25iP-NBOMe

NBOMe compounds are often associated with life-threatening toxicity and death.

NBOMe and NBOHs are regularly sold as LSD in blotter papers,[3]^[11] which have a bitter taste and different safety profiles.^[5][2] Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity.^[2] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,^[7] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".^[5] While most fatalities are due to the physical effects of the drug, there have also been reports of death due to self-harm and suicide under the influence of the substance.^[12][13][5]

Given limited documentation of NBOMe consumption, the long-term effects of the substance remain unknown.

numbness of the tongue and mouth followed by a metallic chemical taste was observed, and researchers describe this physical side effect as one of the main discriminants between NBOMe compounds and LSD.^[16][17][18]

Many of the NBOMe compounds have high potency agonist activity at additional 5-HT receptors and prolonged activation of 5-HT_2B can cause cardiac valvulopathy in high doses and chronic use.^[3][8] 5-HT_2B receptors have been strongly implicated in causing drug-induced valvular heart disease.^[19][20][21] The high affinity of NBOMe compounds for adrenergic α₁ receptor has been reported to contribute to the stimulant-type cardiovascular effects.^[8]

In vitro studies, 25C-NBOMe has been shown to exhibit cytotoxicity on neuronal cell lines SH-SY5Y, PC12, and SN471, and the compound was more potent than methamphetamine at reducing the visibility of the respective cells; the neurotoxicity of the compound involves activation of MAPK/ERK cascade and inhibition of Akt/PKB signaling pathway.^[4] 25C-NBOMe, including the other derivative 25D-NBOMe, reduced the visibility of cardiomyocytes H9c2 cells, and both substances downregulated expression level of p21 (CDC24/RAC)-activated kinase 1 (PAK1), an enzyme with documented cardiac protective effects.^[4]

Preliminary studies on 25C-NBOMe have shown that the substance is toxic to development, heart health, and brain health in zebrafish, rats, and Artemia salina, a common organism for studying potential drug effects on humans, but more research is needed on the topic, the dosages, and if the toxicology results apply to humans. Researchers of the study also recommended further investigation of the drug's potential in damaging pregnant women and their fetus due to the substance's damaging effects to development.^[22][23]

At present, there are no specific antidotes for NBOMes, and all acute intoxication is managed by symptomatic treatments, such as administration of benzodiazepines, antipsychotic drugs, and antiarrhythmic agents, such as beta blockers; some emergency interventions are intended to specifically treat rhabdomyolysis, which may lead to critical complications such as metabolic acidosis and acute kidney injury.^[4]