The club drug ecstasy (3,4-methylenedioxymethylamphetamine or MDMA) is often taken recreationally with ethanol (EtOH). We have shown previously that EtOH potentiates the psychomotor effects of MDMA in rats. More recently, we demonstrated in striatal slices that MDMA produced preferential release of serotonin, but when combined with EtOH, the preferential release shifted to dopamine, raising the possibility that administration of EtOH may increase the reward effect of MDMA. To address this possibility, adult male Long-Evans rats were tested for conditioned place preference following treatment with saline, EtOH (0.75 g/kg), MDMA (6.6 mg/kg) or the combination. The only condition that produced a preference for the compartment associated with the drug was that of the drug combination. The current data are in line with anecdotal reports and one study in humans, indicating that EtOH alters the pharmacological effects of MDMA including self reports of enhanced or prolonged euphoria. Thus, administration of EtOH might increase the risk for compulsive use of MDMA, an issue that warrants further study.
Barrett, SP, Darredeau, C., Pihl, RO ( 2006) Patterns of simultaneous polysubstance use in drug using university students. Hum Psycho-pharmacol21: 255-263.
2.
Ben Hamida, S., Plute, E., Bach, S., Lazarus, C., Tracqui, A., Kelche, C., et al. (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.
3.
Bilsky, EJ, Montegut, MJ, Nichols, ML, Reid, LD ( 1998) CGS 10746B, a novel dopamine release inhibitor, blocks the establishment of cocaine and MDMA conditioned place preferences. Pharmacol Biochem Behav59: 215-220.
4.
Bilsky, EJ, Reid, LD ( 1991) MDL72222, a serotonin 5-HT3 receptor antagonist, blocks MDMA’s ability to establish a conditioned place preference. Pharmacol Biochem Behav39: 509-512.
5.
Cassel, JC, Hamida, SB, Jones, BC ( 2008) Ethanol and MDMA: a comment on the paper by Dumont, et al. Psychopharmacology (Berl) 200: 305-306.
6.
Cassel, JC, Jeltsch, H., Koenig, J., Jones, BC ( 2004) Locomotor and pyretic effects of MDMA-ethanol associations in rats. Alcohol34(2-3): 285-289.
7.
Cassel, JC, Riegert, C., Rutz, S., Koenig, J., Rothmaier, K., Cosquer, B., et al. (2005) Ethanol, 3,4-methylenedioxymethamphetamine (ecstasy) and their combination: long-term behavioral, neurochemical and neuropharmacological effects in the rat. Neuropsychopharmacology30: 1870-1882.
8.
Cole, JC, Sumnall, HR, O’shea, E., Marsden, CA ( 2003) Effects of MDMA exposure on the conditioned place preference produced by other drugs of abuse. Psychopharmacology ( Berl) 166: 383-390.
9.
Dafters, RI ( 1995) Hyperthermia following MDMA administration in rats: effects of ambient temperature, water consumption, and chronic dosing. Physiol Behav58: 877-882.
10.
Dumont, GJ, Wezenberg, E., Valkenberg, MM, de Jong, CA, Buitelaar, JK, van Gerven, JM, et al. (2008) Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers. Psychopharmacology (Berl) 197: 465-474.
11.
Easton, N., Marsden, CA ( 2006) Ecstasy: are animal data consistent between species and can they translate to humans? J Psychopharmacol20: 194-210.
12.
Freedman, RR, Johanson, CE, Tancer, ME ( 2005) Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology ( Berl) 183: 248-256.
13.
Gough, B., Ali, SF, Slikker Jr., W., Holson, RR ( 1991) Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in rat caudate. Pharmacol Biochem Behav39: 619-623.
14.
Green, AR, Mechan, AO, Elliott, JM, O’shea, E., Colado, MI ( 2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacol Rev55: 463-508.
15.
Green, AR, O’shea, E., Colado, MI ( 2004) A review of the mechanisms involved in the acute MDMA (ecstasy)-induced hyperthermic response. Eur J Pharmacol500: 3-13.
16.
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.
17.
Hernandez-Lopez, C., Farre, M., Roset, PN, Menoyo, E., Pizarro, N., Ortuno, J., et al. (2002) 3,4-Methylenedioxymethamphetamine (ecstasy) and alcohol interactions in humans: psychomotor performance, subjective effects, and pharmacokinetics. J Pharmacol Exp Ther300: 236-244.
18.
Hopfer, C., Mendelson, B., Van Leeuwen, JM, Kelly, S., Hooks, S. ( 2006) Club drug use among youths in treatment for substance abuse. Am J Addict15: 94-99.
19.
Iravani, MM, Asari, D., Patel, J., Wieczorek, WJ, Kruk, ZL ( 2000) Direct effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphe nucleus slices. Synapse36: 275-285.
20.
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.
21.
Johnson, EA, O’Callaghan, JP, Miller, DB ( 2004) Brain concentrations of d-MDMA are increased after stress . Psychopharmacology (Berl) 173(3-4): 278-286.
22.
Katz, JL, Terry, P., Witkin, JM ( 1992) Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene) . Life Sci50: 1351-1361.
23.
Pan, WJ, Hedaya, MA ( 1999) Cocaine and alcohol interactions in the rat: effect of cocaine and alcohol pretreatments on cocaine pharmacokinetics and pharmacodynamics . J Pharm Sci88: 1266-1274.
24.
Riegert, C., Wedekind, F., Hamida, SB, Rutz, S., Rothmaier, AK, Jones, BC, 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 Neuropsychopharmacol11: 743-763.
25.
Riley, SC, James, C., Gregory, D., Dingle, H., Cadger, M. ( 2001) Patterns of recreational drug use at dance events in Edinburgh, Scotland. Addiction96: 1035-1047.
26.
Siliquini, R., Faggiano, F., Geninatti, S., Versino, E., Mitola, B., Ippolito, R. ( 2001) Patterns of drug use among young men in Piedmont (Italy) . Drug Alcohol Depend64: 329-335.
27.
Topp, L., Hando, J., Dillon, P., Roche, A., Solowij, N. ( 1999) Ecstasy use in Australia: patterns of use and associated harm. Drug Alcohol Depend55: 105-115.
28.
Wise, RA, Bozarth, MA ( 1987) A psychomotor stimulant theory of addiction. Psychol Rev94: 469-492.
