Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System.
Jae-Gyeong Lee, Kwang-Hyun Hur, Su-Bin Hwang, Sooyeun Lee, Seok-Yong Lee, Choon-Gon Jang
ACS Chemical Neuroscience August 2, 2023 DOI: 10.1021/acschemneuro.3c00196 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Rats and mice |
| Intervention | 25D-NBOMe |
| Dose | 0.03 mg/kg (IVSA); 1 mg/kg (CPP); 1, 3, and 10 mg/kg (microdialysis) |
| Topics | Addiction |
| Keywords | 25d-nbome Cpp Dopamine Self-administration |
| Key points | 25D-NBOMe produced rewarding and reinforcing effects, with increased intravenous self-administration in rats at 0.03 mg/kg and conditioned place preference in mice at 1 mg/kg, alongside altered dopamine-related protein expression and elevated extracellular dopamine and metabolites in the nucleus accumbens. The authors conclude the compound has abuse potential. |
Abstract
2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)_ethanamine (25D-NBOMe), an analogue of the 2C family, is a newly synthesized psychoactive substance. It acts as an agonist at the 5-HT2A receptor and has a similar mechanism to that of NBOMe compounds. However, the pharmacological mechanism for its rewarding and reinforcing effects has not been revealed. In the present study, intravenous self-administration (IVSA) test and conditioned place preference (CPP) test were performed to investigate whether 25D-NBOMe has abuse potential. We also evaluated the effects of 25D-NBOMe on neurochemical changes using western blot analysis and microdialysis. The IVSA test revealed increased self-administration in 25D-NBOMe (0.03 mg/kg)-treated rats. In addition, the CPP test revealed rewarding effects in 25D-NBOMe (1 mg/kg)-treated mice. In the neurochemical studies, 25D-NBOMe treatment affected the expression of dopamine (DA) receptor D1 (DRD1), DA receptor D2 (DRD2), tyrosine hydroxylase, DA transporter (DAT), and phospho-DAT (p-DAT) in the nucleus accumbens (NAc). In addition, microdialysis revealed that treatment with progressively increasing doses (1, 3, and 10 mg/kg) of 25D-NBOMe increased the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the rat NAc. Taken together, our results show the abuse potential and neurochemical changes related to addictive behavior after administration of 25D-NBOMe.
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Citations in the library
Cited by 4
- Molecular and Medical Aspects of Psychedelics International Journal of Molecular Sciences December 23, 2023
- The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents Archives of Pharmacal Research April 1, 2024
- Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential? Toxicology Reports June 1, 2025
- The psychedelic phenethylamine 25C-NBF, a selective 5-HT2A agonist, shows psychoplastogenic properties and rapid antidepressant effects in male rodents Molecular Psychiatry November 14, 2025
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- Zebrafish and Artemia salina in vivo evaluation of the recreational 25C-NBOMe drug demonstrates its high toxicity. Toxicology Reports 2021
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