Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants
Background: Tetrahydrocannabivarin (THCV) is a phytocannabinoid commonly found in cannabis with potential pharmacological properties; however, its post-acute pharmacokinetics (PK) in humans have not been studied yet. THCV has two isomers, Δ9- and Δ8-THCV, which seem to have different pharmacological...
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MDPI AG
2024-11-01
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| author | Cristina Sempio Jorge Campos-Palomino Jelena Klawitter Erica N. Peters Laura MacNair Mehdi Haghdoost Marcel O. Bonn-Miller Amy Harrison Shanna Babalonis Uwe Christians Jost Klawitter |
| author_facet | Cristina Sempio Jorge Campos-Palomino Jelena Klawitter Erica N. Peters Laura MacNair Mehdi Haghdoost Marcel O. Bonn-Miller Amy Harrison Shanna Babalonis Uwe Christians Jost Klawitter |
| author_sort | Cristina Sempio |
| collection | DOAJ |
| description | Background: Tetrahydrocannabivarin (THCV) is a phytocannabinoid commonly found in cannabis with potential pharmacological properties; however, its post-acute pharmacokinetics (PK) in humans have not been studied yet. THCV has two isomers, Δ9- and Δ8-THCV, which seem to have different pharmacological properties. We investigated the PK of the Δ8-THCV isomer after oral administration as part of a two-phase, dose-ranging, placebo-controlled trial in healthy participants. Methods: Participants (<i>n</i> = 21) were enrolled in six study sessions and randomly received the following doses of a medium-chain triglyceride (MCT) oil oral formulation of Δ8-THCV: placebo, 12.5 mg, 25 mg, 50 mg, 100 mg, and 200 mg. Plasma samples from 15 participants were collected up to 8 h after administration and were analyzed by a validated two-dimensional high-performance liquid chromatography–tandem mass spectrometry assay. The trial was registered on clinicaltrials.gov (NCT05210634). Results: After oral administration, 11-nor-9-carboxy-Δ8-THCV (Δ8-THCV-COOH) was the main metabolite detected. The median time-to-maximum concentration (t<sub>max</sub>) ranged 3.8–5.0 h across doses for Δ8-THCV and 4.6–5.3 h for Δ8-THCV-COOH. The maximum concentration (C<sub>max</sub>) and area under the concentration–time curve over the observation period (AUC<sub>last</sub>) appeared to be dose-linear. Median AUC<sub>last</sub> increased 2.3- to 4.8-fold and 1.7- to 2.9-fold for Δ8-THCV and Δ8-THCV-COOH, respectively, every two-fold increase in the dose. The isomers Δ9-THCV and Δ9-THCV-COOH were detected in plasma, despite being undetected in the formulated drug product analyzed by a third-party laboratory. Conclusions: For the first time, we report the pharmacokinetics of Δ8-THCV and its major metabolites after oral administration in humans. Δ8-THCV AUC<sub>last</sub> showed dose linearity but the observed possible conversion to the Δ9-THCV isomer should be further studied. |
| format | Article |
| id | doaj-art-cd20652b379d489ca968d859c4f62f25 |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-cd20652b379d489ca968d859c4f62f252025-08-20T02:56:51ZengMDPI AGPharmaceuticals1424-82472024-11-011712160310.3390/ph17121603Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy ParticipantsCristina Sempio0Jorge Campos-Palomino1Jelena Klawitter2Erica N. Peters3Laura MacNair4Mehdi Haghdoost5Marcel O. Bonn-Miller6Amy Harrison7Shanna Babalonis8Uwe Christians9Jost Klawitter10Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USACanopy Growth Corporation, One Hershey Drive, Smiths Falls, ON K7A 0A8, CanadaCanopy Growth Corporation, One Hershey Drive, Smiths Falls, ON K7A 0A8, CanadaCanopy Growth Corporation, One Hershey Drive, Smiths Falls, ON K7A 0A8, CanadaCanopy Growth Corporation, One Hershey Drive, Smiths Falls, ON K7A 0A8, CanadaCanopy Growth Corporation, One Hershey Drive, Smiths Falls, ON K7A 0A8, CanadaDepartment of Behavioral Science, University of Kentucky, Lexington, KY 40536, USADepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USABackground: Tetrahydrocannabivarin (THCV) is a phytocannabinoid commonly found in cannabis with potential pharmacological properties; however, its post-acute pharmacokinetics (PK) in humans have not been studied yet. THCV has two isomers, Δ9- and Δ8-THCV, which seem to have different pharmacological properties. We investigated the PK of the Δ8-THCV isomer after oral administration as part of a two-phase, dose-ranging, placebo-controlled trial in healthy participants. Methods: Participants (<i>n</i> = 21) were enrolled in six study sessions and randomly received the following doses of a medium-chain triglyceride (MCT) oil oral formulation of Δ8-THCV: placebo, 12.5 mg, 25 mg, 50 mg, 100 mg, and 200 mg. Plasma samples from 15 participants were collected up to 8 h after administration and were analyzed by a validated two-dimensional high-performance liquid chromatography–tandem mass spectrometry assay. The trial was registered on clinicaltrials.gov (NCT05210634). Results: After oral administration, 11-nor-9-carboxy-Δ8-THCV (Δ8-THCV-COOH) was the main metabolite detected. The median time-to-maximum concentration (t<sub>max</sub>) ranged 3.8–5.0 h across doses for Δ8-THCV and 4.6–5.3 h for Δ8-THCV-COOH. The maximum concentration (C<sub>max</sub>) and area under the concentration–time curve over the observation period (AUC<sub>last</sub>) appeared to be dose-linear. Median AUC<sub>last</sub> increased 2.3- to 4.8-fold and 1.7- to 2.9-fold for Δ8-THCV and Δ8-THCV-COOH, respectively, every two-fold increase in the dose. The isomers Δ9-THCV and Δ9-THCV-COOH were detected in plasma, despite being undetected in the formulated drug product analyzed by a third-party laboratory. Conclusions: For the first time, we report the pharmacokinetics of Δ8-THCV and its major metabolites after oral administration in humans. Δ8-THCV AUC<sub>last</sub> showed dose linearity but the observed possible conversion to the Δ9-THCV isomer should be further studied.https://www.mdpi.com/1424-8247/17/12/1603cannabinoidsTHCVpharmacokineticmetabolites |
| spellingShingle | Cristina Sempio Jorge Campos-Palomino Jelena Klawitter Erica N. Peters Laura MacNair Mehdi Haghdoost Marcel O. Bonn-Miller Amy Harrison Shanna Babalonis Uwe Christians Jost Klawitter Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants Pharmaceuticals cannabinoids THCV pharmacokinetic metabolites |
| title | Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants |
| title_full | Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants |
| title_fullStr | Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants |
| title_full_unstemmed | Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants |
| title_short | Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants |
| title_sort | pharmacokinetics of oral cannabinoid δ8 tetrahydrocannabivarin and its main metabolites in healthy participants |
| topic | cannabinoids THCV pharmacokinetic metabolites |
| url | https://www.mdpi.com/1424-8247/17/12/1603 |
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