Acute Effects of the Psychedelic Phenethylamine 25I-NBOMe in C57BL/6J Male Mice.
Sabrine Bilel, Cristina Miliano, Giorgia Corli, Marta Bassi, Massimo Trusel, Raffaella Tonini, Maria Antonietta De Luca, Matteo Marti
International Journal of Molecular Sciences March 20, 2025 DOI: 10.3390/ijms26062815 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Intervention | 25I-NBOMe |
| Dose | 0.1-1 mg/kg i.p. |
| Duration | 30 min after administration for reaction time; acute effects otherwise |
| Topics | Neuroplasticity |
| Keywords | 25i-nbome 5ht2a agonist Ltd Ltp Behavioral tests Dopamine transmission Microdialysis Prepulse inhibition Psychedelics Pharmacology Behavioral neuroscience |
| Citations | 3 |
| Key findings | 25I-NBOMe increases dopamine transmission in the nucleus accumbens shell, impairs prepulse inhibition, prolongs reaction time, and blocks long-term potentiation in the medial prefrontal cortex. |
Abstract
25I-NBOMe (4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl) phenethylamine) is a synthetic psychedelic compound abused for its ambiguous legal state as a counterfeit lysergic acid diethylamide (LSD). 25I-NBOMe acts as a selective agonist of 5HT2A receptors leading to hallucinations, intoxications, and fatalities. Here, we assessed the rewarding properties of 25I-NBOMe and its behavioral and neurotoxic acute effects on the central nervous system of C57BL/6J mice. We evaluated the dopamine (DA) levels using in vivo microdialysis in the nucleus accumbens (NAc) shell after 25I-NBOMe (0.1-1 mg/kg i.p.) injection. We also investigated the effects of 25I-NBOMe (0.1-1 mg/kg i.p.) on locomotor activity, reaction time, and prepulse inhibition. Moreover, we assessed the acute 25I-NBOMe (1 µM) effects on synaptic transmission and plasticity in the medial prefrontal cortex (mPFC) by using ex vivo electrophysiology. Our findings suggest that 25I-NBOMe affects the DA transmission in NAc shell at the highest dose tested, increases the reaction time within 30 min after the administration, and disrupts the PPI. In slices, it prevents long-term synaptic potentiation (LTP) in the mPFC, an effect that could not be reverted by the co-administration of the selective 5HT2A antagonist (MDL100907). Overall, these findings provide valuable new insights into the effects of 25I-NBOMe and the associated risks of its use.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 3
- The effect of psilocin on neurotransmitters release in the claustrum and on rat behavior. Pharmacological Reports February 1, 2026
- Repeated administration of the synthetic cannabinoid AKB48 induces serotonergic neuroadaptation in male and female mice: behavioural and immunohistochemical evidence. Neuropharmacology February 1, 2026
- Psychedelic Modulation of Excitation/Inhibition Balance: A Dual-Phase Neurodevelopmental Model. ACS Chemical Neuroscience January 7, 2026
Cites 44
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Designer drugs: mechanism of action and adverse effects Archives of Toxicology April 1, 2020
- Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology December 1, 2015
- Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants Frontiers in Neuroscience April 19, 2016
- Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response. Neuropharmacology February 1, 2014
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