December 20, 2011 — Mephedrone and methylone, which are the active compounds found in so-called "bath salts," have mechanisms of action similar to those found in 3,4-methylenedioxymethamphetamine (MDMA), popularly known as ecstasy — a finding that may explain the product's potential for addiction, new research suggests.
Investigators found that these compounds bind to monoamine transporters on the surface of some neurons, leading to an increase in both serotonin and, to a lesser degree, dopamine.
"Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation," write lead author Michael H. Baumann, PhD, from the Translational Pharmacology Section and Intramural Research Program at the National Institute on Drug Abuse (NIDA) in Baltimore, Maryland, and colleagues.
In a message posted on NIDA's Web site, Nora Volkow, MD, director of NIDA, notes that because "bath salts" are a product that is "relatively new to the drug abuse scene," knowledge about their precise chemical composition and effects is limited.
"The information we do have is worrisome and warrants a proactive stance to understand and minimize any potential dangers to the health of the public," writes Dr. Volkow.
"Mephedrone is of particular concern because, according to the United Kingdom experience, it presents a high risk for overdose. These chemicals act in the brain like stimulant drugs (indeed they are sometimes touted as cocaine substitutes); thus they present a high abuse and addiction liability," she adds.
The study was published online December 14 in Neuropsychopharmacology.
"The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide," write the investigators.
However, there is little information available on their mechanism of action.
For this study, the researchers examined rats to compare neurological effects after the administration of mephedrone or methylone with the effects after receiving 3,4-metlhylenedioxymethamphetamine (MDMA, or ecstasy) or methamphetamine.
In vitro release assays from the rat brains showed that both mephedrone and methylone "are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity," report the investigators.
In vivo microdialysis of the rats' nucleus accumbens showed that mephedrone and methylone produced dose-related increases in extracellular dopamine, and even greater increases in serotonin.
The peak magnitude of dopamine increase was 1.8-fold above baseline after doses of 0.3 mg/kg of mephedrone were given and 2.9-fold after doses of 1.0 mg/kg were given. The peak magnitude of serotonin increase was 4.2-fold and 11.1 fold, respectively.
For methylone, the peak magnitude of dopamine increase was 1.7-fold above baseline after doses of 1.0 mg/kg were given. For serotonin, it was 6.3-fold above baseline.
Nevertheless, both mephedrone and methylone were considered weaker motor stimulants than methamphetamine.
Repeated high-dose administration of mephedrone or methylone led to hyperthermia but no "long-term change in cortical or striatal amines." On the other hand, extended doses of MDMA let to "robust" hyperthermia and persistent depletion of cortical and striatal serotonin.
"Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study," write the researchers.
"In the meantime, I would like to urge parents, teachers, and the public at large to be aware of the potential dangers associated with the use of these drugs and to exercise a judicious level of vigilance that will help us deal with this problem most effectively," writes Dr. Volkow.
The study was supported by grants from NIDA and from the Retina Research Foundation/UW Eye Research Institute Edwin and Dorothy Gamewell Professorship. Dr. Baumann has disclosed no relevant financial relationships.
Neuropsychopharmacology. Published online December 14, 2011. Abstract
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Cite this: Active Compounds in 'Bath Salts' and Ecstasy Similar - Medscape - Dec 20, 2011.