LAUSR

We appreciate the comments made by KY O’Malley and C Medina-Kirchner, and in this response, we take the opportunity to clarify some of the issues raised. First, the authors defined the conclusion of our study as “baseless and reckless”. However, the recommendations of our study are not so novel in the extant scientific literature to warrant them being baseless or reckless. In this context, numerous studies support similar conclusions to ours and state that the use and abuse of MDPV could present problems for public health. A study published in Neuropharmacology reviewed data regarding the use of MDPV in humans in order to highlight its impact on public health. The study found that overdosing on MDPV could lead to violence, homicidal combative behaviour, self-mutilation and suicide [1]. These findings have also been reported in other publications [2, 3]. In this regard, another study published in Forensic Science International reported that even relatively low plasma concentrations of MDPV are associated with aggressive behaviour and violent crimes, including bodily harm, robbery, homicide and general acts of resistance [4]. Though the comment regarding the Erowid website, which collects available information from human users, not mentioning intravenous injections as a method of administratingMDPV, the studies available on the PubMed archive confirm this eventuality: the study published in Neuropharmacology found that MDPV could be used by intravenous injection, alone (“slam”) or in combination with the oral method, thus increasing the risk of sexually transmitted diseases [1], as already described [5]. In the study published in Forensic Science International, three patients of the subject group explicitly referred to the intravenous application of MDPV [4]. As well as these, a case series published in 2013 reported that intravenous injections comprised a rare but existing method of MDPVadministration [6]. Aside from a criticism of the method of MDPVadministration, the dose regimen used in our experimental protocol was considered by the authors a “fatal limitation” of the study. It was viewed in this way due to our effort to extend the findings from the animal model to forensic reality across the supposedly great distance between human use and our experimental dosage. However, the 20 mg dose is not the highest ever dose reported, as stated by the authors. Rather, it comprises the upper level of the typical dosage range, as they admit. In this context, where redosing is common and tolerance quickly develops, dosages as high as 200 mg have been reported [6]. As well as this, the authors only considered the dose of 10 mg/kg, but the protocol began at 0.01 mg/kg, which corresponds to a human dose of 0.7 mg (following the example of the authors), and continued with 0.1 mg/kg, which corresponds to a human dose of 7 mg. Moreover, considering only experimental studies in this regard, there are numerous examples of protocols that use overlapping doses: 1.5 mg/kg was administered in a CD-1 mouse strain twice a day for seven consecutive days [7], and 0.5–2.0 mg/kg was administered in rats [8]. In relation to the result of our study, O’Malley andMedinaKirchner state that, apart from the highest dose-related effects, a dosage of 0.1 mg/kg causes aggressive behaviour in only one of three tasks – namely, the resident–intruder task in Trials 4 and 5 after the animals had been administered at least two Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00414-019-02176-0) contains supplementary material, which is available to authorized users.