Dissociative Substances in Forensic Toxicology: Pharmacology, Toxicokinetics, and Analytical Detection

Abstract

Dissociative substances are xenobiotics that can cause clinically meaningful disruption to the integration of perception, cognition, bodily awareness, and environmental awareness. This narrative review evaluates eight primary substances grouped across distinct functional and pharmacological classes: arylcyclohexylamines (phencyclidine [PCP] and ketamine), morphinans (dextromethorphan [DXM]), volatile inhalants (nitrous oxide [N2O]), kappa-opioid receptor agonists (salvinorin A from Salvia divinorum), aminoadamantanes (memantine and amantadine), and experimental research compounds (dizocilpine [MK-801]). This is a phenomenological and toxicological grouping rather than a single chemical class or receptor-defined category. PCP and ketamine are included as prototypical dissociative anesthetics; DXM is included because dissociative effects emerge at supratherapeutic doses through DXM and dextrorphan-mediated NMDA-receptor antagonism. Nitrous oxide and salvinorin A are included because they can produce short-lived dissociative phenomenology through distinct mechanisms. Memantine and amantadine are included as therapeutically used aminoadamantane NMDA-channel blockers with uncommon, dose- and context-dependent dissociative or psychotomimetic effects, whereas dizocilpine (MK-801) is included solely as an experimental comparator with strong preclinical relevance and no routine human forensic role. A literature search across PubMed, Scopus, Web of Science, and Google Scholar through June 2026 evaluated analytical methods for biological specimens, seized exhibits, and specialized research applications. LC-MS/MS and GC-MS remain central to biological toxicology, but analytical performance cannot be generalized across matrices or compounds; LOD, LOQ, calibration range, sample preparation, validation status, and intended use must be interpreted separately. SFC, NMR, and XRD are presented as specialized or supplementary techniques rather than routine platforms in most forensic toxicology laboratories. Analytical findings require contextual interpretation because blood, plasma, urine, hair, and postmortem specimens are not interchangeable, and a measured concentration alone cannot establish dose, time of administration, impairment, or contribution to death. Parent/metabolite patterns, specimen timing, stability, postmortem redistribution, tolerance, co-exposures, and therapeutic versus non-medical use must be considered.

The authors' abstract, as published at the source. Journal of Xenobiotics, 2026 · DOI ↗