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Toxicity of amphetamines: an update

  • Review Article
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Abstract

Amphetamines represent a class of psychotropic compounds, widely abused for their stimulant, euphoric, anorectic, and, in some cases, emphathogenic, entactogenic, and hallucinogenic properties. These compounds derive from the β-phenylethylamine core structure and are kinetically and dynamically characterized by easily crossing the blood–brain barrier, to resist brain biotransformation and to release monoamine neurotransmitters from nerve endings. Although amphetamines are widely acknowledged as synthetic drugs, of which amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are well-known examples, humans have used natural amphetamines for several millenniums, through the consumption of amphetamines produced in plants, namely cathinone (khat), obtained from the plant Catha edulis and ephedrine, obtained from various plants in the genus Ephedra. More recently, a wave of new amphetamines has emerged in the market, mainly constituted of cathinone derivatives, including mephedrone, methylone, methedrone, and buthylone, among others. Although intoxications by amphetamines continue to be common causes of emergency department and hospital admissions, it is frequent to find the sophism that amphetamine derivatives, namely those appearing more recently, are relatively safe. However, human intoxications by these drugs are increasingly being reported, with similar patterns compared to those previously seen with classical amphetamines. That is not surprising, considering the similar structures and mechanisms of action among the different amphetamines, conferring similar toxicokinetic and toxicological profiles to these compounds. The aim of the present review is to give an insight into the pharmacokinetics, general mechanisms of biological and toxicological actions, and the main target organs for the toxicity of amphetamines. Although there is still scarce knowledge from novel amphetamines to draw mechanistic insights, the long-studied classical amphetamines—amphetamine itself, as well as methamphetamine and MDMA, provide plenty of data that may be useful to predict toxicological outcome to improvident abusers and are for that reason the main focus of this review.

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Abbreviations

AMPH:

Amphetamine

AUC:

Area under the curve

C max :

Maximum concentration

CNS:

Central nervous system

COMT:

Catechol-o-methyltransferase

CSF:

Cerebrospinal fluid

CYP:

Cytochrome P450

DA:

Dopamine

DAT:

Dopamine transporter

2,3-DHBA:

2,3-Dihydroxybenzoic acid

DIC:

Disseminated intravascular coagulation

DMA:

2,5-Dimethoxyphenylisopropylamine

DOM:

2,5-Dimethoxy-4-methylphenylisopropylamine

DOPAC:

3,4-Dihydroxyphenylacetic acid

EC50 :

Effective concentration 50%

ETC:

Electron respiratory chain

EU:

European Union

fMRI:

Functional magnetic resonance imaging

GABA:

Gamma-aminobutyric acid

GFAP:

Glial fibrillary acidic protein

GPX:

Glutathione peroxidase

GR:

Glutathione redutase

GSH:

Glutathione (reduced form)

GST:

Glutathione S-transferase

γ-GT:

γ-Glutamyl transpeptidase or γ-glutamyltransferase

h:

Hours

5-HIAA:

5-Hydroxyindoleacetic acid

HMA:

4-Hydroxy-3-methoxyamphetamine, 3-O-Me-α-MeDA

HMMA:

4-Hydroxy-3-methoxymethamphetamine; 3-O-Me-N-Me-α-MeDA

HO• :

Hydroxyl radical

5-HT:

5-Hydroxytryptamine, Serotonin

5-HTT:

Serotonin transporter; SERT

HVA:

4-Hydroxy-3-methoxyphenylacetic acid, Homovanillic acid

i.p.:

Intraperitoneal

ICV:

Intracerebroventricular

i.v.:

Intravenous

Ke :

Elimination constant

KO:

Knockout

LSD:

Lysergic acid diethylamide

MAO:

Monoamine oxidase

MAOi:

Monoamine oxidase inhibitor

MDA:

(±)-3,4-Methylenedioxyamphetamine

MDEA:

Methylenedioxyethylamphetamine

MDMA:

(±)-3,4-Methylenedioxymethamphetamine, “Ecstasy”

α-MeDA:

α-Methyldopamine, 3,4-Dihydroxyamphetamine, HHA

METH:

Methamphetamine

4-MTA:

4-Methylthioampethamine

mtDNA:

Mitochondrial DNA

MPT:

Mitochondrial permeability transition

NA:

Noradrenaline

NAC:

N-Acetylcysteine

NAT:

Noradrenaline transporter

NMDA:

N-methyl-d-aspartic acid

N-Me-α-MeDA:

N-methyl-α-methyldopamine, 3,4-Dihydroxymethamphetamine, HHMA

NO• :

Nitric oxide radical

O •−2 :

Superoxide anion

ONOO− :

Peroxynitrite

PET:

Positron emission tomography

PD:

Pharmacodynamic

PK:

Pharmacokinetic

PKC:

Protein kinase C

p.o.:

Per os

PMA:

p-Methoxyamphetamine

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

s.c.:

Subcutaneous

-SH:

Sulfhydryl

SPECT:

Single-photon emission computed tomography

SOD:

Superoxide dismutase

SULT:

Sulfotransferase

t1/2 :

Elimination half-life

TH:

Tyrosine hydroxylase

THC:

Δ9-Tetrahydrocannabinol

T max :

Median time to maximum concentration

TPH:

Tryptophan hydroxylase

UGT:

UDP-glucuronosyltransferase

UK:

United Kingdom

USA:

United States of America

VMAT:

Vesicular monoamine transporter

WT:

Wild type

References

  • Abourashed EA, El-Alfy AT, Khan IA, Walker L (2003) Ephedra in perspective-a current review. Phytother Res 17(7):703–712

    Article  PubMed  CAS  Google Scholar 

  • Ago M, Ago K, Hara K, Kashimura S, Ogata M (2006) Toxicological and histopathological analysis of a patient who died nine days after a single intravenous dose of methamphetamine: a case report. Leg Med (Tokyo) 8(4):235–239

    Article  CAS  Google Scholar 

  • Alsidawi S, Muth J, Wilkin J (2011) Adderall induced inverted-Takotsubo cardiomyopathy. Catheter Cardiovasc Interv 78(6):910–913

    Article  PubMed  Google Scholar 

  • Alves E, Summavielle T, Alves CJ et al (2007) Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria. J Neurosci Off J Soc Neurosci 27(38):10203–10210

    Article  CAS  Google Scholar 

  • Alves E, Summavielle T, Alves CJ et al (2009) Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A. Addict Biol 14(2):185–193

    Article  PubMed  CAS  Google Scholar 

  • Andreu V, Mas A, Bruguera M et al (1998) Ecstasy: a common cause of severe acute hepatotoxicity. J Hepatol 29(3):394–397

    Article  PubMed  CAS  Google Scholar 

  • Angrist B, Corwin J, Bartlik B, Cooper T (1987) Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects. Biol Psychiatry 22(11):1357–1368

    Article  PubMed  CAS  Google Scholar 

  • Antoniou T, Tseng AL (2002) Interactions between recreational drugs and antiretroviral agents. Ann Pharmacother 36(10):1598–1613

    Article  PubMed  CAS  Google Scholar 

  • Azmitia EC, Murphy RB, Whitaker-Azmitia PM (1990) MDMA (ecstasy) effects on cultured serotonergic neurons: evidence for Ca2(+)-dependent toxicity linked to release. Brain Res 26:97–103

    Article  Google Scholar 

  • Bach MV, Coutts RT, Baker GB (1999) Involvement of CYP2D6 in the in vitro metabolism of amphetamine, two N-alkylamphetamines and their 4-methoxylated derivatives. Xenobiotica 29(7):719–732

    Article  PubMed  CAS  Google Scholar 

  • Bach MV, Coutts RT, Baker GB (2000) Metabolism of N, N-dialkylated amphetamines, including deprenyl, by CYP2D6 expressed in a human cell line. Xenobiotica 30(3):297–306

    Article  PubMed  CAS  Google Scholar 

  • Badon LA, Hicks A, Lord K, Ogden BA, Meleg-Smith S, Varner KJ (2002) Changes in cardiovascular responsiveness and cardiotoxicity elicited during binge administration of ecstasy. J Pharmacol Exp Ther 302(3):898–907

    Article  PubMed  CAS  Google Scholar 

  • Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J (2000) Chemical analysis of ecstasy pills. JAMA 284(17):2190

    Article  PubMed  CAS  Google Scholar 

  • Bagley WH, Yang H, Shah KH (2007) Rhabdomyolysis. Intern Emerg Med 2(3):210–218

    Article  PubMed  CAS  Google Scholar 

  • Bai F, Lau SS, Monks TJ (1999) Glutathione and N-acetylcysteine conjugates of alpha-methyldopamine produce serotonergic neurotoxicity: possible role in methylenedioxyamphetamine-mediated neurotoxicity. Chem Res Toxicol 12(12):1150–1157

    Article  PubMed  CAS  Google Scholar 

  • Banks ML, Sprague JE, Kisor DF, Czoty PW, Nichols DE, Nader MA (2007) Ambient temperature effects on 3,4-methylenedioxymethamphetamine-induced thermodysregulation and pharmacokinetics in male monkeys. Drug Metab Dispos 35(10):1840–1845

    Article  PubMed  CAS  Google Scholar 

  • Banks ML, Sprague JE, Czoty PW, Nader MA (2008) Effects of ambient temperature on the relative reinforcing strength of MDMA using a choice procedure in monkeys. Psychopharmacology 196(1):63–70

    Article  PubMed  CAS  Google Scholar 

  • Barbosa DJ, Capela JP, Oliveira JM et al (2012) Pro-oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes. Br J Pharmacol 165(4b):1017–1033. doi:10.1111/j.1476-5381.2011.01453.x

    Article  Google Scholar 

  • Barr AM, Panenka WJ, MacEwan GW et al (2006) The need for speed: an update on methamphetamine addiction. J Psychiatry Neurosci 31(5):301–313

    PubMed  Google Scholar 

  • Bashour TT (1994) Acute myocardial infarction resulting from amphetamine abuse: a spasm-thrombus interplay? Am Heart J 128(6 Pt 1):1237–1239

    Article  PubMed  CAS  Google Scholar 

  • Battaglia G, Yeh SY, O’Hearn E, Molliver ME, Kuhar MJ, Sousa EBD (1987) 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. J Pharmacol Exp Ther 242:911–916

    PubMed  CAS  Google Scholar 

  • Battaglia G, Fornai F, Busceti CL et al (2002) Selective blockade of mGlu5 metabotropic glutamate receptors is protective against methamphetamine neurotoxicity. J Neurosci 22(6):2135–2141

    PubMed  CAS  Google Scholar 

  • Behan WM, Madigan M, Clark BJ, Goldberg J, McLellan DR (2000) Muscle changes in the neuroleptic malignant syndrome. J Clin Pathol 53(3):223–227

    Article  PubMed  CAS  Google Scholar 

  • Beitia G, Cobreros A, Sainz L, Cenarruzabeitia E (1999) 3,4-Methylenedioxymethamphetamine (ecstasy)-induced hepatotoxicity: effect on cytosolic calcium signals in isolated hepatocytes. Liver 19:234–241

    Article  PubMed  CAS  Google Scholar 

  • Beitia G, Cobreros A, Sainz L, Cenarruzabeitia E (2000) Ecstasy-induced toxicity in rat liver. Liver 20(1):8–15

    Article  PubMed  CAS  Google Scholar 

  • Bellis MA, Hughes K, Lowey H (2002) Healthy nightclubs and recreational substance use. From a harm minimisation to a healthy settings approach. Addict Behav 27(6):1025–1035

    Article  PubMed  Google Scholar 

  • Ben Hamida S, Plute E, Bach S et al (2007) Ethanol-MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination. Psychopharmacology 192(4):555–569

    Article  PubMed  CAS  Google Scholar 

  • Benowitz NL (2008) Clinical pharmacology of nicotine: implications for understanding, preventing, and treating tobacco addiction. Clin Pharmacol Ther 83(4):531–541

    Article  PubMed  CAS  Google Scholar 

  • Berger UV, Gu XF, Azmitia EC (1992) The substituted amphetamines 3,4-methylenedioxymethamphetamine, methamphetamine, pchloroamphetamine and fenfluramine induce 5-hydroxytryptamine release via a common mechanism blocked by fluoxetine and cocaine. Eur J Pharmacol 215:153–160

    Article  PubMed  CAS  Google Scholar 

  • Bexis S, Docherty JR (2006) Effects of MDMA, MDA and MDEA on blood pressure, heart rate, locomotor activity and body temperature in the rat involve [alpha]-adrenoceptors. Br J Pharmacol 147(8):926–934

    Article  PubMed  CAS  Google Scholar 

  • Bhave PD, Goldschlager N (2011) An unusual pattern of ST-segment elevation. Arch Intern Med 171(13):1146; (discussion 1147–8)

  • Bindoli A, Rigobello MP, Deeble DJ (1992) Biochemical and toxicological properties of the oxidation products of catecholamines. Free Radic Biol Med 13(4):391–405

    Article  PubMed  CAS  Google Scholar 

  • Bingham C, Beaman M, Nicholls AJ, Anthony PP (1998) Necrotizing renal vasculopathy resulting in chronic renal failure after ingestion of methamphetamine and 3,4-methylenedioxymethamphetamine (‘ecstasy’). Nephrol Dial Transplant 13(10):2654–2655

    Article  PubMed  CAS  Google Scholar 

  • Blessing WW, Seaman B (2003) 5-Hidroxitriptamine2A receptors regulate sympathetic nerves constricting the cutaneous vascular bed in rabbits and rats. Neuroscience 117:939–948

    Article  PubMed  CAS  Google Scholar 

  • Blessing WW, Seaman B, Pedersen NP, Ootsuka Y (2003) Clozapine reverses hyperthermia and sympathetically mediated cutaneous vasoconstriction induced by 3,4-methylenedioxymethamphetamine (Ecstasy) in rabbits and rats. J Neurosci 23(15):6385–6391

    PubMed  CAS  Google Scholar 

  • Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ (2000) Role of quinones in toxicology. Chem Res Toxicol 13(3):135–160

    Article  PubMed  CAS  Google Scholar 

  • Bowyer JF, Ali SF (2006) High doses of methamphetamine that cause disruption of the blood-brain barrier in limbic regions produce extensive neuronal degeneration in mouse hippocampus. Synapse 60:521–532

    Article  PubMed  CAS  Google Scholar 

  • Bowyer JF, Tank AW, Newport GD, Slikker W, Ali SF, Holson RR (1992) The influence of environmental temperature on the transient effects of methamphetamine on dopamine levels and dopamine release in rat striatum. J Pharmacol Exp Ther 260(2):817–824

    PubMed  CAS  Google Scholar 

  • Brauer LH, De Wit H (1997) High dose pimozide does not block amphetamine-induced euphoria in normal volunteers. Pharmacol Biochem Behav 56(2):265–272

    Article  PubMed  CAS  Google Scholar 

  • Brauer RB, Heidecke CD, Nathrath W et al (1997) Liver transplantation for the treatment of fulminant hepatic failure induced by the ingestion of ecstasy. Transpl Int 10(3):229–233

    Article  PubMed  CAS  Google Scholar 

  • Breen C, Degenhardt L, Kinner S et al (2006) Alcohol use and risk taking among regular ecstasy users. Subst Use Misuse 41(8):1095–1109

    Article  PubMed  Google Scholar 

  • Brennan K, Shurmur S, Elhendy A (2004) Coronary artery rupture associated with amphetamine abuse. Cardiol Rev 12(5):282–283

    Article  PubMed  Google Scholar 

  • Breslau K (2002) The ‘sextasy’ craze. Clubland’s dangerous party mix: Viagra and ecstasy. Newsweek 139(22):30

    PubMed  Google Scholar 

  • Brown C, Osterloh J (1987) Multiple severe complications from recreational ingestion of MDMA (‘Ecstasy’). JAMA 258(6):780–781

    Article  PubMed  CAS  Google Scholar 

  • Brown JM, Yamamoto BK (2003) Effects of amphetamines on mitochondrial function: role of free radicals and oxidative stress. Pharmacol Ther 99(1):45–53

    Article  PubMed  CAS  Google Scholar 

  • Brown JM, Riddle EL, Sandoval V et al (2002) A single methamphetamine administration rapidly decreases vesicular dopamine uptake. J Pharmacol Exp Ther 302(2):497–501

    Article  PubMed  CAS  Google Scholar 

  • Brown JM, Quinton MS, Yamamoto BK (2005) Methamphetamine-induced inhibition of mitochondrial complex II: roles of glutamate and peroxynitrite. J Neurochem 95:429–436

    Article  PubMed  CAS  Google Scholar 

  • Burrows KB, Gudelsky G, Yamamoto BK (2000) Rapid and transient inhibition of mitochondrial function following methamphetamine or 3,4-methylenedioxymethamphetamine administration. Eur J Pharmacol 398(1):11–18

    Article  PubMed  CAS  Google Scholar 

  • Busby WF Jr, Ackermann JM, Crespi CL (1999) Effect of methanol, ethanol, dimethyl sulfoxide, and acetonitrile on in vitro activities of cDNA-expressed human cytochromes P-450. Drug Metab Dispos 27(2):246–249

    PubMed  CAS  Google Scholar 

  • Busto U, Bendayan R, Sellers EM (1989) Clinical pharmacokinetics of non-opiate abused drugs. Clin Pharmacokinet 16(1):1–26

    Article  PubMed  CAS  Google Scholar 

  • Caballero F, Lopez-Navidad A, Cotorruelo J, Txoperena G (2002) Ecstasy-induced brain death and acute hepatocellular failure: multiorgan donor and liver transplantation. Transplantation 74(4):532–537

    Article  PubMed  CAS  Google Scholar 

  • Cadet JL, Krasnova IN (2009) Molecular bases of methamphetamine-induced neurodegeneration. Int Rev Neurobiol 88:101–119

    Article  PubMed  CAS  Google Scholar 

  • Cadet JL, Ladenheim B, Baum I, Carlson E, Epstein C (1994) CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal effects of methylenedioxyamphetamine (MDA) and of methylenedioxymethamphetamine (MDMA). Brain Res 655(1–2):259–262

    Article  PubMed  CAS  Google Scholar 

  • Caldwell J (1980) The metabolism of amphetamines and related stimulants in animals and man. In: Caldwell J (ed) Amphetamines and related stimulants: chemical, biological, clinical, and sociological aspects. Drud Dependence Series. CRC Press, Boca Raton, pp 29–46

    Google Scholar 

  • Caldwell J, Dring LG, Williams RT (1972) Metabolism of (14 C)methamphetamine in man, the guinea pig and the rat. Biochem J 129(1):11–22

    PubMed  CAS  Google Scholar 

  • Camarasa J, Pubill D, Escubedo E (2006) Association of caffeine to MDMA does not increase antinociception but potentiates adverse effects of this recreational drug. Brain Res 1111(1):72–82

    Article  PubMed  CAS  Google Scholar 

  • Capela JP, Meisel A, Abreu AR et al (2006a) Neurotoxicity of ecstasy metabolites in rat cortical neurons, and influence of hyperthermia. J Pharmacol Exp Ther 316(1):53–61

    Article  PubMed  CAS  Google Scholar 

  • Capela JP, Ruscher K, Lautenschlager M et al (2006b) Ecstasy-induced cell death in cortical neuronal cultures is serotonin 2A-receptor-dependent and potentiated under hyperthermia. Neuroscience 139(3):1069–1081

    Article  PubMed  CAS  Google Scholar 

  • Capela JP, Fernandes E, Remiao F, Bastos ML, Meisel A, Carvalho F (2007a) Ecstasy induces apoptosis via 5-HT2A-receptor stimulation in cortical neurons. Neurotoxicology 28(4):868–875

    Article  PubMed  CAS  Google Scholar 

  • Capela JP, Macedo C, Branco PS et al (2007b) Neurotoxicity mechanisms of thioether ecstasy metabolites. Neuroscience 146(4):1743–1757

    Article  PubMed  CAS  Google Scholar 

  • Capela JP, Lautenschlager M, Dirnagl U, Bastos ML, Carvalho F, Meisel A (2008) 5,7-Dihydroxitryptamine toxicity to serotonergic neurons in serum free raphe cultures. Eur J Pharmacol 588(2–3):232–238

    Article  PubMed  CAS  Google Scholar 

  • Capela JP, Carmo H, Remião F, Bastos ML, Meisel A, Carvalho F (2009) Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview. Mol Neurobiol 39(3):210–271

    Article  PubMed  CAS  Google Scholar 

  • Carmo H, Brulport M, Hermes M et al (2006) Influence of CYP2D6 polymorphism on 3,4-methylenedioxymethamphetamine (“Ecstasy”) cytotoxicity. Pharmacogenet Genomics 16(11):789–799

    Article  PubMed  CAS  Google Scholar 

  • Carmo H, Brulport M, Hermes M et al (2007) CYP2D6 increases toxicity of the designer drug 4-methylthioamphetamine (4-MTA). Toxicology 229(3):236–244

    Article  PubMed  CAS  Google Scholar 

  • Carvalho F (2003) The toxicological potential of khat. J Ethnopharmacol 87(1):1–2

    Article  PubMed  Google Scholar 

  • Carvalho FD, Bastos ML, Timbrell JA (1993) Depletion of total non-protein sulphydrly groups in mouse tissues after administration of d-amphetamine. Toxicol 83:31–40

    Article  CAS  Google Scholar 

  • Carvalho F, Remiao F, Amado F, Domingues P, Correia AJ, Bastos ML (1996) d-Amphetamine interaction with glutathione in freshly isolated rat hepatocytes. Chem Res Toxicol 9(6):1031–1036

    Article  PubMed  CAS  Google Scholar 

  • Carvalho F, Remião F, Soares ME, Catarino R, Queiroz G, Bastos ML (1997) d-Amphetamine-induced hepatotoxicity: possible contribution of catecholamines and hyperthermia to the effect studied in isolated rat hepatocytes. Arch Toxicol 71:429–436

    Article  PubMed  CAS  Google Scholar 

  • Carvalho M, Carvalho F, Bastos ML (2001) Is hyperthermia the triggering factor for hepatotoxicity induced by 3,4-methylenedioxymethamphetamine (ecstasy)? An in vitro study using freshly isolated mouse hepatocytes. Arch Toxicol 74(12):789–793

    Article  PubMed  CAS  Google Scholar 

  • Carvalho M, Carvalho F, Remiao F, de Lourdes Pereira M, Pires-das-Neves R, de Lourdes Bastos M (2002a) Effect of 3,4-methylenedioxymethamphetamine (“ecstasy”) on body temperature and liver antioxidant status in mice: influence of ambient temperature. Arch Toxicol 76(3):166–172

    Article  PubMed  CAS  Google Scholar 

  • Carvalho M, Hawksworth G, Milhazes N et al (2002b) Role of metabolites in MDMA (ecstasy)-induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells. Arch Toxicol 76(10):581–588

    Article  PubMed  CAS  Google Scholar 

  • Carvalho M, Milhazes N, Remiao F et al (2004a) Hepatotoxicity of 3,4-methylenedioxyamphetamine and alpha-methyldopamine in isolated rat hepatocytes: formation of glutathione conjugates. Arch Toxicol 78(1):16–24

    Article  PubMed  CAS  Google Scholar 

  • Carvalho M, Remiao F, Milhazes N et al (2004b) The toxicity of N-methyl-alpha-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine. Toxicology 200(2–3):193–203

    Article  PubMed  CAS  Google Scholar 

  • Carvalho M, Remiao F, Milhazes N et al (2004c) Metabolism is required for the expression of ecstasy-induced cardiotoxicity in vitro. Chem Res Toxicol 17(5):623–632

    Article  PubMed  CAS  Google Scholar 

  • Carvalho M, Pontes H, Remiao F, Bastos ML, Carvalho F (2010) Mechanisms underlying the hepatotoxic effects of ecstasy. Curr Pharm Biotechnol 11(5):476–495

    Article  PubMed  CAS  Google Scholar 

  • Cassel JC, Ben Hamida S, Jones BC (2007) Attenuation of MDMA-induced hyperthermia by ethanol in rats depends on ambient temperature. Eur J Pharmacol 571(2–3):152–155

    Article  PubMed  CAS  Google Scholar 

  • Catanzarite VA, Stein DA (1995) ‘Crystal’ and pregnancy–methamphetamine-associated maternal deaths. West J Med 162(5):454–457

    PubMed  CAS  Google Scholar 

  • Cerretani D, Riezzo I, Fiaschi AI et al (2008) Cardiac oxidative stress determination and myocardial morphology after a single ecstasy (MDMA) administration in a rat model. Int J Legal Med 122(6):461–469

    Article  PubMed  Google Scholar 

  • Cervinski MA, Foster JD, Vaughan RA (2005) Psychoactive substrates stimulate dopamine transporter phosphorylation and down-regulation by cocaine-sensitive and protein kinase C-dependent mechanisms. J Biol Chem 280(49):40442–40449

    Article  PubMed  CAS  Google Scholar 

  • Chadwick IS, Curry PD, Linsley A, Freemont AJ, Doran B (1991) Ecstasy, 3–4 methylenedioxymethamphetamine (MDMA), a fatality associated with coagulopathy and hyperthermia. J R Soc Med 84(6):371

    PubMed  CAS  Google Scholar 

  • Chao TC, Sinniah R, Pakiam JE (1981) Acute heat stroke deaths. Pathology 13(1):145–156

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Biller J, Willing SJ, Lopez AM (2004) Ischemic stroke after using over the counter products containing ephedra. J Neurol Sci 217(1):55–60

    Article  PubMed  Google Scholar 

  • Chen CK, Lin SK, Huang MC et al (2007) Analysis of association of clinical correlates and 5-HTTLPR polymorphism with suicidal behavior among Chinese methamphetamine abusers. Psychiatry Clin Neurosci 61(5):479–486

    Article  PubMed  CAS  Google Scholar 

  • Cho AK, Narimatsu S, Kumagai Y (1999) Metabolism of drugs of abuse by cytochromes P450. Addict Biol 4:283–301

    Article  PubMed  CAS  Google Scholar 

  • Clemens KJ, Van Nieuwenhuyzen PS, Li KM, Cornish JL, Hunt GE, McGregor IS (2004) MDMA (“ecstasy”), methamphetamine and their combination: long-term changes in social interaction and neurochemistry in the rat. Psychopharmacology (Berl) 173:318–325

    Article  CAS  Google Scholar 

  • Clemens KJ, Cornish JL, Hunt GE, McGregor IS (2006) Intravenous methamphetamine self-administration in rats: effects of intravenous or intraperitoneal MDMA co-administration. Pharmacol Biochem Behav 85(2):454–463

    Article  PubMed  CAS  Google Scholar 

  • Clemens KJ, McGregor IS, Hunt GE, Cornish JL (2007) MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical research. Drug Alcohol Rev 26(1):9–15

    Article  PubMed  Google Scholar 

  • Colado MI, O’Shea E, Granados R, Murray TK, Green AR (1997) In vivo evidence for free radical involvement in the degeneration of rat brain 5-HT following administration of MDMA (‘ecstasy’) and p-chloroamphetamine but not the degeneration following fenfluramine. Br J Pharmacol 121(5):889–900

    Article  PubMed  CAS  Google Scholar 

  • Colado MI, O’Shea E, Esteban B, Granados R, Green AR (1999) In vivo evidence against clomethiazole being neuroprotective against MDMA (“ecstasy”)-induced degeneration of rat brain 5-HT nerve terminals by a free radical scavenging mechanism. Neuropharmacology 38(2):307–314

    Article  PubMed  CAS  Google Scholar 

  • Cole JC, Sumnall HR (2003) Altered states: the clinical effects of Ecstasy. Pharmacol Ther 98(1):35–58

    Article  PubMed  CAS  Google Scholar 

  • Commins DL, Vosmer G, Virus RM, Woolverton WL, Schuster CR, Seiden LS (1987) Biochemical and histological evidence that methylenedioxymethamphetamine (MDMA) is toxic to neurons in the rat brain. J Pharmacol Exp Ther 241:338–345

    PubMed  CAS  Google Scholar 

  • Connolly E, O’Callaghan G (1999) MDMA toxicity presenting with severe hyperpyrexia: a case report. Crit Care Resusc 1(4):368–370

    PubMed  CAS  Google Scholar 

  • Cook CE, Jeffcoat AR, Sadler BM et al (1992) Pharmacokinetics of oral methamphetamine and effects of repeated daily dosing in humans. Drug Metab Dispos 20(6):856–862

    PubMed  CAS  Google Scholar 

  • Cook CE, Jeffcoat AR, Hill JM et al (1993) Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. Drug Metab Dispos 21(4):717–723

    PubMed  CAS  Google Scholar 

  • Coore JR (1996) A fatal trip with ecstasy: a case of 3,4-methylenedioxymethamphetamine/3,4-methylenedioxyamphetamine toxicity. J R Soc Med 89:51–52

    Google Scholar 

  • Copeland J, Dillon P, Gascoigne M (2006) Ecstasy and the concomitant use of pharmaceuticals. Addict Behav 31(2):367–370

    Article  PubMed  Google Scholar 

  • Corcoran GB, Wong BK (1987) Obesity as a risk factor in drug-induced organ injury: increased liver and kidney damage by acetaminophen in the obese overfed rat. J Pharmacol Exp Ther 241(3):921–927

    PubMed  CAS  Google Scholar 

  • Costa VM, Silva R, Ferreira LM et al (2007) Oxidation process of adrenaline in freshly isolated rat cardiomyocytes: formation of adrenochrome, quinoproteins, and GSH adduct. Chem Res Toxicol 20(8):1183–1191

    Article  PubMed  CAS  Google Scholar 

  • Costa VM, Silva R, Tavares LC et al (2009) Adrenaline and reactive oxygen species elicit proteome and energetic metabolism modifications in freshly isolated rat cardiomyocytes. Toxicology 260(1–3):84–96

    Article  PubMed  CAS  Google Scholar 

  • Costa VM, Carvalho F, Bastos ML, Carvalho RA, Carvalho M, Remião F (2011) Contribution of catecholamine reactive intermediates and oxidative stress to the pathologic features of heart diseases. Curr Med Chem 18(15):2272–2314

    PubMed  CAS  Google Scholar 

  • Cowan RL, Lyoo IK, Sung SM et al (2003) Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study. Drug Alcohol Depend 72(3):225–235

    Article  PubMed  CAS  Google Scholar 

  • Crespi D, Mennini T, Gobbi M (1997) Carrier-dependent and Ca(2+)-dependent 5-HT and dopamine release induced by (+)-amphetamine, 3,4-methylendioxymethamphetamine, pchloroamphetamine and (+)-fenfluramine. Br J Pharmacol 121:1735–1743

    Article  PubMed  CAS  Google Scholar 

  • Cruickshank CC, Dyer KR (2009) A review of the clinical pharmacology of methamphetamine. Addiction 104(7):1085–1099

    Article  PubMed  Google Scholar 

  • Cunningham M (1997) Ecstasy-induced rhabdomyolysis and its role in the development of acute renal failure. Intensive Crit Care Nurs 13(4):216–223

    Article  PubMed  CAS  Google Scholar 

  • Dafters RI (1995) Hyperthermia following MDMA administration in rats: effects of ambient temperature, water consuption and chronic dosing. Physiol Behav 58:877–882

    Article  PubMed  CAS  Google Scholar 

  • Dafters RI, Hoshi R, Talbot AC (2004) Contribution of cannabis and MDMA (“ecstasy”) to cognitive changes in long-term polydrug users. Psychopharmacology (Berl) 173(3–4):405–410

    Article  CAS  Google Scholar 

  • Dams R, De Letter EA, Mortier KA et al (2003) Fatality due to combined use of the designer drugs MDMA and PMA: a distribution study. J Anal Toxicol 27:318–322

    PubMed  CAS  Google Scholar 

  • Dar KJ, McBrien ME (1996) MDMA induced hyperthermia: report of a fatality and review of current therapy. Intensive Care Med 22:995–996

    Article  PubMed  CAS  Google Scholar 

  • Davidson C, Gow AJ, Lee TH, Ellinwood EH (2001) Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Res Brain Res Rev 36(1):1–22

    Article  PubMed  CAS  Google Scholar 

  • Davis WM, Babbini M, Pong SF, King WT, White CL (1974) Motility of mice after amphetamine: effects of strain, aggregation and illumination. Pharmacol Biochem Behav 2(6):803–809

    Article  PubMed  CAS  Google Scholar 

  • Daza-Losada M, Rodriguez-Arias M, Aguilar MA, Minarro J (2008) Effect of adolescent exposure to MDMA and cocaine on acquisition and reinstatement of morphine-induce CPP. Prog Neuropsychopharmacol Biol Psychiatry 32(3):701–709

    Article  PubMed  CAS  Google Scholar 

  • de la Torre R, Farre M, Ortuno J et al (2000a) Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans. Br J Clin Pharmacol 49(2):104–109

    Article  PubMed  CAS  Google Scholar 

  • de la Torre R, Farre M, Roset PN et al (2000b) Pharmacology of MDMA in humans. Ann N Y Acad Sci 914:225–237

    Article  PubMed  Google Scholar 

  • de la Torre R, Farre M, Navarro M, Pacifici R, Zuccaro P, Pichini S (2004a) Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices. Clin Pharmacokinet 43(3):157–185

    Article  PubMed  Google Scholar 

  • de la Torre R, Farre M, Roset PN et al (2004b) Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Ther Drug Monit 26(2):137–144

    Article  PubMed  Google Scholar 

  • de la Torre R, Farre M, Mathuna BO et al (2005) MDMA (ecstasy) pharmacokinetics in a CYP2D6 poor metaboliser and in nine CYP2D6 extensive metabolisers. Eur J Clin Pharmacol 61(7):551–554

    Article  PubMed  Google Scholar 

  • De Letter EA, Clauwaert KM, Lambert WE, VanBocxlaer JF, DeLeenheer AP, Piette MH (2002) Distribution study of 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine in a fatal overdose. J Anal Toxicol 26(2):113–118

    PubMed  CAS  Google Scholar 

  • De Letter EA, Bouche MP, VanBocxlaer JF, Lambert WE, Piette MH (2004) Interpretation of a 3,4-methylenedioxymethamphetamine (MDMA) blood level: discussion by means of a distribution study in two fatalities. Forensic Sci Int 141(2–3):85–90

    Article  PubMed  CAS  Google Scholar 

  • De Letter EA, Piette MH, Lambert WE, Cordonnier JA (2006) Amphetamines as potential inducers of fatalities: a review in the district of Ghent from 1976–2004. Med Sci Law 46(1):37–65

    Article  PubMed  Google Scholar 

  • DeLeve L, Kaplowitz N (1991) Glutathione metabolism and its role in hepatotoxicity. Pharmacol Ther 52:287–305

    Article  PubMed  CAS  Google Scholar 

  • de Win MML, Jager G, Booij J et al (2008) Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users. Brain 131(11):2936–2945

    Article  PubMed  Google Scholar 

  • Degenhardt L (2005) Drug use and risk behaviour among regular ecstasy users: Does sexuality make a difference? Cult Health Sex 7(6):599–614

    Article  PubMed  Google Scholar 

  • Delaforge M, Jaouen M, Bouille G (1999) Inhibitory metabolite complex formation of methylenedioxymethamphetamine with rat and human cytochrome P450. Particular involvement of CYP 2D. Environ Toxicol Pharmacol 7(3):153–158

    Article  PubMed  CAS  Google Scholar 

  • Deng X, Wang Y, Chou J, Cadet JL (2001) Methamphetamine causes widespread apoptosis in the mouse brain: evidence from using an improved TUNEL histochemical method. Mol Brain Res 93:64–69

    Article  PubMed  CAS  Google Scholar 

  • Derlet RW, Albertson TE, Rice P (1990) Antagonism of cocaine, amphetamine, and methamphetamine toxicity. Pharmacol Biochem Behav 36(4):745–749

    Article  PubMed  CAS  Google Scholar 

  • Derlet RW, Tseng JC, Albertson TE (1992) Potentiation of cocaine and d-amphetamine toxicity with caffeine. Am J Emerg Med 10(3):211–216

    Article  PubMed  CAS  Google Scholar 

  • Dhalla NS, Sasaki H, Mochizuki S, Dhalla KS, Liu X, Elimban V (2001) Catecholamine-induced cardiomyopathy. In: Acosta D (ed) Cardiovascular toxicity. Raven Press, New York, pp 269–318

    Google Scholar 

  • Dlugos AM, Hamidovic A, Palmer AA, deWit H (2009) Further evidence of association between amphetamine response and SLC6A2 gene variants. Psychopharmacology 206(3):501–511

    Article  PubMed  CAS  Google Scholar 

  • Docherty JR, Green AR (2010) The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives. Br J Pharmacol 160(5):1029–1044

    Article  PubMed  CAS  Google Scholar 

  • Dowling GP, McDonough ET, Bost RO (1987) “Eve” and “Ecstasy”: a report of five deaths associated with the use of MDEA and MDMA. JAMA 257:1615–1617

    Article  PubMed  CAS  Google Scholar 

  • Dreisbach AW, Lertora JJ (2003) The effect of chronic renal failure on hepatic drug metabolism and drug disposition. Semin Dial 16(1):45–50

    Article  PubMed  Google Scholar 

  • Duarte JA, Leao A, Magalhaes J et al (2005) Strenuous exercise aggravates MDMA-induced skeletal muscle damage in mice. Toxicology 206(3):349–358

    Article  PubMed  CAS  Google Scholar 

  • Dykens JA, Stern A, Trenkner E (1987) Mechanism of kainite toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury. J Neurochem 49:1222–1228

    Article  PubMed  CAS  Google Scholar 

  • Dykhuizen RS, Brunt PW, Atkinson P, Simpson JG, Smith CC (1995) Ecstasy induced hepatitis mimicking viral hepatitis. Gut 36:939–941

    Article  PubMed  CAS  Google Scholar 

  • EACD Expert Advisory Committee on Drugs (2004) Advice to the associate minister of health on MDMA. In: Health NZMo (ed)

  • Easton N, Fry J, O’Shea E, Watkins A, Kingston S, Marsden CA (2003) Synthesis, in vitro formation, and behavioural effects of glutathione regioisomers of alpha-methyldopamine with relevance to MDA and MDMA (ecstasy). Brain Res 987(2):144–154

    Article  PubMed  CAS  Google Scholar 

  • Ehrich WE, Lewy FH, Krumbhaar EB (1939) Experimental studies upon the toxicity of Benzedrine sulphate in various animals. Am J M Sc 198:785–803

    Article  CAS  Google Scholar 

  • Ellinwood EH Jr, Kilbey MM (1980) Fundamental mechanisms underlying altered behavior following chronic administration of psychomotor stimulants. Biol Psychiatry 15(5):749–757

    PubMed  CAS  Google Scholar 

  • Ellis AJ, Wendon JA, Portmann B, Williams R (1996) Acute liver damage and ecstasy ingestion. Gut 38:454–458

    Article  PubMed  CAS  Google Scholar 

  • Ellison G, Eison M, Huberman H, Daniel F (1978) Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration. Science 201(4352):276–278

    Article  PubMed  CAS  Google Scholar 

  • EMCDDA (2007) Annual report 2007: the state of the drugs problem in Europe. European Monitoring Centre for Drugs and Drug Addiction, Lisbon

  • EMCDDA European Monitoring Centre for Drugs and Drug Addiction (2010) Annual report on the state of the drugs problem in Europe. Lisbon, pp 50–59

  • Escobedo I, O’Shea E, Orio L et al (2005) A comparative study on the acute and long-term effects of MDMA and 3,4-dihydroxymethamphetamine (HHMA) on brain monoamine levels after i.p. or striatal administration in mice. Br J Pharmacol 144:231–241

    Article  PubMed  CAS  Google Scholar 

  • Ezaki N, Nakamura K, Sekine Y et al (2008) Short allele of 5-HTTLPR as a risk factor for the development of psychosis in Japanese methamphetamine abusers. Ann N Y Acad Sci 1139:49–56

    Article  PubMed  CAS  Google Scholar 

  • Fahal IH, Sallomi DF, Yaqoob M, Bell GM (1992) Acute renal failure after ecstasy. BMJ 305(6844):29

    Article  PubMed  CAS  Google Scholar 

  • Fallon JK, Kicman AT, Henry JA, Milligan PJ, Cowan DA, Hutt AJ (1999) Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans. Clin Chem 45(7):1058–1069

    PubMed  CAS  Google Scholar 

  • Farfel GM, Seiden LS (1995) Role of hypothermia in the mechanism of protection against serotonergic toxicity. II. Experiments with methamphetamine, p-chloroamphetamine, fenfluramine, dizocilpine and dextromethorphan. J Pharmacol Exp Ther 272(2):868–875

    PubMed  CAS  Google Scholar 

  • Farré M, de la Torre R, Mathúna BO et al (2004) Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics. Psychopharmacology 173(3–4):364–375

    Article  PubMed  CAS  Google Scholar 

  • Felton JS, Malfatti MA (2006) What do diet-induced changes in phase I and II enzymes tell us about prevention from exposure to heterocyclic amines? J Nutr 136(10):2683S–2684S

    PubMed  CAS  Google Scholar 

  • Fiaschi AI, Cerretani D (2010) Causes and effects of cellular oxidative stress as a result of MDMA abuse. Curr Pharm Biotechnol 11(5):444–452

    Article  PubMed  CAS  Google Scholar 

  • Fidler H, Dhillon A, Gertner D, Burroughs A (1996) Chronic ecstasy (3,4-methylenedioxymetamphetamine) abuse: a recurrent and unpredictable cause of severe acute hepatitis. J Hepatol 25(4):563–566

    Article  PubMed  CAS  Google Scholar 

  • Filep J, Rosenkranz B (1987) Mechanism of vasopressin-induced platelet aggregation. Thromb Res 45(1):7–15

    Article  PubMed  CAS  Google Scholar 

  • Fineschi V, Masti A (1996) Fatal poisoning by MDMA (ecstasy) and MDEA: a case report. Int J Legal Med 108(5):272–275

    Article  PubMed  CAS  Google Scholar 

  • Fineschi V, Centini F, Mazzeo E, Turillazzi E (1999) Adam (MDMA) and Eve (MDA) misuse: an immunohistochemical study on three fatal cases. Forensic Sci Int 104:65–74

    Article  PubMed  CAS  Google Scholar 

  • Fischer C, Hatzidimitriou G, Wlos J, Katz J, Ricaurte G (1995) Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). J Neurosci 15:5476–5485

    PubMed  CAS  Google Scholar 

  • Fisher AA, Labenski MT, Malladi S et al (2007) Quinone electrophiles selectively adduct “electrophile binding motifs” within cytochrome c. Biochemistry 46(39):11090–11100

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald JL, Reid JJ (1994) Sympathomimetic actions of methylenedioxymethamphetamine in rat and rabbit isolated cardiovascular tissues. J Pharm Pharmacol 46:826–832

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald RL, Blanke RV, Poklis A (1990) Stereoselective pharmacokinetics of 3,4-methylenedioxymethamphetamine in the rat. Chirality 2(4):241–248

    Article  PubMed  CAS  Google Scholar 

  • Flanagan SW, Moseley PL, Buettner GR (1998) Increased flux of free radicals in cells subjected to hyperthermia: detection by electron paramagnetic resonance spin trapping. FEBS Lett 431:285–286

    Article  PubMed  CAS  Google Scholar 

  • Flanagin BA, Cook EHJ, deWit H (2006) An association study of the brain-derived neurotrophic factor Val66Met polymorphism and amphetamine response. Am J Med Genet B Neuropsychiatr Genet 141(6):576–583

    Google Scholar 

  • Fleckenstein AE, Hanson GR (2003) Impact of psychostimulants on vesicular monoamine transporter function. Eur J Pharmacol 479:283–289

    Article  PubMed  CAS  Google Scholar 

  • Fletcher PJ, Robinson SR, Slippoy DL (2001) Pre-exposure to (±)3,4-methylenedioxy-methamphetamine (MDMA) facilitates acquisition of intravenous cocaine self-administration in rats. Neuropsychopharmacology 25(2):195–203

    Article  PubMed  CAS  Google Scholar 

  • Florin SM, Kuczenski R, Segal DS (1994) Regional extracellular norepinephrine responses to amphetamine and cocaine and effects of clonidine pretreatment. Brain Res 654(1):53–62

    Article  PubMed  CAS  Google Scholar 

  • Foley RJ, Kapatkin K, Verani R, Weinman EJ (1984) Amphetamine-induced acute renal failure. South Med J 77:258–260

    Article  PubMed  CAS  Google Scholar 

  • Fowler JS, Kroll C, Ferrieri R et al (2007) PET studies of d-methamphetamine pharmacokinetics in primates: comparison with l-methamphetamine and (–)-cocaine. J Nucl Med 48(10):1724–1732

    Article  PubMed  CAS  Google Scholar 

  • Fowler JS, Volkow ND, Logan J et al (2008) Fast uptake and long-lasting binding of methamphetamine in the human brain: Comparison with cocaine. NeuroImage 43:756–763

    Article  PubMed  Google Scholar 

  • Freedman RR, Johanson CE, Tancer ME (2005) Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl) 183(2):248–256

    Article  CAS  Google Scholar 

  • Freezer A, Salem A, Irvine RJ (2005) Effects of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) and para-methoxyamphetamine on striatal 5-HT when co-administered with moclobemide. Brain Res 1041(1):48–55

    Article  PubMed  CAS  Google Scholar 

  • Fuller R, Hemrick-Luecke S (1980) Long-lasting depletion of striatal dopamine by a single injection of amphetamine in iprindole-treated rats. Science 209(4453):305–307

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli F, Gainetdinov RR, Valenzano KJ, Caron MG (1998) Role of dopamine transporter in methamphetamine-induced neurotoxicity: evidence from mice lacking the transporter. J Neurosci 18(13):4861–4869

    PubMed  CAS  Google Scholar 

  • Gandhi PJ, Ezeala GU, Luyen TT, Tu TC, Tran MT (2005) Myocardial infarction in an adolescent taking Adderall. Am J Health Syst Pharm 62(14):1494–1497

    Article  PubMed  Google Scholar 

  • Garbino J, Henry JA, Mentha G, Romand JA (2001) Ecstasy ingestion and fulminant hepatic failure: liver transplantation to be considered as a last therapeutic option. Vet Hum Toxicol 43(2):99–102

    PubMed  CAS  Google Scholar 

  • Garcia-Rates S, Camarasa J, Escubedo E, Pubill D (2007) Methamphetamine and 3,4-methylenedioxymethamphetamine interact with central nicotinic receptors and induce their up-regulation. Toxicol Appl Pharmacol 223(3):195–205

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Repetto R, Moreno E, Soriano T, Jurado C, Gimenez MP, Menendez M (2003) Tissue concentrations of MDMA and its metabolite MDA in three fatal cases of overdose. Forensic Sci Int 135(2):110–114

    Article  PubMed  CAS  Google Scholar 

  • Gerbershagen MU, Missler G, Schütte JK et al (2012) 3,4-Methylenedioxymethamphetamine (Ecstasy) increases the sensitivity of the contractile apparatus to calcium ions in both malignant hyperthermia-susceptible and normal skeletal muscle fibres. Eur J Anaesthesiol 29(1):42–49

    Article  PubMed  CAS  Google Scholar 

  • Gerevich J (2005) Fatal combination of ecstasy and heroin. Psychosomatics 46(2):189

    Article  PubMed  CAS  Google Scholar 

  • Gesi M, Soldani P, Lenzi P et al (2002) Ecstasy during loud noise exposure induces dramatic ultrastructural changes in the heart. Pharmacol Toxicol 91(1):29–33

    Article  PubMed  CAS  Google Scholar 

  • Gesi M, Ferrucci M, Giusiani M et al (2004) Loud noise enhances nigrostriatal dopamine toxicity induced by MDMA in mice. Microsc Res Tech 64(4):297–303

    Article  PubMed  CAS  Google Scholar 

  • Gilhooly TC, Daly AK (2002) CYP2D6 deficiency, a factor in ecstasy related deaths? Br J Clin Pharmacol 54(1):69–70

    Article  PubMed  CAS  Google Scholar 

  • Gill JR, Stajic M (2000) Ketamine in non-hospital and hospital deaths in New York City. J Forensic Sci 45(3):655–658

    PubMed  CAS  Google Scholar 

  • Ginsberg MD, Hertzman M, Schmidt-Nowara WW (1970) Amphetamine intoxication with coagulopathy, hyperthermia, and reversible renal failure. A syndrome resembling heatstroke. Ann Intern Med 73(1):81–85

    PubMed  CAS  Google Scholar 

  • Giroud C, Augsburger M, Sadeghipour F, Varesio E, Veuthey J-L, Rivier L (1997) Ecstasy-the situation in the French part of Switzerland: composition of the seized drugs, analysis of biological specimens and short review of its pharmacology and toxicology. Praxis (Bern 1994) 86:510–523

    Google Scholar 

  • Gollamudi R, Ali SF, Lipe G et al (1989) Influence of inducers and inhibitors on the metabolism in vitro and neurochemical effects in vivo of MDMA. Neurotoxicology 10(3):455–466

    PubMed  CAS  Google Scholar 

  • Gonzalez LP (1993) Cocaine alters body temperature and behavioral thermoregulatory responses. Neuroreport 4(1):106–108

    Article  PubMed  CAS  Google Scholar 

  • Gordon CJ, Watkinson WP, O’Callaghan JP, Miller DB (1991) Effects of 3,4-methylenedioxymethamphetamine on autonomic thermoregulatory responses of the rat. Pharmacol Biochem Behav 38(2):339–344

    Article  PubMed  CAS  Google Scholar 

  • Gouzoulis-Mayfrank E, Daumann J (2006) The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview. J Psychopharmacol 20(2):188–193

    Article  PubMed  CAS  Google Scholar 

  • Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol Rev 55(3):463–508

    Article  PubMed  CAS  Google Scholar 

  • Green AR, O’Shea E, Colado MI (2004) A review of the mechanisms involved in the acute MDMA (ecstasy)-induced hyperthermic response. Eur J Pharmacol 500(1–3):3–13

    Article  PubMed  CAS  Google Scholar 

  • Greene SL, Dargan PI, O’Connor N, Jones AL, Kerins M (2003) Multiple toxicity from 3,4-methylenedioxymethamphetamine (“ecstasy”). Am J Emerg Med 21(2):121–124

    Article  PubMed  Google Scholar 

  • Greene SL, Kerr F, Braitberg G (2008) Review article: amphetamines and related drugs of abuse. Emerg Med Australas 20(5):391–402

    Article  PubMed  Google Scholar 

  • Greer G, Strassman RJ (1985) Information on “Ecstasy”. Am J Psychiatry 142:1391

    PubMed  CAS  Google Scholar 

  • Grinspoon L, Bakalar JB (1986) Can drugs be used to enhance the psychotherapeutic process? Am J Psychotherapy 40:393–404

    CAS  Google Scholar 

  • Grunau BE, Wiens MO, Brubacher JR (2010) Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review. CJEM 12(5):435–442

    PubMed  Google Scholar 

  • Gudelsky GA, Nash JF (1996) Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implications for serotonin-dopamine interactions. J Neurochem 66:243–249

    Article  PubMed  CAS  Google Scholar 

  • Guilarte TR, Nihei MK, McGlothan JL, Howard AS (2003) Methamphetamine-induced deficits of brain monoaminergic neuronal markers: distal axotomy or neuronal plasticity. Neuroscience 122(2):499–513

    Article  PubMed  CAS  Google Scholar 

  • Haggkvist J, Bjorkholm C, Steensland P, Lindholm S, Franck J, Schilstrom B (2011) Naltrexone attenuates amphetamine-induced locomotor sensitization in the rat. Addict Biol 16(1):20–29. doi:10.1111/j.1369-1600.2009.00199.x

    Article  PubMed  CAS  Google Scholar 

  • Haile CN, Kosten TR, Kosten TA (2009) Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine. Am J Drug Alcohol Abuse 35(3):161–177

    Article  PubMed  Google Scholar 

  • Halachanova V, Sansone RA, McDonald S (2001) Delayed rhabdomyolysis after ecstasy use. Mayo Clin Proc 76(1):112–113

    Article  PubMed  CAS  Google Scholar 

  • Hall W, Hando J (1994) Route of administration and adverse effects of amphetamine use among young adults in Syndney, Australia. Drug Alcohol Rev 13(3):277–284

    Article  PubMed  CAS  Google Scholar 

  • Hall AP, Henry JA (2006) Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth 96(6):678–685

    Article  PubMed  CAS  Google Scholar 

  • Hamida SB, Plute E, Cosquer B, Kelche C, Jones BC, Cassel JC (2008) Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat: thermoregulatory and locomotor effects. Psychopharmacology (Berl) 197(1):67–82

    Article  CAS  Google Scholar 

  • Hamidovic A, Dlugos A, Palmer AA, deWit H (2010) Polymorphisms in dopamine transporter (SLC6A3) are associated with stimulant effects of D-amphetamine: an exploratory pharmacogenetic study using healthy volunteers. Behav Genet 40(2):255–261

    Article  PubMed  Google Scholar 

  • Hanspeter L (1981) Fluorescence histochemistry indicates damage of striatal dopamine nerve terminals in rats after multiple doses of methamphetamine. Life Sci 28(8):911–916

    Article  Google Scholar 

  • Harrington RD, Woodward JA, Hooton TM, Horn JR (1999) Life-threatening interactions between HIV-1 protease inhibitors and the illicit drugs MDMA and gamma-hydroxybutyrate. Arch Intern Med 159(18):2221–2224

    Article  PubMed  CAS  Google Scholar 

  • Harris DS, Boxenbaum H, Everhart ET, Sequeira G, Mendelson JE, Jones RT (2003) The bioavailability of intranasal and smoked methamphetamine. Clin Pharmacol Ther 74(5):475–486

    Article  PubMed  CAS  Google Scholar 

  • Hart CL, Gunderson EW, Perez A et al (2008) Acute physiological and behavioral effects of intranasal methamphetamine in humans. Neuropsychopharmacology 33(8):1847–1855

    Article  PubMed  CAS  Google Scholar 

  • Harvey JK, Todd CW, Howard JW (1949) Fatality associated with benzedrine ingestion; a case report. Del Med J 21(7):111–115

    PubMed  CAS  Google Scholar 

  • Hashimoto K, Maeda H, Hirai K, Goromaru T (1993) Drug effects on distribution of [3H]3,4-methylenedioxymethamphetamine in mice. Eur J Pharmacol 228(5–6):247–256

    PubMed  CAS  Google Scholar 

  • Hashimoto T, Hashimoto K, Matsuzawa D et al (2005) A functional glutathione S-transferase P1 gene polymorphism is associated with methamphetamine-induced psychosis in Japanese population. Am J Med Genet B Neuropsychiatr Genet 135(1):5–9

    Google Scholar 

  • Hatzidimitriou G, McCann UD, Ricaurte GA (1999) Altered serotonin innervation patterns in the forebrain of monkeys treated with (±)3,4-methylenedioxymethamphetamine seven years previously: factors influencing abnormal recovery. J Neurosci 15:5096–5107

    Google Scholar 

  • He SY (1995) Methamphetamine-induced toxicity in cultured adult rat cardiomyocytes. Nihon Hoigaku Zasshi 49(3):175–186

    PubMed  CAS  Google Scholar 

  • Hegadoren KM, Baker GB, Bourin M (1999) 3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans. Neurosci Biobehav Rev 23(4):539–553

    Article  PubMed  CAS  Google Scholar 

  • Helmlin HJ, Bracher K, Bourquin D, Vonlanthen D, Brenneisen R (1996) Analysis of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in plasma and urine by HPLC-DAD and GC-MS. J Anal Toxicol 20(6):432–440

    PubMed  CAS  Google Scholar 

  • Henry J (1992) Ecstasy and the dance of death. Br Med J 350:5–6

    Article  Google Scholar 

  • Henry JA, Hill IR (1998) Fatal interaction between ritonavir and MDMA. Lancet 352(9142):1751–1752

    Article  PubMed  CAS  Google Scholar 

  • Henry JA, Jeffreys KJ, Dawling S (1992) Toxicity and deaths from 3,4-methylenedioxymethamphetamine (“ecstasy”). Lancet 340:384–387

    Article  PubMed  CAS  Google Scholar 

  • Hernandez-Lopez C, Farre M, Roset PN et al (2002) 3,4-Methylenedioxymethamphetamine (ecstasy) and alcohol interactions in humans: psychomotor performance, subjective effects, and pharmacokinetics. J Pharmacol Exp Ther 300(1):236–244

    Article  PubMed  CAS  Google Scholar 

  • Heydari A, Yeo KR, Lennard MS, Ellis SW, Tucker GT, Rostami-Hodjegan A (2004) Mechanism-based inactivation of CYP2D6 by methylenedioxymethamphetamine. Drug Metab Dispos 32(11):1213–1217

    Article  PubMed  CAS  Google Scholar 

  • Hijazi Y, Boulieu R (2002) Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metab Dispos 30(7):853–858

    Article  PubMed  CAS  Google Scholar 

  • Hiramatsu M, Kumagai Y, Unger SE, Cho AK (1990) Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct. J Pharmacol Exp Ther 254(2):521–527

    PubMed  CAS  Google Scholar 

  • Hohoff C, McDonald JM, Baune BT, Cook EH, Deckert J, deWit H (2005) Interindividual variation in anxiety response to amphetamine: possible role for adenosine A2A receptor gene variants. Am J Med Genet B Neuropsychiatr Genet 139(1):42–44

    Google Scholar 

  • Holt SG, Moore KP (2001) Pathogenesis and treatment of renal dysfunction in rhabdomyolysis. Intensive Care Med 27(5):803–811

    Article  PubMed  CAS  Google Scholar 

  • Hong R, Matsuyama E, Nur K (1991) Cardiomyopathy associated with the smoking of crystal methamphetamine. JAMA 265(9):1152–1154

    Article  PubMed  CAS  Google Scholar 

  • Hua YS, Liang R, Liang L, Huang GZ (2009) Contraction band necrosis in two ecstasy abusers: a latent lethal lesion associated with ecstasy. Am J Forensic Med Pathol 30(3):295–297

    Article  PubMed  Google Scholar 

  • Huang N-K, Wan F-J, Tseng C-J, Tung C-S (1997) Amphetamine induces hydroxyl radical formation in the striatum of rats. Life Sci 61(22):2219–2229

    Article  PubMed  CAS  Google Scholar 

  • Hung MJ, Kuo LT, Cherng WJ (2003) Amphetamine-related acute myocardial infarction due to coronary artery spasm. Int J Clin Pract 57(1):62–64

    PubMed  CAS  Google Scholar 

  • Hysek CM, Simmler LD, Ineichen M et al (2011) The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA (“ecstasy”) in humans. Clin Pharmacol Ther 90(2):246–255. doi:10.1038/clpt.2011.78

    Article  PubMed  CAS  Google Scholar 

  • Ide S, Kobayashi H, Ujike H et al (2006) Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms. Pharmacogenomics J 6(3):179–188

    Article  PubMed  CAS  Google Scholar 

  • Imam SZ, Newport GD, Itzhak Y et al (2001) Peroxynitrite plays a role in methamphetamine-induced dopaminergic neurotoxicity: evidence from mice lacking neuronal nitric oxide synthase gene or overexpressing copper–zinc superoxide dismutase. J Neurochem 76(3):745–749

    Article  PubMed  CAS  Google Scholar 

  • Ioannides C (1999) Effect of diet and nutrition on the expression of cytochromes P450. Xenobiotica 29(2):109–154

    Article  PubMed  CAS  Google Scholar 

  • Ishigami A, Tokunaga I, Gotohda T, Kubo S (2003) Immunohistochemical study of myoglobin and oxidative injury-related markers in the kidney of methamphetamine abusers. Leg Med (Tokyo) 5(1):42–48

    Article  CAS  Google Scholar 

  • Islam MN, Jesmine K, Kong Sn Molh A, Hasnan J (2009) Histopathological studies of cardiac lesions after long term administration of Methamphetamine in high dosage: Part II. Legal Medicine 11(Suppl 1):S147–S150

  • Ito H, Yeo KK, Wijetunga M, Seto TB, Tay K, Schatz IJ (2009) A comparison of echocardiographic findings in young adults with cardiomyopathy: with and without a history of methamphetamine abuse. Clin Cardiol 32(6):E18–E22

    Article  PubMed  Google Scholar 

  • Izco M, Orio L, O’Shea E, Colado MI (2007) Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain. Psychopharmacology (Berl) 189(4):459–470

    Article  CAS  Google Scholar 

  • Jacobs LJ (1989) Reversible dilated cardiomyopathy induced by methamphetamine. Clin Cardiol 12(12):725–727

    Article  PubMed  CAS  Google Scholar 

  • Jacobs W (2006) Fatal amphetamine-associated cardio toxicity and its medicolegal implications. Am J Forensic Med Pathol 27(2):156–160

    Article  PubMed  Google Scholar 

  • Jaehne EJ, Salem A, Irvine RJ (2007) Pharmacological and behavioral determinants of cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine, and para-methoxyamphetamine-induced hyperthermia. Psychopharmacology (Berl) 194(1):41–52

    Article  CAS  Google Scholar 

  • Jaehne EJ, Salem A, Irvine RJ (2008) The effect of long-term repeated exposure to 3,4-methylenedioxymethamphetamine on cardiovascular and thermoregulatory changes. Psychopharmacology (Berl) 201(2):161–170

    Article  CAS  Google Scholar 

  • Jayanthi S, Deng X, Noailles P-AH, Ladenheim B, Cadet JL (2004) Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB J 18(2):238–251

    Article  PubMed  CAS  Google Scholar 

  • Jayaram-Lindstrom N, Wennberg P, Hurd YL, Franck J (2004) Effects of naltrexone on the subjective response to amphetamine in healthy volunteers. J Clin Psychopharmacol 24(6):665–669

    Article  PubMed  Google Scholar 

  • Jayaram-Lindstrom N, Konstenius M, Eksborg S, Beck O, Hammarberg A, Franck J (2008) Naltrexone attenuates the subjective effects of amphetamine in patients with amphetamine dependence. Neuropsychopharmacology 33(8):1856–1863

    Article  PubMed  CAS  Google Scholar 

  • Jeng W, Wong AW, Ting-A-Kee R, Wells PG (2005) Methamphetamine-enhanced embryonic oxidative DNA damage and neurodevelopmental deficits. Free Radic Biol Med 39(3):317–326

    Article  PubMed  CAS  Google Scholar 

  • Jimenez A, Jorda EG, Verdaguer E et al (2004) Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells. Toxicol Appl Pharmacol 196(2):223–234

    Article  PubMed  CAS  Google Scholar 

  • Johansson I, Oscarson M, Yue QY, Bertilsson L, Sjoqvist F, Ingelman-Sundberg M (1994) Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol 46(3):452–459

    PubMed  CAS  Google Scholar 

  • Johnson M, Letter AA, Merchant K, Hanson GR, Gibb JW (1988) Effects of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine isomers on central serotonergic, dopaminergic and nigral neurotensin systems of the rat. J Pharmacol Exp Ther 244(3):977–982

    PubMed  CAS  Google Scholar 

  • Johnson EA, O’Callaghan JP, Miller DB (2002a) Chronic treatment with supraphysiological levels of corticosterone enhances D-MDMA-induced dopaminergic neurotoxicity in the C57BL/6 J female mouse. Brain Res 933(2):130–138

    Article  PubMed  CAS  Google Scholar 

  • Johnson EA, Shvedova AA, Kisin E, O’Callaghan JP, Kommineni C, Miller DB (2002b) d-MDMA during vitamin E deficiency: effects on dopaminergic neurotoxicity and hepatotoxicity. Brain Res 933(2):150–163

    Article  PubMed  CAS  Google Scholar 

  • Johnson EA, O’Callaghan JP, Miller DB (2004) Brain concentrations of d-MDMA are increased after stress. Psychopharmacology (Berl) 173(3–4):278–286

    Article  CAS  Google Scholar 

  • Johnson BA, Elkashef AM, Seneviratne C et al (2010) Association between genotype of the serotonin transporter-linked polymorphic region of the serotonin transporter gene and age of onset of methamphetamine use: a preliminary analysis. Front Psychiatry 1:145

    PubMed  CAS  Google Scholar 

  • Jones AW (2005) Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances. Traffic Inj Prev 6(4):317–322

    Article  PubMed  Google Scholar 

  • Jones AL, Jarvie DR, McDermid G, Proudfoot AT (1994) Hepatocellular damage following amphetamine intoxication. Clin Toxicol 32:435–444

    Article  CAS  Google Scholar 

  • Jones DC, Duvauchelle C, Ikegami A et al (2005) Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J Pharmacol Exp Ther 313(1):422–431

    Article  PubMed  CAS  Google Scholar 

  • Jonsson G, Nwanze E (1982) Selective (+)-amphetamine neurotoxicity on striatal dopamine nerve terminals in the mouse. Br J Pharmacol 77(2):335–345

    Article  PubMed  CAS  Google Scholar 

  • Kahlig KM, Binda F, Khoshbouei H et al (2005) Amphetamine induces dopamine efflux through a dopamine transporter channel. Proc Natl Acad Sci 102(9):3495–3500

    Article  PubMed  CAS  Google Scholar 

  • Kahraman A, Miller M, Gieseler RK, Gerken G, Scolaro MJ, Canbay A (2006) Non-alcoholic fatty liver disease in HIV-positive patients predisposes for acute-on-chronic liver failure: two cases. Eur J Gastroenterol Hepatol 18(1):101–105

    Article  PubMed  Google Scholar 

  • Kalant H (2001) The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. Can Med Assoc J 165(7):917–928

    CAS  Google Scholar 

  • Kalant H, Kalant OJ (1975) Death in amphetamine users: causes and rates. Can Med Assoc J 112:299–304

    PubMed  CAS  Google Scholar 

  • Kamei J, Mori T, Igarashi H, Kasuya Y (1992) Serotonin release in nucleus of the solitary tract and its modulation by antitussive drugs. Res Commun Chem Pathol Pharmacol 76(3):371–374

    PubMed  CAS  Google Scholar 

  • Karch SB (2011) The unique histology of methamphetamine cardiomyopathy: A case report. Forensic Sci Int 212(1–3):e1–e4

    Article  PubMed  CAS  Google Scholar 

  • Karila L, Reynaud M (2011) GHB and synthetic cathinones: clinical effects and potential consequences. Drug Test Anal 3(9):552–559

    Article  PubMed  CAS  Google Scholar 

  • Kaye S, McKetin R, Duflou J, Darke S (2007) Methamphetamine and cardiovascular pathology: a review of the evidence. Addiction 102(8):1204–1211

    Article  PubMed  Google Scholar 

  • Kelly MP, Logue SF, Dwyer JM et al (2009) The supra-additive hyperactivity caused by an amphetamine-chlordiazepoxide mixture exhibits an inverted-U dose response: negative implications for the use of a model in screening for mood stabilizers. Pharmacol Biochem Behav 92(4):649–654

    Article  PubMed  CAS  Google Scholar 

  • Kendrick WC, Hull AR, Knochel JP (1977) Rhabdomyolysis and shock after intravenous amphetamine administration. Ann Int Med 86:381–387

    PubMed  CAS  Google Scholar 

  • Khakoo SI, Coles CJ, Armstrong JS, Barry RE (1995) Hepatotoxicity and accelerated fibrosis following 3,4-methylenedioxymetamphetamine (“ecstasy”) usage. J Clin Gastroenterol 20(3):244–247

    Article  PubMed  CAS  Google Scholar 

  • Kidwell DA, Holland JC, Athanaselis S (1998) Testing for drugs of abuse in saliva and sweat. J Chromatogr B Biomed Sci Appl 713(1):111–135

    Article  PubMed  CAS  Google Scholar 

  • Kim SK, Novak RF (2007) The role of intracellular signaling in insulin-mediated regulation of drug metabolizing enzyme gene and protein expression. Pharmacol Ther 113(1):88–120

    Article  PubMed  CAS  Google Scholar 

  • Kim I, Oyler JM, Moolchan ET, Cone EJ, Huestis MA (2004) Urinary pharmacokinetics of methamphetamine and its metabolite, amphetamine following controlled oral administration to humans. Ther Drug Monit 26(6):664–672

    Article  PubMed  CAS  Google Scholar 

  • Kish SJ, Lerch J, Furukawa Y et al (2010) Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[11C]DASB and structural brain imaging study. Brain 133(6):1779–1797

    Article  PubMed  Google Scholar 

  • Kita T, Miyazaki I, Asanuma M, Takeshima M, Wagner GC (2009) Dopamine-induced behavioral changes and oxidative stress in methamphetamine-induced neurotoxicity. Int Rev Neurobiol 88:43–64

    Article  PubMed  CAS  Google Scholar 

  • Klein M, Kramer F (2004) Rave drugs: pharmacological considerations. Aana J 72:61–67

    PubMed  Google Scholar 

  • Kleven MS, Seiden LS (1992) Methamphetamine-induced neurotoxicity: structure activity relationships. Ann N Y Acad Sci 654:292–301

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi H, Ujike H, Iwata N et al (2010) The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population. Behav Brain Funct 6:50

    Article  PubMed  CAS  Google Scholar 

  • Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA (2008) Plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine after controlled oral administration to young adults. Ther Drug Monit 30(3):320–332

    Article  PubMed  CAS  Google Scholar 

  • Konno C, Taguchi T, Tamada M, Hikino H (1979) Ephedroxane, anti-inflammatory principle of Ephedra herbs. Phytochemistry 18:697–698

    Article  CAS  Google Scholar 

  • Kopelman MD, Reed LJ, Marsden P et al (2001) Amnesic syndrome and severe ataxia following the recreational use of 3,4-methylene-dioxymethamphetamine (MDMA, ‘ecstasy’) and other substances. Neurocase 7(5):423–432

    Article  PubMed  CAS  Google Scholar 

  • Kraemer T, Maurer HH (2002) Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives. Ther Drug Monit 24(2):277–289

    Article  PubMed  CAS  Google Scholar 

  • Krasnova IN, Cadet JL (2009) Methamphetamine toxicity and messengers of death. Brain Res Rev 60(2):379–407

    Article  PubMed  CAS  Google Scholar 

  • Krasnova IN, Ladenheim B, Cadet JL (2005) Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway. FASEB J 19:851–853

    PubMed  CAS  Google Scholar 

  • Kreth K, Kovar K, Schwab M, Zanger UM (2000) Identification of the human cytochromes P450 involved in the oxidative metabolism of “Ecstasy”-related designer drugs. Biochem Pharmacol 59(12):1563–1571

    Article  PubMed  CAS  Google Scholar 

  • Kumagai Y, Lin LY, Schmitz DA, Cho AK (1991) Hydroxyl radical mediated demethylenation of (methylenedioxy)phenyl compounds. Chem Res Toxicol 4(3):330–334

    Article  PubMed  CAS  Google Scholar 

  • Kurling S, Kankaanpaa A, Seppala T (2008) Sub-chronic nandrolone treatment modifies neurochemical and behavioral effects of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in rats. Behav Brain Res 189(1):191–201

    Article  PubMed  CAS  Google Scholar 

  • Kuwayama K, Inoue H, Kanamori T et al (2007) Interactions between 3,4-methylenedioxymethamphetamine, methamphetamine, ketamine, and caffeine in human intestinal Caco-2 cells and in oral administration to rats. Forensic Sci Int 170(2–3):183–188

    Article  PubMed  CAS  Google Scholar 

  • Kuypers KP, Samyn N, Ramaekers JG (2006) MDMA and alcohol effects, combined and alone, on objective and subjective measures of actual driving performance and psychomotor function. Psychopharmacology 187(4):467–475

    Article  PubMed  CAS  Google Scholar 

  • Kwon C, Zaritsky A, Dharnidharka VR (2003) Transient proximal tubular renal injury following Ecstasy ingestion. Pediatr Nephrol 18(8):820–822

    Article  PubMed  Google Scholar 

  • Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM (1996) Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6(3):243–250

    Article  PubMed  CAS  Google Scholar 

  • Lansbergen MM, Dumont GJ, van Gerven JM, Buitelaar JK, Verkes RJ (2011) Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol). Psychopharmacology 213(4):745–756

    Article  PubMed  CAS  Google Scholar 

  • Leith NJ, Barrett RJ (1981) Self-stimulation and amphetamine: tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate. Psychopharmacology 74(1):23–28

    Article  PubMed  CAS  Google Scholar 

  • Leitz FH, Stefano FJ (1971) The effect of tyramine, amphetamine and metaraminol on the metabolic disposition of 3 H-norepinephrine released from the adrenergic neuron. J Pharmacol Exp Ther 178(3):464–473

    PubMed  CAS  Google Scholar 

  • Lesch KP, Gutknecht L (2005) Pharmacogenetics of the serotonin transporter. Prog Neuropsychopharmacol Biol Psychiatry 29(6):1062–1073

    Article  PubMed  CAS  Google Scholar 

  • Lester SJ, Baggott M, Welm S et al (2000) Cardiovascular effects of 3,4-methylenedioxymethamphetamine. A double-blind, placebo-controlled trial. Ann Intern Med 133(12):969–973

    PubMed  CAS  Google Scholar 

  • Li T, Chen CK, Hu X et al (2004) Association analysis of the DRD4 and COMT genes in methamphetamine abuse. Am J Med Genet B Neuropsychiatr Genet 129(1):120–124

    Article  Google Scholar 

  • Liang R, Zhou Y, Wu F et al (2010) Effect of methamphetamine on potassium and L-type calcium currents in rat ventricular myocytes. Toxicol Mech Methods 20(8):458–465

    Article  PubMed  CAS  Google Scholar 

  • Liechti ME, Vollenweider FX (2000) The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine (‘Ecstasy’) in healthy volunteers. J Psychopharmacol 14(3):269–274

    Article  PubMed  CAS  Google Scholar 

  • Liechti ME, Baumann C, Gamma A, Vollenweider FX (2000a) Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) are attenuated by the serotonin uptake inhibitor citalopram. Neuropsychopharmacology 22(5):513–521

    Article  PubMed  CAS  Google Scholar 

  • Liechti ME, Saur MR, Gamma A, Hell D, Vollenweider FX (2000b) Psychological and physiological effects of MDMA (“Ecstasy”) after pretreatment with the 5-HT(2) antagonist ketanserin in healthy humans. Neuropsychopharmacology 23(4):396–404

    Article  PubMed  CAS  Google Scholar 

  • Liechti ME, Gamma A, Vollenweider FX (2001) Gender differences in the subjective effects of MDMA. Psychopharmacology 154(2):161–168

    Article  PubMed  CAS  Google Scholar 

  • Liechti ME, Kunz I, Kupferschmidt H (2005) Acute medical problems due to Ecstasy use. Case-series of emergency department visits. Swiss Med Wkly 135(43–44):652–657

    PubMed  Google Scholar 

  • Lile JA, Babalonis S, Emurian C, Martin CA, Wermeling DP, Kelly TH (2011) Comparison of the behavioral and cardiovascular effects of intranasal and oral d-amphetamine in healthy human subjects. J Clin Pharmacol 51(6):888–898

    Article  PubMed  CAS  Google Scholar 

  • Lim HK, Foltz RL (1988) In vivo and in vitro metabolism of 3,4-(methylenedioxy)methamphetamine in the rat: identification of metabolites using an ion trap detector. Chem Res Toxicol 1(6):370–378

    Article  PubMed  CAS  Google Scholar 

  • Lim HK, Foltz RL (1989) Identification of metabolites of 3,4-(methylenedioxy)methamphetamine in human urine. Chem Res Toxicol 2(3):142–143

    Article  PubMed  CAS  Google Scholar 

  • Lim HK, Foltz RL (1991) In vivo formation of aromatic hydroxylated metabolites of 3,4-(methylenedioxy)methamphetamine in the rat: identification by ion trap tandem mass spectrometric (MS/MS and MS/MS/MS) techniques. Biol Mass Spectrom 20(11):677–686

    Article  PubMed  CAS  Google Scholar 

  • Lim HK, Foltz RL (1998) In vivo and in vitro metabolism of 3,4-(methylenedioxy)methamphetamine in the rat: identification of metabolites using an ion trap detector. Chem Res Toxicol 1:370–378

    Article  Google Scholar 

  • Lin LY, Kumagai Y, Cho AK (1992) Enzymatic and chemical demethylenation of (methylenedioxy)amphetamine and (methylenedioxy)methamphetamine by rat brain microsomes. Chem Res Toxicol 5(3):401–406

    Article  PubMed  CAS  Google Scholar 

  • Lin LY, DiStefano EW, Schmitz DA et al (1997) Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos 25(9):1059–1064

    PubMed  CAS  Google Scholar 

  • Lord KC, Shenouda SK, McIlwain E, Charalampidis D, Lucchesi PA, Varner KJ (2010) Oxidative stress contributes to methamphetamine-induced left ventricular dysfunction. Cardiovasc Res 87(1):111–118

    Article  PubMed  CAS  Google Scholar 

  • Lott DC, Kim SJ, Cook EHJ, deWit H (2005) Dopamine transporter gene associated with diminished subjective response to amphetamine. Neuropsychopharmacology 30(3):602–609

    Article  PubMed  CAS  Google Scholar 

  • Lott DC, Kim SJ, Cook EHJ, deWit H (2006) Serotonin transporter genotype and acute subjective response to amphetamine. Am J Addict 15(5):327–335

    Article  PubMed  Google Scholar 

  • Lotta T, Vidgren J, Tilgmann C et al (1995) Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 34(13):4202–4210

    Article  PubMed  CAS  Google Scholar 

  • Lumlertgul D, Chuaychoo B, Thitiarchakul S, Srimahachota S, Sangchun K, Keoplung M (1992) Heat stroke-induced multiple organ failure. Ren Fail 14(1):77–80

    Article  PubMed  CAS  Google Scholar 

  • Lundstrom K, Tenhunen J, Tilgmann C, Karhunen T, Panula P, Ulmanen I (1995) Cloning, expression and structure of catechol-O-methyltransferase. Biochim Biophys Acta 1251(1):1–10

    Article  PubMed  CAS  Google Scholar 

  • Lynch JJ, Regan C, Stump G et al (2009) Hemodynamic and cardiac neurotransmitter-releasing effects in conscious dogs of attention- and wake-promoting agents: a comparison of d-amphetamine, atomoxetine, modafinil, and a novel quinazolinone H3 inverse agonist. J Cardiovasc Pharmacol 53(1):52–59

    Article  PubMed  CAS  Google Scholar 

  • Macedo C, Branco PS, Ferreira LM et al (2007) Synthesis and cyclic voltammetry studies of 3,4-methylenedioxymethamphetamine (MDMA) human metabolites. J Health Sci 53(1):31–42

    Article  CAS  Google Scholar 

  • Maeno Y, Iwasa M, Inoue H, Koyama H, Matoba R (2000a) Methamphetamine induces an increase in cell size and reorganization of myofibrils in cultured adult rat cardiomyocytes. Int J Legal Med 113(4):201–207

    Article  PubMed  CAS  Google Scholar 

  • Maeno Y, Iwasa M, Inoue H, Koyama H, Matoba R, Nagao M (2000b) Direct effects of methamphetamine on hypertrophy and microtubules in cultured adult rat ventricular myocytes. Forensic Sci Int 113(1–3):239–243

    Article  PubMed  CAS  Google Scholar 

  • Makisumi T, Yoshida K, Watanabe T, Tan N, Murakami N, Morimoto A (1998) Sympatho-adrenal involvement in methamphetamine-induced hyperthermia through skeletal muscle hypermetabolism. Eur J Pharmacol 363(2–3):107–112

    Article  PubMed  CAS  Google Scholar 

  • Malberg JE, Seiden LS (1998) Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. J Neurosci 18(13):5086–5094

    PubMed  CAS  Google Scholar 

  • Mandell AJ, Morgan M (1970) Amphetamine induced increase in tyrosine hydroxylase activity. Nature 227(5153):75–76

    Article  PubMed  CAS  Google Scholar 

  • Mantle TJ, Tipton KF, Garrett NJ (1976) Inhibition of monoamine oxidase by amphetamine and related compounds. Biochem Pharmacol 25(18):2073–2077

    Article  PubMed  CAS  Google Scholar 

  • Marks DH (2008) Cardiomyopathy due to ingestion of Adderall. Am J Ther 15(3):287–289

    Article  PubMed  Google Scholar 

  • Mas M, Farré M, de la Torre R et al (1999) Cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetamine in humans. J Pharmacol Exp Ther 290(1):136–145

    PubMed  CAS  Google Scholar 

  • Masimirembwa C, Persson I, Bertilsson L, Hasler J, Ingelman-Sundberg M (1996) A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity. Br J Clin Pharmacol 42(6):713–719

    Article  PubMed  CAS  Google Scholar 

  • Matsunaga T, Kishi N, Higuchi S, Watanabe K, Ohshima T, Yamamoto I (2000) CYP3A4 is a major isoform responsible for oxidation of 7-hydroxy-Delta(8)-tetrahydrocannabinol to 7-oxo-delta(8)-tetrahydrocannabinol in human liver microsomes. Drug Metab Dispos 28(11):1291–1296

    PubMed  CAS  Google Scholar 

  • Mattay VS, Goldberg TE, Fera F et al (2003) Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci USA 100(10):6186–6191

    Article  PubMed  CAS  Google Scholar 

  • Maurer HH (1996) On the metabolism and the toxicological analysis of methylenedioxyphenylalkylamine designer drugs by gas chromatography-mass spectrometry. Ther Drug Monit 18(4):465–470

    Article  PubMed  CAS  Google Scholar 

  • Maurer HH, Bickeboeller-Friedrich J, Kraemer T, Peters FT (2000) Toxicokinetics and analytical toxicology of amphetamine-derived designer drugs (‘Ecstasy’). Toxicol Lett 112–113:133–142

    Article  PubMed  Google Scholar 

  • McCann UD, Ridenour A, Shaham Y, Ricaurte GA (1994) Serotonin neurotoxicity after (+/−)3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”): a controlled study in humans. Neuropsychopharmacology 10(2):129–138

    PubMed  CAS  Google Scholar 

  • McCann UD, Slate SO, Ricaurte GA (1996) Adverse reactions with 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”). Drug Saf 15:107–115

    Article  PubMed  CAS  Google Scholar 

  • McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA (1998) Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings. Lancet 352(9138):1433–1437

    Article  PubMed  CAS  Google Scholar 

  • McCann UD, Mertl M, Eligulashvili V, Ricaurte G (1999) Cognitive performance in 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) users: a controlled study. Psychopharmacology 143:417–425

    Article  PubMed  CAS  Google Scholar 

  • McCann UD, Szabo Z, Seckin E et al (2005) Quantitative PET studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C]DASB. Neuropsychopharmacology 30:1741–1750

    Article  PubMed  CAS  Google Scholar 

  • McCann UD, Szabo Z, Vranesic M et al (2008) Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (±)3,4-methylenedioxymethamphetamine (“ecstasy”) users: relationship to cognitive performance. Psychopharmacology (Berl) 200(3):439–450

    Article  CAS  Google Scholar 

  • McDaid J, Docherty JR (2001) Vascular actions of MDMA involve alpha1 and alpha2-adrenoceptors in the anaesthetized rat. Br J Pharmacol 133(3):429–437

    Article  PubMed  CAS  Google Scholar 

  • McElhatton PR, Bateman DN, Evans C, Pughe KR, Thomas SH (1999) Congenital anomalies after prenatal ecstasy exposure. Lancet 354:1441–1442

    Article  PubMed  CAS  Google Scholar 

  • McLean JR, McCartney M (1961) Effect of D-Amphetamine on Rat Brain Noradrenaline and Serotonin. In: Proceedings of the society for experimental biology and medicine society for experimental biology and medicine, New York, NY. 107(1):77–79

  • McNamara R, Kerans A, O’Neill B, Harkin A (2006) Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA (“Ecstasy”) and MDA (“Love”). Neuropharmacology 50:69–80

    Article  PubMed  CAS  Google Scholar 

  • Mechan AO, Esteban B, O’Shea E, Elliott JM, Colado MI, Green AR (2002) The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats. Br J Pharmacol 135:170–180

    Article  PubMed  CAS  Google Scholar 

  • Meisel C, Gerloff T, Kirchheiner J et al (2003) Implications of pharmacogenetics for individualizing drug treatment and for study design. J Mol Med 81(3):154–167

    PubMed  Google Scholar 

  • Melega WP, Jorgensen MJ, Laćan G et al (2008) Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioral profiles. Neuropsychopharmacology 33(6):1441–1452

    Article  PubMed  CAS  Google Scholar 

  • Mendelson J, Jones RT, Upton R, Jacob P III (1995) Methamphetamine and ethanol interactions in humans. Clin Pharmacol Ther 57(5):559–568

    Article  PubMed  CAS  Google Scholar 

  • Meyer A, Mayerhofer A, Kovar KA, Schmidt WJ (2002a) Enantioselective metabolism of the designer drugs 3,4-methylenedioxymethamphetamine (‘ecstasy’) and 3,4-methylenedioxyethylamphetamine (‘eve’) isomers in rat brain and blood. Neurosci Lett 330(2):193–197

    Article  PubMed  CAS  Google Scholar 

  • Meyer A, Mayerhofer A, Kovar KA, Schmidt WJ (2002b) Rewarding effects of the optical isomers of 3,4-methylenedioxy-methylamphetamine (‘Ecstasy’) and 3,4-methylenedioxy-ethylamphetamine (‘Eve’) measured by conditioned place preference in rats. Neurosci Lett 330(3):280–284

    Article  PubMed  CAS  Google Scholar 

  • Meyer JS, Grande M, Johnson K, Ali SF (2004) Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats. Int J Dev Neurosci 22(5–6):261–271

    Article  PubMed  CAS  Google Scholar 

  • Miller DB, O’Callaghan JP (1994) Environment-, drug- and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57BL/6 J mouse. J Pharmacol Exp Ther 270(2):752–760

    PubMed  CAS  Google Scholar 

  • Miller DB, O’Callaghan JP (2003) Elevated environmental temperature and methamphetamine neurotoxicity. Environ Res 92(1):48–53

    Article  PubMed  CAS  Google Scholar 

  • Miller RT, Lau SS, Monks TJ (1996) Effects of intracerebroventricular administration of 5-(glutathion-S-yl)-α-methyldopamine on brain dopamine, serotonin, and norepinephrine concentrations in male sprague-dawley rats. Chem Res Toxicol 9(2):457–465

    Article  PubMed  CAS  Google Scholar 

  • Miller RT, Lau SS, Monks TJ (1997) 2,5-Bis-(glutathion-S-yl)-alpha-methyldopamine, a putative metabolite of (±)-3,4-methylenedioxyamphetamine, decreases brain serotonin concentrations. Eur J Pharmacol 323(2–3):173–180

    Article  PubMed  CAS  Google Scholar 

  • Mills EM, Banks ML, Sprague JE, Finkel T (2003) Pharmacology: uncoupling the agony from ecstasy. Nature 426(6965):403–404

    Article  PubMed  CAS  Google Scholar 

  • Mills EM, Rusyniak DE, Sprague JE (2004) The role of the sympathetic nervous system and uncoupling proteins in the thermogenesis induced by 3,4-methylenedioxymethamphetamine. J Mol Med (Berl) 82(12):787–799

    Article  CAS  Google Scholar 

  • Milroy CM, Clark JC, Forrest AR (1996) Pathology of deaths associated with “ecstasy” and “eve” misuse. J Clin Pathol 49(2):149–153

    Article  PubMed  CAS  Google Scholar 

  • Molliver ME, Berger UV, Mamounas LA, Molliver DC, O’Hearn E, Wilson MA (1990) Neurotoxicity of MDMA and related compounds: anatomic studies. Ann N Y Acad Sci 600:661–664

    Article  Google Scholar 

  • Monks TJ, Lau SS (1998) The pharmacology and toxicology of polyphenolic-glutathione conjugates. Annu Rev Pharmacol Toxicol 38:229–255

    Article  PubMed  CAS  Google Scholar 

  • Monks TJ, Jones DC, Bai F, Lau SS (2004) The role of metabolism in 3,4-(+)-methylenedioxyamphetamine and 3,4-(+)-methylenedioxymethamphetamine (ecstasy) toxicity. Ther Drug Monit 26(2):132–136

    Article  PubMed  CAS  Google Scholar 

  • Montiel-Duarte C, Varela-Rey M, Oses-Prieto JA et al (2002) 3,4-Methylenedioxymethamphetamine (“Ecstasy”) induces apoptosis of cultured rat liver cells. Biochim Biophys Acta 1588(1):26–32

    Article  PubMed  CAS  Google Scholar 

  • Montiel-Duarte C, Ansorena E, Lopez-Zabalza MJ, Cenarruzabeitia E, Iraburu MJ (2004) Role of reactive oxygen species, glutathione and NF-kappaB in apoptosis induced by 3,4-methylenedioxymethamphetamine (“Ecstasy”) on hepatic stellate cells. Biochem Pharmacol 67(6):1025–1033

    Article  PubMed  CAS  Google Scholar 

  • Moon KH, Upreti VV, Yu LR et al (2008) Mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-mediated mitochondrial dysfunction in rat liver. Proteomics 8(18):3906–3918

    Article  PubMed  CAS  Google Scholar 

  • Moore KE (1963) Toxicity and catecholamine releasing actions of d- and l-amphetamine in isolated and aggregated mice. J Pharmacol Exp Ther 142(1):6–12

    PubMed  CAS  Google Scholar 

  • Moore KA, Mozayani A, Fierro MF, Poklis A (1996) Distribution of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) stereoisomers in a fatal poisoning. Forensic Sci Int 83(2):111–119

    Article  PubMed  CAS  Google Scholar 

  • Morgan ET (1997) Regulation of cytochromes P450 during inflammation and infection. Drug Metab Rev 29(4):1129–1188

    Article  PubMed  CAS  Google Scholar 

  • Morgan CD, Cattabeni F, Costa E (1972) Methamphetamine, fenfluramine and their N-dealkylated metabolites: effect on monoamine concentrations in rat tissues. J Pharmacol Exp Ther 180(1):127–135

    PubMed  CAS  Google Scholar 

  • Morley KC, Li KM, Hunt GE, Mallet PE, McGregor IS (2004) Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA (“Ecstasy”) in rats. Neuropharmacology 46(7):954–965

    Article  PubMed  CAS  Google Scholar 

  • Movahed M-R, Mostafizi K (2008) Reverse or inverted left ventricular apical ballooning syndrome (Reverse Takotsubo Cardiomyopathy) in a young woman in the setting of amphetamine use. Echocardiography 25(4):429–432

    Article  PubMed  Google Scholar 

  • Mueller M, Kolbrich EA, Peters FT et al (2009) Direct comparison of (±) 3,4-Methylenedioxymethamphetamine (“Ecstasy”) disposition and metabolism in squirrel monkeys and humans. Ther Drug Monit 31(3):367–373

    Article  PubMed  CAS  Google Scholar 

  • Murthy BV, Wilkes RG, Roberts NB (1997) Creatine kinase isoform changes following Ecstasy overdose. Anaesth Intensive Care 25(2):156–159

    PubMed  CAS  Google Scholar 

  • Mustafa KY, Omer O, Khogali M et al (1985) Blood coagulation and fibrinolysis in heat stroke. Br J Haematol 61(3):517–523

    Article  PubMed  CAS  Google Scholar 

  • Nagatsu T (2004) Progress in monoamine oxidase (MAO) research in relation to genetic engineering. Neurotoxicology 25:11–20

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa Y, Suzuki T, Tayama S, Ishii H, Ogata A (2009) Cytotoxic effects of 3,4-methylenedioxy-N-alkylamphetamines, MDMA and its analogues, on isolated rat hepatocytes. Arch Toxicol 83(1):69–80

    Article  PubMed  CAS  Google Scholar 

  • Nakama H, Chang L, Fein G, Shimotsu R, Jiang CS, Ernst T (2011) Methamphetamine users show greater than normal age-related cortical gray matter loss. Addiction 106(8):1474–1483. doi:10.1111/j.1360-0443.2011.03433.x

    Article  PubMed  Google Scholar 

  • Nash JF, Yamamoto BK (1992) Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3,4-methylenedioxymethamphetamine. Brain Res 581(2):237–243

    Article  PubMed  CAS  Google Scholar 

  • Nash JF Jr, Meltzer HY, Gudelsky GA (1988) Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphetamine. J Pharmacol Exp Ther 245(3):873–879

    PubMed  CAS  Google Scholar 

  • Navarro M, Pichini S, Farre M et al (2001) Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH. Clin Chem 47(10):1788–1795

    PubMed  CAS  Google Scholar 

  • Newton TF, De La Garza RN, AD Kalechstein, Nestor L (2005a) Cocaine and methamphetamine produce different patterns of subjective and cardiovascular effects. Pharmacol Biochem Behav 82(1):90–97

    Article  PubMed  CAS  Google Scholar 

  • Newton TF, Roache JD, DeLaGarza R II et al (2005b) Safety of intravenous methamphetamine administration during treatment with bupropion. Psychopharmacology 182(3):426–435

    Article  PubMed  CAS  Google Scholar 

  • Newton TF, Roache JD, De La Garza R II et al (2006) Bupropion reduces methamphetamine-induced subjective effects and cue-induced craving. Neuropsychopharmacology 31(7):1537–1544

    Article  PubMed  CAS  Google Scholar 

  • Ninkovic M, Malicevic Z, Selakovic V, Simic I, Vasiljevic I (2004) N-methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: oxidative stress after acute and chronic administration. Vojnosanit Pregl 61(2):125–131

    Article  PubMed  Google Scholar 

  • Ninković M, Selaković V, Dukić M et al (2008) Oxidative stress in rat kidneys due to 3,4-methylenedioxymetamphetamine (ecstasy) toxicity. Nephrology 13(1):33–37

    PubMed  Google Scholar 

  • Nishiyama T, Ikeda M, Iwata N et al (2005) Haplotype association between GABAA receptor gamma2 subunit gene (GABRG2) and methamphetamine use disorder. Pharmacogenomics J 5(2):89–95

    Article  PubMed  CAS  Google Scholar 

  • Nisijima K, Yoshino T, Yui K, Katoh S (2001) Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome. Brain Res 890(1):23–31

    Article  PubMed  CAS  Google Scholar 

  • Nisijima K, Shioda K, Yoshino T, Takano K, Kato S (2003) Diazepam and chlormethiazole attenuate the development of hyperthermia in an animal model of the serotonin syndrome. Neurochem Int 43(2):155–164

    Article  PubMed  CAS  Google Scholar 

  • Nomura A, Ujike H, Tanaka Y et al (2006) Genetic variant of prodynorphin gene is risk factor for methamphetamine dependence. Neurosci Lett 400(1–2):158–162

    Article  PubMed  CAS  Google Scholar 

  • Notarianni LJ (1990) Plasma protein binding of drugs in pregnancy and in neonates. Clin Pharmacokinet 18(1):20–36

    Article  PubMed  CAS  Google Scholar 

  • O’Cain PA, Hletko SB, Ogden BA, Varner KJ (2000) Cardiovascular and sympathetic responses and reflex changes elicited by MDMA. Physiol Behav 70:141–148

    Article  PubMed  Google Scholar 

  • O’Donohoe A, O’Flynn K, Shields K, Hawi Z, Gill M (1998) MDMA toxicity: no evidence for a major influence of metabolic genotype at CYP2D6. Addict Biol 3:309–314

    Article  Google Scholar 

  • Oesterheld JR, Armstrong SC, Cozza KL (2004) Ecstasy: pharmacodynamic and pharmacokinetic interactions. Psychosomatics 45:84–87

    Article  PubMed  CAS  Google Scholar 

  • O’Hearn E, Battaglia G, De Souza EB, Kuhar MJ, Molliver ME (1988) Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity. J Neurosci 8:2788–2803

    PubMed  Google Scholar 

  • Ompad DC, Galea S, Fuller CM, Edwards V, Vlahov D (2005) Ecstasy use among Hispanic and black substance users in New York City. Subst Use Misuse 40(9–10):1399–1407

    Article  PubMed  Google Scholar 

  • Ootsuka Y, Nalivaiko E, Blessing WW (2004) Spinal 5-HT2A receptors regulate cutaneous sympathetic vasomotor outflow in rabbits and rats; relevance for cutaneous vasoconstriction elicited by MDMA (3,4-methylenedioxymethamphetamine, “Ecstasy”) and its reversal by clozapine. Brain Res 1014(1–2):34–44

    Article  PubMed  CAS  Google Scholar 

  • Oyler JM, Cone EJ, JosephJr RE, Moolchan ET, Huestis MA (2002) Duration of detectable methamphetamine and amphetamine excretion in urine after controlled oral administration of methamphetamine to humans. Clin Chem 48(10):1703–1714

    PubMed  CAS  Google Scholar 

  • Pacifici R, Zuccaro P, Hernandez Lopez C et al (2001) Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans. J Pharmacol Exp Ther 296(1):207–215

    PubMed  CAS  Google Scholar 

  • Pacifici R, Zuccaro P, Farre M et al (2007) Combined immunomodulating properties of 3,4-methylenedioxymethamphetamine (MDMA) and cannabis in humans. Addiction 102(6):931–936

    Article  PubMed  Google Scholar 

  • Parkinson A, Mudra DR, Johnson C, Dwyer A, Carroll KM (2004) The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. Toxicol Appl Pharmacol 199(3):193–209

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC (2001) Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research. Hum Psychopharmacol 16(8):557–577

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC (2004) MDMA (3,4-Methylenedioxymethamphetamine) or ecstasy: the neuropsychobiological implications of taking it at dances and raves. Neuropsychobiology 50(4):329–335

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC (2006) MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress. J Psychopharmacol 20(2):147–163

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC (2012) MDMA and temperature: a review of the thermal effects of ‘Ecstasy’ in humans. Drug Alcohol Depend 121(1–2):1–9

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC, Lasky J (1998) Ecstasy (MDMA) effects upon mood and cognition: before, during and after a Saturday night dance. Psychopharmacology 139(3):261–268

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC, Milani RM, Gouzoulis-Mayfrank E, Daumann J (2007) Cannabis and Ecstasy/MDMA (3,4-methylenedioxymethamphetamine): an analysis of their neuropsychobiological interactions in recreational users. J Neural Transm 114(8):959–968

    Article  PubMed  CAS  Google Scholar 

  • Parsons JT, Kelly BC, Wells BE (2006) Differences in club drug use between heterosexual and lesbian/bisexual females. Addict Behav 31(12):2344–2349

    Article  PubMed  Google Scholar 

  • Partilla JS, Dempsey AG, Nagpal AS, Blough BE, Baumann MH, Rothman RB (2006) Interaction of amphetamines and related compounds at the vesicular monoamine transporter. J Pharmacol Exp Ther 319(1):237–246

    Article  PubMed  CAS  Google Scholar 

  • Passie T, Seifert J, Schneider U, Emrich HM (2002) The pharmacology of psilocybin. Addict Biol 7(4):357–364

    Article  PubMed  CAS  Google Scholar 

  • Patel N, Kumagai Y, Unger SE, Fukuto JM, Cho AK (1991) Transformation of dopamine and alpha-methyldopamine by NG108-15 cells: formation of thiol adducts. Chem Res Toxicol 4(4):421–426

    Article  PubMed  CAS  Google Scholar 

  • Patel MM, Belson MG, Longwater AB, Olson KR, Miller MA (2005) Methylenedioxymethamphetamine (ecstasy)-related hyperthermia. J Emerg Med 29(4):451–454

    Article  PubMed  Google Scholar 

  • Pedersen NP, Blessing WW (2001) Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy) in conscious rabbits. J Neurosci 21(21):8648–8654

    PubMed  CAS  Google Scholar 

  • Pereira FC, Rolo MR, Marques E et al (2008) Acute Increase of the glutamate–glutamine cycling in discrete brain areas after administration of a single dose of amphetamine. Ann N Y Acad Sci 1139(1):212–221

    Article  PubMed  CAS  Google Scholar 

  • Perez-Reyes M, White WR, McDonald SA et al (1991a) Clinical effects of daily methamphetamine administration. Clin Neuropharmacol 14(4):352–358

    Article  PubMed  CAS  Google Scholar 

  • Perez-Reyes M, White WR, McDonald SA, Hill JM, Jeffcoat AR, Cook CE (1991b) Clinical effects of methamphetamine vapor inhalation. Life Sci 49(13):953–959

    Article  PubMed  CAS  Google Scholar 

  • Perez-Reyes M, White WR, McDonald SA, Hicks RE (1992) Interaction between ethanol and dextroamphetamine: effects on psychomotor performance. Alcohol Clin Exp Res 16(1):75–81

    Article  PubMed  CAS  Google Scholar 

  • Persico AM, Bird G, Gabbay FH, Uhl GR (1996) D2 dopamine receptor gene TaqI A1 and B1 restriction fragment length polymorphisms: enhanced frequencies in psychostimulant-preferring polysubstance abusers. Biol Psychiatry 40(8):776–784

    Article  PubMed  CAS  Google Scholar 

  • Peterson DI, Hardinge MG (1967) The effect of various environmental factors on cocaine and eph edrine toxicity. J Pharm pharmacol 19(12):810–814

    Article  PubMed  CAS  Google Scholar 

  • Pilgrim JL, Gerostamoulos D, Drummer OH (2010) Deaths involving serotonergic drugs. Forensic Sci Int 198(1–3):110–117

    Article  PubMed  CAS  Google Scholar 

  • Pilgrim JL, Gerostamoulos D, Drummer OH (2011) Deaths involving MDMA and the concomitant use of pharmaceutical drugs. J Anal Toxicol 35(4):219–226

    Article  PubMed  CAS  Google Scholar 

  • Pilgrim JL, Gerostamoulos D, Woodford N, Drummer OH (2012) Serotonin toxicity involving MDMA (ecstasy) and moclobemide. Forensic Sci Int 215(1–3):184–188

    Article  PubMed  CAS  Google Scholar 

  • Pizarro N, Ortuño J, Segura J et al (1999) Quantification of amphetamine plasma concentrations by gas chromatography coupled to mass spectrometry. J Pharm Biomed Anal 21(4):739–747

    Article  PubMed  CAS  Google Scholar 

  • Pizarro N, Farre M, Pujadas M et al (2004) Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites in human samples including the catechol-type metabolite (3,4-dihydroxymethamphetamine). Drug Metab Dispos 32(9):1001–1007

    PubMed  CAS  Google Scholar 

  • Pletscher A, Bartholini G, Bruderer H, Burkard WP, Gey KF (1964) Chlorinated arylalkylamines affecting the cerebral metabolism of 5-hydroxytryptamine. J Pharmacol Exp Ther 145(3):344–350

    PubMed  CAS  Google Scholar 

  • Poklis A, Still J, Slattum PW, Edinboro LF, Saady JJ, Costantino A (1998) Urinary excretion of d-amphetamine following oral doses in humans: implications for urine drug testing. J Anal Toxicol 22(6):481–486

    PubMed  CAS  Google Scholar 

  • Pontes H, Duarte JA, de Pinho PG et al (2008a) Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice. Toxicology 252(1–3):64–71

    Article  PubMed  CAS  Google Scholar 

  • Pontes H, Sousa C, Silva R et al (2008b) Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes. Toxicology 254(1–2):42–50

    Article  PubMed  CAS  Google Scholar 

  • Pontes H, de Pinho PG, Fernandes E et al (2010) Metabolic interactions between ethanol and MDMA in primary cultured rat hepatocytes. Toxicology 270(2–3):150–157

    Article  PubMed  CAS  Google Scholar 

  • Preston KL, Wagner GC, Schuster CR, Seiden LS (1985) Long-term effects of repeated methylamphetamine administration on monoamine neurons in the rhesus monkey brain. Brain Res 338(2):243–248

    Article  PubMed  CAS  Google Scholar 

  • Pu C, Fisher J, Cappon G, Vorhees C (1994) The effects of amfonelic acid, a dopamine uptake inhibitor, on methamphetamine-induced dopaminergic terminal degeneration and astrocytic response in rat striatum. Brain Res 649(1–2):217–224

    Article  PubMed  CAS  Google Scholar 

  • Quinn DI, Wodak A, Day RO (1997) Pharmacokinetic and pharmacodynamic principles of illicit drug use and treatment of illicit drug users. Clin Pharmacokinet 33(5):344–400

    Article  PubMed  CAS  Google Scholar 

  • Quinn ST, Guiry PJ, Schwab T, Keenan AK, McBean GJ (2006) Blockade of noradrenaline transport abolishes 4-methylthioamphetamine-induced contraction of the rat aorta in vitro. Auton Autacoid Pharmacol 26(4):335–344

    Article  PubMed  CAS  Google Scholar 

  • Quinton MS, Yamamoto BK (2006) Causes and consequences of methamphetamine and MDMA toxicity. Aaps J 8(2):E337–E347

    PubMed  Google Scholar 

  • Raimundo S, Fischer J, Eichelbaum M, Griese EU, Schwab M, Zanger UM (2000) Elucidation of the genetic basis of the common ‘intermediate metabolizer’ phenotype for drug oxidation by CYP2D6. Pharmacogenetics 10(7):577–581

    Article  PubMed  CAS  Google Scholar 

  • Ramaekers JG, Kuypers KP (2006) Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on behavioral measures of impulsivity: alone and in combination with alcohol. Neuropsychopharmacology 31(5):1048–1055

    Article  PubMed  CAS  Google Scholar 

  • Ramamoorthy S, Blakely RD (1999) Phosphorylation and Sequestration of Serotonin Transporters Differentially Modulated by Psychostimulants. Science 285(5428):763–766

    Article  PubMed  CAS  Google Scholar 

  • Ramamoorthy Y, Tyndale RF, Sellers EM (2001) Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates. Pharmacogenetics 11(6):477–487

    Article  PubMed  CAS  Google Scholar 

  • Ramamoorthy Y, Yu A, Suh N, Haining RL, Tyndale RF, Sellers EM (2002) Reduced (±)-3,4-methylenedioxymethamphetamine (“Ecstasy”) metabolism with cytochrome P450 2D6 inhibitors and pharmacogenetic variants in vitro. Biochem Pharmacol 63(12):2111–2119

    Article  PubMed  CAS  Google Scholar 

  • Ramcharan S, Meenhorst PL, Otten JM et al (1998) Survival after massive ecstasy overdose. J Toxicol Clin Toxicol 36(7):727–731

    Article  PubMed  CAS  Google Scholar 

  • Randall T (1992) Ecstasy-fueled ‘rave’ parties become dances of death for English youths. JAMA 268(12):1505–1506

    Article  PubMed  CAS  Google Scholar 

  • Reay JL, Hamilton C, Kennedy DO, Scholey AB (2006) MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes. J Psychopharmacol 20(3):385–388

    Article  PubMed  CAS  Google Scholar 

  • Renton KW (2001) Alteration of drug biotransformation and elimination during infection and inflammation. Pharmacol Ther 92(2–3):147–163

    Article  PubMed  CAS  Google Scholar 

  • Renton KW (2004) Cytochrome P450 regulation and drug biotransformation during inflammation and infection. Curr Drug Metab 5(3):235–243

    Article  PubMed  CAS  Google Scholar 

  • Renton KW (2005) Regulation of drug metabolism and disposition during inflammation and infection. Expert Opin Drug Metab Toxicol 1(4):629–640

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte GA, Guillery RW, Seiden LS, Schuster CR, Moore RY (1982) Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain. Brain Res 235(1):93–103

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte GA, Seiden LS, Schuster CR (1984) Further evidence that amphetamines produce long-lasting dopamine neurochemical deficits by destroying dopamine nerve fibers. Brain Res 303(2):359–364

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte GA, Bryan G, Strauss L, Seiden LS, Schuster CR (1985) Hallucinogenic amphetamine selectively destroys brain serotonin nerve terminals. Science 229:986–988

    Article  PubMed  CAS  Google Scholar 

  • Richards JR, Johnson EB, Stark RW, Derlet RW (1999) Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study. Am J Emerg Med 17(7):681–685

    Article  PubMed  CAS  Google Scholar 

  • Riegert C, Wedekind F, Hamida SB et al (2008) Effects of ethanol and 3,4-methylenedioxymethamphetamine (MDMA) alone or in combination on spontaneous and evoked overflow of dopamine, serotonin and acetylcholine in striatal slices of the rat brain. Int J Neuropsychopharmacol 11(6):743–763

    Article  PubMed  CAS  Google Scholar 

  • Roberts L, Wright H (1993) Survival following intentional massive overdose of ‘Ecstasy’. J Accid Emerg Med 11(1):53–54

    Article  Google Scholar 

  • Robledo P, Trigo JM, Panayi F, de la Torre R, Maldonado R (2007) Behavioural and neurochemical effects of combined MDMA and THC administration in mice. Psychopharmacology 195(2):255–264

    Article  PubMed  CAS  Google Scholar 

  • Rohrig TP, Prouty RW (1992) Tissue distribution of methylenedioxymethamphetamine. J Anal Toxicol 16(1):52–53

    PubMed  CAS  Google Scholar 

  • Roiser JP, Cook LJ, Cooper JD, Rubinsztein DC, Sahakian BJ (2005) Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in ecstasy users. Am J Psychiatry 162(3):609–612

    Article  PubMed  Google Scholar 

  • Roiser JP, Rogers RD, Cook LJ, Sahakian BJ (2006) The effect of polymorphism at the serotonin transporter gene on decision-making, memory and executive function in ecstasy users and controls. Psychopharmacology 188(2):213–227

    Article  PubMed  CAS  Google Scholar 

  • Rothman RB, Baumann MH, Dersch CM et al (2001) Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39(1):32–41

    Article  PubMed  CAS  Google Scholar 

  • Rusyniak DE, Sprague JE (2005) Toxin-induced hyperthermic syndromes. Med Clin North Am 89(6):1277–1296

    Article  PubMed  CAS  Google Scholar 

  • Sala M, Braida D (2005) Endocannabinoids and 3,4-methylenedioxymethamphetamine (MDMA) interaction. Pharmacol Biochem Behav 81(2):407–416

    Article  PubMed  CAS  Google Scholar 

  • Salisbury AL, Ponder KL, Padbury JF, Lester BM (2009) Fetal effects of psychoactive drugs. Clin Perinatol 36(3):595–619

    Article  PubMed  Google Scholar 

  • Samyn N, DeBoeck G, Wood M et al (2002) Plasma, oral fluid and sweat wipe ecstasy concentrations in controlled and real life conditions. Forensic Sci Int 128(1–2):90–97

    Article  PubMed  CAS  Google Scholar 

  • Sanan S, Vogt M (1962) Effect of drugs on the noradrenaline content of brain and peripheral tissues and its significance. Br J Pharmacol Chemother 18(1):109–127

    PubMed  CAS  Google Scholar 

  • Sanchez V, Camarero J, Esteban B, Peter MJ, Green AR, Colado MI (2001) The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA (“ecstasy”)-induced degeneration of 5-HT nerve endings in rat brain. Br J Pharmacol 134(1):46–57

    Article  PubMed  CAS  Google Scholar 

  • Sanders-Bush E, Sulser F (1970) p-Chloroamphetamine: in vivo investigations on the mechanism of action of the selective depletion of cerebral serotonin. J Pharmacol Exp Ther 175(2):419–426

    PubMed  CAS  Google Scholar 

  • Sandoval V, Riddle EL, Hanson GR, Fleckenstein AE (2003) Methylphenidate alters vesicular monoamine transport and prevents methamphetamine-induced dopaminergic deficits. J Pharmacol Exp Ther 304(3):1181–1187

    Article  PubMed  CAS  Google Scholar 

  • Sano R, Hasuike T, Nakano M, Kominato Y, Itoh H (2009) A fatal case of myocardial damage due to misuse of the “designer drug” MDMA. Leg Med (Tokyo) 11(6):294–297

    Article  Google Scholar 

  • Schechter MD (1998) ‘Candyflipping’: synergistic discriminative effect of LSD and MDMA. Eur J Pharmacol 341(2–3):131–134

    Article  PubMed  CAS  Google Scholar 

  • Schepers RJ, Oyler JM, JosephJr RE, Cone EJ, Moolchan ET, Huestis MA (2003) Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers. Clin Chem 49(1):121–132

    Article  PubMed  CAS  Google Scholar 

  • Schifano F (2004) A bitter pill. Overview of ecstasy (MDMA, MDA) related fatalities. Psychopharmacology 173(3–4):242–248

    Article  PubMed  CAS  Google Scholar 

  • Schifano F, Di Furia L, Forza G, Minicuci N, Bricolo R (1998) MDMA (‘ecstasy’) consumption in the context of polydrug abuse: a report on 150 patients. Drug Alcohol Depend 52(1):85–90

    Article  PubMed  CAS  Google Scholar 

  • Schmidt CJ (1987) Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. J Pharmacol Exp Ther 240:1–7

    PubMed  CAS  Google Scholar 

  • Schmidt C, Wu L, Lovenberg W (1986) Methylenedioxymethamphetamine: a potentially neurotoxic amphetamine analogue. Eur J Pharmacol 124:175–178

    Article  PubMed  CAS  Google Scholar 

  • Schmidt CJ, Levin JA, Lovenberg W (1987) In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain. Biochem Pharmacol 36:747–755

    Article  PubMed  CAS  Google Scholar 

  • Schmitz Y, Lee CJ, Schmauss C, Gonon F, Sulzer D (2001) Amphetamine distorts stimulation-dependent dopamine overflow: effects on D2 auto receptors, transporters, and synaptic vesicle stores. J Neurosci 21(16):5916–5924

    PubMed  CAS  Google Scholar 

  • Schmued L (2003) Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA. Brain Res 974:127–133

    Article  PubMed  CAS  Google Scholar 

  • Scholey AB, Parrott AC, Buchanan T, Heffernan TM, Ling J, Rodgers J (2004) Increased intensity of Ecstasy and polydrug usage in the more experienced recreational Ecstasy/MDMA users: a WWW study. Addict Behav 29(4):743–752

    Article  PubMed  Google Scholar 

  • Schwab M, Seyringer E, Brauer RB, Hellinger A, Griese EU (1999) Fatal MDMA intoxication. Lancet 353(9152):593–594

    Article  PubMed  CAS  Google Scholar 

  • Schwartz DL, Mitchell AD, Lahna DL et al (2010) Global and local morphometric differences in recently abstinent methamphetamine-dependent individuals. NeuroImage 50(4):1392–1401

    Article  PubMed  Google Scholar 

  • Screaton GR, Cairns HS, Sarner M, Singer M, Thrasher A, Cohen SL (1992) Hyperpyrexia and rhabdomyolysis after MDMA (“ecstasy”) abuse. Lancet 339:677–678

    Article  PubMed  CAS  Google Scholar 

  • Segura M, Ortuno J, Farre M et al (2001) 3,4-Dihydroxymethamphetamine (HHMA). A major in vivo 3,4-methylenedioxymethamphetamine (MDMA) metabolite in humans. Chem Res Toxicol 14(9):1203–1208

    Article  PubMed  CAS  Google Scholar 

  • Segura M, Farre M, Pichini S et al (2005) Contribution of cytochrome P450 2D6 to 3,4-methylenedioxymethamphetamine disposition in humans: use of paroxetine as a metabolic inhibitor probe. Clin Pharmacokinet 44(6):649–660

    Article  PubMed  CAS  Google Scholar 

  • Seiden LS, Fischman MW, Schuster CR (1976) Long-term methamphetamine induced changes in brain catecholamines in tolerant rhesus monkeys. Drug Alcohol Depend 1(3):215–219

    Article  PubMed  CAS  Google Scholar 

  • Selken J, Nichols DE (2007) Alpha1-adrenergic receptors mediate the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) in rats. Pharmacol Biochem Behav 86(4):622–630

    Article  PubMed  CAS  Google Scholar 

  • Shankaran M, Yamamoto BK, Gudelsky GA (1999) Involvement of the SERT in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine. Eur J Pharmacol 385:103–110

    Article  PubMed  CAS  Google Scholar 

  • Shappell SA, Kearns GL, Valentine JL, Neri DF, DeJohn CA (1996) Chronopharmacokinetics and chronopharmacodynamics of dextromethamphetamine in man. J Clin Pharmacol 36(11):1051–1063

    Article  PubMed  CAS  Google Scholar 

  • Shen H, He MM, Liu H et al (2007) Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug Metab Dispos 35(8):1292–1300

    Article  PubMed  CAS  Google Scholar 

  • Shenouda SK, Varner KJ, Carvalho F, Lucchesi PA (2009) Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Cardiovasc Toxicol 9(1):30–38

    Article  PubMed  CAS  Google Scholar 

  • Shenouda SK, Carvalho F, Varner KJ (2010) The cardiovascular and cardiac actions of ecstasy and its metabolites. Curr Pharm Biotechnol 11(5):470–475

    Article  PubMed  CAS  Google Scholar 

  • Shih JC, Grimsby J, Chen K (1999) Molecular biology of monoamine oxidase A and B: their role in the degradation of serotonin. In: Baumgarten HG, Gothert M (eds) Serotoninergic neurons and 5-HT receptors in the SNC. Springer, Berlim, pp 655–670

    Google Scholar 

  • Shulgin AT (1986) The background and chemistry of MDMA. J Psychoactive Drugs 18(4):291–304

    Article  PubMed  CAS  Google Scholar 

  • Sim MS, Mohamed Z, Hatim A, Rajagopal VL, Habil MH (2010) Association of brain-derived neurotrophic factor (Val66Met) genetic polymorphism with methamphetamine dependence in a Malaysian population. Brain Res 1357:91–96

    Article  PubMed  CAS  Google Scholar 

  • Sitte HH, Freissmuth M (2010) The reverse operation of Na +/Cl− -coupled neurotransmitter transporters: why amphetamines take two to tango. J Neurochem 112(2):340–355

    Article  PubMed  CAS  Google Scholar 

  • Skibba JL, Stadnicka A, Kalbfleisch JH, Powers RH (1989) Effects of hyperthermia on xanthine oxidase activity and glutathione levels in the perfused rat liver. J Biochem Toxicol 4:119–125

    Article  PubMed  CAS  Google Scholar 

  • Smilkstein MJ, Smolinske SC, Rumack BH (1987) A case of MAO inhibitor/MDMA interaction: agony after ecstasy. J Toxicol Clin Toxicol 25(1–2):149–159

    Article  PubMed  CAS  Google Scholar 

  • Smith HJ, Roche AH, Jausch MF, Herdson PB (1976) Cardiomyopathy associated with amphetamine administration. Am Heart J 91(6):792–797

    Article  PubMed  CAS  Google Scholar 

  • Sofuoglu M, Poling J, Hill K, Kosten T (2009) Atomoxetine attenuates dextroamphetamine effects in humans. Am J Drug Alcohol Abuse 35(6):412–416

    Article  PubMed  Google Scholar 

  • Solowij N, Hall W, Lee N (1992) Recreational MDMA use in Sydney: a profile of ‘Ecstacy’ users and their experiences with the drug. Br J Addict 87(8):1161–1172

    Article  PubMed  CAS  Google Scholar 

  • Song BJ, Moon KH, Upreti VV, Eddington ND, Lee IJ (2010) Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage. Curr Pharm Biotechnol 11(5):434–443

    Article  PubMed  CAS  Google Scholar 

  • Soni MG, Carabin IG, Griffiths JC, Burdock GA (2004) Safety of ephedra: lessons learned. Toxicol Lett 150(1):97–110

    Article  PubMed  CAS  Google Scholar 

  • Sotaniemi EA, Arranto AJ, Pelkonen O, Pasanen M (1997) Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther 61(3):331–339

    Article  PubMed  CAS  Google Scholar 

  • Spencer JPE, Jenner P, Daniel SE, Lees AJ, Marsden DC, Halliwell B (1998) Conjugates of catecholamines with cysteine and GSH in Parkinson’s disease: possible mechanisms of formation involving reactive oxygen species. J Neurochem 71:2112–2122

    Article  PubMed  CAS  Google Scholar 

  • Sprague JE, Nichols DE (1995) The monoamine oxidase-B inhibitor L-deprenyl protects against 3,4-methylenedioxymethamphetamine-induced lipid peroxidation and long-term serotonergic deficits. J Pharmacol Exp Ther 273(2):667–673

    PubMed  CAS  Google Scholar 

  • Sprague JE, Banks ML, Cook VJ, Mills EM (2003) Hypothalamic-pituitary-thyroid axis and sympathetic nervous system involvement in hyperthermia induced by 3,4-methylenedioxymethamphetamine (Ecstasy). J Pharmacol Exp Ther 305(1):159–166

    Article  PubMed  CAS  Google Scholar 

  • Sprague JE, Moze P, Caden D et al (2005) Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model. Crit Care Med 33(6):1311–1316

    Article  PubMed  CAS  Google Scholar 

  • Sprague JE, Yang X, Sommers J, Gilman TL, Mills EM (2007) Roles of norepinephrine, free fatty acids, thyroid status, and skeletal muscle uncoupling protein 3 expression in sympathomimetic-induced thermogenesis. J Pharmacol Exp Ther 320(1):274–280

    Article  PubMed  CAS  Google Scholar 

  • Sprigg N, Willmot MR, Gray LJ et al (2007) Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333). J Hum Hypertens 21(8):616–624

    Article  PubMed  CAS  Google Scholar 

  • Spruit IP (2001) Monitoring synthetic drug markets, trends, and public health. Subst Use Misuse 36(1–2):23–47

    Article  PubMed  CAS  Google Scholar 

  • Stanley N, Salem A, Irvine RJ (2007) The effects of co-administration of 3,4-methylenedioxymethamphetamine (“ecstasy”) or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats. Neuroscience 146(1):321–329

    Article  PubMed  CAS  Google Scholar 

  • Sticht G, Pluisch F, Bierhoff E, Kaferstein H (2003) Fatal outcome of Ecstasy overdose. Arch Kriminol 211(3–4):73–80

    PubMed  Google Scholar 

  • Stone DM, Hanson GR, Gibb JW (1987a) Differences in the central serotonergic effects of methylenedioxymethamphetamine (MDMA) in mice and rats. Neuropharmacology 26:1657–1661

    Article  PubMed  CAS  Google Scholar 

  • Stone DM, Johnson M, Hanson GR, Gibb JW (1987b) A comparison of the neurotoxic potential of methylenedioxyamphetamine (MDA) and its N-methylated and N-ethylated derivatives. Eur J Pharmacol 134(2):245–248

    Google Scholar 

  • Stuerenburg HJ, Petersen K, Bäumer T, Rosenkranz M, Buhmann C, Thomasius R (2002) Plasma concentrations of 5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine in ecstasy users. Neuro Endocrinol Lett 23(3):259–261

    PubMed  CAS  Google Scholar 

  • Stumm G, Schlegel J, Schafer T et al (1999) Amphetamines induce apoptosis and regulation of bcl-x splice variants in neocortical neurons. FASEB J 13:1065–1072

    PubMed  CAS  Google Scholar 

  • Suarez RV, Riemersma R (1988) “Ecstasy” and sudden cardiac death. Am J Forensic Med Pathol 9(4):339–341

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto K, Okamura K, Tanaka H et al (2009) Methamphetamine directly accelerates beating rate in cardiomyocytes by increasing Ca2 + entry via L-type Ca2 + channel. Biochem Biophys Res Commun 390(4):1214–1220

    Article  PubMed  CAS  Google Scholar 

  • Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A (1995) Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci 15(5):4102–4108

    PubMed  CAS  Google Scholar 

  • Sulzer D, Sonders MS, Poulsen NW, Galli A (2005) Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol 75(6):406–433

    Article  PubMed  CAS  Google Scholar 

  • Suzuki O, Hattori H, Asano M, Oya M, Katsumata Y (1980) Inhibition of monoamine oxidase by d-methamphetamine. Biochem Pharmacol 29(14):2071–2073

    Article  PubMed  CAS  Google Scholar 

  • Suzuki S, Inoue T, Hori H, Inayama S (1989) Analysis of methamphetamine in hair, nail, sweat, and saliva by mass fragmentography. J Anal Toxicol 13(3):176–178

    PubMed  CAS  Google Scholar 

  • Sylvester AL, Agarwala B (2012) Acute myocardial infarction in a teenager due to adderall XR. Pediatr Cardiol 33(1):155–157

    Article  PubMed  Google Scholar 

  • Tancer M, Johanson CE (2007) The effects of fluoxetine on the subjective and physiological effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl) 189(4):565–573

    Article  CAS  Google Scholar 

  • Tanner-Smith EE (2006) Pharmacological content of tablets sold as “ecstasy”: results from an online testing service. Drug Alcohol Depend 83(3):247–254

    Article  PubMed  CAS  Google Scholar 

  • Terada Y, Shinohara S, Matui N, Ida T (1988) Amphetamine-induced myoglobinuria acute renal failure. Jpn J Med 27:305–308

    Article  PubMed  CAS  Google Scholar 

  • Thomas DM, Dowgiert J, Geddes TJ, Francescutti-Verbeem D, Liu X, Kuhn DM (2004) Microglial activation is a pharmacologically specific marker for the neurotoxic amphetamines. Neurosci Lett 367(3):349–354

    Article  PubMed  CAS  Google Scholar 

  • Thompson MR, Li KM, Clemens KJ et al (2004a) Chronic fluoxetine treatment partly attenuates the long-term anxiety and depressive symptoms induced by MDMA (‘Ecstasy’) in rats. Neuropsychopharmacology 29(4):694–704

    Article  PubMed  CAS  Google Scholar 

  • Thompson PM, Hayashi KM, Simon SL et al (2004b) Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci 24(26):6028–6036

    Article  PubMed  CAS  Google Scholar 

  • Thull U, Testa B (1994) Screening of unsubstituted cyclic compounds as inhibitors of monoamine oxidases. Biochem Pharmacol 47(12):2307–2310

    Article  PubMed  CAS  Google Scholar 

  • Tucker GT, Lennard MS, Ellis SW et al (1994) The demethylenation of methylenedioxymethamphetamine (“ecstasy”) by debrisoquine hydroxylase (CYP2D6). Biochem Pharmacol 47(7):1151–1156

    Article  PubMed  CAS  Google Scholar 

  • Ujike H, Harano M, Inada T et al (2003) Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis. Pharmacogenomics J 3(4):242–247

    Article  PubMed  CAS  Google Scholar 

  • Ujike H, Katsu T, Okahisa Y et al (2009) Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis. Prog Neuropsychopharmacol Biol Psychiatry 33(4):625–629

    Article  PubMed  CAS  Google Scholar 

  • United Nations Office on Drugs and Crime (ed) (2011) World Drug Report 2011

  • Upreti VV, Eddington ND (2008) Fluoxetine pretreatment effects pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, ECSTASY) in rat. J Pharm Sci 97(4):1593–1605

    Article  PubMed  CAS  Google Scholar 

  • Uys JD, Niesink RJ (2005) Pharmacological aspects of the combined use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and gamma-hydroxybutyric acid (GHB): a review of the literature. Drug Alcohol Rev 24(4):359–368

    Article  PubMed  Google Scholar 

  • Vallee M, Mayo W, Maccari S, Le Moal M, Simon H (1996) Long-term effects of prenatal stress and handling on metabolic parameters: relationship to corticosterone secretion response. Brain Res 712(2):287–292

    Article  PubMed  CAS  Google Scholar 

  • van Nieuwenhuijzen PS, McGregor IS (2009) Sedative and hypothermic effects of gamma-hydroxybutyrate (GHB) in rats alone and in combination with other drugs: assessment using biotelemetry. Drug Alcohol Depend 103(3):137–147

    Article  PubMed  CAS  Google Scholar 

  • van Nieuwenhuijzen PS, Long LE, Hunt GE, Arnold JC, McGregor IS (2010) Residual social, memory and oxytocin-related changes in rats following repeated exposure to gamma-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination. Psychopharmacology (Berl) 212(4):663–674

    Article  CAS  Google Scholar 

  • Vanattou-Saifoudine N, McNamara R, Harkin A (2010a) Caffeine promotes dopamine D1 receptor-mediated body temperature, heart rate and behavioural responses to MDMA (‘ecstasy’). Psychopharmacology 211(1):15–25

    Article  PubMed  CAS  Google Scholar 

  • Vanattou-Saifoudine N, McNamara R, Harkin A (2010b) Mechanisms mediating the ability of caffeine to influence MDMA (‘Ecstasy’)-induced hyperthermia in rats. Br J Pharmacol 160(4):860–877

    Article  PubMed  CAS  Google Scholar 

  • Vanattou-Saifoudine N, Gossen A, Harkin A (2011) A role for adenosine A(1) receptor blockade in the ability of caffeine to promote MDMA “Ecstasy”-induced striatal dopamine release. Eur J Pharmacol 650(1):220–228

    Article  PubMed  CAS  Google Scholar 

  • Varela-Rey M, Montiel-Duarte C, Beitia G, Cenarruzabeitia E, Iraburu MJ (1999) 3,4-methylenedioxymethamphetamine (“Ecstasy”) stimulates the expression of alpha1(I) procollagen mRNA in hepatic stellate cells. Biochem Biophys Res Commun 259(3):678–682

    Article  PubMed  CAS  Google Scholar 

  • Varner KJ, Ogden BA, Delcarpio J, Meleg-Smith S (2002) Cardiovascular responses elicited by the “Binge” administration of methamphetamine. J Pharmacol Exp Ther 301(1):152–159

    Article  PubMed  CAS  Google Scholar 

  • Vega WA, Kolody B, Hwang J, Noble A (1993) Prevalence and magnitude of perinatal substance exposures in California. N Engl J Med 329(12):850–854

    Article  PubMed  CAS  Google Scholar 

  • Verebey K, Alrazi J, Jaffe JH (1988) The complications of ‘ecstasy’ (MDMA). JAMA 259(11):1649–1650

    Article  PubMed  CAS  Google Scholar 

  • Verrico CD, Lynch L, Fahey MA, Fryer AK, Miller GM, Madras BK (2008) MDMA-induced impairment in primates: antagonism by a selective norepinephrine or serotonin, but not by a dopamine/norepinephrine transport inhibitor. J Psychopharmacol 22(2):187–202

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Fowler JS, Wang G-J et al (2010) Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications. PLoS ONE 5(12):e15269

    Article  PubMed  CAS  Google Scholar 

  • Vollenweider FX, Maguire RP, Leenders KL, Mathys K, Angst J (1998) Effects of high amphetamine dose on mood and cerebral glucose metabolism in normal volunteers using positron emission tomography (PET). Psychiatry Res 83(3):149–162

    Article  PubMed  CAS  Google Scholar 

  • Von Huben SN, Lay CC, Crean RD, Davis SA, Katner SN, Taffe MA (2007) Impact of ambient temperature on hyperthermia induced by (±)3,4-methylenedioxymethamphetamine in rhesus macaques. Neuropsychopharmacology 32(3):673–681

    Article  CAS  Google Scholar 

  • Votyakova TV, Reynolds IJ (2001) ΔΨm-Dependent and -independent production of reactive oxygen species by rat brain mitochondria. J Neurochem 79:266–277

    Article  PubMed  CAS  Google Scholar 

  • Vuori E, Henry JA, Ojanpera I et al (2003) Death following ingestion of MDMA (ecstasy) and moclobemide. Addiction 98(3):365–368

    Article  PubMed  Google Scholar 

  • Wadelius M, Darj E, Frenne G, Rane A (1997) Induction of CYP2D6 in pregnancy. Clin Pharmacol Ther 62(4):400–407

    Article  PubMed  CAS  Google Scholar 

  • Waksman J, Taylor RNJ, Bodor GS, Daly FF, Jolliff HA, Dart RC (2001) Acute myocardial infarction associated with amphetamine use. Mayo Clin Proc 76(3):323–326

    Article  PubMed  CAS  Google Scholar 

  • Walubo A, Seger D (1999) Fatal multi-organ failure after suicidal overdose with MDMA, “ecstasy”: case report and review of the literature. Hum Exp Toxicol 18:119–125

    Article  PubMed  CAS  Google Scholar 

  • Wan SH, Matin SB, Azarnoff DL (1978) Kinetics, salivary excretion of amphetamine isomers, and effect of urinary pH. Clin Pharmacol 23(5):585–590

    CAS  Google Scholar 

  • Wan F-J, Lin H-C, Huang K-L, Tseng C-J, Wong C-S (2000a) Systemic administration of d-amphetamine induces long-lasting oxidative stress in the rat striatum. Life Sci 66(15):205–212

    Article  Google Scholar 

  • Wan F, Shiah I, Lin H, Huang S, Tung C (2000b) Nomifensine attenuates d-amphetamine-induced dopamine terminal neurotoxicity in the striatum of rats. Chin J Physiol 43(2):69–74

    PubMed  CAS  Google Scholar 

  • Wan F-J, Tung C-S, Shiah IS, Lin H-C (2006) Effects of α-phenyl-N-tert-butyl nitrone and N-acetylcysteine on hydroxyl radical formation and dopamine depletion in the rat striatum produced by d-amphetamine. Eur Neuropsychopharmacol 16(2):147–153

    Article  PubMed  CAS  Google Scholar 

  • Wappler F (2001) Malignant hyperthermia. Eur J Anaesthesiol 18(10):632–652

    PubMed  CAS  Google Scholar 

  • Warren MW, Kobeissy FH, Liu MC, Hayes RL, Gold MS, Wang KK (2006) Ecstasy toxicity: a comparison to methamphetamine and traumatic brain injury. J Addict Dis 25(4):115–123

    Article  PubMed  Google Scholar 

  • Warren MW, Larner S, Kobeissy F et al (2007) Calpain and caspase proteolytic markers co-localize with rat cortical neurons after exposure to methamphetamine and MDMA. Acta Neuropathol 114(3):277–286

    Article  PubMed  CAS  Google Scholar 

  • Weinshilboum RM, Otterness DM, Szumlanski CL (1999) Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annu Rev Pharmacol Toxicol 39:19–52

    Article  PubMed  CAS  Google Scholar 

  • Weisler RH, Biederman J, Spencer TJ, Wilens TE (2005) Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr 10(12 Suppl 20):35–43

    PubMed  Google Scholar 

  • Whelan KR, Dargan PI, Jones AL, O’Connor N (2004) Atypical antipsychotics not recommended for control of agitation in the emergency department. Emerg Med J 21(5):649

    Article  PubMed  CAS  Google Scholar 

  • Wichems CH, Hollingsworth CK, Bennett BA (1995) Release of serotonin induced by 3,4-methylenedioxymethamphetamine (MDMA) and other substituted amphetamines in cultured fetal raphe neurons: further evidence for calcium-independent mechanisms of release. Brain Res 695:10–18

    Article  PubMed  CAS  Google Scholar 

  • Wiley JL, Evans RL, Grainger DB, Nicholson KL (2008) Age-dependent differences in sensitivity and sensitization to cannabinoids and ‘club drugs’ in male adolescent and adult rats. Addict Biol 13(3–4):277–286

    Article  PubMed  CAS  Google Scholar 

  • Williams A, Unwin R (1997) Prolonged elevation of serum creatinine kinase (CK) without renal failure after ingestion of ecstasy. Nephrol Dial Transplant 12:361–362

    Article  PubMed  CAS  Google Scholar 

  • Williams H, Dratcu L, Taylor R, Roberts M, Oyefeso A (1998) “Saturday night fever”: ecstasy related problems in a London accident and emergency department. J Accid Emerg Med 15(5):322–326

    Article  PubMed  CAS  Google Scholar 

  • Wills EJ, Findlay JM, McManus JPA (1976) Effects of hyperthermia therapy on the liver. J Clin Path 29:1–10

    Article  PubMed  CAS  Google Scholar 

  • Willson MC, Wilman AH, Bell EC, Asghar SJ, Silverstone PH (2004) Dextroamphetamine causes a change in regional brain activity in vivo during cognitive tasks: a functional magnetic resonance imaging study of blood oxygen level-dependent response. Biol Psychiatry 56(4):284–291

    Article  PubMed  CAS  Google Scholar 

  • Wilson JM, Kalasinsky KS, Levey AI et al (1996) Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nat Med 2(6):699–703

    Article  PubMed  CAS  Google Scholar 

  • Winstock AR, Griffiths P, Stewart D (2001) Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK. Drug Alcohol Depend 64(1):9–17

    Article  PubMed  CAS  Google Scholar 

  • Winterstein AG, Gerhard T, Shuster J, Saidi A (2009) Cardiac safety of methylphenidate versus amphetamine salts in the treatment of ADHD. Pediatrics 124(1):e75–e80

    Article  PubMed  Google Scholar 

  • Wolff K, Winstock AR (2006) Ketamine: from medicine to misuse. CNS Drugs 20(3):199–218

    Article  PubMed  CAS  Google Scholar 

  • Wolff K, Tsapakis EM, Pariante CM, Kerwin RW, Forsling ML, Aitchison KJ (2011) Pharmacogenetic studies of change in cortisol on ecstasy (MDMA) consumption. J Psychopharmacol. doi:10.1177/0269881111415737

    Google Scholar 

  • Woodrow G, Harnden P, Turney JH (1995) Acute renal failure due to accelerated hypertension following ingestion of 3,4-methylenedioxymethamphetamine (‘ecstasy’). Nephrol Dial Transplant 10(3):399–400

    PubMed  CAS  Google Scholar 

  • Woolverton WL, Ricaurte GA, Forno LS, Seiden LS (1989) Long-term effects of chronic methamphetamine administration in rhesus monkeys. Brain Res 486(1):73–78

    Article  PubMed  CAS  Google Scholar 

  • Wu D, Otton SV, Inaba T, Kalow W, Sellers EM (1997) Interactions of amphetamine analogs with human liver CYP2D6. Biochem Pharmacol 53(11):1605–1612

    Article  PubMed  CAS  Google Scholar 

  • Wu C-W, Ping Y-H, Yen J-C et al (2007) Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis. Toxicol Appl Pharmacol 220(3):243–251

    Article  PubMed  CAS  Google Scholar 

  • Wyeth RP, Mills EM, Ullman A, Kenaston MA, Burwell J, Sprague JE (2009) The hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is sensitive to sex differences. Toxicol Appl Pharmacol 235(1):33–38

    Article  PubMed  CAS  Google Scholar 

  • Xie T, Tong L, McLane MW et al (2006) Loss of Serotonin Transporter Protein after MDMA and Other Ring-Substituted Amphetamines. Neuropsychopharmacology 31:2639–2651

    Article  PubMed  CAS  Google Scholar 

  • Yamada H, Shiiyama S, Soejima-Ohkuma T et al (1997) Deamination of amphetamines by cytochromes P450: studies on substrate specificity and regioselectivity with microsomes and purified CYP2C subfamily isozymes. J Toxicol Sci 22(1):65–73

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto BK, Raudensky J (2008) The role of oxidative stress, metabolic compromise, and inflammation in neuronal injury produced by amphetamine-related drugs of abuse. J Neuroimmune Pharmacol 3:203–217

    Article  PubMed  Google Scholar 

  • Yamamoto BK, Zhu W (1998) The effects of methamphetamine on the production of free radicals and oxidative stress. J Pharmacol Exp Ther 287(1):107–114

    PubMed  CAS  Google Scholar 

  • Yamamoto BK, Moszczynska A, Gudelsky GA (2010) Amphetamine toxicities: classical and emerging mechanisms. Ann N Y Acad Sci 1187:101–121

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Jamei M, Heydari A et al (2006) Implications of mechanism-based inhibition of CYP2D6 for the pharmacokinetics and toxicity of MDMA. J Psychopharmacol 20(6):842–849

    Article  PubMed  CAS  Google Scholar 

  • Yeo K-K, Wijetunga M, Ito H et al (2007) The association of methamphetamine use and cardiomyopathy in young patients. Am J Med 120(2):165–171

    Article  PubMed  CAS  Google Scholar 

  • Yi J-H, Hazell AS (2006) Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem Int 48(5):394–403

    Article  PubMed  CAS  Google Scholar 

  • Young R, Glennon RA (1986) Discriminative stimulus properties of amphetamine and structurally related phenalkylamines. Med Res Rev 6(1):99–130

    Article  PubMed  CAS  Google Scholar 

  • Young JM, McGregor IS, Mallet PE (2005) Co-administration of THC and MDMA (‘ecstasy’) synergistically disrupts memory in rats. Neuropsychopharmacology 30(8):1475–1482

    Article  PubMed  CAS  Google Scholar 

  • Yu AM (2008) Indolealkylamines: biotransformations and potential drug-drug interactions. Aaps J 10(2):242–253

    Article  PubMed  CAS  Google Scholar 

  • Zalis EG, Parmley LF Jr (1963) Fatal amphetamine poisoning. Arch Intern Med 112:822–826

    Article  PubMed  CAS  Google Scholar 

  • Zalis EG, Lundberg GD, Knutson RA (1967) The pathophysiology of acute amphetamine poisoning with pathologic correlation. J Pharmacol Exp Ther 158:115–127

    PubMed  CAS  Google Scholar 

  • Zebis LP, Christensen TD, Bøttcher M et al (2007) Severe anterior myocardial infarction caused by amphetamine abuse. Ugeskr Laeger 169(5):423–424

    PubMed  Google Scholar 

  • Zhang F, Dryhurst G (1994) Effects of l-cysteine on the oxidation chemistry of dopamine: new reaction pathways of potential relevance to idiopathic Parkinson’s disease. J Med Chem 37(8):1084–1098

    Article  PubMed  CAS  Google Scholar 

  • Zhao ZY, Castagnoli NJ, Ricaurte GA, Steele T, Martello M (1992) Synthesis and neurotoxicological evaluation of putative metabolites of the serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)phenyl] propane [(methylenedioxy)methamphetamine]. Chem Res Toxicol 5(1):89–94

    Article  PubMed  CAS  Google Scholar 

  • Zhu JPQ, Xu W, Angulo JA (2006) Methamphetamine-induced cell death: selective vulnerability in neuronal subpopulations of the striatum in mice. Neuroscience 140(2):607–622

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Fundaçãopara a CiênciaeTecnologia (FCT) for grant Pest C/EQB/LA0006/2011 and to the project [PTDC/SAU-FCF/102958/2008]-QREN initiative with EU/FEDER financing through COMPETE. VMC and JPC acknowledge FCT for their Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/30776/2006).

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Authors and Affiliations

  1. REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal

    Márcia Carvalho, Helena Carmo, Vera Marisa Costa, João Paulo Capela, Helena Pontes, Fernando Remião, Félix Carvalho & Maria de Lourdes Bastos

  2. Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal

    Márcia Carvalho & João Paulo Capela

Authors
  1. Márcia Carvalho
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  2. Helena Carmo
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  3. Vera Marisa Costa
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  4. João Paulo Capela
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  5. Helena Pontes
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  6. Fernando Remião
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  7. Félix Carvalho
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  8. Maria de Lourdes Bastos
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Corresponding author

Correspondence to Maria de Lourdes Bastos.

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Carvalho, M., Carmo, H., Costa, V.M. et al. Toxicity of amphetamines: an update. Arch Toxicol 86, 1167–1231 (2012). https://doi.org/10.1007/s00204-012-0815-5

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  • DOI: https://doi.org/10.1007/s00204-012-0815-5

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