The aim of the study was to develop a methodology for the determination of γ-hydroxybutyric acid (GHB), ibotenic acid (IBO) and psilocybin (PY) abuse in human saliva. Capillary electrophoresis with a capacitively coupled contactless conductivity detector (CE-C⁴D) was used with an optimized background electrolyte (BGE) consisting of 17.9 mM L-arginine (Arg), 9.6 mM succinic acid (Suc) and 0.0019% (w/v) hexadimethrine bromide (HDMB) with an adjusted pH of 7.3. Saliva samples were spiked with all three analytes of interest as well as the internal standard, before protein precipitation with acetonitrile (ACN) (1 : 2, v/v, saliva : ACN). The limits of detection (LOD) and quantification (LOQ) in the saliva were 1.5 and 5.0 mg L⁻¹ for GHB, 2.1 and 7.9 mg L⁻¹ for IBO and 3.6 and 12.0 mg L⁻¹ for PY. The intraday precision varied from 0.7% to 8.6% and interday precision from 3.9% to 11.4% for all substances. The overall accuracy and combined recovery were from 95% to 123% and 98% to 103%, respectively. The present study demonstrates that the use of oral fluid as an alternative sample matrix which is easy and fast to collect and prepare, and in combination with a portable CE instrument built in-house, provides rapid and efficient determination of psychoactive substance intoxication.