LAUSR

To the Editors: We read with interest the article by De-Giogio et al. [1] investigating the acute and repeated administration of 3,4methylenedioxypyrovalerone (MDPV) on aggressive responding in mice. This is an important issue because MDPV is one of the synthetic cathinones purportedly found in “bath salts,” products that are deceptively sold for their psychoactive effects. However, our enthusiasm was dampened because the manuscript’s conclusions extend beyond the present data and are inconsistent with human laboratory data investigating synthetic cathinones. For example, the manuscript concludes that its results “are suggestive that human MDPV intake could be a problem for public health and the criminal justice system.” This assertion is baseless and reckless. As a result, we feel few issues that warrant further discussion. The MDPV dose (10 mg/kg) that produced aggression on al l three tasks—as operat ional ly def ined by the investigators—is not comparable with doses used by humans. Based on available information from human users, the recreational intranasal dose of MDPV ranges between 10 and 20 mg (there are no reports of human intravenous use) [2]. Thus, the 10 mg/kg dose administered in the current study would equate to nearly 700 mg in a person weighing 150 lb. This is a fatal limitation with respect to extrapolating the present data to the human condition. This observation highlights the importance of using more ecologically relevant models when attempting to extend findings from animal studies to humans. The above point is further accentuated by the following evidence from the present study: When MDPV was administered at a dose of 0.1 mg/kg (a more ecologically relevant dose), aggressive behavior was observed on only 1 of 3 tasks; the resident-intruder task at trials 4 and 5. This effect came after the animals had been administered at least two prior doses of the drug (trials 1–3). It is also important to note that resident mice were excluded from further testing if they “did not fight...during the first test.” Thus, this seems an important selection bias to say nothing about whether the measures of aggression used in the present study sufficiently model human aggression. Furthermore, the assertion in the present manuscript that, “... patients under the influence of MDPV may need physical restraints and high doses of sedatives to avoid self-harm or injuries to other people” is egregious and particularly disturbing. From a scientific perspective alone, the current data conflicts with evidence from well-controlled human laboratory studies investigating the synthetic cathinones. Papaseit and colleagues (2016) administered an ecologically relevant dose of mephedrone, a synthetic cathinone found in “bath salts,” to human participants under controlled lab settings. The investigators found that the drug produced overwhelmingly positive subjective effects that were comparable with 3,4-methylenedioxymethamphetamine (MDMA). There were no reports of aggression or any other untoward effects [3]. The article by De-Giogio et al. could be improved by including a discussion of synthetic cathinone data collected in humans under carefully controlled conditions. In summary, our major concern is that the manuscript wildly overstates its data. In doing so, conclusions appear to be more political advocacy, rather than a dispassionate, accurate depiction of modest scientific data. When scientists engage in such behavior, the profession runs the risk of losing credibility. The recent case of the so-called Miami Cannibal underscores this concern. In 2012, Rudy Eugene attacked Ronald * Kate Y. O’Malley [email protected]