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Published on: February 5, 2018
High ambient temperature increases the toxicity and lethality of 3,4-methylenedioxymethamphetamine and methcathinone
Yu Chen1, Huyen T N Tran1, Yasir H Saber2
1Department of Pharmacology & Experimental Therapeutics, College of Pharmacology and Pharmacological Science, University of Toledo, OH, USA.
Rationale:
Methylenedioxymethamphetamine (MDMA) and methcathinone (MCAT) are abused psychostimulant drugs that produce adverse effects in human users that include hepatotoxicity and death. Recent work has suggested a connection between hepatotoxicity, elevations in plasma ammonia, and brain glutamate function for methamphetamine (METH)-induced neurotoxicity.
Objectives:
These experiments investigated the effect of ambient temperature on the toxicity and lethality produced by MDMA and MCAT in mice, and whether these effects might involve similar mechanisms to those described for METH neurotoxicity.
Results:
Under low (room temperature) ambient temperature conditions, MDMA induced hepatotoxicity, elevated plasma ammonia levels, and induced lethality. Under the same conditions, even a very high dose of MCAT produced limited toxic or lethal effects. High ambient temperature conditions potentiated the toxic and lethal effects of both MDMA and MCAT.
Conclusion:
These studies suggest that hepatotoxicity, plasma ammonia, and brain glutamate function are involved in MDMA-induced lethality, as has been shown for METH neurotoxicity. The toxicity and lethality of both MDMA and MCAT were potentiated by high ambient temperatures. Although an initial mouse study reported that several cathinones were much less toxic than METH or MDMA, the present results suggest that it will be essential to assess the potential dangers posed by these drugs under high ambient temperatures.
Insights
High ambient temperatures significantly increase the toxicity and lethality of Methylenedioxymethamphetamine (MDMA) and methcathinone (MCAT) in mice. These effects may involve hepatotoxicity and elevated ammonia, similar to methamphetamine neurotoxicity.
Area of Science:
- Toxicology
- Neuroscience
- Environmental Health
Background:
- Methylenedioxymethamphetamine (MDMA) and methcathinone (MCAT) are abused psychostimulants with known adverse effects, including hepatotoxicity and lethality.
- Methamphetamine (METH)-induced neurotoxicity has been linked to hepatotoxicity, elevated plasma ammonia, and altered brain glutamate function.
Purpose of the Study:
- To investigate the impact of ambient temperature on MDMA and MCAT toxicity and lethality in mice.
- To determine if these drugs' effects involve mechanisms similar to METH neurotoxicity.
Main Methods:
- Experiments were conducted on mice exposed to MDMA and MCAT at varying ambient temperatures (low and high).
- Toxicity and lethality were assessed, along with plasma ammonia levels.
Main Results:
- At room temperature, MDMA caused hepatotoxicity, elevated ammonia, and lethality, while MCAT showed limited effects.
- High ambient temperatures potentiated the toxic and lethal effects of both MDMA and MCAT.
Conclusions:
- Hepatotoxicity, plasma ammonia, and glutamate function are likely involved in MDMA-induced lethality, mirroring METH neurotoxicity findings.
- The toxicity and lethality of MDMA and MCAT are significantly enhanced by high ambient temperatures, necessitating further risk assessment.
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