Evidence map›Paper›PMID 40643195›Full record

ArticleThe international journal of neuropsychopharmacology2025

Hexahydrocannabinol: pharmacokinetics, systemic toxicity, and acute behavioral effects in Wistar rats.

Klára Šíchová, Barbara Mallarino, Lucie Janečková, Petr Palivec, Magdaléna Vágnerová, Čestmír Vejmola, Marek Nikolič, Lucie Ladislavová, Kristýna Mazochová, Pavel Ryšánek and 6 more

Abstract read
In one paragraph

Article in The international journal of neuropsychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

16 authors.

Klára ŠíchováPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.ORCID 0000-0003-1653-822X
Barbara MallarinoPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.
Lucie JanečkováForensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, Prague 6 166 28, Czech Republic.
Petr PalivecForensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, Prague 6 166 28, Czech Republic.
Magdaléna VágnerováForensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, Prague 6 166 28, Czech Republic.
Čestmír VejmolaPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.
Marek NikoličPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.
Lucie LadislavováPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.
Kristýna MazochováPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.
Pavel RyšánekInstitute of Pharmacology, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, Prague 2 128 00, Czech Republic.
Martin ŠímaInstitute of Pharmacology, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, Prague 2 128 00, Czech Republic.
Adam ŠafandaInstitute of Pathology, 1st Faculty of Medicine, Charles University, Studničkova 2, Prague 2 128 00, Czech Republic.
Bui Quang HiepInstitute of Pathology, 1st Faculty of Medicine, Charles University, Studničkova 2, Prague 2 128 00, Czech Republic.
Isis Rita Anzel KoutrouliPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.
Martin KuchařPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.ORCID 0000-0002-7616-6352
Tomáš PáleníčekPsychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.ORCID 0000-0002-3109-9539

Funding

Ministry of the Interior of the Czech Republic VK01010212
6 · The paper itself

Abstract

backgroundHexahydrocannabinol (HHC) is a new psychoactive substance known for its mind-altering effects and temporary legal status. It is widely used in parts of the Europe and United Kingdom as a legal alternative to ∆9-tetrahydrocannabinol, yet little research has explored its effects and safety. This study examined how HHC is processed in the body, its toxicity, and its impact on behavior in male Wistar rats.

methodsA 1:1 mixture of (9R)-HHC and (9S)-HHC was administered via intragastric gavage at doses of 1, 5, and 10 mg/kg. Behavioral effects were assessed using the open field test and the prepulse inhibition of acoustic startle response.

resultsTwo hours after the highest dose (10 mg/kg), peak concentrations of HHC were detected in blood and brain tissue. The Organization for Economic Co-operation and Development 423 toxicity test classified HHC as a Category 4 substance, estimating a lethal dose of 1000 mg/kg. Compared to controls (administered by sunflower oil), 10 mg/kg HHC reduced movement, increased anxiety, and impaired sensory processing.

conclusionsOverall, HHC crosses the blood-brain barrier, exhibits mild toxicity, and induces behavioral effects similar to tetrahydrocannabinol. Its dose-dependent anxiogenic properties and impact on information processing highlight the importance of the appropriate dosing in any potential therapeutic use.

Indexed as

Behavior, AnimalCannabinolDronabinolPrepulse InhibitionPsychotropic DrugsAnimalsAnxietyBrainDose-Response Relationship, DrugMaleRatsRats, WistarReflex, StartleCannabinolDronabinolPsychotropic Drugsacute toxicitybehaviorhexahydrocannabinolpharmacokineticsrat

Identifiers

PMID40643195
PMCPMC12342381

What OpenQuestion holds

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LicenceCC BY-NC
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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.