title: Association of caffeine to MDMA does not increase antinociception but potentiates adverse effects of this recreational drug.
abstract: Ecstasy (MDMA) street tablets often contain several other compounds in addition to MDMA, particularly caffeine. Then, it becomes necessary to study the consequences of caffeine plus MDMA combination. MDMA (1 mg/kg) elicited an analgesic response both at the spinal and supraspinal levels. However, when associated, MDMA and caffeine did not show any synergistic interaction. When caffeine was administered prior to MDMA, a potentiation of locomotor activity was observed, which consisted in an increase in maximal values and in a prolonged time of activity. In the neurotoxicity studies, a hyperthermic effect of MDMA was observed. Although caffeine alone failed to alter body temperature, it potentiated MDMA-induced hyperthermia. This association also significantly increased MDMA lethality (from 22% to 34%). Following administration of MDMA to rats, there was a persistent decrease in the number of serotonin transporter sites in the cortex, striatum and hippocampus, which was potentiated by caffeine co-treatment. This MDMA toxicity in rats was accompanied by a transient dopaminergic impairment in the striatum, measured as decreased [(3)H]WIN35428 binding sites, by 31% 3 days after treatment, which was not modified by caffeine. A transient down-regulation of 5-HT(2) receptors occurred in the cortex of MDMA-treated rats, whose recovery was slowed by co-treatment with caffeine. In conclusion, the association of MDMA with caffeine does not generate any beneficial effects at the antinociceptive level. The acute effects stemming from this association, in tandem with the final potentiation of serotonergic terminals injury, provide evidence of the potentially greater long-term adverse effects of this particular recreational drug combination.
authors.affiliation: Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Camarasa
authors.forename: David
authors.initials: D
authors.lastname: Pubill
authors.forename: Elena
authors.initials: E
authors.lastname: Escubedo
mesh_terms: D000700:Analgesics / Q000009:adverse effects* / Q000633:toxicity; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002110:Caffeine / Q000009:adverse effects* / Q000633:toxicity; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000633:toxicity; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D006213:Hallucinogens / Q000009:adverse effects / Q000633:toxicity; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects* / Q000633:toxicity; D009498:Neurotoxins / Q000009:adverse effects / Q000633:toxicity; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D000697:Central Nervous System Stimulants; D006213:Hallucinogens; D009498:Neurotoxins; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D002110:Caffeine; D018817:N-Methyl-3,4-methylenedioxyamphetamine