Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love")
by
McNamara R, Kerans A, O'neill B, Harkin A.
Department of Pharmacology,
National University of Ireland,
Galway, Ireland.
Neuropharmacology. 2005 Sep 23;

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 (10mg/kg) enhanced the acute toxicity of MDMA (15mg/kg) and MDA (7.5mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5h following MDMA and +1.5 degrees C for 3h following MDA) when compared to MDMA (+1 degrees C for 3h) and MDA (+1 degrees C for 1h) 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 (10mg/kg) or MDA (5mg/kg) with or without caffeine (10mg/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 4day treatment period. In addition, 4weeks 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 (10mg/kg) and MDMA (2.5mg/kg) were co-administered four times daily for 2days 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.

Club drugs
Abstinence
Parkinson's?
Liver failure
Brain damage?
Kidney damage
Malonate/toxicity
Deaths in New York
Long-term brain damage?
Toxic metabolites of MDMA?
MDMA and sympathetic activity
MDMA and the MAO-b deficient mouse
A toxic intraneuronal metabolite of serotonin?
Electrophysiological evidence of 5-HT damage
Non-neurotoxic and neurotoxic serotonin-releasers
Ecstasy-induced toxicity and the dopamine transporter
5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family