PerspectivePsychoactive “bath salts”: Not so soothing
Section snippets
“Bath salts” products contain synthetic cathinones
In the past few years, there has been an alarming increase in the abuse of so-called “bath salts” products sold on the internet and in retail shops. These products have no legitimate use as bath additives. Instead, they are purchased as “legal highs” that mimic the effects of illicit drugs like cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) (Coppola and Mondola, 2012, Prosser and Nelson, 2012). Bath salts are given evocative names – “Ivory Wave”, “Bliss”, “White
Bath salts cathinones target monoamine transporters
Despite the widespread use of bath salts, there is limited information about the mechanism of action underlying the physiological and behavioral effects produced by most synthetic cathinone derivatives. Emerging evidence indicates that bath salts cathinones interact with plasma membrane transporters for dopamine (i.e., DAT), norepinephrine (i.e., NET) and serotonin (i.e., SERT) (Baumann et al., 2012, Cozzi et al., 1999, Hadlock et al., 2011, Lopez-Arnau et al., 2012, Martinez-Clemente et al.,
Synthetic cathinones produce stimulant effects in animals
A number of studies have examined the in vivo pharmacology of baths salts compounds in rodent models, though the majority of available data pertains to the effects of mephedrone (Angoa-Perez et al., 2012, Baumann et al., 2012, Hadlock et al., 2011, Huang et al., 2012, Kehr et al., 2011, Lisek et al., 2012, Lopez-Arnau et al., 2012, Marusich et al., 2012, Motbey et al., 2012). Because bath salts cathinones interact with monoamine transporters, they would be expected to increase extracellular
Toxicity and adverse effects
Serotonin transporter substrates like MDMA can produce sustained deficits in brain serotonin neurons (Baumann et al., 2007, Fleckenstein et al., 2007), so mephedrone and methylone might be predicted to have similar actions. Binge administration of either drug to single-housed rats (3 or 10 mg/kg, s.c., 3 doses) has no long-lasting effects on brain tissue monoamines (Baumann et al., 2012), while administration of higher doses of mephedrone to group-housed rats (10 or 25 mg/kg, s.c., 4 doses)
Summary
Psychoactive “bath salts” contain one or more synthetic cathinones which target plasma membrane monoamine transporters. In vitro data have identified a mechanistic dichotomy among common bath salts constituents: ring-substituted cathinones like mephedrone act as non-selective transporter substrates, whereas pyrrolidinophenones like MDPV act as potent catecholamine-selective transporter blockers (Baumann et al.,, Nagai et al., 2007, Simmler et al.,). Recent in vivo findings show that bath salts
Acknowledgments
The research described herein was generously supported by the Intramural Research Program at NIDA, NIH. The authors wish to thank Dr. Amy H. Newman for thoughtful comments on this manuscript.
References (54)
- et al.
Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone
Ann. Emerg. Med.
(2012) - et al.
Synthetic cathinones: chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as “bath salts” or “plant food”
Toxicol. Lett.
(2012) - et al.
Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines
Eur. J. Pharmacol.
(1999) - et al.
Methcathinone: a new and potent amphetamine-like agent
Pharmacol. Biochem. Behav.
(1987) - et al.
Evidence that pure uptake inhibitors including cocaine interact slowly with the dopamine neuronal carrier
Eur. J. Pharmacol.
(1994) - et al.
Monoamine transporters and psychostimulant addiction
Biochem. Pharmacol.
(2008) - et al.
Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats
Drug Alcohol Depend.
(2012) - et al.
Mephedrone (‘bath salt’) elicits conditioned place preference and dopamine-sensitive motor activation
Drug Alcohol Depend.
(2012) - et al.
A case of extreme agitation and death after the use of mephedrone in The Netherlands
Forensic Sci. Int.
(2011) - et al.
Interaction of mephedrone with dopamine and serotonin targets in rats
Eur. Neuropsychopharmacol.
(2012)