Frontiers in Neuroscience
April 19, 2016
Cristina Miliano, Giovanni Serpelloni, Claudia Rimondo et al.
195 citations
New psychoactive substances (NPS) are a diverse and rapidly expanding group of molecules sold as substitutes for controlled drugs, often consumed with other substances or alcohol, and linked to rising overdose deaths and emergency admissions. Their chemical classes include phenethylamines, piperazines, cathinones, tryptamines, and synthetic cannabinoids, with the latter accounting for 50% of newly identified NPS. Many NPS show addictive properties. This review examines the rewarding and addictive effects of cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants, including recent lab data showing that JWH-018, a potent CB1/CB2 agonist, increases dopamine signaling in the nucleus accumbens shell, contributing to dependence associated with 'Spice' use.
Brain sciences
September 3, 2020
Liana Fattore, Matteo Marti, Rafaela Mostallino et al.
63 citations
Sex and gender shape how people respond to drugs, with men more likely to use illicit drugs and seek emergency care for serious overdoses, while women are equally prone to substance use disorders and may be more vulnerable to craving and relapse. Research on classic drugs like THC, morphine, and cocaine shows clear male-female differences. With over 900 new psychoactive substances (NPS) now identified—including synthetic cannabinoids, cathinones, opioids, and dissociatives—knowledge of their sex- and gender-specific effects remains minimal. This review gathers the limited evidence from animal and human studies, emphasizing how much remains unknown about NPS effects across sexes and genders.
International journal of molecular sciences
December 17, 2020
Veronica Cocchi, Sofia Gasperini, Patrizia Hrelia et al.
32 citations
Several psychedelic and stimulating phenethylamines, including 2C-H, 2C-I, 2C-B, and 25B-NBOMe, but not MDMA, damaged DNA in a human cell line (TK6 cells). The genetic damage was detected as an increase in micronucleus frequency. All genotoxic substances also elevated reactive oxygen species (ROS) levels, suggesting ROS production as a likely mechanism. Even at doses that do not cause immediate severe harm, exposure to these substances may still pose long-term risks through genotoxicity.
Frontiers in psychiatry
January 1, 2022
Micaela Tirri, Sabrine Bilel, Raffaella Arfè et al.
17 citations
Psychedelic phenethylamines, especially -NBOMe compounds, impair sensorimotor function, reaction time, and sensory gating in mice more potently than LSD or their 2C analogs. Halogenated derivatives 25I-NBOMe and 25B-NBOMe were the most effective at altering visual and acoustic responses, motor activity, and prepulse inhibition. The rank order of potency showed these -NBOMe compounds were stronger than both 2C analogs and LSD. These sensory impairments affected spontaneous movement and reaction time without changing stimulated motor performance. The findings suggest that -NBOMe compounds pose potential public health risks, particularly for driving or hazardous work requiring intact sensorimotor skills.
Brain Sciences
August 25, 2020
Micaela Tirri, Luisa Ponzoni, Sabrine Bilel et al.
9 citations
Two new psychoactive substances, DOB and PMA, which are structurally similar to MDMA and sold as ecstasy, impair motor behavior and sensorimotor responses in mice and induce hallucinatory states in zebrafish. In CD-1 male mice, acute administration of DOB and PMA (0.01–30 mg/kg) reduced spontaneous locomotion and disrupted prepulse inhibition of startle responses to visual, acoustic, and tactile stimuli. In zebrafish, lower doses of DOB (0.075–2 mg/kg) and PMA (0.0005–0.5 mg/kg) decreased swimming activity and reduced a hallucinatory score, indicating pro-psychedelic effects. These findings suggest the substances alter sensorimotor gating and may produce hallucinogen-like states.
Psychopharmacology
March 1, 2024
Marta Bassi, Sabrine Bilel, Micaela Tirri et al.
7 citations
5-MeO-MiPT, a new psychedelic tryptamine first identified in Italy in 2014, dose-dependently inhibits sensorimotor responses and prepulse inhibition in male CD-1 mice, and at high doses (30 mg/kg) impairs stimulated motor activity and causes cardiorespiratory changes. In silico ADMET predictions indicate its toxicokinetic profile resembles those of 5-MeO-DIPT and DMT, with a cytochrome-related risk. Correspondence between effects in mice and symptoms from a human intoxication case suggests consumption can impair activity performance and pose health risks, but the authors argue the compound should not be excluded from psychiatric therapy research.
Drug testing and analysis
May 1, 2023
Marta Massano, Enrico Gerace, Martina Borsari et al.
6 citations
Methoxpropamine (MXPr), a dissociative drug similar to ketamine, was studied in 16 mice to track how it breaks down in the body. After injecting the mice with 1, 3, or 10 mg/kg of MXPr, urine was collected hourly for six hours and then at 12- to 24-hour intervals; plasma was collected after 24 hours. Using high-resolution mass spectrometry, the main metabolite found in urine was desmethyl-MXPr-glucuronide, detectable up to 24 hours after administration. NorMXPr, produced by N-dealkylation, appeared in urine, plasma, and fur. Other metabolites in fur and plasma included desmethyl-MXPr and dihydro-MXPr. Understanding these metabolites can help improve toxicological screening for MXPr in biological samples.
Experimental neurology
November 1, 2021
Matteo Marti, Giuseppe Talani, Cristina Miliano et al.
6 citations
Methoxetamine (MXE), a ketamine-like designer drug, alters serotonin levels in the rat medial prefrontal cortex and nucleus accumbens. Blocking serotonin 5-HT2 receptors with selective antagonists attenuated MXE's motor and sensory effects and prevented its reduction of prepulse inhibition, indicating these receptors are key to MXE's sensorimotor actions. In vitro, MXE inhibited NMDA-mediated field potentials and GABA-mediated spontaneous currents in a concentration-dependent manner but did not affect AMPA components or presynaptic glutamate release. The findings suggest MXE acts as an NMDA receptor antagonist, with 5-HT2 receptors crucial for its sensorimotor effects and NMDA and GABA receptors as additional targets.
International journal of molecular sciences
March 20, 2025
Sabrine Bilel, Cristina Miliano, Giorgia Corli et al.
3 citations
The synthetic psychedelic 25I-NBOMe, a selective 5HT2A receptor agonist abused as a counterfeit LSD, alters dopamine transmission, behavior, and synaptic plasticity in mice. At the highest dose tested (1 mg/kg), it increased dopamine levels in the nucleus accumbens shell. It also increased reaction time within 30 minutes after administration and disrupted prepulse inhibition, indicating sensorimotor gating deficits. In brain slices, 25I-NBOMe prevented long-term potentiation in the medial prefrontal cortex, an effect not reversed by a selective 5HT2A antagonist. These findings highlight risks of 25I-NBOMe use, including altered neurotransmission and impaired cognitive processes.
Neuropharmacology
February 1, 2026
Giorgia Corli, Fabrizio De Luca, Sabrine Bilel et al.
1 citation
Repeated exposure to the synthetic cannabinoid AKB48 worsens the visual sensorimotor, sensory gating, and motor reactivity response to the hallucinogens 2C-I and 25I-NBOMe in mice. This effect is more prolonged in males than in females. The underlying mechanism involves neuroplastic changes in the cerebellum and cortex, specifically at serotonin 2A receptors and the serotonin transporter. These changes occur more markedly and rapidly in female mice. The findings highlight a significant interaction between synthetic cannabinoids and psychedelic drugs, which may be relevant to long-term effects and psychiatric consequences of their consumption.
British Journal of Pharmacology
May 5, 2026
Giorgia Corli, Deborah Rudin, Dino Luethi et al.
Some new synthetic cannabinoid receptor agonists (SCRAs) also directly activate the serotonin 5-HT₂A receptor, which may contribute to unexpected psychiatric side effects. Many SCRAs with a valinamide or tert-leucinamide head moiety showed in vitro activity at the 5-HT₂A receptor at high concentrations. In mice, the compound AB-5′F-BUTINACA caused neurological changes, sensorimotor alteration, antinociception, hypothermia, reduced breath rate, and hypolocomotion. These effects were mediated by both CB₁ and 5-HT₂A receptors, as they were prevented by selective antagonists. The findings indicate potential risks of SCRA consumption that could exacerbate unexpected psychiatric conditions.
International Journal of Molecular Sciences
November 29, 2025
M. Bassi, Elisa Roda, Giorgia Corli et al.
3-chloromethcathinone (3-CMC), a synthetic cathinone involved in many poisonings, causes locomotor stimulation, rapid breathing, hypothermia, and sensorimotor alterations in mice, with prepulse inhibition changes only at high doses and minor sex differences. All 15 human intoxications in Italy from 2014 to 2025 were non-fatal, involving male patients with psychomotor agitation, psychosis, aggressiveness, CNS depression, cardiac arrhythmias, chest pain, and tachypnea. Predicted metabolic reactions include N-dealkylation, N-hydroxylation, and phenyl hydroxylation, and all compounds show potential for drug-drug interactions and cardiotoxicity.
International journal of molecular sciences
July 17, 2021
Sabrine Bilel, Micaela Tirri, Raffaella Arfè et al.
A novel psychoactive substance, 1-cyclohexyl-x-methoxybenzene, exists as three stereoisomers (ortho, meta, para) structurally similar to tramadol and phencyclidine. In vitro tests showed all three stereoisomers and tramadol were inactive at mu, kappa, and delta opioid receptors. In mice, systemic administration of the stereoisomers impaired sensorimotor responses, altered spontaneous motor activity, produced modest analgesia, and affected thermoregulation and cardiorespiratory responses, resembling effects of tramadol and phencyclidine. Naloxone only partially prevented visual sensorimotor impairments from the stereoisomers, not other effects. The findings indicate these derivatives cause pharmaco-toxicological effects through both opioid and non-opioid mechanisms, suggesting potential for abuse and harm.
Neuropharmacology
October 1, 2018
Andrea Ossato, Sabrine Bilel, Adolfo Gregori et al.
Methoxetamine (MXE), a dissociative drug similar to ketamine and phencyclidine, alters neurological and sensorimotor functions in mice in a dose-dependent manner. Acute systemic administration of MXE, ketamine, and phencyclidine (0.01–30 mg/kg i.p.) differentially affected visual, acoustic, and tactile responses, thermal and mechanical pain, motor activity, and acoustic startle reactivity. MXE and ketamine (1 and 30 mg/kg i.p.) and phencyclidine (1 and 10 mg/kg i.p.) also significantly affected cardiorespiratory parameters and systolic and diastolic blood pressure. The findings suggest MXE produces effects comparable to its parent compounds, with specificity depending on dose and parameter examined.