Pharmacology and Toxicology of N-Benzylphenethylamine (“NBOMe”) Hallucinogens

Introduction

Serotonergic hallucinogens produce prominent changes in perception, mood and cognition that are largely mediated by activation of 5-HT2A receptors. Phenylalkylamine hallucinogens form one structural class in which 2,5-dimethoxy-substituted phenethylamines (the 2C-X family) and their α-methyl phenylisopropylamine congeners display high 5-HT2 receptor selectivity. Since about 2010 a new subclass of designer phenethylamine hallucinogens — N-benzylphenethylamines or "NBOMes" — has appeared on the recreational market. Addition of an N-benzyl substituent markedly increases 5-HT2A binding affinity and, reportedly, human potency; substances such as 25I-NBOMe and 25B-NBOMe have been sold on blotter paper and in other forms and associated with numerous toxicity cases and fatalities. Halberstadt sets out to review the structure–activity relationships, behavioural pharmacology, metabolism and clinical toxicology of NBOMe compounds. The chapter summarises in vitro binding and mutagenesis work, rodent behavioural assays used to probe hallucinogenic activity and a series of reported clinical and forensic cases (51 individual toxicity cases discussed in the extracted text), with emphasis on complications such as seizures, hyperthermia and rhabdomyolysis that characterise severe NBOMe intoxication.