Semin Respir Crit Care Med 2002; 23(1): 027-036
DOI: 10.1055/s-2002-20586
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Amphetamine Toxicity

Suzanne R. White
  • Emergency Medicine and Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, and Children's Hospital of Michigan Regional Poison Control Center, Detroit, Michigan
Further Information

Publication History

Publication Date:
07 March 2002 (online)

ABSTRACT

Amphetamine abuse is widespread and associated with significant health risk. The most commonly encountered amphetamines are methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy), and the ephedra alkaloids. Although each of these harbors unique toxicity, they similarly impact the cardiovascular and neurological systems in overdose. Other serious complications associated with amphetamine abuse include severe hyperpyrexia and hyponatremia. Secondary conditions such as rhabdomyolysis, disseminated intravascular coagulation (DIC), gastrointestinal (GI) bleeding, hepatic necrosis, and renal failure are common, especially in those with hyperthermia. Chronic abuse poses risk of vasculitis, neuropsychiatric abnormalities, and cardiomyopathy. In addition, there is a growing body of evidence that even recreational abuse of methamphetamine and MDMA may produce long-lasting damage to dopaminergic and serotonergic neurons. Management principles include adequate sedation, aggressive cooling, and the use of titratable agents in the management of cardiovascular abnormalities.

REFERENCES

  • 1 Myerson A. Effect of benzedrine sulfate on mood and fatigue in normal and neurotic persons.  Arch Neurol Psychiatry . 1936;  36 816-822
  • 2 Heischober B, Derlet R W. Update on methamphetamine abuse.  West J Med . 1989;  151 70-71
  • 3 FDA Proposed Rules: Dietary Supplements Containing Ephedrine Alkaloids. Federal Register June 4, 1997 62(7): 30677-30724
  • 4 Lesch K P, Heils A, Riederer P. The role of neurotransporters in excitotoxicity, neuronal cell death, and other neurodegenrative processes.  J Mol Med . 1996;  74 365-78
  • 5 Leonarid E T, Azmitia E C. MDMA (ecstasy) inhibition of MAO type A and type B: comparisons with fenfluramine and fluoxetine (Prozac).  Neuropsychopharmacology . 1994;  10 231-238
  • 6 Liechti M E, Baumann C, Gamma A, Vollenweider F X. Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, ``Ecstasy'') are attenuated by the serotonin uptake inhibitor Citalopram.  Neuropsychopharmacol . 2000;  22 513-521
  • 7 Zalia E C, Parmly L F. Fatal amphetamine poisoning.  Arch Intern Med . 1963;  112 822-836
  • 8 Demirkiran M, Jankovic J, Dean J M. Ecstasy intoxication: an overlap between serotonin syndrome and neuroleptic malignant syndrome.  Clin Neuropharmacol . 1996;  19 157-164
  • 9 Rella J G, Nelson L S, Hoffman R S. Seven years of 3,4-methylenedioxymethamphetamine (MDMA) toxicity.  IJMT . 2000;  3(5) 28
  • 10 US FDA Center for Food Safety and Applied Nutrition. Office of Special Nutritionals SN/AEMS
  • 11 Haller C A, Benowitz N L. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids.  New Eng J Med . 2000;  343 1833-1838
  • 12 Theoharides T. Sudden death of a healthy college student related to ephedrine toxicity from a Ma Huang-containing drink.  J Clin Psychopharmacol . 1997;  17(5) 437-439
  • 13 Anonymous. Adverse events associated with ephedrine-containing products-Texas, December 1993-September 1995.  JAMA . 1996;  276(21) 1711-1712
  • 14 Backer R, Tautman D, Lowry S. Fatal ephedrine intoxication.  J Forensic Sciences . 1997;  42 157-159
  • 15 Gaultieri J, Harris C. Dilated cardiomyopathy in a heavy ephedrine abuser.  J Toxicol Clin Toxicol . 1996;  34 581-582
  • 16 Zahn K A, Li R L, Purssell R A. Cardiovascular toxicity after ingestion of ``herbal ecstacy''.  J Emerg Med . 1999;  17 289-291
  • 17 Bruno A, Nolte K B, Chapin J. Stroke associated with ephedrine use.  Neurology . 1993;  43 1313-1316
  • 18 Herrideg C F, Brook M F. Ephedrine psychosis.  BMJ . 1968;  2 160
  • 19 Capwell R R. Ephedrine-induced mania from an herbal diet supplement.  Am J Psychiatry . 1995;  152(4) 647
  • 20 Wooten M R, Khangure M S, Murphy M J. Intracerebral hemorrhage and vasculitis related to ephedrine abuse.  Ann Neurol . 1983;  13 337-340
  • 21 Adverse events with Ephedra and other botanical dietary supplements. FDA Medical Bulletin .  1994;  24 3
  • 22 Powell T. Ma-Huang strikes again: ephedrine nephrolithiasis.  Am J Kidney Dis . 1998;  32 153-159
  • 23 Catlin D H, Sekera M, Adelman D C. Erythroderma associated with ingestion of an herbal product.  Western J Med . 1993;  159(4) 491-493
  • 24 Nadir A, Agrawal S, King P D. Acute hepatitis associated with the use of a chinese herbal product, Ma Huang.  Am J Gastroenterol . 1996;  91 1436-1438
  • 25 Blumenthal M, King P. A review of the botany, chemistry, medicinal uses, safety concerns, and legal status of ephedra and its alkaloids.  Herbal Gram . 1995;  334 22-57
  • 26 Woods J D, Henry J A. Hyperpyrexia induced by 3,4-methylenedioxymethamphetamine (``Ecstasy'').  Lancet . 1992;  340 305
  • 27 Logan Ast C, Stickle B, O'Keefe N, Hewitson H. Survival following ``Ecstasy'' ingestion with a peak temperature of 42°C.  Anaesthesia . 1993;  48 1017-1018
  • 28 Kolecki P. Inadvertent methamphetamine poisoning in pediatric patients.  Ped Emerg Care . 1998;  14 385-387
  • 29 Weinmann W, Bohnert M. Lethal monointoxication by overdosage of MDEA.  Forensic Sci Int . 1998;  91(2) 91-101
  • 30 Hall A P. Ecstasy and the anaesthetist.  Br J Anaesth . 1997;  79 697-698
  • 31 Colado M I, Williams J L, Green A R. The hyperthermic and neurotoxic effects of ecstasy (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype.  Br J Pharmacol . 1995;  115 1281-1289
  • 32 Mas M, Farre M, de la Torre R. Cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetamine in humans.  J Pharmacol Exp Ther . 1999;  290 136-145
  • 33 Vollenweider F X, Gamma A, Liechti M, Huber T. Psychological and cardiovascular effects and short-term sequelae of MDMA (``ecstasy'') in MDMA-naïve healthy volunteers.  Neuropsychopharmacol . 1998;  19 241-251
  • 34 Ghuran A, Nolan J. Recreational drug misuse: issues for the cardiologist.  Heart . 2000;  83 627-633
  • 35 Davis G G, Swalwell C I. Acute aortic dissection and ruptured berry aneurysms associated with methamphetamine abuse.  J Forensic Med . 1994;  39 1481-1485
  • 36 Guharoy R, Medicis J, Chol S, Stalder B, Kusiowski K, Allen A. Methamphetamine overdose: experience with six cases.  Vet Hum Toxicol . 1999;  41(1) 28-30
  • 37 Furst S, Fallon S, Reznik G. Myocardial infarction after inhalation of methamphetamine.  N Engl J Med . 1990;  323 1147-1148
  • 38 Bashour T. Acute myocardial infarction resulting from amphetamine abuse: spasm thrombus interplay?.  Am Heart J . 1994;  128 1237-1238
  • 39 Citron B, Halperm M, McCarron M. Necrotising angiitis associated with drug abuse.  N Eng J Med . 1970;  283 1003-1011
  • 40 Hong R, Matsuyama E. Cardiomyopathy associated with the smoking of crystal methamphetamine.  JAMA . 1991;  265 1152-1154
  • 41 Perez J A, Arsura E L, Strategos S. Methamphetamine-related stroke: four cases.  J Emerg Med . 1999;  17 469-471
  • 42 Matthews G, White S R, Smolinske S C. Ephedrine-related stroke in a teenager.  J Toxicol Clin Toxicol . 1996;  34 602
  • 43 Kaku D A, Lowenstein D H. Emergence of recreational drug abuse as a major risk factor for stroke in young adults.  Ann Intern Med . 1990;  113 821-827
  • 44 Matick H, Anderson D, Brumlik J. Cerebral vasculitis associated with oral amphetamine overdose.  Arch Neurol . 1983;  40 253-254
  • 45 Buxton N, McConachie N S. Amphetamine abuse and intracranial haemorrhage.  J Roy Soc of Med . 2000;  93 472-477
  • 46 Rothrock J F, Rubenstein R, Lyden P D. Ischemic stroke associated with methamphetamine inhalation.  Neurology . 1988;  38 589-592
  • 47 Bitsch A M, Thiel A, Rieckmann P, Prange H. Acute inflammatory CNS disease after MDMA (``ecstasy'').  Eur Neurol . 1996;  36 328-329
  • 48 Mintzer S, Hickenbottom S, Gilman S. Parkinsonism after taking ecstasy.  N Eng J Med . 1999;  340 1443
  • 49 Nagorka A R, Bergeson P S. Infant methamphetamine toxicity posing as scorpion envenomation.  Ped Emerg Care . 1998;  14 350-351
  • 50 Rhee K, Albertson T, Douglas J. Choreoathetoid disorders associated with amphetamine-like drugs.  Am J Emerg Med . 1988;  6 131-133
  • 51 White S R, Obradovic T, Imel K M, Wheaton M J. The effects of methylenedioxymethamphetamine (MDMA, ``ecstasy'') on monoaminergic neurotransmission in the central nervous system.  Prog Neurobiol . 1996;  49 455-479
  • 52 Morgan M J. Memory deficits associated with recreational use of ``ecstasy''(MDMA).  Psychopharmacol . 1999;  141 30-36
  • 53 McCann U D, Mertl M, Eligulashvili V, Ricaurte G A. Cognitive performance in (+/-) 3,4-methylenedioxymethamphetamine (MDMA, ``ecstasy'') users: a controlled study.  Psychopharmacology . 1999;  143 417-425
  • 54 Bolla K I, McCann U D, Ricaurte G A. Memory impairment in abstinent MDMA (``Ecstasy'') users.  Neurology . 1998;  51 1532-1537
  • 55 McGuire P. Long-term psychiatric and cognitive effects of MDMA use.  Toxicol Lett . 2000;  112-113 153-156
  • 56 Kelly P A. Does recreational ecstasy use cause long-term cognitive problems?.  West J Med . 2000;  173 129-130
  • 57 Jansen K L. Ecstasy (MDMA) dependence.  Drug Alcohol Depend . 1999;  53(2) 121-124
  • 58 Fischer C, Hatzidimitirou G, Wlos J, Katz J, Ricaurte G. Reorganization of ascending 5-HT axon projections in animals previously exposed to recreational drug (+/-) 3,4-methylenedioxymethamphetamine (MDMA, ``Ecstasy'').  J Neurosci . 1995;  15 5476-5485
  • 59 Ricaurte G A, DeLanney L E, Irwin I, Langston J W. Toxic effects of MDMA on central serotonergic neurons in the primate: importance of route and frequency of drug administration.  Brain Res . 1988;  446 165-168
  • 60 Ricaurte G A, Forno L S, Wilson M A. (+/-) 3,4-methylenedioxymethamphetamine selectively damages central serotonergic neurons in nonhuman primates.  JAMA . 1988;  260 51-55
  • 61 Ricaurte G A, Martello A L, Katz J L, Martello M B. Lasting effects of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates: neurochemical observations.  J Pharamcol Exp Ther . 1992;  261 616-622
  • 62 Hatzidimitriou G, McCann U D, Ricaurte G A. Altered serotonin innervation patterns in the forebrain of monkeys treated with (+/-)3,4-methylenedioxymethamphetamine seven years previously: factors influencing abnormal recovery.  J Neuroscience . 1999;  19 5096-5107
  • 63 Kuhn D M, Geddes T J. Molecular footprints of neurotoxic amphetamine action.  Ann NY Acad Sci . 2000;  914(12) 92-103
  • 64 Ricaurte G A, Seiden L S, Schuster C R. Further evidence that amphetamines produce long-lasting dopamine neurochemical deficits by destroying dopamine nerve fibers.  Brain Research . 1984;  303 359-364
  • 65 Commins D L, Vosmer G, Virus R M, Woolverton W L, Schuster C R, Seiden L S. Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain.  J Pharmacol Exp Ther . 1987;  241 338-345
  • 66 Obradovic T, Imel K M, White S R. Repeated exposure to methylenedioxymethamphetamine(MDMA) alters nucleus accumbens neuronal responses to dopamine and serotonin.  Brain Res . 1998;  785 1-9
  • 67 McCann U D, Szabo Z, Scheffel U, Dannals R F, Ricaurte G A. Positron emission tomographic evidence of toxic effect of MDMA (``Ecstasy'') on brain serotonin neurons in human beings.  Lancet . 1998;  352 1433-1477
  • 68 Kish S J, Furukawa Y, Ang L, Vorce S P, Kalasinski K S. Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user.  Neurology . 2000;  55(2) 294-296
  • 69 Obrocki J, Buchert R, Vaterlein O. Ecstasy long-term effects on the human central nervous system revealed by positron emission tomography.  Br J Psychiatry . 1999;  175 186-188
  • 70 Chang L, Crob C S, Ernst T. Effect of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] on cerebral blood flow: a co-registered SPECT and MRI study.  Psych Research . 2000;  98 15-28
  • 71 Reneman L, Booij J, Schmand B, Van den Brink W, Gunning B. Memory disturbances in ``Ecstasy'' users are correlated with an altered brain serotonin neurotransmission.  Psychopharmacol . 2000;  148 322-324
  • 72 Ernst T, Chang L, Leonido-Lee M, Speck O. Evidence for long-term neurotoxicity associated with methamphetamine abuse: a 1H MRS study.  Neurology . 2000;  54 1344-1349
  • 73 Vollenweider F X, Gamma A, Liechti M, Huber T. Is a single dose of MDMA harmless?.  <~>(letter). Neuropsychopharmacology . 1999;  21 598-600
  • 74 Holmes S B, Banerjee A K, Alexsander W D. Hyponatraemia and seizures after ecstasy use.  Postgrad Med J . 1997;  5 32-33
  • 75 Holden R, Jackson M A. Near fatal hyponatraemic coma due to vasopressin oversecretion after ``Ecstasy'' 3,4-methylenedioxymethamphetamine (MDMA).  Lancet . 1996;  347 1052
  • 76 Kessel B. Hyponatraemia after ingestion of ``ecstasy''.  BMJ . 1994;  308 414
  • 77 Parr M J, Low H M, Botterill P. Hyponatraemia and death after ``ecstasy'' ingestion.  MJA . 1997;  166 136-137
  • 78 Satchell S C, Connaughton M. Inappropriate antidiuretic hormone secretion and extreme rises in serum creatine kinase following MDMA ingestion.  Br J Hosp Med . 1994;  51 495
  • 79 Henry J A, Fallon J K, Kicman A, Hutt A J, Cowan D A, Forsling M. Low dose MDMA (``ecstasy'') induces vasopressin secretion.  Lancet . 1998;  351 1784
  • 80 Ajaelo I, Koenig K, Snoey E. Severe hyponatremia and inappropriate antidiuretic hormone secretion following ecstasy use.  Academic Emerg Med . 1998;  5(8) 839-840
  • 81 O'Connor A, Cluroe A, Couch R, Galler L, Lawrence J, Synek B. Death from hyponatraemia-induced cerebral oedema associated with MDMA (``ecstasy'') use.  NZ Med J . 1999;  112 255-256
  • 82 Henry J A. Metabolic consequences of drug misuse.  British J Anaesthesia . 2000;  85 136-142
  • 83 Albertson T E, Walby W F, Derlet R W. Stimulant-induced pulmonary toxicity.  Chest . 1995;  108 1140-1149
  • 84 McCann U D, Seiden L S, Rubin L J, Ricaurte G A. Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine: a systematic review of the evidence.  JAMA . 1997;  278 666-672
  • 85 Ahmed J M, Salame M Y, Oakley G D. Chest pain in a young girl.  Postgrad Med J . 1998;  74 115-116
  • 86 Selim K, Kaplowitz N. Hepatotoxicity of psychotropic drugs.  Hepatology . 1999;  29 1347-1351
  • 87 Andreu V, Mas A, Bruguera M. Ecstasy: a common cause of severe acute hepatotoxicity.  J hepataology . 1998;  29 394-397
  • 88 Ellis A J, Wendon J A, Portmann B, Williams R. Acute liver damage and ecstasy ingestion.  Gut . 1996;  38 454-458
  • 89 Scully R E, Mark E J, McNeely W F. Case records of the Massachusetts General Hospital.  N Engl J Med . 2001;  344 591-599
  • 90 Fidler H, Dhillon A, Gertner D, Burroughs A. Chronic ecstasy (3,4-methylenedioxymethamphetamine) abuse: a recurrent and unpredictable cause of severe acute hepatitis.  J Hepatol . 1996;  25 563-566
  • 91 Johnson T D, Berenson M M. Methamphetamine-induced ischemic colitis.  J Clin Gastroenterol . 1991;  13 681-689
  • 92 Pecha R E, Prindiville T, Pecha B S, Camp R, Carroll M, Trudeau W. Association of cocaine and methamphetamine use with giant gastroduodenal ulcers.  Am J Gastroeneterol . 1996;  91 2523-2527
  • 93 Richards J R, Johnson E B, Stark R W, Derlet R W. Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study.  Am J Emerg Med . 1999;  17 681-685
  • 94 Murthy B VS, Wilkes R G, Roberts N B. Creatine kinase isoform changes following ecstasy overdose.  Anaesth Intens Care . 1997;  25 156-159
  • 95 Hall A P. Ecstasy: creatinine kinase.  Anaesthesia and Int Care . 1997;  25 586-587
  • 96 Foley R J, Kapatkin K, Verani R, Weinman E J. Amphetamine-induced acute renal failure.  S Med J . 1984;  77 258-269
  • 97 Woodrow G, Turney J H. Ecstasy-induced renal vasculitis.  Nephrol Dial Transplant . 1999;  14 798
  • 98 Marsh J C, Abboudi Z H, Gibson F M. Aplastic anaemia following exposure to 3,4-methylenedioxymethamphetamine (``ecstasy'').  Br J Haematol . 1994;  88 281-285
  • 99 Bouchama A, Cafege A, Devol E B, Labdi O, El-Assil K, Seraj M. Ineffectiveness of dantrolene sodium in the treatment of heatsroke.  Crit Care Med . 1991;  19 176-180
  • 100 Derlet R W, Albertson T E, Rice P. Protection against d-amphetamine toxicity.  Am J Emerg Med . 1990;  8 105-108
  • 101 Richards J R, Derlet R W, Duncan D R. Chemical restraint for the agitated patient in the emergency department: lorazepam versus droperidol.  J Emerg Med . 1998;  16 567-573
  • 102 Dar K J, McBrien M E. MDMA induced hyperthermia: report of a fatality and review of current therapy.  Int Care Med . 1996;  22(9) 995-996
  • 103 Jones A L, Simpson K J. Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications.  Aliment Pharmacol Ther . 1999;  13 129-133
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