Inhalation and oral administration of HHC products – Quantification of (9R)-, (9S)-Hexahydrocannabinol and metabolites in plasma and detectability in on-site drug tests for urine and oral fluid

Abstract

The semisynthetic cannabinoid Hexahydrocannabinol (HHC) has gained recognition among drug users. A GC-MS/MS method for the detection of (9R)- and (9S)-HHC and their respective carboxy- and hydroxy-metabolites in plasma has been developed and validated. The method was applied to authentic plasma samples obtained from a self-administration experiment. HHC was either inhaled (Vapes, 95 % HHC) or ingested (Jellys, 25 mg HHC). Maximum plasma (9R)-HHC and (9S)-HHC concentrations of 3.8 ng/mL and 2.5 ng/mL were detected 1.16 h after ingestion and approx. 65 ng/mL (9R)-HHC and 21 ng/mL (9S)-HHC were measured 0.08 h after inhalation. (9 R)-OH-HHC concentrations ranged from approx. 0.3–1.4 ng/mL after ingestion, and approx. 0.2–1.8 ng/mL after inhalation. (9R)-COOH-HHC was detectable in concentrations of 0.8–17 ng/mL (ingestion) and 0.6–8.7 ng/mL (inhalation). Corresponding S-Hydroxy- and Carboxy-metabolites were detectable after ingestion ((9S)-OH-HHC: approx. 0.1–0.7 ng/mL, (9S)-COOH-HHC: approx. 0.2–0.4 ng/mL), but mainly not after inhalation. Cannabimimetic effects and respective psychomotor impairments such as (slight) vertigo as well as slight headache and dizziness, and mouth dryness could be observed after ingestion. After inhalation, one participant showed distinct impairments. On-site drug tests for cannabinoids in urine (DrugScreen®) and oral fluid (DrugWipe® 5S) were performed. DrugScreen® (cut-off: 25 ng/mL THC-COOH) gave positive results up to 10 h after ingestion and inhalation. Cross-reactivity with DrugWipe® 5S (cut-off: 5 ng/mL THC) was not observed. An immunological CEDIA™ cannabinoid assay showed good cross-reactivity with the plasma samples and gave positive results up to 6.16 h after ingestion and 4.16 h after inhalation.