Citation

Blum K, Foster Olive M, Wang KK, Febo M, Borsten J, Giordano J, Hauser M, Gold MS. Med. Hypotheses 2013; 81(3): 450-455.

Affiliation

Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA; Department of Addiction Research & Therapy, Malibu Beach Recovery Center, Malibu Beach, CA, USA; Department of Holistic Research, G & G Holistic Health Care Services, LLC., North Miami Beach, Florida, USA; Dominion Diagnostics, Inc., North Kingstown, RI, USA; Department of Clinical Neurology, Path Foundation NY, New York, USA; Department of Psychiatry & Global Services Unit and Center for Clinical and Translational Science, University of Vermont, College of Medicine, Burlington, Vermont, USA; Center for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purbe Medinpur, West Bengal, India. Electronic address: drd2gene@ufl.edu.

Copyright

(Copyright © 2013, Elsevier Publishing)

DOI

10.1016/j.mehy.2013.06.007

PMID

23845561

Abstract

Consensus in the most recent literature indicates that psychoactive "bath salts" is a relatively new drug-combination that was added to Schedule I classification in October 2011. Common ingredients include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not yet been well studied. We propose an intensive systematic investigation to determine the potential for cathinones to produce neurotoxic effects in various brain regions. In spite of a lack of evidence, for neurotoxicity there are number of horrific cases now on record that suggest intensification of research is needed. For example, a suicide by hanging had high 3,4-MDPV concentration while a driver under the influence had the highest reported methylone (MEPH) concentration. More interestingly, there have been consistent case reports indicating delayed responses, including: severe agitation with possible psychosis, suicidal ideation, rhabdomyolysis, hypertension, tachycardia, and death. In animal studies, amphetamine (AMPH), methamphetamine (METH) and cocaine release dopamine (DA), similarly to the action of cathinone and particular cathinone analogues. Two components of bath salts, MEPH and MDPV produce opposite effects at human dopamine transporter (hDAT) comparable to METH and cocaine, respectively. Moreover, it has already been found by others that MEPH is almost as potent as METH; and MDPV is much more potent than cocaine with longer lasting effects. It has been conjectured correctly that bath salts containing MDPV and MEPH (or a similar drug) might be expected both, to initially release DA and subsequently prevent its reuptake via hDAT. The null hypothesis, that cathinones do not cause neurotoxicity to dopamine nerve endings of the striatum, seems parsimonious and requires intensive investigation. Our hypothesis is that when consumed by humans, cathinones may induce neurotoxic pathways involving the neuro-glial-microglia and/or specific inflammation, that may help explain the clinically observed delayed response. We intend to explore this hypothesis utilizing a novel proteomic and biomarker technique developed by scientists at the McKnight Brain Institute, University of Florida as well as magnetic-resonance imaging across pre-frontal orbital cortex-cingulate gyrus and mesolimbic pathways of the brain of rodents.

Language: en