Ecstasy (MDMA) and its effects on kidneys and their treatment: a review

Document Type : Review Article


1 Department of Nephrology, Yenimahalle Training and Research Hospital, Yıldırım Beyazıt University, Ankara, Turkey

2 Department of Nephrology, State Hospital, Zonguldak, Turkey

3 Department of Chemistry, Ankara Police Forensic Laboratory, Gölbaşı, Ankara, Turkey


Ecstasy (MDMA; 3,4-methylenedioxymethylamphetamine) is an illicit drug that has been increasingly abused by young people. Its effects include euphoria, enhanced sociability and heightened mental awareness. These come about via the increase of serotonin in both the central nervous system and the sympathetic nervous system. Despite the drug’s prevalent abuse, serious or adverse effects are rare. Due to personal pharmacokinetics, effects from the same dosage vary according to the individual. Fatal instances may include acute hyponatremia, hyperthermia (>42 °C), disseminated intravascular coagulation (DIC) resulting from hyperthermia affecting the kidneys, and non-traumatic rhabdomyolysis. However, it is seldom the case that hyponatremia and hyperthermia co-exist. Hyponatremia is thought to be caused by HMMA – a metabolite of MDMA. Hyponatremia is caused by the inappropriate secretion of arginine vasopressin (AVP) and the excessive intake of hypotonic liquid accompanied by increased hyperthermia. Symptomatic, even deadly hyponatremia is seen more frequently in females, with the effects of oestrogen on arginine vasopressin believed to be the cause. Onset in such cases is acute, and treatment should be given to symptomatic patients as quickly as possible, with 3% saline administered when necessary. Reasons for acute kidney injury may include rhabdomyolysis, malign hypertension, and necrotizing vasculitis.


1.Bora T. Development of the analytical methods used for the qualitative, quantitative analysis and source determination in the seized ecstasy tablets. PhD Thesis (Turkish), Gazi University, Ankara, 2007.
2.UNODC, World Drug Report. 2005; 99-103.
3.Ministry of Internal Affairs, Turkish National Police, Department Of Anti-Smuggling and Organized Crime, 2005 Report, Ankara, 2006.p. 117-165.
4.Jansen KLR. Ecstasy (MDMA) Dependence. Drug Alcohol Depend 1999; 53:121-124.
5.Bora T, Nuralın F, Şenocak N, Aydın H. Determination of the organic compounds in synthetic tablets containing MDMA (Ecstasy) (Turkish). J For Med 2014; 28:164-177.
6.TUBİM, Turkish Drug Report, Ankara, 2014.
7.Bora T, Aydın H, Ataç Y, Şen N, Aksoy Ç. Determination of metals contamination in illicit ecstasy drug samples using ICP-OES and XRF. Atomic Spectroscopy 2014; 35:139-146.
8.Morgan MJ. Ecstasy (MDMA): a review of its possible persistent psychological effects. J Psychopharmacol 2000; 152:230-248.
9.Parrott AC. Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research. Hum Psychopharmacol Clin Exp 2001; 16:557-577.
10.Gimeno P, Besacier F, Chaudron-Thozet, H, Girard J, Lamotte A. A contribution to the chemical profiling of 3,4 methylenedioxymethamphetamin (MDMA) tablets. Forensic Sci Int 2002; 127: 1–44.
11.Fahal IH, Sallomi DF, Yaqoob M, Bell GM. Acute renal failure after ecstasy. BMJ 1992; 305:29.
12.De la Torre R, Farre M, Roset PM, Pizarro N, Abanades S, Segura M, et al. Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Ther Drug Monit 2004; 26:137-144.
13.Wolff K, Tsapakis EM, Winstock AR, Hartley D, Holt D, Forsling ML, et al. Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population. J Psychopharmacol 2006; 20:400-410.
14.Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacol Rev 2003; 55:463-508.
15.Schwartz RH, Miller NS. MDMA (ecstasy) and the rave: a review. Pediatrics 1997; 100:705-708.
16.Hall AP, Henry JA. Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth 2006; 96:678-685.
17.Antoniou T, Tseng AL. Interactions between antiretrovirals and antineoplastic drug therapy. Clin Pharmacokinet 2005; 44:111-145.
18.Henry JA, Hill IR. Fatal interaction between ritonavir and MDMA. Lancet 1998; 352:1751-1752.
19.Nadkarni GN, Hoskote SS, Piotrkowski J, Annapureddy N. Serotonin syndrome, disseminated intravascular coagulation and hepatitis after a single ingestion of MDMA in an Asian woman. Am J Ther 2014; 21:117-119.
20.Dvir Y, Smallwood P. Serotonin syndrome: a complex but easily avoidable condition. Gen Hosp Psychiatry 2008; 30:284-287.
21.Ninković M, Selaković V, Dukić M, Milosavljević P, Vasiljević I, Jovanović M, et al. Oxidative stress in rat kidneys due to 3,4-methylenedioxymetamphetamine (ecstasy) toxicity. Nephrology (Carlton) 2008; 13:33-37.
22.Gore SM. Fatal uncertainty: death-rate from use of ecstasy or heroin. Lancet 1999; 354:1265-1266
23.Boyle NT, Connor TF. Methylenedioxymeth-amphetamine (‘Ecstasy’) - induced immunosuppression: a cause for concern? Review. Br J Pharmacol 2010; 161:17-32
24.Camarasa J, Ros C, Pubill D, Escubedo E. Tumour necrosis factor alpha suppression by MDMA is mediated by peripheral heteromeric nicotinic receptors. Immunopharmacol Immunotoxicol 2010; 244:344-353.
25.Seibert J, Hysek CM, Penno CA, Schmid Y, Kratschmar DV, Liechti ME, et al. Acute effects of 3,4-methylenedioxymethamphetamine and methylpheni-date on circulating steroid levels in healthy subjects. Neuroendocrinology 2014; 100:17-25.
26.Campbell GA, Rosner MH. The agony of ecstasy: MDMA (3,4-methylenedioxymethamphe-tamine) and the kidney. Clin J Am Soc Nephrol 2008; 3:1852-1860.
27.Cherney DZ, Davids MR, Halperin ML. Acute hyponatraemia and 'ecstasy': insights from a quantitative and integrative analysis. QJM 2002; 95:475-483.
28.Henry JA, Fallon JK, Kicman AT, Hutt AJ, Cowan DA, Forsling M. Low-dose MDMA ("ecstasy") induces vasopressin secretion. Lancet 1998; 351:1784.
29.Budisavljevic MN, Stewart L, Sahn SA, Ploth DW. Hyponatremia associated with 3,4 methylenedioxymethylamphetamine ("Ecstasy") abuse. Am J Med Sci 2003; 326:89-93.
30.Iovino M, Steardo L. Effect of substances influencing brain serotonergic transmission on plasma vasopressin levels in the rat. Eur J Pharmacol 1985; 113:99-103.
31.Schuster VL, Seldin DW. Water clearance. In: Seldin DW, Geibisch G. editors. Clinical disturbances of water metabolism. New York: Raven Press; 1996.p. 51-64.
32.Fallon JK, Shah D, Kicman AT, Hutt AJ, Henry JA, Cowan DA, et al. Action of MDMA (ecstasy) and its metabolites on arginine vasopressin release. Ann N Y Acad Sci 2002; 965:399-409.
33.Forsling M, Fallon JK, Kicman AT, Hutt AJ, Cowan DA, Henry JA. Arginine vasopressin release in response to the administration of 3,4-methylenedioxymethamphetamine ("ecstasy"): is metabolism a contributory factor?. J Pharm Pharmacol 2001; 53:1357-1363.
34.Forsling ML, Fallon JK, Shah D, Tilbrook GS, Cowan DA, Kicman AT, et al. The effect of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus. Br J Pharmacol 2002; 135:649-656.
35.Arieff AI, Kozniewska E, Roberts TP, Vexler ZS, Ayus JC, Kucharczyk J. Age, gender, and vasopressin affect survival and brain adaptation in rats with metabolic encephalopathy. Am J Physiol 1995; 268:1143-1152.
36.Walubo A, Seger D. Fatal multi-organ failure after suicidal overdose with MDMA, 'ecstasy': case report and review of the literature. Hum Exp Toxicol 1999; 18:119-125.
37.Rose BD, Post TW. Hypoosmolal states-hyponatremia. Clinical Physicology of acid base and electrolyte disorders. 5th ed. New York: McGraw-Hill; 2001.p. 716-720.
38.Ayus JC, Varon J, Arieff AI. Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners. Ann Intem Med 2000; 132:711-714.
39.Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intem Med 1992; 117:891-897.
40.Ayus JC, Arieff AI. Chronic hyponatremic encephalopathy in postmenopausal women: association of therapies with morbidity and mortality. JAMA 1999; 281:2299-2304.
41.Ayus JC, Achinger SG, Arieff A. Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia. Am J Physiol Renal Physiol 2008; 295:619-624.
42.Forsling ML, Strömberg P, Akerlund M. Effect of ovarian steroids on vasopressin secretion. J Endocrinol 1982; 95:147-151.
43.Stachenfeld NS, Splenser AE, Calzone WL, Taylor MP, Keefe DL. Sex differences in osmotic regulation of AVP and renal sodium handling. J Appl Physiol 2001; 91:1893-1901.
44.Stachenfeld NS, Silva C, Keefe DL, Kokoszka CA, Nadel ER. Effects of oral contraceptives on body fluid regulation. J Appl Physiol 1999; 87:1016-1025.
45.Simmler LD, Hysek CM, Liechti ME. Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjects. J Clin Endocrinol Metab 2011; 96:2844-2850.
46.Grunau BE, Wiens MO, Brubacher JR. Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review. CJEM 2010; 12:435-442.
47.Hoo GW. The agony with ecstasy: lessons from a recent rave. J Intensive Care Med 2013; 28:259-261.
48.Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005; 352:1112-1120.
49.Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore) 2000; 79:201-209.
50.Docherty JR, Green AR. The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives. Br J Pharmacol 2010; 160:1029–1044.
51.Mills EM, Banks ML, Sprague JE, Finkel T. Pharmacology: uncoupling the agony from ecstasy. Nature 2003; 426:403-404.
52.Sprague JE, Moze P, Caden D, Rusyniak DE, Holmes C, Goldstein DS, et al. Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model. Crit Care Med 2005; 33:1311-1316.
53.Sprague JE, Yang X, Sommers J, Gilman TL, Mills EM. Roles of norepinephrine, free fatty acids, thyroid status, and skeletal muscle uncoupling protein 3 expression in sympathomimetic- induced thermogenesis. J Pharmacol Exp Ther 2007; 320:274-280.
54.Shankaran M, Gudelsky GA. Effect of 3,4-methylenedioxymethamphetamine (MDMA) on hippocampal dopamine and serotonin. Pharmacol Biochem Behav 1998; 61:361-366.
55.Bronstein DM, Hong JS. Effects of sulpiride and SCH 23390 on methamphetamine-induced changes in body temperature and lethality. J Pharmacol Exp Ther 1995; 274:943-950.
56.Hall AP, Lyburn ID,f Spears FD, Riley B. An unusual case of ecstasy poisoning. Intensive Care Med 1996; 22:670-671.
57.Rusyniak DE, Tandy SL, Hekmatyar SK, Mills E, Smith DJ, Bansal N, et al. The role of mitochondrial uncoupling in 3,4-methylenedioxymethamphetamine-mediated skeletal muscle hyperthermia and rhabdomyolysis. J Pharmacol Exp Ther 2005; 313:629-639.   
58.Ejaz AA, Mu W, Kang DH, Roncal C, Sautin YY, Henderson G, et al.  Could uric acid have a role in acute renal failure?.  Clin J Am Soc Nephrol 2007; 2:16-21.
59.Lin PY, Lin CC, Liu HC, Lee MD, Lee HC, Ho CS, et al. Rasburicase improves hyperuricemia in patients with acute kidney injury secondary to rhabdomyolysis caused by ecstasy intoxication and exertional heat stroke. Pediatr Crit Care Med 2011; 12:424-427.
60.Bryden AA, Rothwell PJ, O'Reilly PH. Urinary retention with misuse of "ecstasy". BMJ 1995; 310:504.
61.Woodrow G, Harnden P, Turney JH. Acute renal failure due to accelerated hypertension following ingestion of 3,4-methylenedioxymethamphetamine ('ecstasy'). Nephrol Dial Transplant 1995; 10:399-400.
62.Kwon C, Zaritsky A, Dharnidharka VR. Transient proximal tubular renal injury following Ecstasy ingestion. Pediatr Nephrol 2003; 18:820-822.
63.Bingham C, Beaman M, Nicholls AJ, Anthony PP.  Necrotizing renal vasculopathy resulting in chronic renal failure after ingestion of methamphetamine and 3,4-methylenedioxymethamphetamine ('ecstasy'). Nephrol Dial Transplant 1998; 13:2654-2655.
64.Eldehni MT, Ian SDR, Naik R, Vaux E. Case report of ecstasy-induced renal venous thrombosis. NDT Plus 2010; 3:459-460.
65.Hurault de Ligny B, El Haggan W, Comoz F, Lobbedez T, Pujo M, Griveau AM, et al. Early loss of two renal grafts obtained from the same donor: role of ecstasy?. Transplant 2005; 80:153-156.
66.Song BJ, Moon KH, Upreti VV, Eddington ND, Lee IJ. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage. Curr Pharm Biotechnol 2010; 11:434-443.
67.Paris JM, Cunningham KA. Lack of serotonin neurotoxicity after intraraphe microinjection of (+)-3,4-methylenedioxymethamphetamine (MDMA). Brain Res Bull 1992; 28:115-119.
68.Carvalho M1, Remião F, Milhazes N, Borges F, Fernandes E, Monteiro Mdo C, et al. Metabolism is required for the expression of ecstasy-induced cardiotoxicity in vitro. Chem Res Toxicol 2004; 17:623-632.
69.Pacher P, Beckman JS, Liaudet L. Nitric oxide and  peroxynitrite in health and disease. Physiol Rev 2007; 87:315-424.
70.Carvalho M, Remião F, Milhazes N, Borges F, Fernandes E, Carvalho F, et al.The toxicity of N-methyl-alpha-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine. Toxicology 2004; 200:193-203.
71.Jayanthi S, Ladenheim B, Andrews AM, Cadet JL. Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy). Neuroscience 1999; 91:1379-1387.
72.Peate WF. Hyponatremia in marathon runners. N Engl J Med 2005; 353:427-428.
73.Bouchama A, Knochel JP. Heat stroke. N Engl J Med 2002; 346:1978-1988.
74.Grunau BE, Wiens MO, Greidanus M. Dantrolene for the treatment of MDMA toxicity. CJEM 2010; 12:457-459.
75.Grunau BE, Wiens MO, Brubacher JR. Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review. CJEM 2010; 12:435-442.
76.Hysek CM, Schmid Y, Rickli A, Simmler LD, Donzelli M, Grouzmann E, et al. Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans. Br J Pharmacol 2012; 166: 2277-2288.
77.Tatay VS, Castilla JD, Ponce JM, Hurtado JM, Cantero E, Abril ML. Rasburicase versus allopurinol in the treatment of hyperuricaemia in tumour lysis syndrome. An Pediatr (Barc) 2010; 72:103-110.
78.Ricaurte GA, McCann UD. Recognition and management of complications of new recreational drug use. Lancet 2005; 365:2137-2145.
79.Karami M, Nokabadi FK, Ebrahimzadeh MA, Naghshvar F. Nephroprotective effects of Feijoa sellowiana leaves extract on renal injury induced by acute dose of ecstasy (MDMA) in mice.  Iran J Basic Med Sci 2014; 17:69-72.
80.Akkina SK, Ricardo AC, Patel A, Das A, Bazzano LA, Brecklin C, et al. Illicit drug use, hypertension, and chronic kidney disease in the US adult population. Translational Res 2012; 160:391-398
81.Vupputuri S, Batuman V, Muntner P, Bazzano LA, Lefante JJ, Whelton PK, et al. The risk for mild kidney function decline associated with illicit drug use among hypertensive men. Am J Kidney Dis 2004; 43:629-635.