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 nonfatal 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.

Novel Psychoactive Phenethylamines: Impact on Genetic Material

“…Indeed, even in our case, 2C-B and 25B-NBOMe were found to be stronger genotoxic agents than 2C-I and 2C-H. 25X-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 , and they have higher selectivity and affinity for the serotonin 5-HT 2A receptor than their corresponding compounds of the 2C-X series [ 7 , 50 , 51 ]. This pharmacokinetic profile is reflected in their more potent in vitro activity and psychedelic and even toxic in vivo effect [ 23 , 52 , 53 , 54 ]. In vitro studies have shown that 25X-NBOMe have greater potency on 5HT 2A receptors (EC50 = 0.758–0.819 nM) than 2C-X compounds (EC50 = 3.16–8.46 nM) [ 55 ], and this agrees with the in vivo studies showing that 25X-NBOMe induced a head twitch response in rodents (HTR; a behavioral marker in rodents for hallucinogen effects in humans) with a potency several-fold higher than their 2C-X counterparts [ 56 , 57 , 58 ].…”

“…These preclinical studies are in agreement with the dosages used by consumers. In fact, the active dosages of 25X-NBOMe range from 20 to 100 times lower than those of the compounds of the class 2C-X [ 23 , 59 , 60 , 61 , 62 ].…”

“…Most of the studies currently available regarding the toxicity of psychoactive phenethylamines focus exclusively on the acute effects and mainly on the fatal and non-fatal acute intoxication cases due to psychedelics phenethylamines, in particular related to “NBOMe” [ 22 , 23 , 24 , 25 ] and “2C” [ 26 , 27 , 28 ] series intake. On the contrary, studies showing the potential long-term effects of psychoactive phenethylamines are very limited.…”

Drug-induced Hyperthermic Syndromes in Psychiatry

“…Lysergic acid diethylamide (LSD) and other synthetic “designer” psychedelic drugs with serotonergic properties (phenethylamine analogs or “N-Bombs”, mescaline), may produce hyperthermia along with other effects on the autonomic nervous system [ 57 - 60 ]. Patients typically experience hallucinations, agitation and tachycardia, but occasionally may develop a more severe syndrome of psychosis, catatonic stupor, hyperactivity or rigidity, rhabdomyolysis, and sympathetic activation leading to hyperthermia, coagulopathies, respiratory arrest, and coma.…”

Voltammetric Determination of LSD with a Schiff Base – Chemically Modified Electrode in Aqueous Solution

“…In addition to LSD, other drugs with halucinogenic effects, such as N-benzylsubstituted phenethylamines (NBOMes), are also available in blotters and are widely consumed in recent years, being commonly confused with LSD 10,12 . Due to this similarity, the correct identification of the seized drug is extremely important.…”