Effect of -NBOMe Compounds on Sensorimotor, Motor, and Prepulse Inhibition Responses in Mice in Comparison With the 2C Analogs and Lysergic Acid Diethylamide: From Preclinical Evidence to Forensic Implication in Driving Under the Influence of Drugs

Abstract

In the last decade, the market for new psychoactive substances has been enriched by numerous psychedelic phenethylamines, which mimic the psychoactive effect of lysergic acid diethylamide (LSD). In particular, the -NBOMe series, which are more potent than their 2C compounds analogs, are considered worthy substitutes for LSD by users. The purpose of this study was to assess the effects of 25H-NBOMe and its halogenated derivatives (25I-NBOMe and 25B-NBOMe) in comparison to their 2C compounds analogs and LSD on the sensorimotor (visual, acoustic, and overall tactile), reaction time, spontaneous (total distance traveled) and stimulated (drag, accelerod test) motor activity, grip strength test, and prepulse inhibition (PPI) responses in mice. Systemic administration of -NBOMe, 2C compounds analogs, and LSD (0.001–10 mg/kg) differently impaired the sensorimotor, reaction time, motor, and PPI responses in mice. In particular, halogenated (25I and 25B)-NBOMe derivatives appear to be more effective than the entire class of 2C compounds analogs in altering visual and acoustic responses, affecting reaction time, and motor and sensory gating in PPI test. In fact, the specific rank order of compounds potency for nearly all of the experiments showed that (25I and 25B)-NBOMe were more potent than 2C compounds analogs and LSD. -NBOMe and 2C compounds analogs impaired not only the reception of incoming sensory stimuli (visual and acoustic), but their correct brain processing (PPI) in an equal and sometimes stronger way than LSD. This sensory impairment directly affected the spontaneous motor response and reaction time of mice, with no change in performance in stimulated motor activity tests. These aspects should be carefully considered to better understand the potential danger that psychedelic phenethylamines, in particular -NBOMe, may pose to public health, with particular reference to decreased performance in driving and hazardous works that require special sensorimotor skills.

Molecular and Medical Aspects of Psychedelics

“…When administered subcutaneously, 25I-NBOMe (0.03–3 mg/kg) produced a bell-shaped effect on C57BL/6J mouse activity [ 40 ]. In line with this finding, the researchers have also shown that low (0.001–1 mg/kg) and moderate (0.1–1 mg/kg) doses of 25I-NBOMe increase mobility, while a high dose (10 mg/kg) causes a sharp decline in the spontaneous motor activity of male ICR mice [ 41 ]. Similarly, 25B-NBOMe inhibited the motor activity of Wistar Han rats measured in an open field (0.3–3 mg/kg) [ 37 ].…”

Sex‐specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice

“…The effects of AKB48 were evaluated using a series of behavioural tests (visual object and visual placing response test, acoustic test, tactile test, tail pinch test, core temperature test, breath rate test, and mobility time test) routinely used in our laboratories to describe the effects of synthetic cannabinoids in mice (Bilel et al, 2020;Canazza et al, 2016Canazza et al, , 2017Ossato et al, 2015Ossato et al, , 2016Vigolo et al, 2015) and widely validated for the preclinical characterization of the pharmacotoxicological effects of NPSs in rodents (Arfè et al, 2021;Bilel et al, 2021Bilel et al, , 2022De-Giorgio et al, 2020;Ossato et al, 2018;Tirri et al, 2022).…”