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  3. Preliminary pharmacokinetic investigations of hydroxylated metabolites after controlled inhalative and oral consumption of hexahydrocannabinol (HHC).

Preliminary pharmacokinetic investigations of hydroxylated metabolites after controlled inhalative and oral consumption of hexahydrocannabinol (HHC).

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DOI
10.48620/99713
Publisher DOI
10.1038/s41598-026-62767-x
PubMed ID
42477038
Abstract
The pharmacokinetics of the semisynthetic cannabinoid hexahydrocannabinol (HHC) and its 11-nor-carboxy- as well as 11-hydroxy-metabolites has already been the subject of research in various recent publications. However, further metabolism studies showed the presence of other, especially (side-chain-)hydroxylated metabolites in urine and serum. This study aimed to investigate the pharmacokinetics of these metabolites after oral (25 mg fruit gum) and inhalative (three puffs from vape) consumption, using serum and urine samples from a previous study. Serum (up to 48 h) and urine (up to five days) samples of six participants (three per consumption group) were collected at different time points and analyzed by LC-QqTOF and LC-QqLIT. Three metabolites (M1: side-chain-hydroxylated; M2: hydroxylated on alicyclic moiety; M3: 8-OH-HHC) were further investigated. The peak area ratios of analytes and internal standards were plotted against the time after consumption to obtain pharmacokinetic information. Overall, this study proved the presence of these metabolites in biological samples and provided pharmacokinetic insights for the first time. Differences between serum and urine, oral and inhalative consumption as well as inter-individual differences were observed. The investigated metabolites could partially serve as unambiguous consumption markers for HHC, as they are unlikely to be formed in vivo from corresponding Δ9-tetrahydrocannabinol (THC) metabolites.
Date Issued
2026-07-20
Publication Type
Article
Subjects
Cannabinoids
•
Forensic toxicology
•
Hexahydrocannabinol
•
Metabolism
•
Pharmacokinetics
Language(s)
en
Author(s)
Höfert, Lisa
Schirmer, Willi  
Institute of Forensic Medicine, Forensic Chemistry and Toxicology  
Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)  
Mösch, Isabelle  
Institut für Rechtsmedizin (IRM) - FTC Toxikologie  
Franz, Benjamin
Groß, Cedric
Becker, Susen
Baumann, Sven
Additional Credits
Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)  
Institut für Rechtsmedizin (IRM) - FTC Toxikologie  
Institute of Forensic Medicine, Forensic Chemistry and Toxicology  
Journal
Scientific Reports
Publisher
Nature Research
ISSN
2045-2322
Access(Rights)
open.access
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