PMID- 16188283
OWN - NLM
STAT- MEDLINE
DCOM- 20060501
LR  - 20131121
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 50
IP  - 1
DP  - 2006 Jan
TI  - Caffeine promotes hyperthermia and serotonergic loss following co-administration 
      of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love").
PG  - 69-80
AB  - 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.
FAU - McNamara, Ruth
AU  - McNamara R
AD  - Department of Pharmacology, National University of Ireland, Galway.
FAU - Kerans, Aoife
AU  - Kerans A
FAU - O'Neill, Barry
AU  - O'Neill B
FAU - Harkin, Andrew
AU  - Harkin A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050926
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Hallucinogens)
RN  - 333DO1RDJY (Serotonin)
RN  - 3G6A5W338E (Caffeine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*toxicity
MH  - Animals
MH  - Area Under Curve
MH  - Behavior, Animal/drug effects
MH  - Body Temperature/drug effects
MH  - Brain Chemistry/drug effects
MH  - Caffeine/*toxicity
MH  - Central Nervous System Stimulants/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Drug Tolerance
MH  - Fever/*chemically induced/physiopathology
MH  - Hallucinogens/*toxicity
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Male
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Seizures/chemically induced/psychology
MH  - Serotonin/*metabolism
EDAT- 2005/09/29 09:00
MHDA- 2006/05/02 09:00
CRDT- 2005/09/29 09:00
PHST- 2005/06/28 00:00 [received]
PHST- 2005/08/10 00:00 [revised]
PHST- 2005/08/11 00:00 [accepted]
PHST- 2005/09/29 09:00 [pubmed]
PHST- 2006/05/02 09:00 [medline]
PHST- 2005/09/29 09:00 [entrez]
AID - S0028-3908(05)00311-4 [pii]
AID - 10.1016/j.neuropharm.2005.08.006 [doi]
PST - ppublish
SO  - Neuropharmacology. 2006 Jan;50(1):69-80. doi: 10.1016/j.neuropharm.2005.08.006. 
      Epub 2005 Sep 26.