NBOMes-Highly Potent and Toxic Alternatives of LSD

Abstract

Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT_2A and 5-HT_2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT_2A compared with 5-HT_1A. They display higher affinity for 5-HT_2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT_2B receptor compared to 5-HT_2A or 5-HT_2C. The drugs are sold as blotter papers, or in powder, liquid, or tablet form, and they are administered sublingually/buccally, intravenously, via nasal insufflations, or by smoking. Since their introduction in the early 2010s, numerous reports have been published on clinical intoxications and fatalities resulting from the consumption of NBOMe compounds. Commonly observed adverse effects include visual and auditory hallucinations, confusion, anxiety, panic and fear, agitation, uncontrollable violent behavior, seizures, excited delirium, and sympathomimetic signs such mydriasis, tachycardia, hypertension, hyperthermia, and diaphoresis. Rhabdomyolysis, disseminated intravascular coagulation, hypoglycemia, metabolic acidosis, and multiorgan failure were also reported. This survey provides an updated overview of the pharmacological properties, pattern of use, metabolism, and desired effects associated with NBOMe use. Special emphasis is given to cases of non-fatal and lethal intoxication involving these compounds. As the analysis of NBOMes in biological materials can be challenging even for laboratories applying modern sensitive techniques, this paper also presents the analytical methods most commonly used for detection and identification of NBOMes and their metabolites.

Keywords: NBOMe; analytical methods; metabolism; new psychoactive substances; phenethylamines; psychedelics; toxicity.

FIGURE 1

Chemical structures of main classes of psychedelics.

FIGURE 2

Main phase I metabolic pathways of 25I-NBOMe.