Evidence map›Paper›PMID 38804224›Full record

ArticleDrug testing and analysis2025

Human metabolism of the semi-synthetic cannabinoids hexahydrocannabinol, hexahydrocannabiphorol and their acetates using hepatocytes and urine samples.

Karin Lindbom, Caitlyn Norman, Steven Baginski, Lucas Krebs, Darta Stalberga, Tobias Rautio, Xiongyu Wu, Robert Kronstrand, Henrik Gréen

Abstract read
In one paragraph

Article in Drug testing and analysis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Interpol review of forensic drug chemistry, 2022-2025.Forensic science international. Synergy · 2026
    Review
  2. Article
  3. Article
  4. In Vitro Metabolism of ΔDrug testing and analysis · 2026
    Article
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  6. Review
  7. Article
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Karin LindbomDivision of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Caitlyn NormanDivision of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.ORCID https://orcid.org/0000-0003-2322-0367
Steven BaginskiLeverhulme Research Centre for Forensic Science, School of Science and Engineering, University of Dundee, Dundee, UK.ORCID https://orcid.org/0000-0001-5615-1199
Lucas KrebsInstitute for Chemistry and Bioanalytics, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Muttenz, Switzerland.ORCID https://orcid.org/0009-0005-7679-4403
Darta StalbergaDivision of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.ORCID https://orcid.org/0000-0001-6712-652X
Tobias RautioDepartment of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.ORCID https://orcid.org/0000-0002-0857-6261
Xiongyu WuDepartment of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.ORCID https://orcid.org/0000-0001-6756-2276
Robert KronstrandDivision of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.ORCID https://orcid.org/0000-0002-4222-9597
Henrik GréenDivision of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.ORCID https://orcid.org/0000-0002-8015-5728

Funding

European Commission E! 113377European Union's Horizon 2020Leverhulme Trust RC-2015-011Strategic Research Area in Forensic Sciences (Strategiområdet forensiska vetenskaper) at Linköping UniversitySweden's Innovation Agency 2019-03566
6 · The paper itself

Abstract

Hexahydrocannabinol (HHC), hexahydrocannabiphorol (HHCP) and their acetates, HHC-O and HHCP-O, respectively, are emerging in Europe as alternatives to tetrahydrocannabinol (THC). This study aimed to elucidate the metabolic pathways of the semi-synthetic cannabinoids HHC, HHCP, HHC-O and HHCP-O from incubation with human hepatocytes. The metabolites of HHC were also identified in authentic urine samples. HHC, HHCP, HHC-O and HHCP-O were incubated with primary human hepatocytes for 1, 3 and 5 h. Authentic urine samples from cases screened positive for cannabis in blood using ELISA but confirmed negative were analysed both non-hydrolysed and hydrolysed for HHC metabolites. Potential metabolites were identified using ultra-high performance liquid chromatography (UHPLC) coupled to a quadrupole time-of-flight mass spectrometer (QToF-MS). HHC and HHCP were primarily metabolised through monohydroxylation (monoOH), followed by oxidation to a carboxylic acid metabolite. HHC-O and HHCP-O were rapidly metabolised to HHC and HHCP, respectively. In authentic urine samples, 18 different metabolites were identified, and 99.3% of hydroxylated metabolites were glucuronidated. 11-OH-HHC, 5'OH-HHC and another metabolite with a monoOH on the side chain were the only metabolites present in all 16 urine samples. The metabolism of HHC and HHCP were similar, although the longer alkyl side chain of HHCP (heptyl) led to greater hydroxylation on the side chain than HHC (pentyl). The use of HHC and HHCP can be differentiated from the use of THC and other phytocannabinoids, but the use of the acetate analogues may not be differentiable from their non-acetate analogues.

Indexed as

AcetatesCannabinoidsCannabinolHepatocytesCells, CulturedChromatography, High Pressure LiquidDronabinolHumansMaleSubstance Abuse DetectionTandem Mass SpectrometryAcetatesCannabinoidsCannabinolDronabinolhexahydrocannabinolhexahydrocannabiphorolHHC acetateHHCP acetatemetabolism

Identifiers

PMID38804224
PMCPMC11922685

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.