3,916
Views
5
CrossRef citations to date
0
Altmetric
Review Articles

Combining ecstasy and ethanol: higher risk for toxicity? A review

ORCID Icon & ORCID Icon
Pages 1-14 | Received 08 Sep 2020, Accepted 18 Dec 2020, Published online: 19 Feb 2021

References

  • Aberg M, Wade D, Wall E, Izenwasser S. 2007. Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats. Neurotoxicol Teratol. 29:37–46.
  • Abrahao KP, Oliveira Goeldner F, Souza-Formigoni MLO. 2014. Individual differences in ethanol locomotor sensitization are associated with dopamine D1 receptor intra-cellular signaling of DARPP-32 in the nucleus accumbens. PloS One. 9:e98296.
  • van Amsterdam J, Pennings E, van den Brink W. 2020. Fatal and non-fatal health incidents related to recreational ecstasy use. J Psychopharmacol. 34:591–599.
  • Baumann M, Wang X, Rothman R. 2007. 4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings. Psychopharmacol. 3:407–424. 189.
  • Baylen C, Rosenberg H. 2006. A review of the acute subjective effects of MDMA/ecstasy. Addiction. 101:933–947.
  • Bilsky E, Hubbell C, Delconte J, Reid L. 1991. MDMA produces a conditioned place preference and elicits ejaculation in male rats: a modulatory role for the endogenous opioids. Pharmacol Biochem Behav. 40:443–447.
  • Calle P, Maudens K, Lemoyne S, Geerts S, Van Sassenbroeck D, Jensen P, Van Overloop J, Deconinck E, Blanckaert P. 2019. Lessons to be learned from toxicological analyses in intoxicated patients and seized materials at an electronic music dance festival. Forensic Sci Int. 299:174–179.
  • Calle P, Sundahl N, Maudens K, Wille SM, Van Sassenbroeck D, De Graeve K, Gogaert S, De Paepe P, Devriese D, Arno G, et al. 2018. Medical emergencies related to ethanol and illicit drugs at an annual, nocturnal, indoor, electronic dance music event. Prehosp Disaster Med. 33:71–76.
  • Carvalho M, Pontes H, Remião F, Bastos M, Carvalho F. 2010. Mechanisms underlying the hepatotoxic effects of ecstasy. Curr Pharm Biotechnol. 11:476–495.
  • Cassel JC, Hamida S, Ben Jones BC. 2007. Attenuation of MDMA-induced hyperthermia by ethanol in rats depends on ambient temperature. Eur J Pharmacol. 571:152–155.
  • Cassel JC, Jeltsch H, Koenig J, Jones BC. 2004. Locomotor and pyretic effects of MDMA-ethanol associations in rats. Alcohol. 34:285–289.
  • Cassel JC, Riegert C, Rutz S, Koenig J, Rothmaier K, Cosquer B, Lazarus C, Birthelmer A, Jeltsch H, Jones BC, et al. 2005. Ethanol, 3,4-methylenedioxymethamphetamine (Ecstasy) and their combination: long-term behavioral, neurochemical and neuropharmacological effects in the rat. Neuropsychopharmacology. 30:1870–1882.
  • Charlet K, Beck A, Heinz A. 2013. The dopamine system in mediating alcohol effects in humans. Curr Top Behav Neurosci. 13:461–488.
  • Cohen C, Perrault G, Sanger DJ. 1997. Evidence for the involvement of dopamine receptors in ethanol-induced hyperactivity in mice. Neuropharmacology. 36:1099–1108.
  • Crawshaw LI, Wallace H, Crabbe J. 1998. Ethanol, body temperature and thermoregulation. Clin Exp Pharmacol Physiol. 25:150–154.
  • Davies O, Batajoo-Shrestha B, Sosa-Popoteur J, Olibrice M. 2014. Full recovery after severe serotonin syndrome, severe rhabdomyolysis, multi-organ failure and disseminated intravascular coagulopathy from MDMA. Heart Lung. 43:117–119.
  • Dinis-Oliveira JR, Magalhaes T, Queiros O, Proenca JB, Moreira R, de Lourdes Bastos M, Carvalho F. 2015. Signs and related mechanisms of ethanol hepatotoxicity. Curr Drug Abuse Rev. 8:86–103.
  • Dumont GJ, Kramers C, Sweep F, Willemsen J, Touw D, Schoemaker R, van Gerven J, Buitelaar J, Verkes R. 2010. Ethanol co-administration moderates 3,4-methylenedioxymethamphetamine effects on human physiology. J Psychopharmacol. 24:165–174.
  • Dumont GJ, Schoemaker R, Touw D, Sweep F, Buitelaar J, van Gerven J, Verkes R. 2010. Acute psychomotor effects of MDMA and ethanol (co-) administration over time in healthy volunteers. J Psychopharmacol. 24:155–164.
  • Dumont GJH, Wezenberg E, Valkenberg MMGJ, de Jong CAJ, Buitelaar JK, van Gerven JMA, Verkes RJ. 2008. Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers. Psychopharmacology (Berl). 197:465–474.
  • Dunlap L, Andrews A, Olson D. 2018. Dark classics in chemical neuroscience: 3,4-methylenedioxymethamphetamine. ACS Chem Neurosci. 9:2408–2427.
  • [EMCDDA] European Monitoring Centre for Drugs and Drug addiction. 2019. European drug report 2019: trends and developments. Luxembourg: Publications Office of the European Union.
  • [EMCDDA] European Monitoring Centre for Drugs and Drug addiction. 2020. Drug-related hospital emergency presentations in Europe: update from the Euro-DEN Plus expert network, technical report. Luxembourg: Publications Office of the European Union.
  • Eyer F, Zilker T. 2007. Bench-to-bedside review: mechanisms and management of hyperthermia due to toxicity. Crit Care. 11:236.
  • Fagan D, Tiplady B, Scott DB. 1994. Effects of ethanol on psychomotor performance under steady-state conditions. J Psychopharmacol. 8:75–80.
  • Farquhar K, Lambert K, Drummond GB, Tiplady B, Wright P. 2002. Effect of ethanol on psychomotor performance and on risk taking behaviour. J Psychopharmacol. 16:379–384.
  • Filev R, Engelke DS, Da Silveira DX, Mello LE, Santos-Junior JG. 2017. THC inhibits the expression of ethanol-induced locomotor sensitization in mice. Alcohol. 65:31–35.
  • García-Pardo M, Escobar-Valero C, Rodríguez-Arias M, Miñarro J, Aguilar M. 2015. Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA. Behav Pharmacol. 26:411–417.
  • Van der Gouwe D, Vrolijk R. 2019. Jaarlijks rapport 2018: drugs informatie en monitoring system [Annual report 2018 drug information and monitoring system]. Trimbos Institute. Dutch.
  • 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. 55:463–508.
  • Hall AP, Henry JA. 2006. Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth. 96:678–685.
  • Hamida SB, Bach S, Plute E, Jones BC, Kelche C, Cassel JC. 2006. Ethanol-ecstasy (MDMA) interactions in rats: preserved attenuation of hyperthermia and potentiation of hyperactivity by ethanol despite prior ethanol treatment. Pharmacol Biochem Behav. 84:162–168.
  • Hamida SB, Plute E, Bach S, Lazarus C, Tracqui A, Kelche C, de Vasconcelos AP, Jones BC, Cassel JC. 2007. Ethanol–MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination. Psychopharmacology (Berl). 192:555–569.
  • 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). 197:67–82.
  • Hamida SB, Tracqui A, de Vasconcelos AP, Szwarc E, Lazarus C, Kelche C, Jones BC, Cassel JC. 2009. Ethanol increases the distribution of MDMA to the rat brain: possible implications in the ethanol-induced potentiation of the psychostimulant effects of MDMA. Int J Neuropsychopharmacol. 12:749–759.
  • Hamida SB, Lecourtier L, Loureiro M, Cosquer B, Tracqui A, Simmoneaux V, Nehlig A, Jones B, Pereira de Vasconcelos A, Cassel J. 2020. Ventral striatum regulates behavioral response to ethanol and MDMA combination. Addict Biol. e12938.
  • Harper KM, Knapp DJ, Criswell HE, Breese GR. 2018. Vasopressin and alcohol: a multifaceted relationship. Psychopharmacology (Berl). 235:3363–3379.
  • Hendler RA, Ramchandani VA, Gilman J, Hommer DW. 2013. Stimulant and sedative effects of alcohol. Curr Top Behav Neurosci. 13:489–509.
  • Hernández-López C, Farré M, Roset PN, Menoyo E, Pizarro N, Ortuño J, Torrens M, Camí J, de La Torre R. 2002. 3,4-Methylenedioxymethamphetamine (Ecstasy) and alcohol interactions in humans: psychomotor performance, subjective effects, and pharmacokinetics. J Pharmacol Exp Ther. 300:236–244.
  • Hernandez-Rabaza V, Navarro-Mora G, Velazquez-Sanchez C, Ferragud A, Marin MP, Garcia-Verdugo JM, Renau-Piqueras J, Canales JJ. 2010. Neurotoxicity and persistent cognitive deficits induced by combined MDMA and alcohol exposure in adolescent rats. Addict Biol. 15:413–423.
  • Hernández-Vázquez F, Reyes-Guzmán C, Méndez M. 2018. Impact of a novel environment on alcohol-induced locomotor activity in Wistar rats. Alcohol. 71:5–13.
  • Hondebrink L, Zwartsen A, Westerink RHS. 2018. Effect fingerprinting of new psychoactive substances (NPS): what can we learn from in vitro data? Pharmacol Ther. 182:193–224.
  • 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). 189:459–470.
  • Johnson EA, O'Callaghan JP, Miller DB. 2004. Brain concentrations of d-MDMA are increased after stress. Psychopharmacology (Berl). 173:278–286.
  • Jones A, Holmgren A, Ahlner J. 2016. Post-mortem concentrations of drugs determined in femoral blood in single-drug fatalities compared with multi-drug poisoning deaths. Forensic Sci Int. 267:96–103.
  • Jones B, Hamida S, Ben Pereira de Vasconcelos A, Kelche C, Lazarus C, Jackisch R, Cassel J. 2010. Effects of ethanol and ecstasy on conditioned place preference in the rat. J Psychopharmacol. 24:275–279.
  • Kawano K. 2010. Physio-pathological effects of alcohol on the cardiovascular system: its role in hypertension and cardiovascular disease. Hypertens Res. 33:181–191.
  • Kuypers KPC, 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 (Berl). 187:467–475.
  • Liechti ME. 2014. Effects of MDMA on body temperature in humans. Temperature (Austin). 1:192–200.
  • Lovinger DM. 1997. Serotonin’s role in alcohol’s effects on the brain. Alcohol Health Res World. 21:114–120.
  • Mallick A, Bodenham AR. 1997. MDMA induced hyperthermia: a survivor with an initial body temperature of 42.9 degrees C. J Accid Emerg Med. 14:336–338.
  • Massey VL, Arteel GE. 2012. Acute alcohol-induced liver injury. Front Physiol. 3:193.
  • Matthews DB, Silvers JR. 2004. The use of acute ethanol administration as a tool to investigate multiple memory systems. Neurobiol Learn Mem. 82:299–308.
  • Meyer J. 2013. 3,4-methylenedioxymethamphetamine (MDMA): current perspectives. Subst Abuse Rehabil. 4:83–99.
  • Mohamed W, Hamida S, Ben Cassel J, de Vasconcelos A, Jones B. 2011. MDMA: interactions with other psychoactive drugs. Pharmacol Biochem Behav. 99:759–774.
  • Mohamed WMY, Hamida S, Ben Pereira de Vasconcelos A, Cassel JC, Jones BC. 2009. Interactions between 3,4-methylenedioxymethamphetamine and ethanol in humans and rodents. Neuropsychobiology. 60:188–194.
  • Monks TJ, Jones DD, Bai F, Lau S. 2004. The role of metabolism in 3,4-(+)-methylenedioxyamphetamine and 3,4-(+)-methylenedioxymethamphetamine (ecstasy) toxicity. Ther Drug Monit. 26:132–136.
  • Monshouwer K, van der Pol P, Drost YC, van Laar MW. 2016. Het Grote Uitgaansonderzoek 2016 [The major nightlife study]. Trimbos Institute. Dutch.
  • Moore TO, June HL, Lewis MJ. 1993. Ethanol-induced stimulation and depression on measures of locomotor activity: effects of basal activity levels in rats. Alcohol. 10:537–540.
  • Morefield K, Keane M, Felgate P, White J, Irvine R. 2011. Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational ‘ecstasy’ users. Addiction. 106:1293–1300.
  • Navarro-Zaragoza J, Ros-Simó C, Milanés MV, Valverde O, Laorden ML. 2015. Binge ethanol and MDMA combination exacerbates toxic cardiac effects by inducing cellular stress. PLoS One. 10:e0141502.
  • Navarro-Zaragoza J, Ros-Simó C, Milanés MV, Valverde O, Laorden ML. 2019. Binge ethanol and MDMA combination exacerbates HSP27 and Trx-1 (biomarkers of toxic cardiac effects) expression in right ventricle. Life Sci. 220:50–57.
  • Noseda R, Schmid Y, Scholz I, Liakoni E, Liechti M. 2020. MDMA-related presentations to the emergency departments of the European Drug Emergencies Network plus (Euro-DEN Plus) over the four-year period 2014–2017. Clin Toxicol.
  • Pacifici R, Zuccaro P, Hernandez López C, Pichini S, Di Carlo S, Farré M, Roset PN, Ortuño J, Segura J, Torre RL. 2001. Acute effects of 3, 4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans. J Pharmacol Exp Ther. 296:207–215.
  • Palamar JJ. 2020. Diffusion of ecstasy in the electronic dance music scene. Subst Use Misuse. 55:2243–2250.
  • Palamar JJ, Acosta P. 2020. Virtual raves and happy hours during COVID-19: new drug use contexts for electronic dance music partygoers. Int J Drug Policy.
  • Patel M, Belson M, Longwater A, Olson K, Miller M. 2005. Methylenedioxymethamphetamine (ecstasy)-related hyperthermia. J Emerg Med. 29:451–454.
  • Piano MR. 2017. Alcohol’s effects on the cardiovascular system. Alcohol Res. 38:219–241.
  • Pontes H, Duarte JA, de Pinho PG, Soares ME, Fernandes E, Dinis-Oliveira RJ, Sousa C, Silva R, Carmo H, Casal S, et al. 2008. Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice. Toxicology. 252:64–71.
  • Pontes H, de Pinho PG, Fernandes E, Branco PS, Ferreira LM, Carmo H, Remião F, Carvalho F, Bastos ML. 2010. Metabolic interactions between ethanol and MDMA in primary cultured rat hepatocytes. Toxicology. 270:150–157.
  • Pontes H, Santos-Marques M, Fernandes E, Duarte J, Remião F, Carvalho F, Bastos M. 2008. Effect of chronic ethanol exposure on the hepatotoxicity of ecstasy in mice: an ex vivo study. Toxicol Vitr. 22:910–920.
  • Pontes H, Sousa C, Silva R, Fernandes E, Carmo H, Remião F, Carvalho F, Bastos ML. 2008. Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes. Toxicology. 254:42–50.
  • Prus AJ, James JR, Rosecrans JA. 2009. Methods of behavior analysis in neuroscience. 2nd ed. Boca Raton (FL): Buccafusco JJ. Chapter 4, Conditioned place preference.
  • Ramaekers JG, Kuypers KPC. 2006. Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on behavioral measures of impulsivity: Alone and in combination with alcohol. Neuropsychopharmacology. 31:1048–1055.
  • Ribeiro Do Couto B, Daza-Losada M, Rodríguez-Arias M, Nadal R, Guerri C, Summavielle T, Miñarro J, Aguilar MA. 2012. Adolescent pre-exposure to ethanol and 3,4-methylenedioxymethylamphetamine (MDMA) increases conditioned rewarding effects of MDMA and drug-induced reinstatement. Addict Biol. 17:588–600.
  • Ribeiro Do Couto B, Rodríguez-Arias M, Fuentes S, Gagliano H, Armario A, Miñarro J, Aguilar MA. 2011. Adolescent pre-exposure to ethanol or MDMA prolongs the conditioned rewarding effects of MDMA. Physiol Behav. 103:585–593.
  • Rickli A, Hoener MC, Liechti ME. 2015. Monoamine transporter and receptor interaction profiles of novel psychoactive substances: para-halogenated amphetamines and pyrovalerone cathinones. Eur Neuropsychopharmacol. 25:365–376.
  • Riegert C, Wedekind F, Hamida S, Ben Rutz S, Rothmaier AK, Jones BC, Cassel JC, Jackisch R. 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. 11:743–763.
  • Rietjens SJ, Hondebrink L, Westerink RHS, Meulenbelt J. 2012. Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug-drug interactions. Crit Rev Toxicol. 42:854–876.
  • Rodríguez-Arias M, Maldonado C, Vidal-Infer A, Guerri C, Aguilar MA, Miñarro J. 2011. Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice. Psychopharmacology (Berl). 218:429–442.
  • Roger-Sánchez C, Rodríguez-Arias M, Miñarro J, Aguilar M. 2013. Involvement of 5-hydroxytryptamine 5-HT3 serotonergic receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA. Eur J Pharmacol. 714:132–141.
  • Ros-Simó C, Ruiz-Medina J, Valverde O. 2012. Behavioural and neuroinflammatory effects of the combination of binge ethanol and MDMA in mice. Psychopharmacology (Berl). 221:511–525.
  • Ros-Simó C, Moscoso-Castro M, Ruiz-Medina J, Ros J, Valverde O. 2013. Memory impairment and hippocampus specific protein oxidation induced by ethanol intake and 3, 4-Methylenedioxymethamphetamine (MDMA) in mice. J Neurochem. 125:736–746.
  • Rostami M, Rezayof A, Alijanpour S, Sharifi KA. 2017. Hippocampal nicotinic receptors have a modulatory role for ethanol and MDMA interaction in memory retrieval. Brain Res. 1669:11–17.
  • Ryczko D, Dubuc R. 2017. Dopamine and the brainstem locomotor networks: from lamprey to human. Front Neurosci. 11:295.
  • Salathe C, Blanc A, Tagan D. 2018. SIADH and water intoxication related to ecstasy. BMJ Case Rep.
  • Schenk S. 2009. MDMA self-administration in laboratory animals: a summary of the literature and proposal for future research. Neuropsychobiology. 60:130–136.
  • Schürmann L, Croes E, Lameijer M, Valkenberg H. 2019. Monitor drugsincidenten 2018 [Monitor drugs incidents 2018]. Trimbos Institute. Dutch.
  • Sessa B, Sakal C, O’Brien S, Nutt D. 2019. First study of safety and tolerability of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with ethanol use disorder: preliminary data on the first four participants. BMJ Case Rep. 12:e230109.
  • Sommer WH, Spanagel R. 2013. Behavioral neurobiology of alcohol addiction. Berlin (Germany): Springer.
  • Spronk DB, Dumont GJH, Verkes RJ, De Bruijn ERA. 2014. The acute effects of MDMA and ethanol administration on electrophysiological correlates of performance monitoring in healthy volunteers. Psychopharmacology (Berl). 231:2877–2888.
  • Trantham-Davidson H, Chandler LJ. 2015. Alcohol-induced alterations in dopamine modulation of prefrontal activity. Alcohol. 49:773–779.
  • Upreti VV, Eddington ND, Moon KH, Song BJ, Lee IJ. 2009. Drug interaction between ethanol and 3,4-methylenedioxymethamphetamine (“ecstasy”). Toxicol Lett. 188:167–172.
  • Veldstra JL, Brookhuis KA, de Waard D, Molmans BHW, Verstraete AG, Skopp G, Jantos R. 2012. Effects of alcohol (BAC 0.5‰) and ecstasy (MDMA 100 mg) on simulated driving performance and traffic safety. Psychopharmacology (Berl). 222:377–390.
  • Vidal-Infer A, Aguilar MA, Miñarro J, Rodríguez-Arias M. 2012. Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice. Behav Brain Funct. 8:32.
  • Vizeli P, Liechti ME. 2017. Safety pharmacology of acute MDMA administration in healthy subjects. J Psychopharmacol. 31:576–588.
  • Wasielewski JA, Holloway FA. 2001. Alcohol’s interactions with circadian rhythms. A focus on body temperature. Alcohol Res Health. 25:94–100.
  • WDR. World Drug Report 2019. United Nations publication; 2019. Sales No. E.19.XI.8.
  • Zuniga A, Ryabinin AE, Cunningham CL. 2020. Effects of pharmacological inhibition of the centrally-projecting Edinger-Westphal nucleus on ethanol-induced conditioned place preference and body temperature. Alcohol. 87:121–131.
  • Zwartsen A, Verboven AHA, van Kleef RGDM, Wijnolts FMJ, Westerink RHS, Hondebrink L. 2017. Measuring inhibition of monoamine reuptake transporters by new psychoactive substances (NPS) in real-time using a high-throughput, fluorescence-based assay. Toxicol in Vitro. 45:60–71.