Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe

Herian, Monika; Skawski, Mateusz; Wojtas, Adam; Sobocińska, Małgorzata; Noworyta-Sokołowska, Karolina; Gołembiowska, Krystyna

doi:10.1007/s00213-021-05860-5

Cited by 20 publications

(17 citation statements)

References 113 publications

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“…Extracellular DA and 5-HT levels were analyzed using an Ultimate 3000 System (Dionex, Sunnyvale, CA, USA), electrochemical detector Coulochem III (model 5300; ESA, Chelmsford, MA, USA) with a 5020 guard cell, a 5040 amperometric cell and a Hypersil Gold C18 analytical column (3 μm, 100 × 3 mm; Thermo Fisher Scientific, Sunnyvale, CA, USA). The details of the method have been described elsewhere [ 29 , 69 ]. The chromatographic data were processed by the Chromeleon v.6.80 (Dionex, Sunnyvale, CA, USA) software package run on a personal computer.…”

Section: Methodsmentioning

confidence: 99%

Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior

Wojtas

Bysiek

Wawrzczak-Bargieła

et al. 2022

IJMS

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Clinical studies provide evidence that ketamine and psilocybin could be used as fast-acting antidepressants, though their mechanisms and toxicity are still not fully understood. To address this issue, we have examined the effect of a single administration of ketamine and psilocybin on the extracellular levels of neurotransmitters in the rat frontal cortex and reticular nucleus of the thalamus using microdialysis. The genotoxic effect and density of glutamate receptor proteins was measured with comet assay and Western blot, respectively. An open field test, light–dark box test and forced swim test were conducted to examine rat behavior 24 h after drug administration. Ketamine (10 mg/kg) and psilocybin (2 and 10 mg/kg) increased dopamine, serotonin, glutamate and GABA extracellular levels in the frontal cortex, while psilocybin also increased GABA in the reticular nucleus of the thalamus. Oxidative DNA damage due to psilocybin was observed in the frontal cortex and from both drugs in the hippocampus. NR2A subunit levels were increased after psilocybin (10 mg/kg). Behavioral tests showed no antidepressant or anxiolytic effects, and only ketamine suppressed rat locomotor activity. The observed changes in neurotransmission might lead to genotoxicity and increased NR2A levels, while not markedly affecting animal behavior.

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Section: Methodsmentioning

confidence: 99%

Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior

Wojtas

Bysiek

Wawrzczak-Bargieła

et al. 2022

IJMS

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“…Our recent study confirmed the contribution of 5-HT 2A and 5-HT 2C receptors in effect on both brain neurotransmission and hallucinogenic activity in rats 9 . Moreover, the tolerance development in the neurotransmitters’ release and animals behavior was observed after 7-days treatment with 25I-NBOMe 10 . Due to their similar pharmacological effects on a human, NBOMe series were sold as LSD 11 .…”

Section: Introductionmentioning

confidence: 95%

Neurotoxicological profile of the hallucinogenic compound 25I-NBOMe

Herian

Wojtas

Maćkowiak

et al. 2022

Sci Rep

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Abstract4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a new psychoactive substance with strong hallucinogenic properties. Our previous data reported increased release of dopamine, serotonin, and glutamate after acute injections and a tolerance development in the neurotransmitters release and rats’ behavior after chronic treatment with 25I-NBOMe. The recreational use of 25I-NBOMe is associated with severe intoxication and deaths in humans. There is no data about 25I-NBOMe in vivo toxicity towards the brain tissue. In this article 25I-NBOMe-crossing through the blood–brain barrier (BBB), the impact on DNA damage, apoptosis induction, and changes in the number of cortical and hippocampal cells were studied. The presence of 25I-NBOMe in several brain regions shortly after the drug administration and its accumulation after multiple injections was found. The DNA damage was detected 72 h after the chronic treatment. On the contrary, at the same time point apoptotic signal was not identified. A decrease in the number of glial but not in neural cells in the frontal (FC) and medial prefrontal cortex (mPFC) was observed. The obtained data indicate that 25I-NBOMe passes easily across the BBB and accumulates in the brain tissue. Observed oxidative DNA damage may lead to the glial cells’ death.

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“…Our results are in agreement with studies on drugs that promote serotonergic transmission as 3,4-methylenedioxymethamphetamine [MDMA; ( 42 )] or that act on the serotonergic receptor as 25I-NBOMe ( 37 ) and 2C-B ( 70 ) that induce a dispersive state that alters the visual and acoustic responses in rodents without affecting motor performance, especially at doses lower than 1 mg/kg. In contrast, some studies have shown opposite results, whereby doses of 25C- and 25I-NBOMe dose-dependent reduced locomotor activity in mice and rats ( 41 , 71 ). Therefore, LSD also interacts with several 5-HT (e.g., 5-HT 1A , 5-HT 2C , 5-HT 5 , and 5-HT 7 ) and DA (D 2l ike ) receptors [ Table 3 ; ( 58 ); Rickli).…”

Section: Discussionmentioning

confidence: 93%

“…Previous studies have also investigated the attenuated stimulant effect of LSD in the exploratory activity of mice lacking the 5HT 5A receptor, suggesting that this receptor subtype may be involved in the psychostimulant effect of LSD ( 72 , 73 ). Therefore, a study by Herian et al confirmed that 25I-NBOMe may have effects on short-term memory, locomotor function, and anxiety ( 71 ). In addition, studies on locomotion and exploratory activity in rats showed an increase in response following the administration of DOI similar to that induced by LSD, despite influencing more different receptors; consequently the mechanisms of action of DOI and LSD may not be identical ( 74 – 76 ).…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2022

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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.

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Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe

Cited by 20 publications

References 113 publications

Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior

Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior

Neurotoxicological profile of the hallucinogenic compound 25I-NBOMe

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

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