Preliminary pharmacokinetic and psychophysical investigations after controlled oral and inhalative consumption of hexahydrocannabinol (HHC)
Lisa Höfert, Benjamin Franz, Cedric Groß, Delen Kuntze, Bronislav Jurásek, Martin Kuchař, Jan Dressler, Susen Becker, Sven Baumann
Scientific Reports March 24, 2025 DOI: 10.1038/s41598-025-93931-4 via OpenAlex
Summary
After oral (25 mg fruit gum) or inhalative (three puffs from a vape) consumption of the semi-synthetic cannabinoid hexahydrocannabinol (HHC), its pharmacokinetics and psychoactive effects are comparable to those of tetrahydrocannabinol (THC). The route of administration and inter-individual factors strongly influence maximum concentrations, pharmacokinetic profiles, and the subjective 'high' feeling. Serum, urine, and saliva samples were analyzed for HHC and its metabolites. Three commercially available immunological tests were also evaluated for detectability.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 6 |
| Population | Three participants per consumption group (oral and inhalative) |
| Intervention | HHC vape |
| Dose | 25 mg (oral), three puffs (inhalative) |
| Duration | 48 hours (serum and saliva), up to five days (urine) |
| Keywords | Pharmacokinetics Pharmacology Cannabinoid Saliva Urine |
| Citations | 2 |
| Key finding | The pharmacokinetics and effects of HHC are comparable to THC, but the route of administration and inter-individual factors significantly affect maximum concentrations and psychoactive effects. |
Abstract
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.