE to"Action Reaction Ph.ee I Midge I I I I I I I r. I I I I Base bile Mood Repeated intravenous Exhaustion Depressive I inject ions Syndrome Symptoms followed by I rush or flash

I I I I

I I I I

I I

Acute and Chronic Toxicity Low-dose arryhetamine The acute toxic effects of amphetamines include restlessness, tremor, talkativeness, , insomnia, anorexia, assaultiveness, , delirium, hallucination, panic states, paranoid ideation, phlpitation, cardiac , hypertension or hypotension, circulatory collapse, dry mouth, , , labile affect (mood swings), abdominal cramps, convulsions and coma. The toxic dose varies widely and may occur as an idiosyncrasy after as little as 2 mg. but more usually in excess of 30 to 60 mg.

Anecdotal reports indicate that chronic amphetamine use may predispose certain individuals to violent behavior. George Bach-Y-Bits (1971), in a study of 130 violent patients manifesting "episodic dyscontrol" with violent behavior, noted that chronic amphetamine use played a role in 12 of his 130 patients. Hemmi (1969). 1ST WY AVAILABLE reporting ',n the Japaneseamphetamine experience, noted that pri:ionerswho had uses: amphetkr,ines had aconsiderably higher proportion of violentoffenses. such as assaults, than note- users.Family members of chronic amphetamine usersnotice personality changes and increased irritabilitywhich may not he apparent to the user. With increasingdoses, irritability , insomnia, and paranoidthought may caus the ut:er toseek medical or psychiatric treatment.

Iligh-dose intravenous methamphetamine In an analysis cf 310 cases of high-dosemethamphetamine abuse. David Smith (1970) divided psychological adverse reactions intofive categories:

I) Anxiety reactions, in which the individualbecomes fearful and tremulous. ith concerns about his physicalwell-being.

2)Amphetamine psychosis, in which theindividual misinterprets the actions others, hallucinates, and becomes unrealisticallysuspicious.

3)Exhaustion syndrome. an intense feeling offatigue and need to sleep following the stimulation phase.

4)Prolonged depression.

5)Prolonged hallucinosis, in which the individualcontinues to hallucinate after the drug has been metabolized. Secondary effects of the use of the druginclude skin lesions, abscesses, respiratory problems, acute gastrointestinal distress, andabdominal cramps resulting from factors in the user's environment. High-dose usersusually sustain a marked weight loss, multiple vitamin deficiencies anddental caries (decay). The possibility of brain damage has beensuggested, since coma and its resultant brain damage can occur from amphetamine overdose.Cerebral vascular changes with resulting fir ain damage have been documentedin monkeys.

In addition to direct high-dose amphetaminetoxicity, the intravenous amphetamine user is exposed to anumber of medical complications resulting from injection of drug contaminants, undissolved particles, ornon-sterile injection techniques. He may also contract serumhepatitis. ale may inject live fungus or bacteria into the bloodstream,resulting in tetanus, syphilis, malaria, septic pulmonary emboli. endocarditis (an infectionof heart valves), or p-eripheral obstruction of arteries. Septic pulmonary emboli(infected blood clots which .lodge in the lungs) may originate frominfected heart valves or septic thrombophlebitis (an infection of the veins at aninjection site). Peripheral

9 LEST OMAMIABLE eft :tructi'n It teries :nay by due to injection of small particles of undissolved matrll. or !..11. 4it:(,11 ft41tiie,oclot Within the artery,usually associated with infection.

31wt:triive Wididt-awal Syndrome

For many year; the medicalcon-.en-.u.-: w-qi that amphetamines were not addicting bcauf, of the supposed absence ofa withdrawal syndrome. Part of the difficulty :a in ch-ak!renint over;lc dOfitlition of addiction, buta greater part was the failure to recognise' the withdrawalsyndrome because of its qualitative difference' from the narcot:c orgenerdepre,sant withdrawal syndrome. Theamphetamine" -xitheirav al syndrome is cilaracteri7el fayapathy, decreased activity, and sleep disturbances whichcan l,t for weeks or months. Another withdrawal signwAs rioted and Thacare 11(1r,3).Following abrupt withdrawal of large dose- titamphetarr:ne-,. 3n increIse in the percent of rapid eye-movement sleep (Rri,v) occurred.p': N! returned to normal whenamphetamine was given, but increased again vher. arilenetarrine was withheld. This phenomenonprovides additional c.vi- cience for the existnc of .Since suicides have occurred during ariphtarane withdrawal, doctorshave been advised to bring about with- drawal :;lowlyin a controlled environment.

Treatment for nverdose

Clinical Mani_uiement of Drug Abuse Crises(073) recommends certain procedures for doctor-: in cleating with overdoses ofstimulant., including amphetamines. The following description, ofcourse. is not a substitute for consultation bya physician who would vary treatment in accordancewith clinical judgment ina real overdose crisis.

A patient enters the physicians office showing the symptoms of very high dosage of amphetamine. After examining the patient andtaking his medical history, the physician must resolve conflicts betweenthe patient's statements and his clinical condition using, his own clinical judgment.If during the consultation the patient expresses suspicion or feels that he is being threatened, thephysician must reassure him that he is safe and that treatment, not punishment,is being given. The physician's overall attitude should beone of calm acceptance. He can administer diazepam (a ) to reducesevere anxiety and in the case of amphetamine poisoning, he can give ammonium ch!orideto acidify the urine, thus allowing the amphetamine to be more readily excreted.

If a patient is withdrawing froman acute toxic episode, the physician should take general supportivemeasures and show calm reassurance. Continuedobservation and supermion are required for severaldays, in part because of possible suicidal tendencies on the part of the patient. Leealtitatus REST COPYAVAILABLE

Since eterl:L.nct. :n an ovel the counterin!talt:r in the li#30'4,, amphetamine has been olacetl under detined controls. he Comprehen,.ive Drug Abuse Prevention .0Control Act tA 19;0 SChtdilleS, .)r lists, of controlled sub!;tances, rang:ne dtM21W.ircl potential few abuse. Amphetamines were first ;)!act.. in Schedule 111, but on .1111v 7,II1 7 I, weremoved to Schedule II.Ac corti:ng to the Act. this schedule is de_;igned for drugswhich have a high potential for abu,-ei which have a currently accepted medical use in treatment inthe United States, orcurrently accented medical use with severe r4.'4triCtiOnzi; or which may :eat! to ,e..-ere j -ycholeuical or 1)11V:iicaI dependence. Other drugs inSchedule II include ,ert.un orate, illothadenc*, and , The Act also g,s .4 the' Attorney General authority to regulate the registrationand control distribution, and dispensing of controlled substances." Spcific;t:y. every manulacturordistributor. or dispenser of amphetamines must t-egi the Attorney General. "Dispensers" include scientists who are wtll .is doctors ant' pharmacists. In addition, certain re,:u;rement., amoLetamines.iuch as securely sealing the:r container.-are in 4.!teCt.

A tontrei 1,z that the AttorrieN Cciser,11 t:iternorier annual liroduction .;I:ot.t- cLA-ta:ri a.ontro114LI :-.1i1.):;tanCeb.It had been vAimated that before quota.s, yer:etii bi.nion CIOSer: of amphetamines had been manufactured annually inthe United States.During 1972, production quotas were established, reducing production approximately 80 percent belov. 1971 levels. The Can-idian government established new control... on amphetamine liSe asof January 1, 1973. The drug is restricted to the treatment of narcolepsyhyperkinetic (E..,tirder:-: in children, mental retardation (minimal brain dysfunction), epilepsy, parkinsunism, and hypotensive states associated with anesthesia. In short-term therapy, the doctor must report all prescriptions to the government. In long-term therapy (over 30 days), the diagnosis must be confirmed by another physicianand his name and address reported. Amphetamines may also be used for certainresearch projects with government permission.

Comments After several decades of widespread popularity among the medical profession and the general public, amphetamine has come under severe scrutiny. The reasons for this decline in popularity include questions as to its effectiveness in some medical treatment, and observation of its toxicity and potential for physical dependence.

12 11 hen. ,wreerrient among, psychiatrists that psycho- rrot,,r .-;uch as amphetamine::, dextroamphetamine, methy-.phr.idate c.....anol and nipradrol have little value in the treatment sev, . depression.. .A series of i..tticlics showed ainpi:etar :nes te: .)e less effecti% e than placebo with tie:Dressed outpatients.

--Donald F. Klein and John M. Da les (1969)

A proLlerl now being considered in most of the capitals e.if the free world k whether the benefits derived from amphetamines olit.veigh their toNicity.. it is the consensus of the world C:entific literature that the amphetamines are of very little t.enetit to tr.ankind. They are, however, quite toxic. --John D. Griffith (1972) of whether or not amphetamines are addictive f,r namtuating is a natter lYf semantics. Habitual users develop a marked psychological dependence on the drug and evidence definite withdrawal symptoms,including tenseness, anxiety, tremor and nervousness, which may be of such degree as to incapacitate the user during his period of withdrawal.

--Edward R. Bloomquist (1970) It .s 4enerally felt that the behavior of heavy amphetamine i.sers is consistent with the stereotype of the "dope fiend." From all amphetan-inns tend to set up conditions ;n which violent behavior is more likely to occur than would 'De the case had an indivithial not used it.Suspiciousness ;111(i hperactivity may combine to induce precipitous and unwarranted assaultive behavior, --John C. Kramer (1967)

12 I I BEST Reference:, and St:,-zested Additional Reading COPY11114,1ABit

Gordon A.:lit co!no.rat-e physioleical actions of d1-13-plienylisopropyia- mines:1. Pre-sor effects and toxicity .Journal of Pharmaceutical and Experimental ...1,erapeutics ,47(3): 33Q- 354. 1933. Alle,. Cord,m A., and Prinzmetal, Myron. The comparativephysiological acti( ns dl-plienv!isomenviamines:II. Bronchial effect. Journal of Pharma- ceutical and Experimental Therapeutics, 48,_!):161-174,1933. Bach-N.-Rita, George; Lion, John R.: Climent, Carlos C.: and Ervin, Frank R. Episodic dyscontrol: a study of 136 violent patients. American Journal of , 127(11): 49-53. May 1971. Bloorr:uist. 17(lward R. The use and abuse of stimulants.In: Clark, William C.1 . rind del Giudice, Joseph. Principles of Ps-ychopharmacoloy, New York: Academic Press , 1)7

Brecher, Edward ,and the Editors of Consumer Reports. Licit and Illicit Boston: Little, Brown & Co.. 1972.

Brietner, Carl. The hazard of amphetamine medication. Psychosomatics,6:217-21Q, 1965.

Clyde, .T.11.The use of ampliztamines. South African Medical Journal, 46(13): 380, 1972.

Conneli. C.linical aspects of . In: ed. The Iharmacolcnd F..pidEmiologica1 Aspects of Adolet cent Drug lispendence. New York: PergamonPress, 1968. pp. 41-53.

Connell. Phillip 1i.Clinical manifestations and treatment of amphetamine type of dependence. Journal of -.he American Medical Association, 196(8): 718-723, May 23, 1966. Costa, E., and Garaffini, S., eds. International Symposium on Amphetamines and Related Compounds. New York: Raven Press, 1970. 962 pp. Edison, George R. Amphetamines; a dangerous illusion. Annals of Internal Medicine, 74: 605-610, 1971.

Ellinwood, Everett H.,Jr. Amphetamine psychosis:11. Theoretical implications. Journal of P.;ychedelic Drugs, 2(2):121-140, 1969. Elbnwood, Everett H., Jr., and Cohen, Sidney, eds. Current Concepts on Amphetamine Abuse. Washington, D.C.: U.S. Government Printing Office, 1972. 238 pp.

2 BEST WIAMIABLE Geekit., 11.A.11.tlw the Federal Ciovernment's amphetamine controls will work. Canadian !.1ttlik:il A,-sociation Journal, 108(1): 83- 84, January 6, 1973.

Goodman, Louis S.,and Gilman, Alfred, eds. Pharmacological Basis of Thera- peutic:.4th ed.'New York: Miemi Ilan, 1970. 1,794 pp. Criffiti-., ...kln I). :Caranatiol., it' lin: !leis, Joan; and Oates, John A. Dextro- amplietamineevaluatitm of psychomiiiitic properties inman. Archives of General Psychiatry.26:97-100, February 1972.

Grindley-Ferris, Margaret. The use of amphetamines. South AfricanMedical Journal, 46(15):451, April 8, 1972. Grinspoon, Lester, and liedbloni. Peter. Amphetamines reconsidered. Ptview, 55(28): 33-46, July 8, 1972.

Hemmi, T.hiow we have handled the problem of drug abuse in Japan.In: Sjoqui,:t, ,and Tottie, M., eds. Abuse of Central Stimulants. New York: Raven Press, 19t,41.

Journal of Psychedelic Drugs. Glossary c.f drug relatedternit.i.Journal of Psychedelic Dr ug ,4(2): 205- 210Winter, 1971.

Donald ,and Davies. John M. Diagnosis and Drug Treatment of Psy- chi.-itric sor de-rni .Baltimore: Williams & Wilkins, 1969.480 pp. Kratrt r, c:.: vitez.,lav S.: anti Littlefitld, Don C. Amphetamine abl.sepattern and effects of high doses taken intravenously. Journal of the American Medical Association, 201(5):89 -93, July 31, 1967. Kramer, :ohn C. Introduction to amphetairne abuse. Journal of Psychedelic Drugs. 2: S-1 i. PO.

Leake, Ci,..iuntey D. The Amphetamines. Springfield. 111.:Charles C. Thomas. 1958.

Nc Zealand M.eclical 'ournal. Amphetamines. New Zealand Medical Journal (Dunedin), 75(748):160, March 1972.

Oss James N. (editorial coordinator), et at.Clinical Management of Drug Abuse Crises. Nutley, N.J.: Hof fman-LaRoche,1973.32 pp.

Oswald, Ian, and Thacore, V.R. Amphetamine and phenmetrazineaddiction physiolugical abnormalities in the abstinence syndrome. BritishMedical Journal, (5354); 427-431, August 17, 1963.

14 1 5 REST COPYAVII/Liot 1),n:cr, ,:nor B., V .I).Amphetaraines in obesitN-!4etninars in Psychiatry, 1(2): 144 190.

Ida }',);tk I el: S. 1)ru, Secietv Ilunian Behavior. St. Louis: Tl:e C.V. Nlosby Co., 1Q72,.299 pp.

is:arr.1)au,::11, Calvin L.: Scalan, Pobert L.; Teal, James S. Sega11., liarvev harry (*.P.; and McCormick, Ruth. Cerebral eilaliges secondar- to araplietarrine abuse in the experimentalanimal. Padiology,101() : 345- 351, 1.0 ember 1971.

Davi.? F.,rind ri.Zher, 0: Arles M.. An analysis of 311) cases of acute highdose :;:et:ia:: ;oxicity . Clinical ,3(1): 11:.:24, March 1970. characte:!-,ties of dependence ;n high-dose methamphetamine International Journal of the Addictions, 4(3): 453 -459, September !":

!.t .P.. 18551. Cen.i.ehensie Drug Abuse Prevention and Act ,f 19";0.Public Law 41-513. Washington, D.C.: U.S. Govern- Printing Office, Ortober 27, 1970.

.S. liearings beforc. the Subcommittee on and Narcotics 11:e nee on Labor and Public Welfare. Lailietamine Abuse Among Dr:vt.rs. Washington, D.C.: U.S. Government Printing Office, October 1, 1071.459 pp.

S. Session, Hearings before the Select Committee on Crime. Cr: n:t.in Americ a Light. Billion Amphetamines? Washington, D.C.: '..SGo,..,...rnmen; Printing Office, 1970. U.S. 92nd Cc:r.gress, Hearings before the Subcommittee to Investigate Juvenile Dclinciucncy .Amphetamine Legislation, 1971. Washington, D.C.: U.S. or nine nt Printing Office, 1971.1,039 pp.

The National Clearinghouse for Drug Abuse Information, operated by the National Institute on Drug Abuse on behalf of the Special Action Office for Drug Abuse Prevention and the Federal agencies rengaged in drug abuse education programs , is the focal point for Federal information on drug abuse. The Clearinghouse distributes publications and refers specialized and technical inquiries to Federal, State. local, and private information resources. Inquiries should be directed to the National Clearinghouse for Drug Abuse Informaticn, P.O. Box 1908, Rockville, Maryland 20850. L

15 4 ;