AMPHETAMINE
CASRN: 300-62-9
Chemical structure for AMPHETAMINE
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Overview:

Amphetamine is used as a medication or supplement. An overview is available from MedlinePlus, a consumer health web site produced by the National Library of Medicine, at https://www.nlm.nih.gov/medlineplus/druginfo/meds/a601234.html. An overview on illegal use of amphetamines as very addictive drugs is available at https://www.nlm.nih.gov/medlineplus/ency/patientinstructions/000792.htm.
[For more information: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0008972/ **PEER REVIEWED**


Human Health Effects:


Toxicity Summary:


IDENTIFICATION AND USE: Amphetamine is a colorless liquid with characteristic amine odor (similar to geranium leaves) and an acrid taste. It is used for the following indications: Psychostimulant: Accepted indications: Narcolepsy; Hyperkinetic states in children (as an adjunct to psychological, educational and social measures). The drug is misused for performance enhancement. Abuse either orally or by injection is extremely common. HUMAN EXPOSURE AND TOXICITY: Main risks include: acute central nervous system (CNS) stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Cardiovascular effects include: palpitation, chest pain, tachycardia, arrhythmias and hypertension; cardiovascular collapse can occur in severe poisoning, as well as, myocardial ischemia, infarction and ventricular dysfunction. CNS effects include: stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia. Stroke and cerebral vasculitis have been observed. Gastrointestinal effects include: vomiting, diarrhea and cramps. Acute transient ischemic colitis has occurred with chronic methamphetamine abuse. Genitourinary effects: increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Transient hyperthyroxinemia may be noted. Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Hypo- and hyperkalemia have been reported. Dehydration is common. Fasciculations and rigidity may be noted. Rhabdomyolysis is an important consequence of severe amphetamine poisoning. Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Amphetamine appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especially norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Children appear to be more susceptible than adults and are less likely to have developed tolerance. The use of amphetamine for medical indications does not pose a significant risk to the fetus for congenital anomalies. Amphetamines generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long-term sequelae. Illicit maternal use or abuse of amphetamine presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties of amphetamines. 65 children whose mothers were addicted to amphetamine during pregnancy, at least during the first trimester, were studied. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. ANIMAL STUDIES: Testing for toxicity to the retina has been negative; 10 mg/kg given daily to dogs for three months caused occasional slight ophthalmoscopic appearance of blanching of the fundus, but no histologic change in the retina. The behavioral effects of d-amphetamine administration were studied in 17 adult cats. The doses of amphetamine administered were 0.1, 0.5, 1.0 and 5.0 mg/kg sc. Amphetamine administration induced a dose-dependent hypomotility, which was marked with the higher doses. In addition, rhythmic, bilateral slow movements of the head as a mode of stereotype, indifference to the environment and dose-dependent incr in respiratory rate were observed in amphetamine-treated cats. Amphetamine damages cerebral arteries in experimental animal models. ECOTOXICITY STUDIES: In the freshwater bivalve Dreissena polymorpha the bell-shaped trend of antioxidants showed at the highest tested amphetamine concentration (5000 ng/L) suggested an overproduction of reactive oxygen species, leading to oxidative damage, as confirmed by the significant increase of protein carbonylation and DNA fragmentation.
**PEER REVIEWED**


Human Toxicity Excerpts:


/SIGNS AND SYMPTOMS/ Overdose of an amphetamine may be manifested initially by cardiovascular symptoms including flushing or pallor, palpitation, tachypnea, tremor, labile pulse rate and blood pressure (hypertension or hypotension), cardiac arrhythmias (e.g., extrasystoles), heart block, circulatory collapse, and chest pain.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2530] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Adverse effects of amphetamines may include nervousness, insomnia, irritability, talkativeness, changes in libido, dizziness, headaches, increased motor activity, chilliness, pallor or flushing, blurred vision, mydriasis, and hyperexcitability. Exacerbation of motor or phonic tics, Tourette's syndrome, dyskinesia, seizures, euphoria, dysphoria, emotional lability, and impotence have been reported in patients receiving amphetamines. Psychotic episodes have occurred rarely in patients receiving amphetamines at recommended dosages.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2528] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ The acute toxic effects of amphetamine are usually extensions of its therapeutic actions and, as a rule, result from overdosage. The central effects commonly include restlessness, dizziness, tremor, hyperactive reflexes, talkativeness, tenseness, irritability, weakness, insomnia, fever, and sometimes euphoria. Confusion, assaultiveness, changes in libido, anxiety, delirium, paranoid hallucinations, panic states, and suicidal or homicidal tendencies occur, esp in mentally ill pt. However, these psychotic effects can be elicited in any individual if sufficient quantities of amphetamine are ingested for a prolonged period. Fatigue and depression usually follow central stimulation. Cardiovascular effects are common and include headache, chilliness, pallor or flushing, palpitation, cardiac arrhythmias, anginal pain, hypertension or hypotension, and circulatory collapse. Excessive sweating occurs. Symptoms referable to the GI system include dry mouth, metallic taste, anorexia, nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma, and cerebral hemorrhages are the main pathological findings.
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 220] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Amphetamine given orally raises both systolic & diastolic blood pressures. Heart rate is often reflexly slowed; with large doses, cardiac arrhythmias may occur. Cardiac output is not enhanced by therapeutic doses, & cerebral blood flow does not change much. The l-isomer is slightly more potent than the d-isomer in its cardiovascular actions. In general, smooth muscles respond to amphetamine as they do to other sympathomimetic amines. ... Pain & difficulty in micturition occasionally occur. The GI effects of amphetamine are unpredictable. If enteric activity is pronounced, amphetamine may cause relaxation & delay the movement of intestinal contents; if the gut is already relaxed, the opposite effect may occur. The response of the human uterus varies, but usually there is an increase in tone.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 219] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Because tolerance develops to the hyperthermic and cardiovascular effects of amphetamine, acute intoxication is more likely to occur in the neophyte. The syndrome includes dizziness, tremor, irritability, confusion, hallucinations, chest pain, palpitation, hypertension, sweating, and cardiac arrhythmias. There may be hyperpyrexia and convulsions. Death is usually preceded by hyperpyrexia, convulsions, and shock.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 554] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Perivascular infiltration of amphetamines can produce local necrosis, cellulitis, granulomas, & abscess formation. Intra-arterial injection causes intense vasospasm with distal cyanosis, ecchymosis, petechiae, edema, paresthesias, pain, weakness, necrosis, & decreased capillary filling. Immediate intense vasospasm is obvious after intra-arterial injections.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 635] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Chronic intoxication with amphetamine causes symptoms similar to those of acute overdosage, but abnormal mental conditions are more common. Weight loss may be marked. A psychotic reaction with vivid hallucinations and paranoid delusions, often mistaken for schizophrenia, is the most common serious effect. Recovery usually is rapid after withdrawal of the drug, but occasionally the condition becomes chronic. In these persons, amphetamine may act as a precipitating factor hastening the onset of an incipient schizophrenia.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 220] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Chronic use of high doses of amphetamines has been reported to produce microvascular damage, neuronal chromatolysis (primarily in brain areas rich in adrenergic neurons), and profound and long lasting (or permanent) depletion of dopamine in the caudate nucleus.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 554] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ The psychic effects depend on the dose & the mental state & personality of the individual. The main results of an oral dose of 10-30 mg include wakefulness, alertness, & a decreased sense of fatigue; elevation of mood with increased initiative, self-confidence, & ability to concentrate; often, elation & euphoria; and increase in motor & speech activities. Performance of simple mental tasks is improved, but, although more work may be accomplished, the number of errors may increase. Physical performance - in athletes, for example - is improved, & the drug is often abused for this purpose. These effects are not invariable, & may be reversed by overdosage or repeated usage. Prolonged use or large doses are nearly always followed by depression & fatigue. Many individuals given amphetamine experience headache, palpitation, dizziness, vasomotor disturbances, agitation, confusion, dysphoria, apprehension, delirium, or fatigue.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 219] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ The fully developed toxic syndrome from amphetamine is characterized by vivid visual, auditory, and sometimes tactile hallucinations; picking and excoriation of the skin and delusions of parasitosis are not uncommon. There is also paranoid ideation, loosening of assoc, and changes in affect occurring in assoc with clear sensorium. In chronic users, there may be a striking paucity of sympathomimetic effects, and the blood pressure is not unduly elevated. It is often extremely difficult to differentiate this syndrome from a schizophrenic reaction. The syndrome may be seen as early as 36 to 48 hr after the ingestion of a single large dose of amphetamine; in apparently sensitive individuals, psychosis may be produced by 55 to 75 mg of dextroamphetamine. With high enough doses, psychosis can probably be induced in anyone. Unless the individual continues to use the drug, the psychosis usually clears within a week, the hallucinations being the first symptoms to disappear.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 553] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Amphetamine ... in large doses systemically can dilate the pupils and cause slight blurring of near vision. Applied to the eye, amphetamine dilates the pupil and retracts the upper lid, but these actions are prevented by previous depletion of catecholamines such as is brought about by local guanethidine.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Renal failure assoc with amphetamine use is usually the result of rhabdomyolysis, but it has also been found in patients without evidence of muscle damage or other apparent predisposing factors.
[Knoben, J.E. and P.O. Anderson (eds.) Handbook of Clinical Drug Data. 6th ed. Bethesda, MD: Drug Intelligence Publications, Inc. 1988., p. 90] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Abrupt discontinuation of amphetamines produces neither seizures nor life threatening symptoms, even in those patients who habitually consume large quantities. The abstinence syndrome assoc with chronic use of amphetamine ... is characterized by apathy, depression, lethargy, anxiety, & sleep disturbances. Myalgias, abdominal pain, voracious appetite, & a profound depression with suicidal tendencies may complicate the immediate postwithdrawal period & peak in 2-3 days. Symptoms persisting 6-7 days indicate an underlying disease process.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 636] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ During the early phases of iv use, 3 to 4 doses of 20 to 40 mg of amphetamine are usually considered sufficient /by abusers to produce euphoric effects/. In addition to the marked euphoria, the user experiences a sense of markedly enhanced physical strength & mental capacity, & feels little need for either sleep or food. Difficult to substantiate by objective means is the claim made by many users that orgasm in both male & female is delayed, permitting extended periods of sexual activity finally culminating in orgasms reported to be more intense & pleasurable. The sensation of "flash" or "rush" that immediately follows iv admin, while qualitatively distinct from the opioid "rush", is nevertheless described as being intensely pleasurable & somewhat akin to sexual orgasm.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 551] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Anorexia is a common finding /in chronic toxicity from abuse/. Occasionally it may be so pronounced that the amphetamine abuser experiences considerable difficulty in swallowing. Chronic abusers are reported to force themselves to eat small amt of highly nutritious food & take vitamin supplements to compensate for decr in appetite. ... Constant grinding of teeth is also a common finding ...
[Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975., p. 630] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Bleeding within the cranial vault is a rare but well-reported complication of amphetamine use. About 20 cases, which are about evenly divided between iv & oral exposures, have been reported in the American literature. Ages range from 16-60, & most patients are habitual & often multidrug abusers. However, intracranial hemorrhages have been reported after the ingestion of as few as 2-4 tablets of amphetamine or structurally related anorectic drugs ...
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 634] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ The etiology of intracerebral & subarachnoid hemorrhages associated with amphetamine use appears multifactorial. Inflammation & necrosis of small cerebral arteries (ie, vasculitis) secondary to particulate foreign bodies or bacterial endocarditis can develop after iv drug use. Subsequently, the hypertension seen in amphetamine use may lead to vessel rupture & hemorrhage. However, vasculitis has occurred in the setting of oral acute dextroamphetamine overdose, amphetamine withdrawal, & therapeutic use as an anorectic drug. The presence of vasculitis after exposure by different routes suggests an immunopathological abnormality. Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 633] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Repetitive behavior may occur /from the use of amphetamines/ (e.g. repeatedly cleans dishes or continually grooms hair). Amphetamines also will extenuate hostile, aggressive, and antisocial behavior. Progression to paranoia, panic states, violence, and even suicide may occur.
[Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 84-3] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ Amphetamines used in large doses over a long period of time may lead to substantial weight loss, liver disease, hypertensive disorders, kidney damage, stroke, heart attack, nonhealing ulcers, and sores in the skin.
[Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 84-3] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ The use of amphetamine for medical indications does not pose a significant risk to the fetus for congenital anomalies. Amphetamines generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long-term sequelae. Illicit maternal use or abuse of amphetamine presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties of amphetamines. 65 children whose mothers were addicted to amphetamine during pregnancy, at least during the first trimester, were studied. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive.
[International Programme on Chemical Safety; Poisons Information Monograph: Amphetamine (PIM 934 ) (1998) Available from, as of May 16, 2008: http://www.inchem.org/pages/pims.html **PEER REVIEWED**

/CASE REPORTS/ In an acute poisoning in a child ... external stimuli precipitated increased hyperactivity.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-27] **PEER REVIEWED**

/CASE REPORTS/ Although comparable clinical data are lacking, hyperpyrexia has been noted as a frequent & prominent sign in acute human intoxication. During a grueling bicycle race a cyclist collapsed with symptoms closely resembling heat exhaustion, &, despite vigorous treatment, he died /after/ cardiovascular collapse; it was learned subsequently that he had consumed 105 mg of amphetamine during the race.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-27] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ Data on the effect of prenatal amphetamines, both prescribed and abused, are conflicting; however no consistent pattern of abnormalities has emerged. A large prospective evaluation of amphetamines prescribed during pregnancy found no incr in severe congenital malformations, but did report three cases of oral clefts. Another prospective study evaluating infants of amphetamine addicted women failed to demonstrate an incr in birth defects, but did note an incr in premature births, respiratory distress and jitteriness. The use of other drugs and alcohol may have confounded these findings.
[Knoben, J.E. and P.O. Anderson (eds.) Handbook of Clinical Drug Data. 6th ed. Bethesda, MD: Drug Intelligence Publications, Inc. 1988., p. 203] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ Epidemiological studies of the association between drug use and involvement in road traffic crashes (RTCs) published from January 1998 to February 2015 have been reviewed. Cohort andpopulation studies compared RTC involvement among drug users and non-drug users, case-control studies compared drug use among RTC-involved and non-RTC-involved drivers, and responsibility studies and case-crossover studies were performed for RTC-involved drivers. Difficulties associated with the types of studies are discussed with a special focus on case-control studies. Statistically significant associations between drug use and RTC involvement were found for benzodiazepines and z-hypnotics in 25 out of 28 studies, for cannabis in 23 out of 36 studies, for opioids in 17 out of 25 studies, for amphetamines in 8 out of 10 studies, for cocaine in 5 out of 9 studies, and for antidepressants in 9 out of 13 studies. It was a general trend among studies that did not report significant associations between the use of these drugs and increased RTC risk that they often had either poor statistical power or poor study design compared to studies that found an association. Simultaneous use of two or more psychoactive drugs was associated with higher RTC risk. Studies on the combination of alcohol and drugs have not been reviewed in this article even though this combination is known to be associated with the highest RTC risk.
[Gjerde H et al; Forensic Sci Rev 27 (2): 89-113 (2015)] **PEER REVIEWED** PubMed Abstract

/SURVEILLANCE/ Fatal poisonings among drug addicts in Denmark in 2012 were examined. Cause of death, abuse pattern and geographic differences are discussed and data are compared with previous studies. METHODS: All fatal poisonings examined at the three institutes of forensic medicine in Denmark in 2012 were included in the study. RESULTS: A total of 188 fatal intoxications were recorded. The median age increased from 37.5 in 2007 to 41.5 in 2012. The majority were men (77%). Methadone (59%) was the main intoxicant. The decrease in the frequency of heroin/morphine deaths since 1997 (71%) continued, declining to 44% in 2002, 33% in 2007 and finally to 27% in 2012. Few deaths from central stimulants (amphetamine and cocaine) occurred. Multiple drug use was common and consisted mainly of opioids, cocaine, amphetamine, cannabis, benzodiazepines and alcohol. Heroin/morphine use was most frequent on Funen and in South Jutland. Cocaine was most frequently detected in East Denmark, while amphetamine was more frequent in West Denmark. CONCLUSIONS: The number of fatal poisonings among drug addicts has stabilized around 200. The increase in methadone deaths continued and, as in 2007, methadone was the main intoxicant. The increase in methadone deaths seems to be associated with use of methadone in substitution treatment. Nevertheless, methadone treatment also seems to save lives, as indicated by the increasing median age. Use of antidepressants and antipsychotics increased to a high level compared with 2007, indicating that a considerable number of drug addicts also have psychiatric illness.
[Simonsen KW et al; Dan Med J 62 (10) pii: A5147 (2015)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ The toxic dose of amphetamine varies widely. ... Severe reactions have occurred with 30 mg, yet doses of 400 to 500 mg are not uniformly fatal. Larger doses can be tolerated after chronic use of the drug.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 220] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Many of those who use amphetamine ... are best described as "recreational" or occasional users, but some become dependent. A small percentage of the latter (eg, those taking the drugs for control of obesity) seem able to restrict drug intake & function productively (stabilized addicts). Others show progressive social & occupational deterioration, punctuated by periods of hospitalization for toxic psychosis. In terms of the compulsion to continue use, the degree to which a drug pervades the life of the user, & the tendency to relapse following withdrawal, some compulsive users of amphetamine ... are addicts. The risk of developing patterns of compulsive use is not limited to those who use drugs intravenously ... It is not clear whether the dependence syndromes caused by amphetamine ... are as persistent as that produced by opioids. In the US the waves of amphetamine use did not leave large numbers of chronic users in their wake. However, many iv users eventually became heroin users.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 552] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ The history, chemistry, pharmacology, medical use, illicit use & addiction & tolerance potential of amphetamines are presented. Although there are few published accounts of death known to result directly from amphetamines, deaths may result indirectly from effects such as violent behavior & hepatitis.
[HART JB, WALLACE J; CLIN TOXICOL 8 (2): 179-90 (1975)] **PEER REVIEWED** PubMed Abstract

/OTHER TOXICITY INFORMATION/ Few deaths have ... been attributed to amphetamine overdose. Amphetamines have a relatively low ratio of effective dose to fatal dose. Fatalities resulting from amphetamine use are usually the result of one of the following processes: 1) combinations with other drugs; 2) complications of iv injections, such as septicemia, bacterial endocarditis, or homicide, during withdrawal depression.
[Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975., p. 629] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ In postmortem cases where the cause of death is hanging, toxicological analyses may be considered unnecessary by some medical examiners, toxicologists, and other persons involved in medico-legal investigations because the cause of death seems "obvious." To ascertain if toxicological analyses are necessary when the cause of death is hanging, all 102 hanging cases (25 females; 77 males) from 2011 to 2013 that came under the jurisdiction of the San Francisco Office of the Chief Medical Examiner were examined from a total of 3912 sudden, unexpected, or violent death cases in the same period. Suicide was the manner of death in 99 of these cases, with two accidental and one undetermined death. The average age of decedents was 43.9 years (median 41), the youngest was an 11-year old male and the oldest was an 86-year old female. Of the 102 cases, 33 had negative toxicology while 69 cases had at least one positive toxicology result. Females were equally likely to have negative or positive results (12 and 13 cases respectively), but males were 37.5% more likely to have positive toxicology (n=56) rather than negative toxicology (n=21). For females, alcohol, mirtazapine, venlafaxine, and trazodone were the top psychoactive substances in peripheral blood while THC, cocaine, hydrocodone, bupropion, olanzapine, doxylamine, quetiapine and dextromethorphan were also reported. For males, alcohol, THC, cocaine, amphetamine, methamphetamine, bupropion, and diphenhydramine were the top psychoactive substances in blood, but several other drugs were also found in individual cases. Our study of hanging cases over a 3-year period support the idea that complete postmortem toxicology investigation of hangings should be performed, even when the "obvious" cause of death is asphyxia due to hanging. Many of these cases involved psychoactive substances (most often alcohol and cannabis), and having such knowledge provides a better understanding of the circumstances surrounding the decedent's death, their possible state of impairment, including the possibility of a staged suicide if the decedent was too impaired to perform a self-hanging.
[San Nicolas AC, Lemos NP; Forensic Sci Int 255: 146-55 (2015)] **PEER REVIEWED** PubMed Abstract

/OTHER TOXICITY INFORMATION/ In Oslo, the majority of patients with acute poisoning are treated in primary care, at an emergency outpatient clinic with limited diagnostic and treatment resources. We describe the poisonings currently seen in this setting. We compare our findings with previous studies, with special concern for the appearance of new toxic agents, and changes in overall numbers and patterns of poisoning. Observational study. Patients above the age of 12 years presenting at Oslo Accident and Emergency Outpatient Clinic (Oslo Legevakt) with acute poisoning were included consecutively from October 2011 through September 2012. Physicians and nurses registered data on preset forms. Main outcome measures were toxic agents, age, sex, intention, referral and time of presentation. RESULTS: There were 2923 episodes of acute poisoning in 2261 patients. Median age of the patients was 32 years, and 1430 (63%) were males. The most frequent toxic agents were ethanol in 1684 (58%) episodes, heroin in 542 (19 %), benzodiazepines in 521 (18%), amphetamine in 275 (9%), fire smoke in 192 (7%), gamma-hydroxybutyrate (GHB) in 144 (5%), and cannabis in 143 (5%). In 904 (31%) poisonings there were more than one toxic agent. In 493 episodes (17%), the patient was hospitalised, and in 60 episodes (2%) admitted to a psychiatric ward. Most poisonings, 2328 (80%), were accidental overdoses with substances of abuse, 276 (9%) were suicide attempts, and 312 (11%) were accidents. ... The poisonings treated in this primary care setting were mostly due to accidental overdoses with ethanol or other substances of abuse. ...
[Vallersnes OM et al; BMC Emerg Med 15: 18 (2015)] **PEER REVIEWED** PubMed Abstract Full text: PMC4535826

/OTHER TOXICITY INFORMATION/ The abuse of amphetamines by combining the oral and inhalation routes of administration usually leads to a more intense effect and/or more toxic effect than if either was taken alone. /Amphetamines/
[Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 84-4] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Doses as little as 2 mg, but more likely between 15 and 30 mg, may induce toxic effects. However, even doses of 400-500 mg are not uniformly fatal.
[Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 84-5] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Illicit maternal use /of amphetamines is/ associated with intrauterine growth retardation, premature birth, and increased fetal and newborn morbidity. /From table/
[Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 45-7] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Intrauterine ... amphetamine exposure may cause neonates to exhibit abnormal sleep patterns, tremors, poor feeding, hypotonia, fever, and vomiting.
[Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 81-9] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Amphetamine, and to a lesser extent the secondary amine methamphetamine, are major recreational drugs of abuse in Sweden. These central stimulant amines are identified in blood from roughly 50% of people arrested for driving under the influence of drugs (DUID). However, much less information is available about the presence of amphetamine in blood of drivers killed in road-traffic crashes. This retrospective 10-year study (2001-2010) used a forensic toxicology database (TOXBASE) to retrieve information about road-traffic crashes when the driver had amphetamine and/or methamphetamine in autopsy blood. Forensic toxicology results were available from over 95% of all drivers killed on Swedish roads during this 10-year period. Amphetamine was present in the blood of 106 drivers (3.9%) either alone or together with other psychoactive substances (e.g. alcohol, cannabis, diazepam, alprazolam, etc.). The vast majority of fatalities were male (95%) with a mean age (+/-standard deviation) of 37+/-11.4 years (range 16-67 years). The mean (median) and highest concentrations of amphetamine in femoral blood were 1.36 mg/L (1.0mg/L) and 6.74 mg/L, respectively. Many of the victims (75%) had been arrested previously for use of illicit drugs or DUID. The median number of previous arrests was 4 (range 0-83) and amphetamine or methamphetamine were among the drugs identified in blood samples from 89% of cases (0-100%). The high prevalence of repeat DUID offending and/or use of illicit drugs among the drivers killed in road-traffic crashes suggests that an early intervention and treatment for stimulant abuse might have been more beneficial than conventional punishments for such drug-related crimes
[Jones AW et al; Int J Drug Policy 26 (8): 790-3 (2015)] **PEER REVIEWED** PubMed Abstract

/OTHER TOXICITY INFORMATION/ The American Psychiatric Association estimates that 3-7% of US school-aged children exhibit attention-deficit/hyperactivity disorder (ADHD). Adderall (amphetamine dextroamphetamine) and a variety of brand names and generic versions of this combination are available by prescription to treat ADHD and narcolepsy. Both immediate and sustained release products are used as are single agent amphetamine medication. Knowing the exact agent ingested can provide information of dose labeled and length of clinical effects. These drugs are used off label by college students for memory enhancement, test taking ability, and for study marathons. These agents are DEA Schedule II controlled substances with high potential for abuse. For humans with ADHD or narcolepsy, standard recommended dosage is 5-60 mg daily. Amphetamine and its analogues stimulate the release of norepinephrine affecting both a- and beta-adrenergic receptor sites. a-Adrenergic stimulation causes vasoconstriction and an increase in total peripheral resistance. beta-Adrenergic receptor stimulation leads to an increase in heart rate, stroke volume, and skeletal muscle blood flow. Clinical signs of Adderall overdose in humans and dogs include hyperactivity, hyperthermia, tachycardia, tachypnea, mydriasis, tremors, and seizures. ... /Adderall/
[Fitzgerald KT, Bronstein AC; Top Companion Anim Med 28 (1): 2-7 (2013)] **PEER REVIEWED** PubMed Abstract

/OTHER TOXICITY INFORMATION/ Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-theraputic use or distribution to others, and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**


Human Toxicity Values:


Therapeutic or normal amphetamine blood concentration: 2-3 ug/dL; Toxic amphetamine blood concentration: 50 ug/dL; Lethal amphetamine blood concentration: 200 ug/dL /From table/
[Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 420] **PEER REVIEWED**


Drug Warnings:


/BOXED WARNING/ Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-theraputic use or distribution to others, and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines are distributed into milk in concentrations 3-7 times maternal blood concentrations. A decision should be made whether to discontinue nursing or the drug.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2530] **PEER REVIEWED**

Amphetamines should be used during pregnancy only if the potential benefits justify the possible risks to the fetus. During pregnancy it is questionable whether potential benefits from amphetamines outweigh potential risks. Infants born to women dependent on amphetamines have an increased risk of prematurity, low birthweight, and withdrawal symptoms (e.g., dysphoria, lassitude, agitation).
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2529] **PEER REVIEWED**

Adverse effects of amphetamines may include nervousness, insomnia, irritability, talkativeness, changes in libido, dizziness, headaches, increased motor activity, chilliness, pallor or flushing, blurred vision, mydriasis, and hyperexcitability. Exacerbation of motor or phonic tics, Tourette's syndrome, dyskinesia, seizures, euphoria, dysphoria, emotional lability, and impotence have been reported in patients receiving amphetamines. Psychotic episodes have occurred rarely in patients receiving amphetamines at recommended dosages.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2528] **PEER REVIEWED**

CONTRAINDICATIONS: Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines.; Agitated states.; Patients with a history of drug abuse.; During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result).
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Pregnancy Category C. Evekeo should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmHg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% ( 4 patients with events out of 3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Stimulants, including Evekeo, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**


Populations at Special Risk:


Hepatic function impairment: Hepatic impairment has the potential to inhibit the elimination of amphetamine and result in prolonged exposures.
[Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 1302] **PEER REVIEWED**

Renal function impairment: Renal impairment has the potential to inhibit the elimination of amphetamine and result in prolonged exposures.
[Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 1302] **PEER REVIEWED**

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**


Reported Fatal Dose:


In adults, 120 mg of amphetamine has caused death, but in one patient 200 mg produced only mild signs of peripheral sympathomimetic activity. Death usually is preceded by seizures and coma and usually results from cardiovascular collapse or from seizures.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2530] **PEER REVIEWED**

The acute lethal dose in adults has been reported at 20-25 mg/kg, and in children, 5 mg/kg. Death from as little as 1.5 mg/kg in an adult has also been noted.
[Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 348] **PEER REVIEWED**

Toxic amphetamine blood concentration: 50 ug/dL; Lethal amphetamine blood concentration: 200 ug/dL /From table/
[Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 420] **PEER REVIEWED**


Emergency Medical Treatment:


Emergency Medical Treatment:


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The following Overview, *** AMPHETAMINES AND RELATED DRUGS ***, is relevant for this HSDB record chemical.

Life Support:
o   This overview assumes that basic life support measures
       have been instituted.
Clinical Effects:
0.2.1 SUMMARY OF EXPOSURE
   0.2.1.1 ACUTE EXPOSURE
     A)  USES: Amphetamines and related agents are CNS
         stimulants. They are sold as commercial pharmaceutical
         agents to treat medical conditions (eg, attention
         deficit disorder, narcolepsy, and obesity). Illicit
         amphetamines, such as hallucinogenic amphetamines,
         methamphetamine, and methylphenidate, are covered in
         separate managements.
     B)  PHARMACOLOGY: Amphetamines are sympathomimetic agents
         structurally related to norepinephrine. They have
         greater stimulant effects than other catecholamines.
         Peripherally, amphetamines promote the release of
         norepinephrine from stores in adrenergic nerve
         terminals and directly stimulate alpha- and
         beta-adrenergic receptors. They also inhibit
         catecholamine metabolism by inhibiting monoamine
         oxidase enzymes. Centrally, amphetamines stimulate the
         cerebral cortex, medullary respiratory center, and
         reticular activating system.
     C)  TOXICOLOGY: Overdose or chronic excessive use causes a
         sympathomimetic toxidrome (eg, tachycardia,
         hypertension, agitation, and, in severe cases,
         psychosis).
     D)  EPIDEMIOLOGY: Exposures are common. Severe effects are
         rare but may be seen in large overdoses and chronic
         exposures. Diversion and abuse of pharmaceutical
         amphetamines is common.
     E)  WITH THERAPEUTIC USE
      1)  Tachycardia, hypertension, agitation, dyskinesias,
          psychosis, and seizures. Dose response may be
          unpredictable. Chronic amphetamine abuse may result in
          cardiomyopathy, heart failure, malnutrition, weight
          loss, cerebral vasculitis, permanent psychiatric
          illness including depression and paranoid psychoses,
          bruxism, and infection. Amphetamine exposure to the
          fetus may cause neonatal withdrawal symptoms. An adult
          withdrawal syndrome has been described in chronic
          abusers, including severe depression.
     F)  WITH POISONING/EXPOSURE
      1)  MILD TO MODERATE POISONING: Hyperactivity,
          diaphoresis, flushing, mydriasis, nausea, vomiting,
          abdominal pain, hypertension, palpitations,
          tachycardia, chest pain, headache, hyperventilation,
          and confusion.
      2)  SEVERE POISONING: Generally only seen after illicit
          use (usually by injection, insufflations, or smoking)
          of high doses. May cause hyperthermia (greater than 40
          degrees C can be life-threatening), dehydration,
          severe hypertension, tachydysrhythmia, myocardial
          infarction, vasospasm, aortic dissection, cerebral
          vascular accidents, sudden cardiac death,
          pneumothorax, psychosis, seizures, ischemic colitis,
          rhabdomyolysis, renal failure, hepatic failure,
          serotonin syndrome, delirium, paranoia, and coma.
          Rarely, severe acidosis, multiorgan failure, and death
          occur.
  0.2.3 VITAL SIGNS
  0.2.20 REPRODUCTIVE HAZARDS
    A)  Benzphetamine, phendimetrazine, and phentermine (as
        monotherapy or in combination with topiramate) are
        classified as FDA pregnancy category X.
        Amphetamines/dextroamphetamines, amphetamine sulfate,
        dextroamphetamine, methamphetamines, and
        lisdexamfetamine are classified as FDA pregnancy
        category C. Diethylpropion is classified by the
        manufacturer as FDA pregnancy category B. Amphetamine
        use during pregnancy has been associated with congenital
        anomalies (ie, biliary atresia and cleft palate),
        aggressive behavior, withdrawal symptoms, low birth
        weights, premature births, fetal distress, and, in some
        cases, death. Methamphetamines have been shown to cross
        the placenta.
    B)  Amphetamines have been measured in breast milk in
        several case reports.
  0.2.21 CARCINOGENICITY
   0.2.21.1 IARC CATEGORY
     A)  IARC Carcinogenicity Ratings for CAS300-62-9
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
     B)  IARC Carcinogenicity Ratings for CAS139-10-6
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
     C)  IARC Carcinogenicity Ratings for CAS156-08-1
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
     D)  IARC Carcinogenicity Ratings for CAS5411-22-3
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
     E)  IARC Carcinogenicity Ratings for CAS51-63-8
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
     F)  IARC Carcinogenicity Ratings for CAS90-84-6
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
     G)  IARC Carcinogenicity Ratings for CAS22232-71-9
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
     H)  IARC Carcinogenicity Ratings for CAS2152-34-3
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
     I)  IARC Carcinogenicity Ratings for CAS122-09-8
         (International Agency for Research on Cancer (IARC),
         2016; International Agency for Research on Cancer,
         2015; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2010; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2010a; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2008; IARC Working Group
         on the Evaluation of Carcinogenic Risks to Humans,
         2007; IARC Working Group on the Evaluation of
         Carcinogenic Risks to Humans, 2006; IARC, 2004):
      1)  Not Listed
   0.2.21.2 HUMAN OVERVIEW
     A)  AMPHETAMINE SULFATE
      1)  At the time of this review, the manufacturer does not
          report any carcinogenic potential of amphetamine
          sulfate in humans (Prod Info EVEKEO(TM) oral tablets,
          2015).
   0.2.21.3 ANIMAL OVERVIEW
     A)  AMPHETAMINE SULFATE
      1)  At the time of this review, the manufacturer does not
          report any carcinogenic potential of amphetamine
          sulfate in animals (Prod Info EVEKEO(TM) oral tablets,
          2015).
  0.2.22 GENOTOXICITY
    A)  AMPHETAMINE
     1)  There was no evidence of mutagenicity in the in vivo
         mouse bone marrow micronucleus test or the E. coli
         component of the in vitro Ames test. The d,
         l-amphetamine enantiomer produced a positive response
         in the mouse bone marrow micronucleus test and Ames
         test and a negative response in the in vitro sister
         chromatid exchange and chromosomal aberration assay
         (Prod Info DYANAVEL(TM) XR extended-release oral
         suspension, 2015).
Laboratory:
A)  Monitor vital signs (including core temperature) and
       mental status.
   B)  Serum concentrations of amphetamine and related agents
       are not readily available or clinically useful.
   C)  Urine toxicology screens may detect amphetamines as a
       class, but do not distinguish between pharmaceutical and
       illicit forms. False positive amphetamine results may
       occur after exposure to over-the-counter cold
       preparations containing ephedrine or pseudoephedrine.
   D)  No specific lab work is needed in patients with mild
       clinical signs and symptoms.
   E)  In patients with severe toxicity, monitor serum
       electrolytes, CK, renal function, and troponin.
   F)  Obtain an ECG and institute continuous cardiac
       monitoring.
   G)  Consider chest radiograph or CT to exclude pneumothorax
       or aortic dissection as clinically indicated.
   H)  Consider a brain CT to exclude traumatic injury or
       cerebrovascular accident as clinically indicated.
Treatment Overview:
0.4.2 ORAL EXPOSURE
    A)  MANAGEMENT OF MILD TO MODERATE TOXICITY
     1)  Most amphetamine related toxicity may be safely managed
         with supportive care that includes monitoring airway,
         breathing, and circulation, and control of agitation
         with benzodiazepines. Intravenous fluids may be needed
         for mild dehydration, and sedation for agitation.
         Charcoal may be indicated if recent ingestion, airway
         controlled, and low seizure risk.
    B)  MANAGEMENT OF SEVERE TOXICITY
     1)  Severe agitation requires aggressive treatment to avoid
         malignant hypertension, rhabdomyolysis, hyperthermia,
         and seizures. Large doses of benzodiazepines may be
         needed. Severe cases may require neuromuscular
         paralysis, intubation, and active cooling measures. For
         tachycardia, treat with intravenous fluids, sedation.
         For severe hypertension unresponsive to sedation,
         consider IV nitroprusside. Rhabdomyolysis is best
         treated with adequate 0.9% normal saline; monitor CK,
         electrolytes, and creatinine. Diuretics and urinary
         alkalinization are not recommended. Ventricular
         dysrhythmias should be treated with standard ACLS
         protocols.
    C)  DECONTAMINATION
     1)  PREHOSPITAL: Not recommended because of potential for
         agitation, seizures.
     2)  HOSPITAL: Activated charcoal binds amphetamines. For
         oral exposures, consider charcoal administration if
         patient is able to drink safely, low risk for seizures.
    D)  AIRWAY MANAGEMENT
     1)  Intubate if unable to protect airway, to control
         agitation, hyperthermia, and status epilepticus.
    E)  ANTIDOTE
     1)  None
    F)  PSYCHOMOTOR AGITATION
     1)  Sedate patient with benzodiazepines as necessary; large
         doses may be required.
    G)  HYPERTENSIVE EPISODE
     1)  Consider IV nitroprusside for severe hypertension
         unresponsive to sedation. DOSE: Start at 0.5 to 1
         mcg/kg/min and titrate as needed.
    H)  ENHANCED ELIMINATION
     1)  Hemodialysis and hemoperfusion are not useful because
         of the large volume of distribution.
    I)  PATIENT DISPOSITION
     1)  HOME CRITERIA: Inadvertent ingestions in asymptomatic
         patients, and pediatric exposures of commercial
         pharmaceutical agents within published pediatric
         therapeutic dose, who have no synergistic
         co-ingestions, may be monitored at home.
     2)  OBSERVATION CRITERIA: Patients with deliberate
         ingestions, synergistic co-ingestions, unclear history,
         symptomatic or intoxicated patients, exposure to doses
         outside published therapeutic ranges, or those in
         unstable social situations should be sent to a
         healthcare facility for observation.
     3)  ADMISSION CRITERIA: Patients with persistent or
         worsening vital sign abnormalities, continued or
         difficult to control agitation or psychosis, multiple
         seizures, cardiac ischemia, or dysrhythmias should be
         admitted. Intensive care unit is indicated for
         aggressive airway or cardiac monitoring.
     4)  CONSULT CRITERIA: Consult a poison center or medical
         toxicologist for assistance in managing patients with
         severe toxicity (ie, progressive agitation, psychosis,
         dysrhythmias, malignant hypertension, hyperthermia),
         concerns about decontamination, or in whom the
         diagnosis is unclear.
    J)  PITFALLS
     1)  Drug effect may be prolonged, requiring extended
         observation times or admission until symptoms resolve.
         Prolonged toxicity may develop after ingestion of
         sustained-release formulations. Other complications of
         drug abuse may be present (eg, trauma, infection).
    K)  PHARMACOKINETICS
     1)  Most amphetamines are well absorbed from the
         gastrointestinal tract. Peak plasma levels occur in
         about 2 to 3 hours after oral amphetamine exposure.
         Amphetamine protein binding is approximately 16%.
         Volume of distribution for amphetamine is 3.2 to 5.6
         L/kg. Amphetamine is hepatically metabolized by
         hydroxylation and n-dealkylation pathways.
         P-hydroxyamphetamine, a potent hallucinogen, is a major
         metabolite of amphetamine. Non-metabolized amphetamine
         is excreted in the urine. Duration of effect varies
         depending on agent and urine pH. Excretion is enhanced
         in more acidic urine. Half-life is 7 to 34 hours and
         is, in part, dependent on urine pH (half-life is longer
         with alkaline urine).
    L)  DIFFERENTIAL DIAGNOSIS
     1)  Cocaine intoxication, phencyclidine (PCP) toxicity,
         anticholinergic poisoning, sepsis, encephalitis,
         trauma. In pediatric population, also consider scorpion
         envenomation, intussusception, meningitis, and sepsis.
Range of Toxicity:
A)  TOXICITY: Dose response is variable. In adults, the acute
       lethal dose of amphetamine has been reported to be 20 to
       25 mg/kg. Patients who chronically abuse amphetamines
       develop tolerance, and up to 15,000 mg/day has been
       ingested without lethal result.
   B)  THERAPEUTIC DOSE: ADULT: Amphetamine: 5 to 60 mg/day in
       divided doses for narcolepsy or 20 mg daily as an
       extended-release tablet for the treatment of adult ADHD;
       Benzphetamine: 25 to 50 mg 1 to 3 times daily;
       Diethylpropion: 75 mg/day; Lisdexamfetamine: 30 to 70 mg
       once daily; Phendimetrazine: 35 mg two to three times
       daily or 105 mg as a sustained-release capsule once
       daily; Phentermine: 18.75 or 37.5 mg once daily.
       PEDIATRIC: Amphetamine (6 years and older): 5 mg once or
       twice daily; rare for dose to exceed 40 mg/day for ADHD,
       or 10 mg extended-release capsule once daily not to
       exceed 30 mg daily for ADHD; Lisdexamfetamine (6 to 17
       years of age): Initially 30 mg once daily, up to a
       maximum dose of 70 mg once daily for the treatment of
       ADHD.

[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2017; CCIS Volume 172, edition expires May, 2017. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2017; CCIS Volume 172, edition expires May, 2017.] **PEER REVIEWED**


Antidote and Emergency Treatment:


Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat agitation, seizures, coma, and hyperthermia if they occur. 3. Continuously monitor the temperature, other vital signs, and the ECG for a minimum of 6 hours. /Amphetamines/
[OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 79] **PEER REVIEWED**

Specific drugs and antidotes. There is no specific antidote. 1. Agitation. Benzodiazepines are usually satisfactory, although antipsychotic agents may be added as needed. 2. Hypertension is best treated with sedation and, if this is not effective, a parenteral vasodilator such as phentolamine or nitroprusside. 3. Treat tachyarrhythmias with propranolol or esmolol. NOTE: Paradoxical hypertension can occur owing to unopposed alpha-adrenergic effects when beta2-mediated vasodilation is blocked; be prepared to give a vasodilator if needed. 4. Treat arterial vasospasm ... . /Amphetamines/
[OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 79] **PEER REVIEWED**

Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Consider whole-bowl irrigation and repeated doses of charcoal after ingestion of drug-filled packets (body stuffers). /Amphetamines/
[OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 79] **PEER REVIEWED**

Enhanced elimination. Dialysis and hemoperfusion are not effective. repeat-dose charcoal has not been studied. Renal elimination of dextroamphetamine may be enhanced by acidification of the urine, but this is not recommended because of the risk for aggravating the nephrotoxicity of myoglobinuria. /Amphetamines/
[OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 79] **PEER REVIEWED**

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160] **PEER REVIEWED**

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160] **PEER REVIEWED**

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160-1] **PEER REVIEWED**


Animal Toxicity Studies:


Toxicity Summary:


IDENTIFICATION AND USE: Amphetamine is a colorless liquid with characteristic amine odor (similar to geranium leaves) and an acrid taste. It is used for the following indications: Psychostimulant: Accepted indications: Narcolepsy; Hyperkinetic states in children (as an adjunct to psychological, educational and social measures). The drug is misused for performance enhancement. Abuse either orally or by injection is extremely common. HUMAN EXPOSURE AND TOXICITY: Main risks include: acute central nervous system (CNS) stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Cardiovascular effects include: palpitation, chest pain, tachycardia, arrhythmias and hypertension; cardiovascular collapse can occur in severe poisoning, as well as, myocardial ischemia, infarction and ventricular dysfunction. CNS effects include: stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia. Stroke and cerebral vasculitis have been observed. Gastrointestinal effects include: vomiting, diarrhea and cramps. Acute transient ischemic colitis has occurred with chronic methamphetamine abuse. Genitourinary effects: increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Transient hyperthyroxinemia may be noted. Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Hypo- and hyperkalemia have been reported. Dehydration is common. Fasciculations and rigidity may be noted. Rhabdomyolysis is an important consequence of severe amphetamine poisoning. Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Amphetamine appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especially norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Children appear to be more susceptible than adults and are less likely to have developed tolerance. The use of amphetamine for medical indications does not pose a significant risk to the fetus for congenital anomalies. Amphetamines generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long-term sequelae. Illicit maternal use or abuse of amphetamine presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties of amphetamines. 65 children whose mothers were addicted to amphetamine during pregnancy, at least during the first trimester, were studied. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. ANIMAL STUDIES: Testing for toxicity to the retina has been negative; 10 mg/kg given daily to dogs for three months caused occasional slight ophthalmoscopic appearance of blanching of the fundus, but no histologic change in the retina. The behavioral effects of d-amphetamine administration were studied in 17 adult cats. The doses of amphetamine administered were 0.1, 0.5, 1.0 and 5.0 mg/kg sc. Amphetamine administration induced a dose-dependent hypomotility, which was marked with the higher doses. In addition, rhythmic, bilateral slow movements of the head as a mode of stereotype, indifference to the environment and dose-dependent incr in respiratory rate were observed in amphetamine-treated cats. Amphetamine damages cerebral arteries in experimental animal models. ECOTOXICITY STUDIES: In the freshwater bivalve Dreissena polymorpha the bell-shaped trend of antioxidants showed at the highest tested amphetamine concentration (5000 ng/L) suggested an overproduction of reactive oxygen species, leading to oxidative damage, as confirmed by the significant increase of protein carbonylation and DNA fragmentation.
**PEER REVIEWED**


Non-Human Toxicity Excerpts:


/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Testing for toxicity to the retina has been negative; 10 mg/kg given daily to dogs for three months caused occasional slight ophthalmoscopic appearance of blanching of the fundus, but no histologic change in the retina.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96] **PEER REVIEWED**

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In rats, continuous admin of amphetamine for 10 days can cause a significant decr in the activity of tyrosine hydroxylase in the nigrostriatum that lasts for more than 3 mo. After chronic use, animals ... begin to exhibit behaviors not seen after initial doses; these incl exaggerated "startle" reactions, dyskinesias, and postural abnormalities.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 554] **PEER REVIEWED**

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Linear sweep voltammetry with carbon paste electrodes was used to monitor extracellular ascorbic acid in the caudate nucleus and nucleus accumbens of behaving male Sprague Dawley rats. Amphetamine (2 or 5 mg/kg) was administered 4, 6 and 8 days after surgery. In general the amphetamine-induced incr in ascorbic acid was greater in the caudate /nucleus/ than in the nucleus accumbens. In the nucleus accumbens the amphetamine-induced incr in ascorbic acid was very similar on all test days, but in the caudate /nucleus/ the incr in ascorbic acid produced by 5 mg/kg amphetamine was progressively larger on each test day.
[Mueller K; Brain Res 494 (1): 30-5 (1989)] **PEER REVIEWED** PubMed Abstract

/BEHAVIORAL STUDIES/ Chronic amphetamine use results in compulsive behavior patterns of searching & examining. In lower animals this stereotyped behavior consists primarily of sniffing, but biting & looking movements are also frequent. In primates, hand eye examination patterns, in addn to the above, are characteristic of amphetamine induced stereotyped behavior.
[Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975., p. 630] **PEER REVIEWED**

/BEHAVIORAL STUDIES/ Animals self administering ... amphetamine often show a cyclic pattern of use, with periods of spontaneous abstinence interposed between periods of use. A small priming dose during abstinence will reinitiate self admin. With round the clock access to the /drug/ ... there is weight loss, self mutilation, and death within about 2 weeks.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 552] **PEER REVIEWED**

/BEHAVIORAL STUDIES/ Drug Discrimination: Rats learned to discriminate between injection of d,l-amphetamine and saline, and in addition, generalization was obtained with methylphenidate but not with atropine.
[Harris LS, Balster RL; p.111-32 in Stimulus Properties of Drugs; Thompson T, Pickens R, eds (1971) as cited in DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability p.67 (1984) DHHS Pub No. (ADM)87-1332] **PEER REVIEWED**

/BEHAVIORAL STUDIES/ Drug Discrimination: Animals trained to respond to sedative/hypnotics responded to amphetamine as if it were saline (ie, no cross generalization between drug classes was observed).
[Overton DA, Lebman RI; Proc Amer Psychol Assoc (1973) as cited in DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability p.67 (1984) DHHS Pub No. (ADM)87-1332] **PEER REVIEWED**

/ALTERNATIVE and IN VITRO TESTS/ Previous research has shown that nitric oxide (NO) synthase inhibitors prevent rodents' sensorimotor gating impairments induced by dopamine releasing drugs, such as amphetamine (Amph) and methylphenidate. The mechanisms of this effect have not been entirely understood. In the present work, we investigated some possible mechanisms by which the NO donor, NOC-12 (3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene), influence spontaneous and Amph-induced dopamine release, using rat mesencephalic primary cultured neurons preparations. Our results showed that NOC-12 increased dopamine release in a concentration-dependent manner and potentiated the Amph-induced one. Dopamine release induced by NOC-12 was disrupted by N-acetyl-L-cysteine (NAC-a free radical scavenger) and MK-801, a NMDA (N-methyl-D-aspartate) non-competitive antagonist, and was concentration dependently affected by oxadiazolo[4,3]quinoxalin-1-one, an inhibitor of the soluble guanylate cyclase (sGC). In contrast, dopamine released by Amph was facilitated by NAC and by MK-801 and not affected by nifedipine (a L-type-Ca+2 channel blocker), which enhanced NOC-12-induced dopamine release. The present work demonstrates that DA release induced by NOC-12 is partially dependent on sGC and on NMDA activation, and is modulated by L-type Ca+2 channel and the antioxidant NAC. This mechanism differs from the Amph-induced one, which appears not to depend on L-type Ca+2 channel and seems to be facilitated by NMDA channel blocking and by NAC. These results suggest that Amph and NOC-12 induce dopamine release through complementary pathways, which may explain the potentiation of Amph-induced dopamine release by NOC-12. These findings contribute to understand the involvement of NO in dopamine-related neuropsychiatric and neurodegenerative diseases.
[Salum C et al; Neurotox Res. 2015 Sep 21. [Epub ahead of print]] **PEER REVIEWED** PubMed Abstract

/VETERINARY CASE REPORTS/ Ephedrine & other sympathomimetic drugs such as amphetamine & methylamphetamine, if given in excessive amt, produce signs of sympathetic stimulation, manifested by anxiety & restlessness. If the dosage involved is larger, muscular tremors & even convulsion may occur.
[Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 87] **PEER REVIEWED**

/VETERINARY CASE REPORTS/ The American Psychiatric Association estimates that 3-7% of US school-aged children exhibit attention-deficit/hyperactivity disorder (ADHD). Adderall (amphetamine dextroamphetamine) and a variety of brand names and generic versions of this combination are available by prescription to treat ADHD and narcolepsy. Both immediate and sustained release products are used as are single agent amphetamine medication. Knowing the exact agent ingested can provide information of dose labeled and length of clinical effects. These drugs are used off label by college students for memory enhancement, test taking ability, and for study marathons. These agents are DEA Schedule II controlled substances with high potential for abuse. For humans with ADHD or narcolepsy, standard recommended dosage is 5-60 mg daily. Amphetamine and its analogues stimulate the release of norepinephrine affecting both a- and beta-adrenergic receptor sites. a-Adrenergic stimulation causes vasoconstriction and an increase in total peripheral resistance. beta-Adrenergic receptor stimulation leads to an increase in heart rate, stroke volume, and skeletal muscle blood flow. Clinical signs of Adderall overdose in humans and dogs include hyperactivity, hyperthermia, tachycardia, tachypnea, mydriasis, tremors, and seizures. In addition, Adderall intoxication in dogs has been reported to cause hyperthermia, hypoglycemia, hypersegmentation of neutrophils, and mild thrombocytopenia. Diagnosis can be confirmed by detecting amphetamine in stomach contents or vomitus, or by positive results obtained in urine tests for illicit drugs. Treatment is directed at controlling life-threatening central nervous system and cardiovascular signs. Seizures can be controlled with benzodiazepines, phenothiazines, pentobarbital, and propofol. Cardiac tachyarrhythmias can be managed with a beta-blocker such as propranolol. Intravenous fluids counter the hyperthermia, assist in maintenance of renal function, and help promote the elimination of amphetamine and its analogues. Prognosis after poisoning with Adderall depends upon the severity and duration of clinical signs at presentation. Differential diagnoses that should be considered in cases of suspected amphetamine overdose are any other agents that can cause central nervous system stimulation, tremors, and seizures. This article discusses our present understanding of Adderall intoxication and examines 3 dogs presented to our practice after ingestion of large amounts of the drug. /Adderall/
[Fitzgerald KT, Bronstein AC; Top Companion Anim Med 28 (1): 2-7 (2013)] **PEER REVIEWED** PubMed Abstract

/OTHER TOXICITY INFORMATION/ The acute toxicity of amphetamine is strongly influenced by certain environmental factors. For example, crowding or aggregation markedly increases the toxicity in mice. ... Elevated environmental temperatures are associated with incr acute toxicity in animals. Hyperpyrexia, perhaps secondary to a hypermetabolic state produced by release of endogenous catecholamines, is a prominent feature of amphetamine poisoning in many species. ... Dehydration has been found to incr amphetamine toxicity in animals, as does forced exercise, various stresses incl cold & high altitude.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-27] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Experimental regeneration of the lens in amphibian eyes is found to be delayed when the animals are placed in a solution containing amphetamine.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Amphetamine given intramuscularly has been claimed to cause elevation of pressure in eyes with primary glaucoma and not in normal eyes, but this claim needs further investigation with careful attention to gonioscopy and comparative observations with amphetamine. In monkeys no elevation of ocular pressure has been found when amphetamine is given systemically unless given in doses so large that a rapid rise of blood pressure is induced, which is reflected in a brief small elevation of ocular pressure.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Amphetamine ... damages cerebral arteries in experimental animal models.
[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995., p. 519] **PEER REVIEWED**


Ecotoxicity Excerpts:


/AQUATIC SPECIES/ Illicit drugs have been recognized as emerging aquatic pollutants due to their presence in aquatic ecosystems up to ug/L level. Among these, the synthetic psycho-stimulant drug amphetamine (AMPH) is commonly found in both surface and wastewaters worldwide. Even though the environmental occurrence of AMPH is well-known, the information on its toxicity towards non-target freshwater organisms is completely lacking. This study investigated the imbalance of the oxidative status and both oxidative and genetic damage induced by a 14-day exposure to two concentrations (500 ng/L and 5000 ng/L) of AMPH on the freshwater bivalve Dreissena polymorpha by the application of a biomarker suite. ...The activity of antioxidant enzymes (SOD, CAT and GPx), the phase II detoxifying enzyme GST, the lipid peroxidation level (LPO) and protein carbonyl content (PCC), as well as primary (Single Cell Gel Electrophoresis assay) and fixed (DNA diffusion assay and Micronucleus test) genetic damage /was examined/. /The/ results showed that a current ... AMPH concentration (500 ng/L) did /not/ ...cause notable imbalances in enzymatic activities, ... /or/ oxidative and genetic damage to cellular macromolecules. In contrast, the bell-shaped trend of antioxidants showed at the highest tested concentration (5000 ng/L) suggested an overproduction of reactive oxygen species, leading to oxidative damage, as confirmed by the significant increase of protein carbonylation and DNA fragmentation.
[Parolini M et al; Chemosphere 144: 207-213 (2015)] **PEER REVIEWED** PubMed Abstract


National Toxicology Program Studies:


Toxicology and carcinogenesis studies were conducted by administering dl-amphetamine sulfate (USP grade) in feed to groups of F344/N rats and B6C3F1 mice of each sex for ... 2 yr. ... Diets containing 0, 20, or 10 ppm dl-amphetamine sulfate was administered to groups of 50 rats or 50 mice of each sex. ... Under the conditions of these 2 yr studies, there was no evidence of carcinogenic activity of dl-amphetamine sulfate for male or female F344/N rats or male or female B6C3F1 mice. /dl-Amphetamine sulfate/
[DHHS/NTP; Toxicology & Carcinogenesis Studies of dl-Amphetamine Sulfate in F344/N Rats and B6C3F1 Mice Technical Report Series No. 387 (1991) NIH Publication No. 91-2842] **PEER REVIEWED**


Non-Human Toxicity Values:


LD50 Rat ip 125 mg/kg
[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 245] **PEER REVIEWED**

LD50 Rat sc 39 mg/kg
[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 245] **PEER REVIEWED**

LD50 Mouse oral 22 mg/kg
[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 245] **PEER REVIEWED**

LD50 Mouse ip 16 mg/kg
[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 245] **PEER REVIEWED**

LD50 Mouse sc 2800 ug/kg
[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 245] **PEER REVIEWED**

LD50 Mouse iv 18 mg/kg
[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 245] **PEER REVIEWED**


Ongoing Test Status:


The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /DL-Amphetamine sulfate/
[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=60-13-9


Metabolism/ Pharmacokinetics:


Metabolism/ Metabolites:


Amphetamine is metabolized in the liver by aromatic hyroxylation, N-dealkylation, and deamination. Although the enzymes involved in amphetamine metabolism have not been clearly defined, cytochrome P450 (CYP-450) 2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Because CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a posibility.
[Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 1302] **PEER REVIEWED**

Metabolism that results in aromatic hydroxylation, aliphatic hydroxylation, and n-dealkylation of amphetamines can give rise to active metabolites such as the potent hallucinogen p-hydroxyamphetamine. Other metabolic pathways, including deamination and subsequent side chain oxidation, produce inactive amphetamine derivatives.
[Haddad, L.M. (Ed). Clinical Management of Poisoning and Drug Overdose 3rd Edition. Saunders, Philadelphia, PA. 1998., p. 563] **PEER REVIEWED**


Absorption, Distribution & Excretion:


Children: Children eliminated amphetamine faster than adults.
[Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 1302] **PEER REVIEWED**

/MILK/ Amphetamines are excreted in human milk.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines are readily absorbed from the GI tract and effects persist for 4-24 hours. Amphetamines are distributed into most body tissues with high concentrations occurring in the brain and CSF. Amphetamine appears in the urine within about 3 hours following oral administration. Urinary excretion of the amphetamines is pH-dependent and excretion is enhanced in acidic urine. Following oral administration of racemic amphetamine to humans, approximately equal amounts of both isomers were excreted during the first 12 hours; after the first 12 hours, a continually decreasing proportion of the d-isomer was excreted.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2531] **PEER REVIEWED**

Amphetamine has been measured in human sweat at a median range of 15.5 (low dose 6.5-40.5) and 53.8 (high dose 34.0-83.4) ng per patch(1).
[(1) Daughton CG, Ruhoy IS; Environ Toxicol Chem 28(12): 2495-521 (2009)] **PEER REVIEWED**

/MILK/ Amphetamines are distributed into milk in concentrations 3-7 times maternal blood concentrations.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2530] **PEER REVIEWED**

There was considerable species difference in biotransformation, but not in the excretion of (14)C, after admin of (14)C-amphetamine ... Much of the (14)C was excreted in the 24 hr urine after ip admin of amphetamine to dogs & guinea pigs, & oral admin to other species. Three days after a dose of (+ or -)-amphetamine, human subjects had excreted 91% of the (14)C in the urine, rats 86%, rabbits 86%, & dogs 78%. The last 3 species excreted 5%, 7%, & 0% of the dose respectively in 3 day feces. Since excretion of (14)C over broad time intervals did not differ significantly within each species whether (+ or -)-amphetamine or its optical isomers was given, the above data can be compared with results obtained when an optical isomer was given to monkeys, mice, & guinea pigs. Thus, after a dose of (+)-amphetamine, (also known as dexamphetamine ...), guinea pigs excreted 88% of the (14)C in the 2 day urine, mice excreted 87% in the 3-day urine, & a monkey excreted 80% in the 3 day urine. Another monkey excreted less than 58%. Of interest was that man, monkey, dog, & mouse excreted about 30% of the (14)C as unchanged amphetamine in 24 hr, whereas guinea pig excreted 22%, rat excreted 13%, & rabbit only excreted 4%. These results confirmed an earlier study of the excretion of (14)C & of unchanged amphetamine in rats given (+ or -)-amphetamine at 4 different dose levels orally & at 1 level sc. ... These earlier studies showed that rates of excretion of (14)C were similar after oral or ip dosing, thus indicating comparable & rapid absorption of amphetamine in these animals by two routes.
[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 1: A Review of the Literature Published Between 1960 and 1969. London: The Chemical Society, 1970., p. 65] **PEER REVIEWED**

The excretion of a drug into saliva depends on the ability of the drug to pass through the epithelial cells of the salivary glands into the saliva. The concentration of a drug in saliva could be higher, such as amphetamine, or lower, such as methaqualone, than that in plasma.
[DHHS/NIDA; Research Monograph Series 73: Urine Testing for Drugs of Abuse p.70 (1986) DHHS Pub No. (ADM)87-1481] **PEER REVIEWED**


Biological Half-Life:


Biological half-life is between 10-13 hr in adults and 9-11 hr in children.
[Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 1302] **PEER REVIEWED**


Mechanism of Action:


Inactivation of sympathomimetic noncatecholamines largely depends on breakdown by monoamine oxidase and since substitution of an alkyl group for hydrogen on the a-carbon atom blocks enzymatic inactivation of the amino group, the duration of action of noncatecholamines (but not of catecholamines, which are inactivated largely by a different mechanism) is prolonged by a-substitution. The absence of a hydroxyl group on the aromatic ring of amphetamine reduces inactivation of the drug in the GI tract and the amphetamines are active following oral administration.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2531] **PEER REVIEWED**


Interactions:


Amphetamines inhibit the hypotensive effect of veratrum alkaloids.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may delay intestinal absorption of Phenobarbital. Co-administration of phenobarbital may produce a synergistic anticonvulsant action.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines enhance the adrenergic effect of norepinephrine.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Urinary excretion of amphetamines is increased, and efficacy is reduced by acidifying agents used in methenamine therapy.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines potentiate the analgesic effect of meperidine.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

The antiobesity and stimulatory effects of amphetamines may be inhibited by lithium carbonate.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant affects of amphetamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may delay intestinal absorption of ethosuximide.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamine, and can be used to treat amphetamine poisoning.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may antagonize the hypotensive effects of antihypertensives.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may counteract the sedative effect of antihistamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the action of amphetamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Adrenergic blockers are inhibited by amphetamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

The effects of D-Trp11-neurotensin (0-8 ug/rat, iv, ventricle) and alpha-flupenthixol (0-1 mg/kg ip) on hyperactivity induced by d-amphetamine (1.5 mg/kg, ip) was studied in male Wistar rats. The usual total counts index of activity suggested that alpha-flupenthixol and D-Trp11-neurotensin blocked the incr activity. In contrast, conditional count data suggested that only alpha-flupenthixol was effective. Both measures indicated that amphetamine, administered separately, enhanced activity.
[Sahgal A et al; Neuropharmacol 28 (3): 283-9 (1989)] **PEER REVIEWED**

In animals ibogaine enhances amphetamine ... induced increases in brain dopamine levels.
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 935] **PEER REVIEWED**

BACKGROUND: Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. METHODS: Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/hr), methylphenidate (0.032-0.32mg/kg/hr), or cocaine (0.1-0.32mg/kg/hr). RESULTS: During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/hr d-amphetamine did eliminate methamphetamine choice in two monkeys. CONCLUSIONS: The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice.
[Schwienteck KL, Banks ML; Drug Alcohol Depend 155: 16-23 (2015)] **PEER REVIEWED** PubMed Abstract Full text: PMC4582002

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopment disorder occurring during childhood. However, ADHD persists into adulthood in 45.7% of cases. The global prevalence of adult ADHD is estimated to 5.3%, with no difference between Europe and North America. ADHD is often comorbid with substance use disorder (SUD), with Odds Ratio ranges from 1.5 to 7.9, depending on the substance and the dependence level. Conversely, the prevalence of ADHD among patients with SUD is 10.8%, versus 3.8% for patients without SUD. Methylphenidate (MPH) alleviates ADHD symptoms and, as such, is currently considered as a first choice medication. MPH blocks the dopamine and norepinephrine transporters leading to an increase in extracellular dopamine. It should be noted that its subjective effects are highly dependent on the pharmacokinetic and especially on the rate of input, which highlights the importance of choosing a sustained-release formulation. Meanwhile, prescribing MPH to patients with comorbid SUD has always been challenging for clinicians. The aim of this review is to address the benefits and pitfalls of using MPH in adults with ADHD comorbid SUD, depending on each of the following types of SUD: amphetamine, cocaine, nicotine, alcohol, cannabis and opiates. Overall, due to the prevalence of ADHD in SUD and to the benefits of MPH observed in this population, and considering the mild or low side effects observed, the response to MPH treatment should be evaluated individually in adults with comorbid ADHD and SUD. The choice of the formulation should favor sustained- release MPH over immediate release MPH. Cardiovascular parameters also have to be monitored during long-term use.
[Simon N et al; Curr Pharm Des 21 (23): 3359-66 (2015)] **PEER REVIEWED** PubMed Abstract

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids-TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.
[Kuhn FT et al; Neurotox Res 28 (4): 319-31 (2015)] **PEER REVIEWED** PubMed Abstract

Amphetamine ... in large doses systemically can dilate the pupils and cause slight blurring of near vision. Applied to the eye, amphetamine dilates the pupil and retracts the upper lid, but these actions are prevented by previous depletion of catecholamines such as is brought about by local guanethidine.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96] **PEER REVIEWED**


Pharmacology:


Therapeutic Uses:


Adrenergic Agents; Adrenergic Uptake Inhibitors; Central Nervous System Stimulants; Dopamine Agents; Dopamine Uptake Inhibitors; Sympathomimetics
[National Library of Medicine's Medical Subject Headings. Amphetamine. Online file (MeSH, 2015). Available from, as of November 23, 2015: https://www.nlm.nih.gov/mesh/2015/mesh_browser/MBrowser.html] **PEER REVIEWED**

/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Amphetamine is included in the database.
[NIH/NLM; ClinicalTrials.Gov. Available from, as of September 30, 2015: https://clinicaltrials.gov/search/intervention=Amphetamine] **PEER REVIEWED**

Evekeo (amphetamine sulfate tablets, USP) is indicated for: 1. Narcolepsy 2. Attention Deficit Disorder with Hyperactivity as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability , and impulsivity. The diagnosis of the syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or not be warranted. 3. Exogenous Obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy, e.g., repeated diets, group programs, and other drugs. /Included in US product label/
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Vet: to alleviate anesthetic overdosage, particularly with barbiturates. To incr ... response to external stimuli such as depressive states & milk fever in cows. May have value in selected cases of encephalomyelitis (horses) & epileptic (cattle) or hyperkinetic syndromes.
[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 17] **PEER REVIEWED**


Drug Warnings:


/BOXED WARNING/ Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-theraputic use or distribution to others, and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines are distributed into milk in concentrations 3-7 times maternal blood concentrations. A decision should be made whether to discontinue nursing or the drug.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2530] **PEER REVIEWED**

Amphetamines should be used during pregnancy only if the potential benefits justify the possible risks to the fetus. During pregnancy it is questionable whether potential benefits from amphetamines outweigh potential risks. Infants born to women dependent on amphetamines have an increased risk of prematurity, low birthweight, and withdrawal symptoms (e.g., dysphoria, lassitude, agitation).
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2529] **PEER REVIEWED**

Adverse effects of amphetamines may include nervousness, insomnia, irritability, talkativeness, changes in libido, dizziness, headaches, increased motor activity, chilliness, pallor or flushing, blurred vision, mydriasis, and hyperexcitability. Exacerbation of motor or phonic tics, Tourette's syndrome, dyskinesia, seizures, euphoria, dysphoria, emotional lability, and impotence have been reported in patients receiving amphetamines. Psychotic episodes have occurred rarely in patients receiving amphetamines at recommended dosages.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2528] **PEER REVIEWED**

CONTRAINDICATIONS: Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines.; Agitated states.; Patients with a history of drug abuse.; During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result).
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Pregnancy Category C. Evekeo should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmHg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% ( 4 patients with events out of 3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Stimulants, including Evekeo, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**


Interactions:


Amphetamines inhibit the hypotensive effect of veratrum alkaloids.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may delay intestinal absorption of Phenobarbital. Co-administration of phenobarbital may produce a synergistic anticonvulsant action.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines enhance the adrenergic effect of norepinephrine.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Urinary excretion of amphetamines is increased, and efficacy is reduced by acidifying agents used in methenamine therapy.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines potentiate the analgesic effect of meperidine.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

The antiobesity and stimulatory effects of amphetamines may be inhibited by lithium carbonate.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant affects of amphetamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may delay intestinal absorption of ethosuximide.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamine, and can be used to treat amphetamine poisoning.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may antagonize the hypotensive effects of antihypertensives.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may counteract the sedative effect of antihistamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the action of amphetamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Adrenergic blockers are inhibited by amphetamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines.
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

The effects of D-Trp11-neurotensin (0-8 ug/rat, iv, ventricle) and alpha-flupenthixol (0-1 mg/kg ip) on hyperactivity induced by d-amphetamine (1.5 mg/kg, ip) was studied in male Wistar rats. The usual total counts index of activity suggested that alpha-flupenthixol and D-Trp11-neurotensin blocked the incr activity. In contrast, conditional count data suggested that only alpha-flupenthixol was effective. Both measures indicated that amphetamine, administered separately, enhanced activity.
[Sahgal A et al; Neuropharmacol 28 (3): 283-9 (1989)] **PEER REVIEWED**

In animals ibogaine enhances amphetamine ... induced increases in brain dopamine levels.
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 935] **PEER REVIEWED**

BACKGROUND: Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. METHODS: Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/hr), methylphenidate (0.032-0.32mg/kg/hr), or cocaine (0.1-0.32mg/kg/hr). RESULTS: During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/hr d-amphetamine did eliminate methamphetamine choice in two monkeys. CONCLUSIONS: The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice.
[Schwienteck KL, Banks ML; Drug Alcohol Depend 155: 16-23 (2015)] **PEER REVIEWED** PubMed Abstract Full text: PMC4582002

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopment disorder occurring during childhood. However, ADHD persists into adulthood in 45.7% of cases. The global prevalence of adult ADHD is estimated to 5.3%, with no difference between Europe and North America. ADHD is often comorbid with substance use disorder (SUD), with Odds Ratio ranges from 1.5 to 7.9, depending on the substance and the dependence level. Conversely, the prevalence of ADHD among patients with SUD is 10.8%, versus 3.8% for patients without SUD. Methylphenidate (MPH) alleviates ADHD symptoms and, as such, is currently considered as a first choice medication. MPH blocks the dopamine and norepinephrine transporters leading to an increase in extracellular dopamine. It should be noted that its subjective effects are highly dependent on the pharmacokinetic and especially on the rate of input, which highlights the importance of choosing a sustained-release formulation. Meanwhile, prescribing MPH to patients with comorbid SUD has always been challenging for clinicians. The aim of this review is to address the benefits and pitfalls of using MPH in adults with ADHD comorbid SUD, depending on each of the following types of SUD: amphetamine, cocaine, nicotine, alcohol, cannabis and opiates. Overall, due to the prevalence of ADHD in SUD and to the benefits of MPH observed in this population, and considering the mild or low side effects observed, the response to MPH treatment should be evaluated individually in adults with comorbid ADHD and SUD. The choice of the formulation should favor sustained- release MPH over immediate release MPH. Cardiovascular parameters also have to be monitored during long-term use.
[Simon N et al; Curr Pharm Des 21 (23): 3359-66 (2015)] **PEER REVIEWED** PubMed Abstract

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids-TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.
[Kuhn FT et al; Neurotox Res 28 (4): 319-31 (2015)] **PEER REVIEWED** PubMed Abstract

Amphetamine ... in large doses systemically can dilate the pupils and cause slight blurring of near vision. Applied to the eye, amphetamine dilates the pupil and retracts the upper lid, but these actions are prevented by previous depletion of catecholamines such as is brought about by local guanethidine.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96] **PEER REVIEWED**


Drug Idiosyncrasies:


Toxic manifestations /of amphetamine/ occasionally occur as an idiosyncrasy after as little as 2 mg, but are rare with doses of less than 15 mg.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 220] **PEER REVIEWED**


Drug Tolerance:


Tolerance develops to some of the central effects of amphetamines, and the chronic user often incr the dose to continue to obtain the desired effect. Some users are able to take several hundred milligrams per day over prolonged periods. By supressing appetite, high doses of amphetamine may foster ketosis; and, since amphetamine is excreted much more rapidly in acidic urine, some of the apparent tolerance may be due to more rapid elimination of the drug. At the same time there is increased sensitivity to other effects on the CNS. ... Cross tolerance between the amphetamine-like sympathomimetic agents has been observed clinically, & cross tolerance between the anorectic effect of cocaine & amphetamine has been demonstrated in rats.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 553] **PEER REVIEWED**

Tolerance does not develop to certain of the toxic effects of amphetamine on the CNS, & a toxic psychosis may occur after periods of weeks to months of continued use. Those who develop such a psychosis may have a lowered threshold during subsequent episodes if they resume use of amphetamine.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 553] **PEER REVIEWED**

Psychological dependence often occurs when amphetamine or dextroamphetamine is used chronically. ... Tolerance almost invariably develops to the anorexigenic effect of amphetamines, & is often seen also in the need for increasing doses to maintain improvement of mood in psychiatric patients. Tolerance is striking in individuals who are dependent on the drug, and a daily intake of 1.7 g without apparent ill effects has been reported. Development of tolerance is not invariable, and cases of narcolepsy have been treated for years without requiring an incr in the initially effective dose.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 220] **PEER REVIEWED**

With time, tolerance develops to the euphorigenic effects of amphetamine; higher & more frequent doses are used, & toxic symptoms & signs then appear. These include bruxism, touching, & picking of the face & extremities, suspiciousness, & a feeling of being watched.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 552] **PEER REVIEWED**

A detailed examination of the effects of single (0.1 ml/g of body wt) and repeated equiactive doses (1.25, 2.5 and 5.0 mg/kg, sc of d-amphetamine and 2.50, 5.0 and 10.0 mg/kg, sc of l-amphetamine) of d- and l-amphetamine on food consumption by adult male Sprague Dawley rats was undertaken with emphasis on aspects of tolerance development. Wt loss and pattern of daily food intake differed depending upon the isomer, dose, and degree of tolerance. Two types of tolerance were seen with both isomers, an initial tolerance with a decr in efficacy between days 1 and 2, and a later gradual decr in efficacy over 12 days of repeated dosage. Rats tolerant to the anorectic effects of d-amphetamine were only minimally affected when challenged with an equiactive anorectic dose of l-amphetamine, while rats tolerant to the anorectic effects of l-amphetamine showed a significantly depressed food intake and modified eating pattern when challenged with an equiactive dose of d-amphetamine.
[Nichols MB, Maickel RP; Pharmacol Biochem Behav 33 (1): 181-8 (1989)] **PEER REVIEWED** PubMed Abstract


Reported Fatal Dose:


In adults, 120 mg of amphetamine has caused death, but in one patient 200 mg produced only mild signs of peripheral sympathomimetic activity. Death usually is preceded by seizures and coma and usually results from cardiovascular collapse or from seizures.
[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2530] **PEER REVIEWED**

The acute lethal dose in adults has been reported at 20-25 mg/kg, and in children, 5 mg/kg. Death from as little as 1.5 mg/kg in an adult has also been noted.
[Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 348] **PEER REVIEWED**

Toxic amphetamine blood concentration: 50 ug/dL; Lethal amphetamine blood concentration: 200 ug/dL /From table/
[Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 420] **PEER REVIEWED**


Environmental Fate & Exposure:


Environmental Fate/Exposure Summary:


Amphetamine's production and administration as a medication and illicit drug may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.24 mm Hg at 25 deg C indicates amphetamine will exist solely as a vapor in the atmosphere. Vapor-phase amphetamine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 3 hrs. Amphetamine does not contain chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, amphetamine is expected to have low mobility based upon an estimated Koc of 760. The pKa of amphetamine is 10.1, indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Amphetamine has a low vapor pressure and exists as a liquid under environmental conditions; therefore, amphetamine may volatilize from dry soil. A 76% degradation in 15 days using a river water/sediment bioreator suggests that biodegradation may be an important environmental fate process in soil. If released into water, amphetamine is expected to adsorb to suspended solids and sediment based upon the estimated Koc. An 85% degradation in 15 days using a river water bioreactor suggests tha biodegradation may be an important environmental fate process in water. The pKa indicates amphetamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 7 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to amphetamine may occur through inhalation and dermal contact with this compound at workplaces where amphetamine is produced or used. Monitoring data indicate that the general population may be exposed to amphetamine via ingestion of contaminated water. Exposure to amphetamine among the general population will be by direct medical treatment and also occurs among those abusing this drug. (SRC)
**PEER REVIEWED**


Artificial Pollution Sources:


Amphetamine's production and administration as a medication and drug of abuse(1) may result in its release to the environment through various waste streams(SRC).
[(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 99 (2013)] **PEER REVIEWED**


Environmental Fate:


TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 760(SRC), determined from a structure estimation method(2), indicates that amphetamine is expected to have low mobility in soil(SRC). The pKa of amphetamine is 10.13(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Amphetamine has a low vapor pressure of 0.24 mm Hg(5) and exists as a liquid under environmental conditions; therefore, amphetamine may volatilize from dry soil. An 76% degradation in 15 days using a river water/sediment bioreator(6) suggests that biodegradation may be an important environmental fate process in soil(SRC).
[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 27, 2015: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm (3) Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965) (4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000) (5) Lawrence AH et al; Can J Chem 62: 1886-88 (1984) (6) Bagnall J et al; Water Res 47: 5708-18 (2013)] **PEER REVIEWED**

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 760(SRC), determined from a structure estimation method(2), indicates that amphetamine is expected to adsorb to suspended solids and sediment(SRC). A pKa of 10.24(3) indicates amphetamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water or moist soil surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 7(SRC), from its log Kow of 1.76(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). An 85% degradation in 15 days using a river water bioreactor(6) suggests that biodegradation may be an important environmental fate process in water(SRC).
[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 27, 2015: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm (3) Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965) (4) Franke C et al; Chemosphere 29: 1501-14 (1994) (5) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 61 (1995) (6) Bagnall J et al; Water Res 47: 5708-18 (2013)] **PEER REVIEWED**

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), amphetamine, which has a vapor pressure of 0.24 mm Hg at 25 deg C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase amphetamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3 hrs(SRC), calculated from its rate constant of 4.9X10-11 cu cm/molecule-sec at 25 deg C(SRC) that was derived using a structure estimation method(3). Amphetamine does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
[(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Lawrence AH et al; Can J Chem 62: 1886-88 (1984) (3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993) (4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)] **PEER REVIEWED**


Environmental Biodegradation:


AEROBIC: Amphetamine, present at 800 ng/L, decreased in concentration to 120 and 190 ng/L over 15 days using river microcosm bioreactors with and without sediment, respectively, maintained under dark conditions at pH 8.3, 28.5 deg C and 7.1 mg/L dissolved oxygen. River water was collected from the River Avon at Saltford (West of Bath UK), collected during September 2011. Amphetamine, present at 475 ng/L, decreased in concentration to 120 and 0 ng/L in 8 days using river microcosm bioreactors with and without sediment, respectively, maintained under light conditions at pH 8.3, 28.5 deg C and 7.1 mg/L dissolved oxygen. River water was collected from the River Avon at Saltford (West of Bath UK), collected during September 2011(1).
[(1) Bagnall J et al; Water Res 47: 5708-18 (2013)] **PEER REVIEWED**


Environmental Abiotic Degradation:


The rate constant for the vapor-phase reaction of amphetamine with photochemically-produced hydroxyl radicals has been estimated as 4.9X10-11 cu cm/molecule-sec at 25 deg C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Amphetamine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Amphetamine, present at 820 ng/L, showed no decrease in concentration over 15 days using river microcosm abiotic reactors with and without sediment, respectively, maintained under light conditions at pH 9.3, 29 deg C and 9.0 mg/L dissolved oxygen. River water was from the River Avon at Saltford (West of Bath UK), collected during September 2011(3). Amphetamine does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
[(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990) (3) Bagnall J et al; Water Res 47: 5708-18 (2013)] **PEER REVIEWED**


Environmental Bioconcentration:


An estimated BCF of 7 was calculated in fish for amphetamine(SRC), using a log Kow of 1.76(1) and a regression-derived equation(2). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
[(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 61 (1995) (2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 27, 2015: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm/ (3) Franke C et al; Chemosphere 29: 1501-14 (1994)] **PEER REVIEWED**


Soil Adsorption/Mobility:


Using a structure estimation method based on molecular connectivity indices(1), the Koc of amphetamine can be estimated to be 760(SRC). According to a classification scheme(2), this estimated Koc value suggests that amphetamine is expected to have low mobility in soil. The pKa of amphetamine is 10.13(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
[(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 27, 2015: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm (2) Swann RL et al; Res Rev 85: 17-28 (1983) (3) Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965) (4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)] **PEER REVIEWED**


Volatilization from Water/Soil:


A pKa of 10.13(1) indicates amphetamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water or moist soil surfaces is not expected to be an important fate process(SRC). Amphetamine has a low vapor pressure of 0.24 mm Hg(2) and exists as a liquid under environmental conditions; therefore, amphetamine may volatilize from dry soil(SRC).
[(1) Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965) (2) Lawrence AH et al; Can J Chem 62: 1886-88 (1984)] **PEER REVIEWED**


Environmental Water Concentrations:


DRINKING WATER: Amphetamine was present at a 2% frequency (mean concentration was below the limit of quantitation of 0.8 ng/L) with a maximum concentration of 1.7 ng/L using fifty samples of tap water from 43 cities in Spain, sampled from fall 2008 to summer 2009. A maximum concentration of 0.6 ng/L (4% frequency) was reported for 26 samples collected from Europe, Japan and Latin America(1). Amphetamine was not detected in finished drinking water from a treatment plant on the Llobregat River in northeast Spain, monitored from January 2007 to June 2007(2).
[(1) Rosa Boleda M et al; Chemosphere 84: 1601-7 (2011) (2) Huerta-Fontela M et al; Environ Sci Technol 42(48): 6809-16 (2008)] **PEER REVIEWED**

SURFACE WATER: Amphetamine was not detected in river water samples from the Llobregat River in northeast Spain and the tributary, Cardener River and Rubi Creek sampled in January, March and May 2007. An estimated load of 4 g/day during January was calculated for the tributary Anoia River(1). Amphetamine estimated loadings of 0.08, 8, 7, 2 and 0.08 g/day were calculated for spring 2006, summer, 2006, fall 2006, winter 2006/2007 and spring 2007, respectively, in samples from the Llobregat River collected near a drinking water plant intake(12). The compound was detected at a mean concentration of 6.8 ng/L (range 1.6-12.1 ng/L; 7% of 28 samples positive) in surface water samples from the Ebro River Basin, Spain, sampled in October 2007 and July 2008(2). Amphetamine was not detected in the Jarama and Manzanares Rivers of the Madrid Region, Spain, sampled in February and March, 2012(3). Global analysis pf freshwater ecosystems reveals that amphetamine is present at a mean concentration of 10.3 ng/L with a mean detection frequency of 29.7%(4).
[(1) Huerta-Fontela M et al; Environ Sci Technol 42(48): 6809-16 (2008) (2) Postigo C et al; Environ Int 36(1): 75-84 (2010) (3) Mendoza A et al; Chemosphere 95: 247-55 (2014) (4) Hughes SR et al; Environ Sci Technol 47: 661-77 (2013)] **PEER REVIEWED**


Effluent Concentrations:


Amphetamine was present at an average loading rate of 114 and <10 g/day in influent and effluent, respectively, collected from a wastewater treatment plant in conjunction with a US major sporting event (National Football League's Super Bowl). Non-event loadings were 125 and <10 g/day(1). The compound was detected at a mean concentration of 148.0 ng/L (range 3.3-6640 ng/L; 93% of 14 samples positive) in influent sewage samples from the Ebro River Basin, Spain, sampled in October 2007 and July 2008. A median concentration of 25.7 ng/L (range 0.5-7.6 ng/L; 36% of 14 samples positive) was reported for effluent samples(2).
[(1) Gerrity D et al: Water Res 45: 5399-11 (2011) (2) Postigo C et al; Environ Int 36(1): 75-84 (2010)] **PEER REVIEWED**


Milk Concentrations:


The drug is concentrated in human milk. /From Table 2/
[Report of the American Academy of Pediatrics Committee on Drugs in Pediatrics 93 (1): 138 (1994)] **PEER REVIEWED**

Amphetamine readily passes into and is concentrated in breast milk.
[Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 84-6] **PEER REVIEWED**


Other Environmental Concentrations:


Occupational exposure to amphetamine may occur through inhalation and dermal contact with this compound at workplaces where amphetamine is produced or used. Monitoring data indicate that the general population may be exposed to amphetamine via ingestion of contaminated water. Exposure to amphetamine among the general population will be by direct medical treatment and also occurs among those abusing this drug. (SRC)
**PEER REVIEWED**


Environmental Standards & Regulations:


CERCLA Reportable Quantities:


Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Amphetamine is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 1,000 lbs.
[40 CFR 355 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of November 24, 2015: http://www.ecfr.gov **PEER REVIEWED**


FDA Requirements:


The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including amphetamine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Amphetamine sulfate/
[DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of September 30, 2015: http://www.fda.gov/cder/ob/ **PEER REVIEWED**

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including amphetamine aspartate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Amphetamine aspartate/
[DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of September 30, 2015: http://www.fda.gov/cder/ob/ **PEER REVIEWED**

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... (d) Stimulants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous system: Amphetamine, its salts, optical isomers, and salts of its optical isomers (DEA Code Number: 1100) is included on this list. /Amphetamine, its salts, optical isomers, and salts of its optical isomers/
[21 CFR 1308.12(d) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 7, 2015: http://www.ecfr.gov **PEER REVIEWED**


Chemical/Physical Properties:


Molecular Formula:


C9-H13-N
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**


Molecular Weight:


135.206
[Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-456] **PEER REVIEWED**


Color/Form:


Mobile liquid
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**

Colorless, volatile liquid
[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 75] **PEER REVIEWED**


Odor:


Amine odor
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**

Characteristic strong odor
[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 75] **PEER REVIEWED**


Taste:


Acrid, burning taste
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**

Slightly burning taste
[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 75] **PEER REVIEWED**


Boiling Point:


200-203 deg C at 760 mm Hg
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**


Density/Specific Gravity:


0.936 g/cu cm at 25 deg C
[Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-456] **PEER REVIEWED**


Dissociation Constants:


pKa = 10.13
[Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965)] **PEER REVIEWED**


Octanol/Water Partition Coefficient:


log Kow = 1.76
[Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 61] **PEER REVIEWED**


pH:


Aqueous solutions are alkaline to litmus
[American Conference of Governmental Industrial Hygienists. Documentation of the TLVs and BEIs with Other World Wide Occupational Exposure Values. 7th Ed. CD-ROM Cincinnati, OH 45240-1634 2013., p. 99] **PEER REVIEWED**


Solubilities:


In water, 2.8X10+4 mg/L at 25 deg C (est)
[US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm **PEER REVIEWED**

Sparingly soluble in water (1:50)
[McEvoy, G.K. (ed.). American Hospital Formulary Service-Drug Information 19 98. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1998 (Plus Supplements)., p. 1905] **PEER REVIEWED**

Slightly soluble in water
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**

Readily sol in acids
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**

Slightly soluble inethyl ether; soluble in ethanol and chloroform
[Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-456] **PEER REVIEWED**


Spectral Properties:


Index of refraction: 1.518 at 26 deg C/D
[Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-456] **PEER REVIEWED**

Intense mass spectral peaks: 44 m/z, 65 m/z, 91 m/z, 120 m/z, 135 m/z
[Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 174] **PEER REVIEWED**

MASS: 42276 (NIST/EPA/MSDC Mass Spectral Database, 1990 version); 305 (National Bureau of Standards)
[Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. V1: 933] **PEER REVIEWED**


Vapor Pressure:


0.24 Torr /mm Hg/ at 20 deg C
[Lawrence AH et al; Can J Chem 62: 1886-88 (1984)] **PEER REVIEWED**


Other Chemical/Physical Properties:


Volatilizes slowly at room temp
[Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 99] **PEER REVIEWED**

Crystals; bitter taste; sinters at about 150 deg C; decomposes around 300 deg C; pH of 10% solution is about 4.6. More soluble in water than amphetamine sulfate; slightly soluble in alcohol; practically insoluble in benzene, chloroform, ether /Amphetamine phosphate/
[Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 99] **PEER REVIEWED**

Crystals; slightly bitter taste followed by sensation of numbness; MP above 300 deg C (decomposes); solution of 1 g/10 mL water has pH 5-6; 1 part dissolves in 8.8 parts water, 515 parts 95% alcohol /Amphetamine sulfate/
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**

MASS: 20962 (NIST/EPA/MSDC Mass Spectral Database, 1990 version); IR: 2:673E (Aldermaston, Eight Peak Index of Mass Spectra U.K.) /N-Methylbenzeneethanamine/
[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V1: 934] **PEER REVIEWED**

IR: 2:660B (Aldermaston, Eight Peak Index of Mass Spectra U.K.) /4-Methylbenzeneethanamine/
[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V1: 934] **PEER REVIEWED**

MASS: 90173 (NIST/EPA/MSDC Mass Spectral Database, 1990 version) /beta-Methylbenzeneethanamine/
[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V1: 934] **PEER REVIEWED**

MASS: 305 (National Bureau of Standards); IR: 2:673F (Aldermaston, Eight Peak Index of Mass Spectra U.K.) /alpha-Methylbenzeneethanamine/
[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V1: 934] **PEER REVIEWED**

Henry's Law constant = 1.08X10-6 atm-cu m/mol at 25 deg C (est)
[US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm **PEER REVIEWED**

Hydroxy radical reaction rate constant = 4.94X10-11 cu cm/molec-sec at 25 deg C (est)
[US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm **PEER REVIEWED**


Chemical Safety & Handling:


Globally Harmonized System:


The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) developed by the United Nations Economic Commission for Europe (UNECE) is an internationally-harmonized system to address the handling, transport, use, and disposal of chemicals while protecting human health and the environment. GHS is being implemented globally including by U.S. government agencies. The information in this section addresses basic label elements of GHS and is not all-inclusive. For more GHS information including a more detailed explanation of the codes and statements go to: http://www.unece.org/trans/danger/publi/ghs/ghs_welcome_e.htmlNOINDEX> **PEER REVIEWED**
**PEER REVIEWED**

GHS Classification in accordance with 29 CFR 1910 (OSHA HCS)

GHS Classification Category Hazard ID
Flammable liquids 2 H225
Acute toxicity, Oral 3 H301
Acute toxicity, Inhalation 3 H331
Acute toxicity, Dermal 3 H311
Specific target organ toxicity - single exposure 1 H370

[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**

Signal word: Dange
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**

Hazard statements

Hazard ID Statement
H225 Highly flammable liquid and vapour.
H301 + H311 + H331 Toxic if swallowed, in contact with skin or if inhaled
H370 Causes damage to organs.

[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**

Precautionary statements

Precautionary ID Statement
P210 Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P233 Keep container tightly closed
P240 Ground/bond container and receiving equipment.
P241 Use explosion-proof electrical/ ventilating/ lighting/ equipment.
P242 Use only non-sparking tools.
P243 Take precautionary measures against static discharge.
P260 Do not breathe dust/ fume/ gas/ mist/ vapours/ spray.
P264 Wash skin thoroughly after handling
P270 Do not eat, drink or smoke when using this product.
P271 Use only outdoors or in a well-ventilated area
P280 Wear protective gloves/ protective clothing/ eye protection/ face protection.
P301 + P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/ physician.
P303 + P361 + P353 IF ON SKIN (or hair): Remove/ Take off immediately all contaminated clothing. Rinse skin with water/ shower.
P304 + P340 IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P307 + P311 IF exposed: Call a POISON CENTER or doctor/ physician.
P322 Specific measures (see supplemental first aid instructions on this label).
P330 Rinse mouth.
P361 Remove/Take off immediately all contaminated clothing.
P363 Wash contaminated clothing before reuse.
P370 + P378 In case of fire: Use dry sand, dry chemical or alcohol-resistant foam for extinction.
P403 + P233 Store in a well-ventilated place. Keep container tightly closed.
P403 + P235 Store in a well-ventilated place. Keep cool.
P405 Store locked up.
P501 Dispose of contents/ container to an approved waste disposal plant.

[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**


Flash Point:


</= 100 deg C
[Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 213] **PEER REVIEWED**


Fire Fighting Procedures:


Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**


Hazardous Reactivities & Incompatibilities:


Incompatible materials: Acids, Oxidizing agents, Alkali metals, Strong oxidizing agents, Strong acids, Acid chlorides, Acid anhydrides, Reducing agents, Strong reducing agents, Phosphorus halides
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**


Hazardous Decomposition:


When heated to decomposition it emits toxic fumes of nitroxides.
[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 245] **PEER REVIEWED**


Protective Equipment & Clothing:


Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**

Body Protection: Complete suit protecting against chemicals, Flame retardant antistatic protective clothing., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**

Skin protection: Handle with gloves.
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**

Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**


Preventive Measures:


Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**

Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Use explosion-proof equipment.Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge.
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**


Stability/Shelf Life:


Stable under recommended storage conditions.
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**


Storage Conditions:


Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature -20 deg C
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**


Cleanup Methods:


ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to form explosive concentrations. Vapours can accumulate in low areas.; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.; Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.
[Sigma-Aldrich; Material Safety Data Sheet for (+/-)-Amphetamine solution, Product Number: A-007, Version 5.4 (Revision Date 05/05/2015). Available from, as of November 23, 2015: http://www.sigmaaldrich.com/safety-center.html **PEER REVIEWED**


Disposal Methods:


SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
**PEER REVIEWED**

Dissolve or mix material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. All federal, state, and local environmental regulations must be observed.
[Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 214] **PEER REVIEWED**


Manufacturing/Use Information:


Uses:


MEDICATION (VET)   (See also: Therapeutic Uses)
**PEER REVIEWED**

MEDICATION   (See also: Therapeutic Uses)
**PEER REVIEWED**

Amphetamine, its salts, optical isomers, and salts of its optical isomers (DEA Code Number: 1100) are Schedule II controlled substances. /Amphetamine, its salts, optical isomers, and salts of its optical isomers/
[21 CFR 1308.12(d) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 7, 2015: http://www.ecfr.gov **PEER REVIEWED**

Schedule II Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; and (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.
[US Department of Justice/Office of Diversion Control; Schedule of Controlled Substances. Available from, as of October 7, 2015: http://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm **PEER REVIEWED**

Amphetamines have been used in sports ... as "energy" chemicals. Athletes trying to achieve the "competitive edge" may use amphetamines to increase their sports performances, especially in track and field, football, and swimming. The use of amphetamines ... has been banned by the International Olympic Committee (IOC), the National Collegiate Athletic Association (NCAA) and most professioinal sport organizations. /Amphetamines/
[Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 84-1] **PEER REVIEWED**

Adrenergic Agents; Adrenergic Uptake Inhibitors; Central Nervous System Stimulants; Dopamine Agents; Dopamine Uptake Inhibitors; Sympathomimetics
[National Library of Medicine's Medical Subject Headings. Amphetamine. Online file (MeSH, 2015). Available from, as of November 23, 2015: https://www.nlm.nih.gov/mesh/2015/mesh_browser/MBrowser.html] **PEER REVIEWED**


Manufacturers:


DailyMed lists 55 formulators for Amphetamine.
[US NLM; DailyMed. Current Medical Information. US Natl Lib Med, Natl Inst Health, Health Human Serv. Available from, as of Oct 27, 2015: http://dailymed.nlm.nih.gov/dailymed/about.cfm **PEER REVIEWED**


Methods of Manufacturing:


Amphetamine is prepared by treating phenylacetone with formic acid and ammonia under the Leuckart-Wallach conditions.
[Houlihan WJ; Anti-Obesity Drugs. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2015). NY, NY: John Wiley & Sons. Online Posting Date: June 15, 2000] **PEER REVIEWED**

Preparation: Goggin, USA patent 2507468 (1950 to Clarke & Clarke) /Amphetamine phosphate/
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**

Preparation: ... F. P. Nabenhauer, USA patent 1921424 (1933 to SK & F).
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 99] **PEER REVIEWED**

Phenylacetone + hydroxylamine sulphate (oxime formation/hydrogenation)
[Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 84] **PEER REVIEWED**


General Manufacturing Information:


Amphetamine, the racemic mixture of levo- and dextroamphetamine ...
[Briggs, G.G, R.K. Freeman, S.J. Yaffe. A Reference Guide to Fetal and Neonatal Risk. Drugs in Pregnancy and Lactation. 4th ed. Baltimore, MD: Williams & Wilkins 1994., p. 49] **PEER REVIEWED**

Amphetamine is the prototype of a class of noncatecholamine compounds that produce strong CNS stimulation.
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 340] **PEER REVIEWED**

The illicit manufacture, trafficking, and abuse of amphetamine increased during 1988 after remaining relatively stable during the previous 4 years. /The highest number of seizures/ occured in the Dallas Field Division. The second highest number of seizures occurred in the Houston Field Division.
[National Narcotics Intelligence Consumers Committee (NNICC); NNICC Report 1988, The Supply of Illicit Drugs to the USA p.56 (1989)] **PEER REVIEWED**

Manufacture is restricted in most countries.
[Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 84] **PEER REVIEWED**


Formulations/Preparations:


Oral: amphetamine sulfate tablets, 5 mg, 10 mg, Evekeo. /Amphetamine sulfate/
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

... Heroin-amphetamine ("poor man's speedball") combinations.
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 342] **PEER REVIEWED**

Amphetamine Sulfate Combination Preparations

Route of Administration Dosage Form Strength Brand or Generic Name (Manufacturer)
Oral Capsules, extended-release 5 mg total amphetamine (as 1.25 mg, with Amphetamine Asparate 1.25 mg, Dextroamphetamine Saccharate 1.25 mg, and Dextroamphetamine Sulfate 1.25 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 10 mg total amphetamine (as 2.5 mg, with Amphetamine Aspartate 2.5 mg, Dextroamphetamine Saccharate 2.5 mg, and Dextroamphetamine Sulfate 2.5 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 15 mg total amphetamine (as 3.75 mg, with Amphetamine Aspartate 3.75 mg, Dextroamphetamine Saccharate 3.75 mg, and Dextroamphetamine Sulfate 3.75 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 20 mg total amphetamine (as 5 mg, with Amphetamine Aspartate 5 mg, Dextroamphetamine Saccharate 5 mg, and Dextroamphetamine Sulfate 5 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 25 mg total amphetamine (as 6.25 mg, with Amphetamine Aspartate 6.25 mg, Dextroamphetamine Saccharate 6.25 mg, and Dextroamphetamine Sulfate 6.25 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 30 mg total amphetamine (as 7.5 mg, with Amphetamine Aspartate 7.5 mg, Dextroamphetamine Saccharate 7.5 mg, and Dextroamphetamine Sulfate 7.5 mg) Adderall XR, C-II (Shire)
Oral Tablets 5 mg total amphetamine (as 1.25 mg, with Amphetamine Aspartate 1.25 mg, Dextroamphetamine Saccharate 1.25 mg, and Dextroamphetamine Sulfate 1.25 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 5 mg total amphetamine (as 1.25 mg, with Amphetamine Aspartate 1.25 mg, Dextroamphetamine Saccharate 1.25 mg, and Dextroamphetamine Sulfate 1.25 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 7.5 mg total amphetamine (as 1.875 mg, with Amphetamine Aspartate 1.875 mg, Dextroamphetamine Saccharate 1.875 mg, and Dextroamphetamine Sulfate 1.875 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 7.5 mg total amphetamine (as 1.875 mg, with Amphetamine Aspartate 1.875 mg, Dextroamphetamine Saccharate 1.875 mg, and Dextroamphetamine Sulfate 1.875 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 10 mg total amphetamine (as 2.5 mg, with Amphetamine Aspartate 2.5 mg, Dextroamphetamine Saccharate 2.5 mg, and Dextroamphetamine Sulfate 2.5 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 10 mg total amphetamine (as 2.5 mg, with Amphetamine Aspartate 2.5 mg, Dextroamphetamine Saccharate 2.5 mg, and Dextroamphetamine Sulfate 2.5 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 12.5 mg total amphetamine (as 3.125 mg, with Amphetamine Aspartate 3.125 mg, Dextroamphetamine Saccharate 3.125 mg, and Dextroamphetamine Sulfate 3.125 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 12.5 mg total amphetamine (as 3.125 mg, with Amphetamine Aspartate 3.125 mg, Dextroamphetamine Saccharate 3.125 mg, and Dextroamphetamine Sulfate 3.125 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 15 mg total amphetamine (as 3.75 mg, with Amphetamine Aspartate 3.75 mg, Dextroamphetamine Saccharate 3.75 mg, and Dextroamphetamine Sulfate 3.75 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 15 mg total amphetamine (as 3.75 mg, with Amphetamine Aspartate 3.75 mg, Dextroamphetamine Saccharate 3.75 mg, and Dextroamphetamine Sulfate 3.75 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 20 mg total amphetamine (as 5 mg, with Amphetamine Aspartate 5 mg, Dextroamphetamine Saccharate 5 mg, and Dextroamphetamine Sulfate 5 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 20 mg total amphetamine (as 5 mg, with Amphetamine Aspartate 5 mg, Dextroamphetamine Saccharate 5 mg, and Dextroamphetamine Sulfate 5 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 30 mg total amphetamine (as 7.5 mg, with Amphetamine Aspartate 7.5 mg, Dextroamphetamine Saccharate 7.5 mg, and Dextroamphetamine Sulfate 7.5 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 30 mg total amphetamine (as 7.5 mg, with Amphetamine Aspartate 7.5 mg, Dextroamphetamine Saccharate 7.5 mg, and Dextroamphetamine Sulfate 7.5 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)

[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2532] **PEER REVIEWED**

Common street names: Bennies, Black Beauties, Crank, Ice, Speed, and Uppers.
[USDOJ/DEA; Drugs of Abuse - A DEA Resource Guide p.46 (2015 edition). Available from, as of April 20, 2016: http://www.dea.gov/pr/multimedia-library/publications/drug_of_abuse.pdf#page=41 **PEER REVIEWED**


Impurities:


Di(1-phenylisopropyl)formamide is a by-product in the Leuckart synthesis of N-formylamphetamine, which is a reaction precursor to illegally produced dl-amphetamine. Side reactions and incomplete conversions lead to a variety of impurities and intermediate products, including benzyl methyl ketone, dibenzyl ketone, formamide, formic acid, methylamine, N,N-dimethylamphetamine, N-formylamphetamine, di(1-fenylisopropyl)amine, benzylamine, and several pyrimidine, pyridine, and pyridone compounds. Analysis of street samples suggests that amphetamines may be present in as little as 60% of purported samples. These illicit drugs contain varying amt of phencyclidine, LSD, STP, cocaine, atropine, mescaline, strychnine, and adulterants (eg, cornstarch, maltose, lactose, magnesium silicate, quinine, fibrous material).
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 627] **PEER REVIEWED**


Laboratory Methods:


Clinical Laboratory Methods:


An alternate to type C procedure (immunoassay) is avail for the direct analysis of a biological specimen (urine). Immunoassay of drugs is based on classical immunochemical procedures & utilizes an antigen-antibody reaction as an analytical tool. The reagents for the enzyme multiplied immunoassay technique (emit) used for the analysis of amphetamine in urine is avail commercially. The sensitivity of the EMIT for the analysis of amphetamine is 1.0 ug/mL. The reagents for the radioimmunoassay (ria) procedure used for the analysis of amphetamine are avail commercially. The sensitivity of RIA for amphetamine is 0.1 ug/mL.
[Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 22] **PEER REVIEWED**

A method of acetylating amphetamines quickly to permit rapid analysis by gas chromatography/mass spectrometry is presented. Amphetamine, methamphetamine, methylenedioxyamphetamine, & mescaline were acetylated with trifluoracetic anhydride in the presence of mercuric trifluoracetate as a catalyst. The reagent can acetylate the amine directly in the form of free base or salt. Slightly varying procedures were used, depending on whether the drugs were in solid form or were obtained in organic fluids such as urine. Samples were analyzed on a gas chromatography/mass spectrometry with an electron impact source. Advantages of this method of analysis are: rapidity, no previous cleanup to remove adulterants, & detection at the picomole level.
[WU A; CLIN TOXICOL 8 (2): 225-32 (1975)] **PEER REVIEWED** PubMed Abstract

When using capillary gas chromatography with nitrogen-specific detection for rapid screening of drugs, to overcome problems associated with the use of retention indices based on homologous series determined with nitrogen-specific detectors, a retention indices reference system was developed based on molecular masses and retention times of nitrogen-containing compounds. The standards chosen are readily available in highly purified form and can be detected by the unmodified nitrogen-specific detector. By using temperature programming, a linear relationship can be obtained between the molecular masses of standards and their retention times. Used in conjunction with microcomputer data handling, this screening system is rugged and reliable, operating 22 hr/day. Using the present method the retention time in min for amphetamine standard was 3.340 on a DB-1 column, and 1.295 on a DB-17 column with retention indices of 1350 (initial temperature 120 deg C for 1 min, incr by 8 deg C/min and held for 22 min).
[Manca D et al; Clin Chem 35 (4): 601-7 (1989)] **PEER REVIEWED** PubMed Abstract

A multi-column system has been developed for automated analysis of basic drugs in urine. Two polymeric precolumns, containing PRP-1 and Aminex A-28, were used to isolate the drugs. A short reversed phase column, coupled to a 150 x 4.6 mm I.D. silica column, produced the analytical separation. Sample preparation consisted of dilution and centrifugation. The entire procedure required less than 30 min. Urine from healthy laboratory employees was spiked with amphetamine. Levels of 0.2 mg/l produced peaks that could be matched against stored spectra with a computerized library search program. The retention value k' for amphetamine on a 10 x 3.2 mm I.D. Aminex A-28 column was 0.1 at a phase ratio of from 0.1 to 0.7. The retention value k' for amphetamine was 2.5 for the fully automated four column system, for isocratic analysis on the reversed phase and silica columns only, and for isocratic analysis on the silica column only. 2.5 ug amphetamine added to 500 ul urine had a retention time of 10.43 + or - 0.012 min for 10 consecutive injections. When concn from 0.3 to 10 mg/l were analyzed, the slope of the regression line was 4.5X10-5 for amphetamine.
[Binder SR et al; J Chromatogr 473 (2): 325-41 (1989)] **PEER REVIEWED** PubMed Abstract

The use of a gas chromatography system equipped with dual flame ionization & nitrogen selective rubidium bead detectors in the identification of drugs is presented. With the method, drugs are chromatographed along with a caffeine std on a 3% ov-17 column programmed from 100 to 250 deg C at 4 deg/min. In addn to characterizing the drug in terms of retention time relative to caffeine, the drug can also be characterized by the ratio of the nitrogen/flame ionization detector response of the drug to the response of the caffeine std. The response index & relative retention time of 71 nitrogen containing drugs commonly encountered in forensic & toxicology applications are presented. The drugs analyzed incl amphetamine.
[BAKER JK; ANAL CHEM 49 (6): 906-8 (1977)] **PEER REVIEWED** PubMed Abstract

Thin layer chromatography- as basic drugs, amphetamines are extracted from alkaline urine by an organic solvent. This solvent may be evaporated to dryness & the residue thin-layer chromatographed. ... Amphetamine is present (procedure a). Amphetamine, amphetamine sulfate, amphetamine hydrochloride, & methamphetamine are determined by this procedure. ... Amphetamine can be detected in urine samples up to 24 hr after admin of a 10.0 mg therapeutic dose. The ninhydrin-phenylacetaldehyde spray test is used in this procedure and is sensitive to as little as 0.3 ug of amphetamine.
[Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 22] **PEER REVIEWED**

Gas chromatography. As basic drugs, amphetamines are extracted from alkaline urine by an organic solvent. ... Back-extraction of the organic solvent extract into an acid, the addn of base to make the acid extract basic once again, & reextraction with a small vol of organic solvent sufficiently cleans the specimen for gas-chromatographic analysis. Free amphetamine drugs are separated by a 10% apiezon-10% potassium hydroxide column. Further confirmation is obtained by reacting the amphetamine drugs with trichloroacetyl chloride to obtaiN amphetamine n-trichloroamide derivatives which are separated by a 3% ov-17 column. Amphetamine, amphetamine sulfate, methamphetamine hydrochloride, & methamphetamine in blood or urine are determined by this procedure. The method is sensitive to 0.1 ug/mL of ... methamphetamine. The quantitation is accurate to + or - 7%. Greater sensitivity may be obtained if an electron-capture detector is used instead of a flame ionization detector. This method of amphetamine analysis shows a coefficient of variation of 6.5% over the range of 0.025 to 5.0 ug/mL. Recoveries over the range 0.1 to 5.0 ug/mL are 60 to 65%. Below 0.1 ug/mL they gradually decrease to a value of 40 to 45% at o.025% ug/mL. Sensitivity is limited by the decreasing recovery & the presence of solvent impurities. If a sample is known to contain amphetamine, it can usually be quantitated in concn as low as 0.005 to 0.010 ug/mL. If the analysis must identify as well as quantitate amphetamine, then 0.015 to 0.020 ug/mL is a reasonable limit of sensitivity.
[Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 22] **PEER REVIEWED**

BACKGROUND: Conventional methods for analysis of drugs of abuse require multiple assays which can be both expensive and time-consuming. This work describes a novel, rapid, simple and sensitive method for the quantification of 14 illicit drugs and their metabolites in whole blood. Results/methodology: This method employed a rapid liquid-liquid sample extraction of whole blood followed by UPLC-MS/MS analysis. Calibration curves were validated for analysis of appropriate concentrations. Inter- and intra-assay variations were <14.8%. Deviation of accuracy was <14.9% from target concentration for each quality control level. CONCLUSION: This work described the development and the full validation of a precise, sensitive and accurate assay. After validation, this new assay was successfully applied to routine toxicological analysis.
[Feliu C et al; Bioanalysis 7 (20): 2685-700 (2015)] **PEER REVIEWED**

Nails (fingernails and toenails) are made of keratin. As the nail grows, substances incorporate into the keratin fibers where they can be detected 3-6 months after use. Samples are collected by clipping of 2-3 mm of nail from all fingers (100 mg). We present drug testing results from 10,349 nail samples collected from high-risk cases during a 3-year period of time. Samples were analyzed by validated analytical methods. The initial testing was performed mostly using enzyme-linked immunosorbent assay, but by liquid chromatography-tandem mass spectrometry (LC-MS-MS) as well. Presumptive positive samples were subjected to confirmatory testing with sample preparation procedures including washing, pulverizing, digestion and extraction optimized for each drug class. The total of 7,799 samples was analyzed for amphetamines. The concentrations ranged from 40 to 572,865 pg/mg (median, 100-3,687) for all amphetamine analytes. Amphetamine and methamphetamine were present in 14% of the samples, 22 samples were positive for 3,4-methylenedioxymethamphetamine (0.3%), 7 for methylenedioxyamphetamine (0.09%) and 4 for 3,4-methylenedioxy-N-ethylamphetamine (0.05%). Cocaine and related analytes were found in 5% samples (7,787 total), and the concentration range was 20-265,063 pg/mg (median 84-1,768). Opioids overall ranged from 40 to 118,229 pg/mg (median 123-830). The most prevalent opioid was oxycodone (15.1%) and hydrocodone (11.4%) compared with 1.0-3.6% for the others, including morphine, codeine, hydromorphone, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine and oxymorphone. Carboxy-?-9-tetrahydrocannabinol positivity rate was 18.1% (0.04-262 pg/mg, median 6.41). Out of 3,039 samples, 756 were positive (24.9%) for ethyl glucuronide (20-3,754 pg/mg, median 88). Other drugs found in nails included barbiturates, benzodiazepines, ketamine, meperidine, tramadol, zolpidem, propoxyphene, naltrexone and buprenorphine. Nail analyses have become a reliable way of determining the long-term use and abuse of drugs. Extraction techniques are simple and produce accurate and precise results. Sensitive analytical instrumentation, mainly LC-MS-MS, allows for detection of femtogram (10(-15) g) quantities of substances in nails. Samples were from a high-risk population, therefore the extraordinary positivity rate was observed.
[Shu I et al; J Anal Toxicol 39 (8): 624-8 (2015)] **PEER REVIEWED** PubMed Abstract

Some amphetamine (AMP) and ecstacy (MDMA) urine immunoassay (IA) kits are prone to false-positive results due to poor specificity of the antibody. We employed two techniques, high-resolution mass spectrometry (HRMS) and an in silico structure search, to identify compounds likely to cause false-positive results. Hundred false-positive IA specimens for AMP and/or MDMA were analyzed by an Agilent 6230 time-of-flight (TOF) mass spectrometer. Separately, SciFinder (Chemical Abstracts) was used as an in silico structure search to generate a library of compounds that are known to cross-react with AMP/MDMA IAs. Chemical formulas and exact masses of 145 structures were then compared against masses identified by TOF. Compounds known to have cross-reactivity with the IAs were identified in the structure-based search. The chemical formulas and exact masses of 145 structures (of 20 chemical formulas) were compared against masses identified by TOF. Urine analysis by HRMS correlates accurate mass with chemical formulae, but provides little information regarding compound structure. Structural data of targeted antigens can be utilized to correlate HRMS-derived chemical formulas with structural analogs.
[Marin SJ et al; J Anal Toxicol. 2015 Sep 4. pii: bkv101. [Epub ahead of print]] **PEER REVIEWED** PubMed Abstract Full text: PMC4731401

To assess whether analysis of oral fluid can be used to identify individual drivers with drug concentrations in blood above 25ng/mL for amphetamine and methamphetamine, 10ng/mL for cocaine and 1.0ng/mL for tetrahydrocannabinol (THC), which are the cut-off concentrations used in the European DRUID Project, by calculating the diagnostic accuracies when using the analytical cut-off concentrations in oral fluid as well as for the optimal cut-off concentrations. METHODS: Paired samples of whole blood and oral fluid collected with the Statsure SalivaSampler were obtained from 4080 drivers in four European countries and analysed for amphetamine, methamphetamine, cocaine and THC using GC-MS or LC-MS. The vast majority (89%) were random drivers not suspected of drug-impaired driving. Receiver-Operating Characteristic analysis was used to evaluate the analytical results. RESULTS: The prevalence of drug findings above the cut-off concentrations in blood was 1.3% for amphetamine, 1.0% for methamphetamine, 0.6% for cocaine and 1.3% for THC. The cut-off concentrations in oral fluid that gave the highest diagnostic accuracy were for amphetamine 130ng/mL (accuracy 99.8%), methamphetamine 280ng/mL (accuracy 99.9%), cocaine 570ng/mL (accuracy 99.6%), and THC 38ng/mL (accuracy 98.3%). The proportion of false positives were 0.2%, 0.1%, 0.1% and 0.9%; and the proportion of false negatives were 0.1%, 0.0%, 0.3% and 0.8%, respectively, when using those cut-offs. The positive predictive values were 87.9%, 92.9%, 84.6% and 35.7% for amphetamine, methamphetamine, cocaine and THC, respectively. CONCLUSIONS: Analysis of concentrations of illicit drugs in oral fluid could not be used to accurately identify drivers with drugs concentrations above the selected cut-offs in blood in a cohort of drivers with low prevalence of drugs.
[Gjerde H et al; Forensic Sci Int 256: 42-5 (2015)] **PEER REVIEWED** PubMed Abstract

Freely dissolved concentrations are considered to be the most relevant concentration in pharmacology and toxicology, as they represent the active concentration available for interaction with its surroundings. Here, a solid-phase microextraction (SPME) coating that combines octadecyl and propylsulfonic acid groups as strong cation exchange sites, known as C18/SCX or "mixed-mode" SPME, is used to measure freely dissolved concentrations of amitriptyline, amphetamine, diazepam and tramadol to different binding matrices, including bovine serum albumin (BSA), human serum albumin (HSA), human plasma and human whole blood. A potential confounding factor in binding studies is that proteins may sorb to the fiber coating leading to incorrect measurement of protein sorption or changes in uptake kinetics to the fiber coating. Sorption of bovine serum albumin (BSA) was observed and quantified using a Lowry assay. BSA binds to the C18/SCX fiber in small amounts, but large changes in uptake kinetics were not observed. All experiments were performed at equilibrium. In addition, however, the effect of depletion and non-equilibrium extraction on the estimation of protein binding affinities was also studied. Binding affinities to BSA and human serum albumin (HSA) were calculated as log KBSA or log KHSA. These values were very similar to reported literature values. Sampling at either equilibrium or non-equilibrium resulted in similar binding affinities. Furthermore, SPME fibers were used to measure freely dissolved concentrations in undiluted human plasma and whole blood. Analysis of SPME extracts could be performed using HPLC-UV or HPLC with fluorescence detection without prior clean-up of the samples. Measured bound fractions in plasma using this SPME approach were comparable to literature reference values. Bound fractions in whole blood were always higher than in plasma, due to red blood cell partitioning. This work shows the potential of SPME as sampling tool for freely dissolved concentrations, especially for highly protein-bound compounds. Conventional SPME coatings such as polyacrylate (PA) or polydimethylsiloxane (PDMS) might be lacking sensitivity when sampling the small neutral fraction of highly protein-bound positively charged compounds, but the C18/SCX fiber is able to sorb the charged species of organic cations, thereby improving sensitivity for these types of compounds.
[Peltenburg H et al; J Pharm Biomed Anal 115: 534-42 (2015)] **PEER REVIEWED** PubMed Abstract

In forensic toxicology, body fluids are important materials not only as alternatives to blood but also for investigation of postmortem drug redistributions and pharmaco-/toxicokinetic analysis; however, there are limited data on postmortem drug distributions in cerebrospinal fluid (CSF). The present study reviewed toxicological data of autopsy cases (n=103), in which drugs were detected in CSF using gas chromatography/mass spectrometry (GC/MS), to investigate drug concentrations in CSF, compared with blood and pericardial fluid (PCF) concentrations. Oral/injected amphetamines (n=23) showed similar CSF and blood/PCF concentrations with partly lower CSF concentrations (about x0.5-1.1). CSF concentrations of the venous anesthetic midazolam (n=7) were lower with poor correlations. Oral caffeine (n=15), acetaminophen (n=7), chlorpheniramine (n=6), dihydrocodeine (n=6), and phenobarbital (n=21) showed equivalent to lower CSF concentrations (about x0.2-1.2), compared with blood and PCF concentrations; however, CSF phenobarbital concentrations were high in a fatal intoxication case. CSF concentrations of phenothiazine derivatives (n=29) were markedly lower (about x0.1) than blood/PCF concentrations. The distribution of the local anesthetic lidocaine used in critical medical care (n=49) markedly varied by case. These findings suggest that CSF is useful in routine forensic toxicology as an alternative to blood as well as for investigating pharmaco-/toxicokinetics and postmortem redistributions.
[Tominaga M et al; Forensic Sci Int 254: 118-25 (2015)] **PEER REVIEWED** PubMed Abstract

The present study aimed to verify the prevalence of psychoactive drug use (amphetamines, methamphetamines, cannabinoids, cocaine, opioids and benzodiazepines) among military police officers in the state of Goias. Data were obtained from urine samples voluntarily provided by the officers participating in the study, who were informed of the study methods and signed a free and informed consent form. The samples were subject to screening analysis by immunochromatography (Multi-DrugOneStep Test), with positive tests confirmed by gas chromatography- mass spectrometry (GC-MS) and data analyzed by descriptive statistics. The results indicated the presence of the following drugs: amphetamines (0.33%), cannabinoids (0.67%) and benzodiazepines (1.34%); 97.66% showed negative results. The positive cases were distributed as follows: benzodiazepines (57.1%); cannabinoids (28.6%) and amphetamines (14.3%). In conclusion, the detection of psychoactive substances in voluntary sampling of military police officers indicates the need to implement drug testing among active military officers and preventive public policies aimed at eliminating the abusive consumption of psychotropic drugs.
[Costa SH et al; Cien Saude Colet 20 (6): 1843-9 (2015)] **PEER REVIEWED** PubMed Abstract


Analytic Laboratory Methods:


AOAC Method 954.14. Amphetamine drugs. Stereochemical composition.
[Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 520] **PEER REVIEWED**

AOAC Method 972.47. Amphetamine in drugs. Gas chromatographic method. /d-Amphetamine sulfate; dl-amphetamine sulfate/
[Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 520] **PEER REVIEWED**

AOAC Method 974.39. Amphetamine in presence of antihistamines and barbituates and other drugs.
[Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 521] **PEER REVIEWED**

AOAC Method 960.55. Sympathomimetic drugs. Microchemical tests. /dl-Amphetamine/
[Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 536] **PEER REVIEWED**

AOAC Method 988.28. Enantionmers of amphetamine in bulk drugs, syrups, and capsules. Liquid chromatographic method. /d-Amphetamine sulfate; dl-amphetamine sulfate/
[Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 622] **PEER REVIEWED**

Use of electron capture negative ion chem ionization mass spectrometry in analyzing amphetamine, amphetamine hydrochloride, dopamine hydrochloride, & tetrahydrocannabinol is discussed. Data are provided which define the lowest level of sample detection achieved & furnish experimental details on the operation of a negative ion chemical ionization quadrupole mass spectrometer. Detection at the attomole (10-18) level by conventional gc/MS selected ion monitoring methodology is reported.
[HUNT DF, CROW FW; ANAL CHEM 50 (11): 1781-4 (1978)] **PEER REVIEWED**

A GLC procedure was developed to determine amphetamine salts in tablets & capsules. Amphetamine was extracted from the solid matrix with dilute hydrochloric acid & reacted with cyclohexanone in a strongly basic aqueous methanolic solution. The schiff base reaction product was extracted with hexane for GLC determination. Reaction time & optimum conditions were studied. Phenethylamine was used as an internal std. Results compared favorably with those obtained by using USP methods.
[CLARK CC; J ASSOC OFF ANAL CHEM 58 (11): 1174-7 (1975)] **PEER REVIEWED** PubMed Abstract

A method of acetylating amphetamines quickly to permit rapid analysis by gas chromatography/mass spectrometry is presented. Amphetamine, methamphetamine, methylenedioxyamphetamine, & mescaline were acetylated with trifluoracetic anhydride in the presence of mercuric trifluoracetate as a catalyst. The reagent can acetylate the amine directly in the form of free base or salt. Slightly varying procedures were used, depending on whether the drugs were in solid form or were obtained in organic fluids such as urine. Samples were analyzed on a gas chromatography/mass spectrometry with an electron impact source. Advantages of this method of analysis are: rapidity, no previous cleanup to remove adulterants, & detection at the picomole level.
[WU A; CLIN TOXICOL 8 (2): 225-32 (1975)] **PEER REVIEWED** PubMed Abstract

Amphetamines & related arylalkylamines were converted in high yields to the corresponding 4-nitrobenzamides to enhance their UV detectability. The derivatives are chemically stable & can be rapidly prepared & purified by extraction. These amides were separated by reverse phase high pressure liquid chromatography using an isocratic solvent system. The derivatives exhibited excellent gas chromatographic properties on 3% ov-17 liquid phase. The amides are much less volatile than the parent amines requiring column temperatures in excess of 240 deg C for elution. The derivatives were thermally stable at these temperatures.
[CLARK CR ET AL; ANAL CHEM 49 (6): 912-5 (1977)] **PEER REVIEWED** PubMed Abstract

A comparison of fluorometric procedures for assay of amphetamine is presented.
[MEHTA AC, SCHULMAN SG; J PHARM SCI 63 (7): 1150-1 (1975)] **PEER REVIEWED**

The concentrations of 17 drugs of abuse, including cocaine, several amphetamines, opioid drugs, and 2 metabolites-benzoylecgonine, a metabolite of cocaine, and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine, a metabolite of methadone-were investigated in an urban watershed that is heavily impacted by discharges of municipal wastewater. The artificial sweetener sucralose was also monitored as a persistent tracer of contamination from municipal wastewater. Monitoring was conducted in a municipal wastewater treatment plant (WWTP) and at sites upstream and downstream of the WWTP discharge, as well as in a drinking water treatment plant (DWTP) located 19 km downstream of the WWTP discharge that withdraws raw water from the river. Drug concentrations were monitored with polar organic chemical integrative samplers deployed for 2 wk in the river and in the WWTP and DWTP. Several of the investigated compounds exhibited a decrease in concentration with distance downstream from the wastewater discharge into the river, but there was little attenuation of sucralose, cocaine, benzoylecgonine, morphine, acetylmorphine, acetylcodeine, and oxycodone. Heroin and methadone were not detected at any sample locations. Amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine, and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine were not detected in the samples collected at the drinking water intake. Many of the drugs of abuse were not removed effectively in the DWTP, including cocaine, benzoylecgonine, methylenedioxyamphetamine, ephedrine, and several prescription opioids, most probably because the DWTP was operating at or above its rated treatment capacity. These data indicate that there can be transport of drugs of abuse from wastewater sources into drinking water in urban watersheds.
[Rodayan A et al; Environ Toxicol Chem. 2015 Jul 18. doi: 10.1002/etc.3085. [Epub ahead of print]] **PEER REVIEWED** PubMed Abstract

BACKGROUND: Wastewater analysis is a new approach developed to estimate drug (of abuse) consumption in large communities, such as cities or even whole countries. AIMS: This paper presents data on the loads of amphetamine and methamphetamine measured in ten wastewater treatment plants in different parts of a German federal state. It provides an estimation of the intensity of the consumption and a comparison to other regions in Germany and Europe. METHODS: Consumption of amphetamine and methamphetamine was estimated by analysis of drug residues in composite 24 hr samples of wastewater after mechanical treatment over one week by liquid chromatography-high resolution tandem mass spectrometry. Samples were collected from the inlet of ten wastewater treatment plants (WWTP) in the federal state of Saarland, representing bigger cities (>200,000 inhabitants), medium sized cities (>50,000 inhabitants), small cities (>25,000 inhabitants), and villages (<25,000 inhabitants). In each WWTP, samples were taken daily for seven consecutive days in July 2014. RESULTS: We observed differences of amphetamine versus methamphetamine loads (expressed as mg/day/1000 inhabitants): Amphetamine loads were much higher in all tested WWTPs indicating a low prevalence of methamphetamine abuse in the federal state of Saarland at the tested period. These findings are in line with previous reports about the distribution of amphetamine and methamphetamine in Germany and Europe. CONCLUSIONS: The approach confirms that wastewater analysis can provide valuable data about the abuse pattern of drugs of abuse in cities and larger areas. It can be useful for planning interventions aimed at specific areas and substances.
[Meyer MR et al; Drug Alcohol Depend 156: 311-4 (2015)] **PEER REVIEWED**

A method was developed for the analysis of amphetamines and cocaine (Coc) in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Seven stimulant-type drugs and metabolites were analyzed. These drugs included amphetamine (Amp), methamphetamine (Meth), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), Coc and benzoylecgonine (BE, the major metabolite of Coc). These drugs were chosen because of their widespread use. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. Samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain Amp, Meth, MDMA, Coc and BE. The concentrations of Amp and BE significantly rose in the university wastewater during football games.
[Gul W et al; J Anal Toxicol. 2015 Nov 4. pii: bkv124. [Epub ahead of print]] **PEER REVIEWED** PubMed Abstract

There is currently a gap in on-site drug of abuse monitoring. Current detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. While remote laboratories then may provide confirmation and quantitative assessment of a presumptive positive, this instrumentation is expensive and decoupled from the initial sampling making the current drug-screening program inefficient and costly. The authors applied a noninvasive oral fluid sampling approach integrated with the in-development chip-based Programmable bio-nano-chip (p-BNC) platform for the detection of drugs of abuse. METHOD: The p-BNC assay methodology was applied for the detection of tetrahydrocannabinol, morphine, amphetamine, methamphetamine, cocaine, methadone and benzodiazepines, initially using spiked buffered samples and, ultimately, using oral fluid specimen collected from consented volunteers. RESULTS: Rapid (~10min), sensitive detection (~ng/mL) and quantitation of 12 drugs of abuse was demonstrated on the p-BNC platform. Furthermore, the system provided visibility to time-course of select drug and metabolite profiles in oral fluids; for the drug cocaine, three regions of slope were observed that, when combined with concentration measurements from this and prior impairment studies, information about cocaine-induced impairment may be revealed. CONCLUSIONS: This chip-based p-BNC detection modality has significant potential to be used in the future by law enforcement officers for roadside drug testing and to serve a variety of other settings, including outpatient and inpatient drug rehabilitation centers, emergency rooms, prisons, schools, and in the workplace.
[Christodoulides N et al; Drug Alcohol Depend 153: 306-13 (2015)] **PEER REVIEWED** PubMed Abstract Full text: PMC4509839


Sampling Procedures:


Drug testing is an important clinical tool that is available to physicians who are assessing the effectiveness of drug treatment as well as patient compliance to the administered program. While urine has traditionally been the matrix of choice for drug monitoring, oral fluid, a filtrate of the blood, has shown great promise as an alternative matrix for such applications. Oral fluid collection can be accomplished without the need for highly trained medical staff through the use of a simple, noninvasive oral fluid collection device, which obtains an adequate sample in only a few minutes. There has been a significant amount of research performed on the use of oral fluid for forensic toxicology application; however, more studies assessing the use of oral fluid drug testing are required to validate its ability to achieve clinical drug monitoring goals. Testing for various drugs in oral fluid may yield a different result when compared to the same drugs in urine, requiring an assessment of the utility of oral fluid for such practices. The purpose of this study was to examine the application of oral fluid drug testing in patients undergoing buprenorphine treatment for opioid dependence. A retrospective analysis of drug testing results obtained from 6,928 patients (4,560 unobserved urine collections and 2,368 observed oral fluid collections) monitored for heroin metabolite, amphetamine, benzodiazepines, buprenorphine, tetrahydrocannabinol, cocaine, codeine, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone was completed. Results of this statistical exercise indicated that patients undergoing observed oral fluid collection tested positive more frequently than those unobserved urine collections for several illicit drugs and prescription medications targeted. Oral fluid was shown to detect illicit drug use as well as noncompliance in this patient population under the studied conditions more often than the urine specimens.
[Kunkel F et al; J Opioid Manag 11 (5): 435-42 (2015)] **PEER REVIEWED** PubMed Abstract


Special References:


Special Reports:


Johnston, L. D. et al; Monitoring the Future, National Survey Results on Drug Use: 1975-2014: Overview, key findings on adolescent drug use. Ann Arbor: Institute for Social Research, The University of Michigan.
[Available from, as of April 20, 2016: http://www.monitoringthefuture.org/pubs/monographs/mtf-overview2014.pdf

Caldwell J, Sever PS; Clin Pharmacol Ther 16 (10): 625-38 (1974). Pharmacology, metabolism, tolerance & manifestation of abuse of amphetamines, cocaine & lysergic acid diethylamide are reviewed.

DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability (1984) DHHS Pub No. (ADM)87-1332

DHHS/NIDA; Research Monograph Series 54: Mechanisms of Tolerance and Dependence (1984) DHHS Pub No. (ADM)88-1330

DHHS/NIDA; Research Monograph Series 56: Etiology of Drug Abuse: Implications for Prevention (1987) DHHS Pub No. (ADM)87-1335

DHHS/NIDA; Research Monograph Series 59: Current Research on the Consequences of Maternal Drug Abuse (1985) DHHS Pub No. (ADM)85-1400

DHHS/NIDA; Research Monograph Series 60: Prenatal Drug Exposure: Kinetics and Dynamics (1985) DHHS Pub No. (ADM)85-1413

DHHS/NIDA; Research Monograph Series 65: Woman and Drugs: A New Era for Research (1986) DHHS Pub No. (ADM)87-1447

DHHS/NIDA; Research Monograph Series 73: Urine Testing for Drugs of Abuse (1986) DHHS Pub No. (ADM)87-1481

DHHS/NIDA; Research Monograph Series 90: Problems of Drug Dependence 1988 (1988) DHHS Pub No. (ADM)89-1605

DHHS/NTP; Toxicology & Carcinogenesis Studies of dl-Amphetamine Sulfate in F344/N Rats and B6C3F1 Mice (Feed Studies) Technical Report Series No. 387 (1991) NIH Publication No. 91-2842


Synonyms and Identifiers:


Related HSDB Records:


3055 [DEXTROAMPHETAMINE] (analog)


Synonyms:


Adderall XR
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Adderall
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Actedron
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Adipan
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Allodene
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beta-Aminopropylbenzene
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(+-)-alpha-Methylbenzeneethanamine
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alpha-Methylphenethylamine
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(+-)-alpha-Methylphenethylamine
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(+-)-alpha-Methylphenylethylamine
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(+-)-Benzedrine
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(Phenylisopropyl)amine
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1-Methyl-2-phenylethylamine
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1-Phenyl-2-amino-propan
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1-Phenyl-2-aminopropane
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1-Phenyl-2-propylamine
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2-Amino-1-phenylpropane
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3-Amino-1-propylbenzene
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3-Phenyl-2-propylamine
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Associated Chemicals:


Amphetamine sulfate; 60-13-9
Amphetamine phosphate; 139-10-6
Amphetamine aspartate; 25333-81-7

Formulations/Preparations:


Oral: amphetamine sulfate tablets, 5 mg, 10 mg, Evekeo. /Amphetamine sulfate/
[NIH; DailyMed. Current Medication Information for EVEKEO- amphetamine sulfate tablet (Revised: November 2015). Available from, as of November 23, 2015: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb12811f-4cce-4010-aa48-d17c46ca1d3a **PEER REVIEWED**

... Heroin-amphetamine ("poor man's speedball") combinations.
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 342] **PEER REVIEWED**

Amphetamine Sulfate Combination Preparations

Route of Administration Dosage Form Strength Brand or Generic Name (Manufacturer)
Oral Capsules, extended-release 5 mg total amphetamine (as 1.25 mg, with Amphetamine Asparate 1.25 mg, Dextroamphetamine Saccharate 1.25 mg, and Dextroamphetamine Sulfate 1.25 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 10 mg total amphetamine (as 2.5 mg, with Amphetamine Aspartate 2.5 mg, Dextroamphetamine Saccharate 2.5 mg, and Dextroamphetamine Sulfate 2.5 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 15 mg total amphetamine (as 3.75 mg, with Amphetamine Aspartate 3.75 mg, Dextroamphetamine Saccharate 3.75 mg, and Dextroamphetamine Sulfate 3.75 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 20 mg total amphetamine (as 5 mg, with Amphetamine Aspartate 5 mg, Dextroamphetamine Saccharate 5 mg, and Dextroamphetamine Sulfate 5 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 25 mg total amphetamine (as 6.25 mg, with Amphetamine Aspartate 6.25 mg, Dextroamphetamine Saccharate 6.25 mg, and Dextroamphetamine Sulfate 6.25 mg) Adderall XR, C-II (Shire)
Oral Capsules, extended-release 30 mg total amphetamine (as 7.5 mg, with Amphetamine Aspartate 7.5 mg, Dextroamphetamine Saccharate 7.5 mg, and Dextroamphetamine Sulfate 7.5 mg) Adderall XR, C-II (Shire)
Oral Tablets 5 mg total amphetamine (as 1.25 mg, with Amphetamine Aspartate 1.25 mg, Dextroamphetamine Saccharate 1.25 mg, and Dextroamphetamine Sulfate 1.25 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 5 mg total amphetamine (as 1.25 mg, with Amphetamine Aspartate 1.25 mg, Dextroamphetamine Saccharate 1.25 mg, and Dextroamphetamine Sulfate 1.25 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 7.5 mg total amphetamine (as 1.875 mg, with Amphetamine Aspartate 1.875 mg, Dextroamphetamine Saccharate 1.875 mg, and Dextroamphetamine Sulfate 1.875 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 7.5 mg total amphetamine (as 1.875 mg, with Amphetamine Aspartate 1.875 mg, Dextroamphetamine Saccharate 1.875 mg, and Dextroamphetamine Sulfate 1.875 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 10 mg total amphetamine (as 2.5 mg, with Amphetamine Aspartate 2.5 mg, Dextroamphetamine Saccharate 2.5 mg, and Dextroamphetamine Sulfate 2.5 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 10 mg total amphetamine (as 2.5 mg, with Amphetamine Aspartate 2.5 mg, Dextroamphetamine Saccharate 2.5 mg, and Dextroamphetamine Sulfate 2.5 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 12.5 mg total amphetamine (as 3.125 mg, with Amphetamine Aspartate 3.125 mg, Dextroamphetamine Saccharate 3.125 mg, and Dextroamphetamine Sulfate 3.125 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 12.5 mg total amphetamine (as 3.125 mg, with Amphetamine Aspartate 3.125 mg, Dextroamphetamine Saccharate 3.125 mg, and Dextroamphetamine Sulfate 3.125 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 15 mg total amphetamine (as 3.75 mg, with Amphetamine Aspartate 3.75 mg, Dextroamphetamine Saccharate 3.75 mg, and Dextroamphetamine Sulfate 3.75 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 15 mg total amphetamine (as 3.75 mg, with Amphetamine Aspartate 3.75 mg, Dextroamphetamine Saccharate 3.75 mg, and Dextroamphetamine Sulfate 3.75 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 20 mg total amphetamine (as 5 mg, with Amphetamine Aspartate 5 mg, Dextroamphetamine Saccharate 5 mg, and Dextroamphetamine Sulfate 5 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 20 mg total amphetamine (as 5 mg, with Amphetamine Aspartate 5 mg, Dextroamphetamine Saccharate 5 mg, and Dextroamphetamine Sulfate 5 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Oral Tablets 30 mg total amphetamine (as 7.5 mg, with Amphetamine Aspartate 7.5 mg, Dextroamphetamine Saccharate 7.5 mg, and Dextroamphetamine Sulfate 7.5 mg) Adderall, C-II; double-scored (Shire)
Oral Tablets 30 mg total amphetamine (as 7.5 mg, with Amphetamine Aspartate 7.5 mg, Dextroamphetamine Saccharate 7.5 mg, and Dextroamphetamine Sulfate 7.5 mg) Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets, C-II; double-scored (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)

[American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2532] **PEER REVIEWED**

Common street names: Bennies, Black Beauties, Crank, Ice, Speed, and Uppers.
[USDOJ/DEA; Drugs of Abuse - A DEA Resource Guide p.46 (2015 edition). Available from, as of April 20, 2016: http://www.dea.gov/pr/multimedia-library/publications/drug_of_abuse.pdf#page=41 **PEER REVIEWED**


Administrative Information:


Hazardous Substances Databank Number:

3287

Last Revision Date:

20170414

Last Review Date:

Reviewed by SRP on 1/14/2016

Update History:


Complete Update on 2017-04-14, 62 fields added/edited/deleted
Field Update on 2008-10-01, 1 fields added/edited/deleted
Field Update on 2008-08-25, 1 fields added/edited/deleted
Field Update on 2008-05-19, 1 fields added/edited/deleted
Field Update on 2008-05-19, 1 fields added/edited/deleted
Field Update on 2008-05-19, 1 fields added/edited/deleted
Complete Update on 11/08/2002, 1 field added/edited/deleted.
Complete Update on 02/13/2002, 1 field added/edited/deleted.
Complete Update on 01/14/2002, 1 field added/edited/deleted.
Complete Update on 08/09/2001, 1 field added/edited/deleted.
Complete Update on 05/15/2001, 1 field added/edited/deleted.
Complete Update on 03/02/2000, 45 fields added/edited/deleted.
Field Update on 02/09/2000, 1 field added/edited/deleted.
Field Update on 02/08/2000, 1 field added/edited/deleted.
Field Update on 02/02/2000, 1 field added/edited/deleted.
Field Update on 09/21/1999, 1 field added/edited/deleted.
Field Update on 08/26/1999, 1 field added/edited/deleted.
Complete Update on 10/20/1998, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 02/27/1998, 1 field added/edited/deleted.
Complete Update on 10/26/1997, 1 field added/edited/deleted.
Complete Update on 09/17/1997, 1 field added/edited/deleted.
Complete Update on 05/09/1997, 1 field added/edited/deleted.
Complete Update on 03/17/1997, 2 fields added/edited/deleted.
Complete Update on 10/18/1996, 1 field added/edited/deleted.
Complete Update on 01/26/1996, 1 field added/edited/deleted.
Complete Update on 11/10/1995, 1 field added/edited/deleted.
Complete Update on 12/30/1994, 1 field added/edited/deleted.
Complete Update on 06/07/1994, 2 fields added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Complete Update on 08/27/1993, 1 field added/edited/deleted.
Field update on 12/29/1992, 1 field added/edited/deleted.
Complete Update on 12/03/1992, 1 field added/edited/deleted.
Complete Update on 09/03/1992, 2 fields added/edited/deleted.
Complete Update on 09/26/1991, 1 field added/edited/deleted.
Complete Update on 02/01/1991, 44 fields added/edited/deleted.
Express Update on 10/13/1989, 4 fields added/edited/deleted.
Express Update on 08/08/1989, 2 fields added/edited/deleted.
Complete Update on 01/04/1985
Created 19830401 by GCF