Preliminary pharmacokinetic and psychophysical investigations after controlled oral and inhalative consumption of hexahydrocannabinol (HHC)

. 2025 Mar 24 ; 15 (1) : 10086. [epub] 20250324

Jazyk angličtina Země Velká Británie, Anglie Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid40128283
Odkazy

PubMed 40128283
PubMed Central PMC11933371
DOI 10.1038/s41598-025-93931-4
PII: 10.1038/s41598-025-93931-4
Knihovny.cz E-zdroje

The semi-synthetic cannabinoid hexahydrocannabinol (HHC) has become a highly discussed topic in forensic toxicology since 2022 due to its legal availability at this time and its psychoactive effects. This study aimed to investigate the pharmacokinetics, effects, and immunological detectability of HHC after oral (25 mg HHC fruit gum) and inhalative (three puffs from HHC vape) consumption with three participants per group. Serum (up to 48 h), urine (up to five days), and saliva (up to 48 h) samples were collected at different relevant time points and analyzed by HPLC-MS/MS for (9R)/(9S)-HHC, 11-hydroxy-HHC, and (9R)/(9S)-HHC carboxylic acid with a fully validated method. Additionally, immunological detectability was investigated with three different commercially available tests. To address the psychoactive effects, the subjective "high" feeling (scale 0-10) was monitored and different psychophysical tests (e.g. modified Romberg test, walk and turn) were conducted. Overall, the pharmacokinetics and effects of HHC were comparable to tetrahydrocannabinol (THC). However, the route of administration as well as inter-individual factors played a crucial role regarding maximum concentrations, pharmacokinetic profiles, and psychoactive effects.

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Casati, S. et al. Hexahydrocannabinol on the light cannabis market: the latest ‘new’ entry. Cannabis Cannabinoid Res.9, (2022). PubMed

Ujváry, I. Hexahydrocannabinol and closely related semi-synthetic cannabinoids: A comprehensive review. Drug Test. Anal.16, 127–161 (2023). PubMed

Nationalrat Österreich. Bundesgesetz über den Schutz vor Gesundheitsgefahren im Zusammenhang mit Neuen Psychoaktiven Substanzen (Neue-Psychoaktive-Substanzen-Gesetz, NPSG). (accessed 31 May 2024); https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=20007605

Gesetz über den Verkehr mit Betäubungsmitteln (BtMG). (accessed 24 April 2024); https://www.gesetze-im-internet.de/btmg_1981/

Eidgenössisches Departement des Innern. Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien (Betäubungsmittelverzeichnisverordnung, BetmVV-EDI). (accessed 31 May 2024); https://www.fedlex.admin.ch/eli/cc/2011/363/de#annex_1/lvl_u1

Bundesministerium für Gesundheit. Fünfte Verordnung zur Änderung der Anlage des Neue-psychoaktive-Stoffe-Gesetzes. (accessed 28 June 2024); https://www.recht.bund.de/bgbl/1/2024/210/VO.html

Höfert, L., Becker, S., Dreßler, J. & Baumann, S. Quantification of (9R)- and (9S)-hexahydrocannabinol (HHC) via GC–MS in serum/plasma samples from drivers suspected of cannabis consumption and immunological detection of HHC and related substances in serum, urine, and saliva. Drug Test. Anal.16, 489–497 (2024). PubMed

Schirmer, W., Auwärter, V., Kaudewitz, J., Schürch, S. & Weinmann, W. Identification of human hexahydrocannabinol metabolites in urine. Eur. J. Mass. Spectrom.29, (2023). PubMed

Falck Jørgensen, C., Rasmussen, S., Linnet, B., Thomsen, R. & K. & Evidence of 11-hydroxy-hexahydrocannabinol and 11-Nor-9-carboxy-hexahydrocannabinol as novel human metabolites of ∆9-tetrahydrocannabinol. Metabolites13, 1169 (2023). PubMed PMC

Manier, S. K., Valdiviezo, J. A., Vollmer, A. C., Eckstein, N. & Meyer, M. R. Analytical toxicology of the semi-synthetic cannabinoid hexahydrocannabinol studied in human samples, pooled human liver S9 fraction, rat samples and drug products using HPLC–HRMS-MS. J. Anal. Toxicol.47, 818–825 (2023). PubMed

Höfert, L. et al. Verteilung von Hexahydrocannabinol (HHC) und dessen Metaboliten in verschiedenen sektionstoxikologischen Asservaten. Poster presentation at the annual meeting of the German society of forensic medicine. Potsdam10.13140/RG.2.2.31198.65607 (2024).

Reggio, P. H., Greer, K. V. & Cox, S. M. The importance of the orientation of the C9 substituent to cannabinoid activity. J. Med. Chem.32, (1989). PubMed

Edery, H., Grunfeld, Y., Ben-Zvi, Z. & Mechoulam, R. Structural requirements for cannabinoid activity. Ann. N.Y. Acad. Sci.191, 40–53 (1971).

Graziano, S. et al. Hexahydrocannabinol pharmacology, toxicology, and analysis: the first evidence for a recent new psychoactive substance. Curr. Neuropharmacol.21, 2424–2430 (2023). PubMed PMC

Janssens, L. K. et al. Investigation of the intrinsic cannabinoid activity of hemp-derived and semisynthetic cannabinoids with β-arrestin2 recruitment assays—and how this matters for the harm potential of seized drugs. Arch. Toxicol.98, 2619–2630 (2024). PubMed

Lindbom, K. et al. Human metabolism of the semi-synthetic cannabinoids hexahydrocannabinol, hexahydrocannabiphorol and their acetates using hepatocytes and urine samples. Drug Test. Anal. Early view. (2024). PubMed PMC

Di Trana, A. et al. Disposition of hexahydrocannabinol epimers and their metabolites in biological matrices following a single administration of smoked hexahydrocannabinol: A preliminary study. Pharmaceuticals17, 249 (2024). PubMed PMC

Kronstrand, R., Roman, M., Green, H. & Truver, M. T. Quantitation of hexahydrocannabinol (HHC) and metabolites in blood from DUID-cases. J. Anal. Toxicol.48, 235–241 (2024). PubMed

Peters, F. T. et al. Anhang B Zur Richtlinie der GTFCh Zur qualitätssicherung Bei forensisch-toxikologischen Untersuchungen—Anforderungen an die validierung von analysenmethoden. Toxichem. Krimtech.76, 185–208 (2009).

Newmeyer, M. N. et al. Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration. J. Appl. Tox.37, 922–932 (2017). PubMed

Karlovšek, M. Z. & Balažic, J. Evaluation of the post-rotational nystagmus test (PRN) in determining alcohol intoxication. J. Anal. Toxicol.29, 390–393 (2005). PubMed

The National Highway Traffic Safety Administration (NHTSA). Standardized field sobriety testing procedures (PDF). New Jersey (US) police reference card. (2024).

Shouse California Law Group. The finger-to-nose test in DUI investigations. (accessed 29 January 2025); https://www.shouselaw.com/ca/dui/fst/finger-to-nose-test

Kobidze, G. et al. The first LC-MS/MS stereoselective bioanalytical methods to quantitatively detect 9R- and 9S-hexahydrocannabinols and their metabolites in human blood, oral fluid and urine. J. Pharm. Biomed. Anal.240, (2024). PubMed

Wachtel, S., ElSohly, M., Ross, S., Ambre, J. & de Wit, H. Comparison of the subjective effects of ∆9-tetrahydrocannabinol and marijuana in humans. Psychopharmacology161, 331–339 (2002). PubMed

Karschner, E. L., Darwin, W. D., Goodwin, R. S., Wright, S. & Huestis, M. A. Plasma cannabinoid pharmacokinetics following controlled oral ∆9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin. Chem.57, 66–75 (2011). PubMed PMC

Huestis, M. A., Henningfield, J. E. & Cone, E. J. Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J. Anal. Toxicol.16, 276–282 (1992). PubMed

Di Trana, A. et al. QuEChERS extraction and simultaneous quantification in GC-MS/MS of hexahydrocannabinol epimers and their metabolites in whole blood, urine, and oral fluid. Molecules29, 3440 (2024). PubMed PMC

Chiang, C. W. & Barnett, G. Marijuana effect and delta-9-tetrahydrocannabinol plasma level. Clin. Pharmacol. Ther.36, 234–238 (1984). PubMed

Hollister, L. E. et al. Do plasma concentrations of ∆9-tetrahydrocannabinol reflect the degree of intoxication? J. Clin. Pharmacol.21, 171S–177S (1981). PubMed

Bondallaz, P. et al. Cannabis and its effects on driving skills. Forensic. Sci. Int.268, 92–102 (2016). PubMed

Derne, A. S. et al. Immunological detection of hexahydrocannabinol (HHC) in oral fluid. Drug Test. Anal.16, 638–640 (2024). PubMed

Wolf, C. E., Pokhai, A. A., Poklis, J. L. & Williams, G. R. The cross-reactivity of cannabinoid analogs (delta-8-THC, delta-10-THC and CBD), their metabolites and chiral carboxy HHC metabolites in urine of six commercially available homogeneous immunoassays. J. Anal. Toxicol.47, 732–736 (2023). PubMed

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