Perspective
Psychoactive “bath salts”: Not so soothing

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Abstract

Recently there has been a dramatic rise in the abuse of so-called “bath salts” products that are purchased as legal alternatives to illicit drugs like cocaine and 3,4-methylenedioxymethamphetamine (MDMA). Baths salts contain one or more synthetic derivatives of the naturally-occurring stimulant cathinone. Low doses of bath salts produce euphoria and increase alertness, but high doses or chronic use can cause serious adverse effects such as hallucinations, delirium, hyperthermia and tachycardia. Owing to the risks posed by bath salts, the governments of many countries have made certain cathinones illegal, namely: 4-methylmethcathinone (mephedrone), 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV). Similar to other psychomotor stimulants, synthetic cathinones target plasma membrane transporters for dopamine (i.e., DAT), norepinephrine (i.e., NET) and serotonin (i.e, SERT). Mephedrone and methylone act as non-selective transporter substrates, thereby stimulating non-exocytotic release of dopamine, norepinephrine and serotonin. By contrast, MDPV acts as a potent blocker at DAT and NET, with little effect at SERT. Administration of mephedrone or methylone to rats increases extracellular concentrations of dopamine and serotonin in the brain, analogous to the effects of MDMA. Not surprisingly, synthetic cathinones elicit locomotor activation in rodents. Stimulation of dopamine transmission by synthetic cathinones predicts a high potential for addiction and may underlie clinical adverse effects. As popular synthetic cathinones are rendered illegal, new replacement cathinones are appearing in the marketplace. More research on the pharmacology and toxicology of abused cathinones is needed to inform public health policy and develop strategies for treating medical consequence of bath salts abuse.

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.

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