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MDMA ('Ecstasy') and methamphetamine combined: order of administration influences hyperthermic and long-term adverse
Kelly J Clemens1, Jennifer L Cornish, Kong M Li
1School of Psychology, University of Sydney, A19, Sydney, NSW 2006, Australia.
Abstract:
The acute and long-term dangers of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') and methamphetamine (METH) are well described individually, but their effect in combination is largely unknown. Here groups of female rats were given four MDMA or METH injections within a single session with each injection separated by 2h. Treatments included MDMA only, METH only, MDMA and METH in a cocktail (MDMA/METH), MDMA (two injections) followed by METH (two injections) (MDMA-->METH), or METH followed by MDMA (METH-->MDMA). Each injection involved 4mg/kg of total drug. Drug administration occurred at a high ambient temperature of 28 degrees C. All treatments produced hyperactivity while the treatments where MDMA was administered first (MDMA, MDMA-->METH and MDMA/METH) produced hyperthermia. All treatments involving METH caused significant head weaving. Six weeks after drug treatment all groups showed reduced social interaction relative to controls. MDMA/METH treatment was associated with reduced swimming in the forced swim test. MDMA given alone caused 5-HT depletion in several brain regions while METH given alone caused dopamine depletion in the striatum. The three treatments involving MDMA and METH combinations caused significant depletion of serotonin, dopamine and noradrenaline in several brain regions. Interestingly, the MDMA-->METH treatment produced greater hippocampal and cortical 5-HT depletion than the METH-->MDMA treatment suggesting an effect of order. These results extend our recent findings of additive toxic effects when METH is combined with MDMA. This has potentially important implications for party drug users who appear to frequently use this combination.
Insights
Combining MDMA and methamphetamine in rats caused long-term social interaction deficits and significant depletion of key neurotransmitters. The order of drug administration influenced the severity of serotonin depletion, highlighting additive toxic effects.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- The individual dangers of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) are known.
- The combined effects and long-term consequences of MDMA and METH are largely uncharacterized.
Purpose of the Study:
- To investigate the acute and long-term neurotoxic effects of combined MDMA and METH administration in female rats.
- To determine if the order of drug administration impacts neurotoxicity and behavioral outcomes.
Main Methods:
- Female rats received four injections of MDMA, METH, or a combination (cocktail, sequential) over a single session at high ambient temperature.
- Behavioral tests (locomotion, social interaction, forced swim test) and neurochemical analyses (neurotransmitter levels) were conducted six weeks post-treatment.
Main Results:
- All treatments induced hyperactivity; MDMA-first treatments and the cocktail caused hyperthermia. METH-containing treatments led to head weaving.
- Six weeks later, all drug-treated groups exhibited reduced social interaction. MDMA/METH combination reduced swimming behavior.
- Combined MDMA and METH treatments significantly depleted serotonin, dopamine, and noradrenaline. MDMA followed by METH (MDMA-->METH) caused greater 5-HT depletion than METH followed by MDMA (METH-->MDMA).
Conclusions:
- Combined administration of MDMA and METH results in additive neurotoxic effects, impacting social behavior and neurotransmitter systems long-term.
- The sequence of drug exposure influences the extent of neurochemical damage, particularly serotonin depletion.
- Findings have significant implications for individuals using combined MDMA and METH ('party drugs').
