Stimulants in “Bath Salts” Produce Effects Similar to MDMA

August 19, 2013

Mephedrone and methylone, two stimulants commonly found in designer drugs such as “bath salts,” act on the brain much like methylenedioxymethamphetamine (MDMA, Ecstasy). According to recent studies, the two may be addictive, but may not have the same propensity for causing toxicity as MDMA.

Figure 1A and 1B. Mephedrone and Methylone Increase Extracellular Serotonin and Dopamine Direct measurements of neurochemical release in the nucleus accumbens of living rats show that the higher the dose of mephedrone and methylone, the greater the increase in extracellular dopamine and serotonin levels. Like MDMA, the drugs produce a greater effect on serotonin (Figure 1A) than on dopamine (Figure 1B). Asterisks indicate a significant difference compared to saline-injected controls at a particular time point.Text Description of Graphic
Dr. Michael Baumann of NIDA’s Intramural Research Program and researchers at several centers collaborated to pin down the drugs’ pharmacological and behavioral effects. The researchers sampled rats’ extracellular brain fluid while the animals moved about after being dosed with one of the three stimulants or saline. Assays of the fluid revealed that all the drugs elevated extracellular concentrations of the neurotransmitters dopamine and serotonin, as shown by comparison with levels in the animals given saline. For all three drugs, the impact on serotonin was greater than that on dopamine (see Figure 1A and 1B).
Analysis of rats’ brain tissue revealed an underlying mechanism for the heightened neurotransmitter presence: All three drugs caused transporters in cellular membranes to release dopamine and serotonin into the extracellular space. This effect reverses the normal activity of the transporters, which is to draw the neurotransmitters out of the extracellular space.

Figure 2. Designer Drugs Are Chemically Related to MDMA Mephedrone, methylone, and MDMA all share the chemical structures shown in green.Text Description of Graphic
The fact that the three drugs produce similar pharmacologic effects is consistent with their similar chemical structures (see Figure 2). However, the researchers also found important differences between the drugs.
Whereas repeated high doses of MDMA markedly reduced serotonin concentrations in the cortex and striatum, the researchers did not see this effect with mephedrone or methylone. Moreover, although rats given acute doses of all three drugs exhibited locomotor stimulation and hyperthermia, repeated high doses of the drugs produced different behavioral responses. Specifically, instead of the flattened body posture and forepaw treading seen with MDMA, mephedrone and methylone induced rearing behavior.
Dr. Baumann and colleagues note that much research has shown that drugs which increase extracellular dopamine—as do all the drugs they tested—have high potential for addiction. They speculate that the differences in rats’ serotonin and behavioral responses to the drugs are linked, and may indicate that mephedrone and methylone have less toxic potential than MDMA. However, they emphasize that this hypothesis needs to be tested.
This study was supported by NIH grants DA017675 and DA027191.

Baumann, M.H., et al. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 37(5):1192–1203, 2012. Full Text

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