Toxicities Associated With NBOMe Ingestion-A Novel Class of Potent Hallucinogens: A Review of the Literature

NBOMes are a recently emerged class of synthetic hallucinogens derived from the 2C family of phenethylamines. Structurally related to mescaline, these N‑benzylmethoxy derivatives were developed as potent agonists at the 5‑HT2A serotonin receptor and have substantially higher affinity at that receptor than earlier 2C compounds. Their potency is notable: sublingual doses as low as 50 μg may produce psychoactive effects. NBOMes circulate in the recreational market under names such as “Smiles,” “N‑bombs,” or shortened chemical identifiers (25I, 25B, 25C) and are commonly sold on blotter paper, sometimes masquerading as LSD. Suzuki and colleagues set out to systematically review published, analytically confirmed human cases of NBOMe ingestion in order to characterise the clinical toxicities, routes of administration, laboratory findings, management, and outcomes. The study focuses on reports that provided laboratory confirmation of NBOMe exposure, aiming to clarify the spectrum and severity of adverse effects associated with this novel class of hallucinogens.

The investigators conducted a systematic search of the MEDLINE (PubMed) database through October 2014 using terms including “N‑benzylmethoxy,” “NBOMe,” “25I,” “25B,” “25C,” and “N‑bomb.” Inclusion criteria required English‑language reports of human NBOMe ingestion with analytical confirmation of the compound. An initial search was performed by J. S., with additional searches and assessments by other members of the team; reference lists of identified articles were also reviewed to find further citations. From eligible reports the researchers extracted data on the product(s) consumed and analytically confirmed, any quantitative analysis available, patient demographics and substance‑use history, clinical toxic effects, management interventions, and outcomes. The methods focused on identifying case reports and case series that met the laboratory‑confirmation requirement rather than on broader unconfirmed anecdotal reports.

Twelve citations were identified by the search, of which two were excluded (one non‑English and one lacking analytical confirmation); a further case from a multi‑case series was excluded for the same reason. Ten citations met the inclusion criteria, representing 20 individual patients. Demographics and substance‑use history: Seventeen patients (85%) were male. The mean age was 20.3 years (range 15–31). Reported prior substance use included marijuana in 7 patients (35%), MDMA in 3 (15%), and single cases (5% each) reporting prior LSD, amphetamine, or cocaine use. One patient (5%) had a history of depression. Clinical course and outcomes: Three patients (15%) died. Seven (35%) were discharged after a short observation period (<15 hours), while eight (40%) required admission to an intensive care unit (ICU). One patient required surgery to repair a self‑inflicted stab wound. The most frequent clinical features were agitation and tachycardia (each in 85% of patients), hypertension in 65%, mydriasis (dilated pupils) in 55%, delirium and hallucinations in 40% each, and seizures in 40%. Tachypnoea and fever were recorded in 25% of cases. Laboratory and toxicology findings: The common laboratory abnormalities included elevated creatine kinase in 45% of cases, leukocytosis in 25%, hyperglycaemia in 20%, transaminitis in 15%, and raised creatinine in 10%. Routine urine toxicology panels were unremarkable in most cases; marijuana metabolites were detected in 3 patients (15%). Routes of administration and confirmed compounds: Oral administration was reported by nine patients (45%)—of these, four explicitly swallowed the substance, three used the sublingual route, and two did not specify. Insufflation was reported in three cases (15%), intravenous administration in one case (5%), and three reports (15%) listed either oral or insufflation; three cases (15%) lacked route information. Analytical confirmation identified 25I‑NBOMe in 17 cases (85%), 25B‑NBOMe in 3 (15%), 25C‑NBOMe in 2 (10%), 25H‑NBOMe in 1 (5%), and 2C‑I in 5 cases (25%). Quantitative findings for 25I‑NBOMe were reported: mean urine and serum concentrations were 15.3 ng/mL and 0.49 ng/mL respectively; urine concentrations ranged from 2.0–36.0 ng/mL and serum concentrations from 0.034–0.75 ng/mL. Single‑case concentrations were reported for 25B (urine 1.9 ng/mL, serum 0.18 ng/mL) and 25H (urine 0.9 ng/mL). The authors note that not all adverse effects and laboratory tests were assessed in every case.

The investigators interpret their findings as indicative that NBOMe ingestion can produce a distinct toxidrome combining prominent neuropsychiatric effects (agitation, delirium, perceptual disturbances, seizures) and autonomic instability (tachycardia, hypertension, diaphoresis, mydriasis) with a spectrum from mild to life‑threatening illness. Although most patients recovered, a substantial proportion required ICU care and some cases were fatal, which is concerning given the limited human pharmacologic data for these compounds. Comparisons with earlier literature suggest that the NBOMe clinical picture resembles toxidromes reported with synthetic cathinones, phencyclidine, MDMA, anticholinergics, cocaine and other stimulants, where agitation and cardiovascular effects are prominent. The authors consider whether severe presentations might represent serotonin syndrome—an excess serotonergic state typically involving autonomic instability, altered mental status and neuromuscular signs—but note that neuromuscular findings common in serotonin syndrome (hyperreflexia, tremor, clonus) were relatively uncommon in these reports, which argues against a straightforward classification as serotonin syndrome. The review highlights several uncertainties. It is difficult to determine dose‑response relationships because NBOMes are extremely potent and visual dosing (‘‘eye‑balling’’) can result in substantial unintentional overdoses; a single grain of salt could represent many times the psychoactive dose. Route of administration may affect severity: the lone intravenous case described a markedly protracted and complicated course, suggesting that parenteral use could be particularly hazardous. Mislabeling of NBOMes as LSD is another concern because users expecting the safety profile of LSD may be at greater risk; in this review 4 patients believed they had taken LSD, and among those 2 died and 1 attempted suicide. Public health context and testing limitations are emphasised. Survey data cited by the authors indicate NBOMe use is uncommon in the general population but appears to have emerged rapidly since 2012 among some users; acquisition frequently occurs via websites or peers. Standard hospital toxicology screens do not detect NBOMes. Detection and quantification require specialised methods (high‑performance liquid chromatography with mass spectrometry) available only in certain reference laboratories, and the authors provide practical specimen handling recommendations for clinicians. On management, the cases were generally treated with intravenous fluids and benzodiazepines, with mechanical ventilation when necessary. The authors suggest managing NBOMe toxicity along similar lines to severe stimulant or serotonin‑related toxicities, and note cyproheptadine (a 5‑HT2A antagonist with antihistaminic properties) was used in one reported case. Harm‑reduction advice recommended by the authors includes warning users about inadvertent NBOMe exposure, advising against using hallucinogens alone, avoiding visual dosing, and discouraging insufflation or injection. The authors conclude that limited data preclude reliable prediction of who will develop severe reactions and call for further research and clinician education regarding NBOMe dangers.