Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love").
Ruth Mcnamara, Aoife Kerans, Barry O'Neill, Andrew Harkin
Neuropharmacology January 2006 DOI: 10.1016/j.neuropharm.2005.08.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA MDA Caffeine |
| Dose | MDMA 15 mg/kg, MDA 7.5 mg/kg, caffeine 10 mg/kg; repeated: MDMA 10 mg/kg, MDA 5 mg/kg, caffeine 10 mg/kg; high-dose: MDMA 2.5 mg/kg, caffeine 10 mg/kg |
| Duration | 4 days of repeated administration, 2 days of high-dose administration, 4-week follow-up |
| Measures | core body temperature, lethality, serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) concentrations |
| Topics | MDMA Serotonin |
| Key findings | Caffeine enhanced MDMA- and MDA-induced hyperthermia and lethality, and co-administration of caffeine with MDA (but not MDMA) reduced serotonin and 5-HIAA concentrations in frontal cortex, hippocampus, striatum, and amygdala four weeks later. High-dose MDMA with caffeine also caused hippocampal serotonin loss. The authors conclude that caffeine promotes acute and long-term toxicity of MDMA and MDA. |
Abstract
The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of control). Neither MDMA nor MDA alone induced a significant reduction in regional 5-HT or 5-HIAA concentrations following repeated administration. In conclusion, caffeine promotes the acute and long-term toxicity associated with MDMA and MDA. This is a serious drug interaction, which could have important acute and long-term health consequences for recreational drug users.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 20
- Caffeine provokes adverse interactions with 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators British Journal of Pharmacology June 1, 2012
- A developmental comparison of the neurobehavioral effects of ecstasy (MDMA) Neurotoxicology and Teratology October 21, 2006
- Methylenedioxymethamphetamine (‘Ecstasy’)‐induced immunosuppression: a cause for concern? British Journal of Pharmacology May 27, 2010
- Mechanisms mediating the ability of caffeine to influence MDMA (‘Ecstasy’)‐induced hyperthermia in rats British Journal of Pharmacology May 24, 2010
- The Role of Adenosine A1 and A2A Receptors in the Caffeine Effect on MDMA-Induced DA and 5-HT Release in the Mouse Striatum Neurotoxicity Research November 13, 2014
and 15 more in the library
Cites 19
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- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Clinical Studies Neuropsychobiology 2000
- Lasting Neuropsychiatric Sequelae of (??)Methylenedioxymethamphetamine (???Ecstasy???) in Recreational Users Journal of Clinical Psychopharmacology October 1, 1991
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
and 14 more in the library