Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation

Abstract Purpose The oral bioavailability of cannabinoids is limited due to extensive first-pass metabolism, reducing their therapeutic efficacy. This study aimed to evaluate the pharmacokinetics and relative bioavailability of cannabinoids delivered via delta-9-tetrahydrocannabinol/cannabidiol self...

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Main Authors: Vered Hermush, Nisim Mizrahi, Tal Brodezky, Rafael Ezra
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Cannabis Research
Subjects:
Online Access:https://doi.org/10.1186/s42238-025-00294-8
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author Vered Hermush
Nisim Mizrahi
Tal Brodezky
Rafael Ezra
author_facet Vered Hermush
Nisim Mizrahi
Tal Brodezky
Rafael Ezra
author_sort Vered Hermush
collection DOAJ
description Abstract Purpose The oral bioavailability of cannabinoids is limited due to extensive first-pass metabolism, reducing their therapeutic efficacy. This study aimed to evaluate the pharmacokinetics and relative bioavailability of cannabinoids delivered via delta-9-tetrahydrocannabinol/cannabidiol self-emulsifying (THC/CBD-SE) powder, a self-nanoemulsifying drug delivery system, compared to standard oil-based drops. Methods Fourteen healthy volunteers (3 men, 11 women) participated in a crossover study. Each received a single oral doses of 8 mg THC and 8 mg CBD in both formulations, with a 30-day washout period between treatments. Blood samples were collected at specified intervals post-administration to assess pharmacokinetic parameters, including maximum plasma concentration (Cmax) and time to reach Cmax (Tmax). Results THC/CBD-SE Powder significantly enhanced Cmax for THC (32.79 ± 44.37 ng/mL) and its metabolite 11-OH-THC (10.91 ± 6.64 ng/mL) compared to oil-based drops (THC: 10.17 ± 11.41 ng/mL; 11-OH-THC: 4.64 ± 2.55 ng/mL). Similarly, Cmax for 7-OH-CBD was higher with THC/CBD-SE Powder (2.38 ± 1.63 ng/mL vs. 0.86 ± 0.56 ng/mL). Tmax for 11-OH-THC and 7-OH-CBD was shorter with THC/CBD-SE Powder (0.86 ± 0.36 h vs. 4.54 ± 3.44 h and 1.11 ± 0.59 h vs. 4.68 ± 3.38 h, respectively), indicating a faster onset of action. The THC/CBD-SE Powder exhibited over double the relative bioavailability of cannabinoids compared to oil drops, suggesting improved absorption and rapid onset. Both formulations were well tolerated with no serious adverse events. Conclusion THC/CBD-SE Powder significantly improves cannabinoid bioavailability and absorption rates compared to oil-based drops, offering a promising oral delivery method for enhanced therapeutic potential.
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institution Kabale University
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publishDate 2025-06-01
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series Journal of Cannabis Research
spelling doaj-art-69d368c4f6b440839b7fd8ec8b8e383b2025-08-20T03:45:32ZengBMCJournal of Cannabis Research2522-57822025-06-01711910.1186/s42238-025-00294-8Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulationVered Hermush0Nisim Mizrahi1Tal Brodezky2Rafael Ezra3Geriatric Wing, Laniado HospitalGeriatric Wing, Laniado HospitalGeriatric Wing, Laniado HospitalPharmaceutical Association of IsraelAbstract Purpose The oral bioavailability of cannabinoids is limited due to extensive first-pass metabolism, reducing their therapeutic efficacy. This study aimed to evaluate the pharmacokinetics and relative bioavailability of cannabinoids delivered via delta-9-tetrahydrocannabinol/cannabidiol self-emulsifying (THC/CBD-SE) powder, a self-nanoemulsifying drug delivery system, compared to standard oil-based drops. Methods Fourteen healthy volunteers (3 men, 11 women) participated in a crossover study. Each received a single oral doses of 8 mg THC and 8 mg CBD in both formulations, with a 30-day washout period between treatments. Blood samples were collected at specified intervals post-administration to assess pharmacokinetic parameters, including maximum plasma concentration (Cmax) and time to reach Cmax (Tmax). Results THC/CBD-SE Powder significantly enhanced Cmax for THC (32.79 ± 44.37 ng/mL) and its metabolite 11-OH-THC (10.91 ± 6.64 ng/mL) compared to oil-based drops (THC: 10.17 ± 11.41 ng/mL; 11-OH-THC: 4.64 ± 2.55 ng/mL). Similarly, Cmax for 7-OH-CBD was higher with THC/CBD-SE Powder (2.38 ± 1.63 ng/mL vs. 0.86 ± 0.56 ng/mL). Tmax for 11-OH-THC and 7-OH-CBD was shorter with THC/CBD-SE Powder (0.86 ± 0.36 h vs. 4.54 ± 3.44 h and 1.11 ± 0.59 h vs. 4.68 ± 3.38 h, respectively), indicating a faster onset of action. The THC/CBD-SE Powder exhibited over double the relative bioavailability of cannabinoids compared to oil drops, suggesting improved absorption and rapid onset. Both formulations were well tolerated with no serious adverse events. Conclusion THC/CBD-SE Powder significantly improves cannabinoid bioavailability and absorption rates compared to oil-based drops, offering a promising oral delivery method for enhanced therapeutic potential.https://doi.org/10.1186/s42238-025-00294-8Cannabinoid bioavailabilitySelf-Nanoemulsifying drug delivery systemsSNEDDSPharmacokineticsDelta-9-tetrahydrocannabinolTHC
spellingShingle Vered Hermush
Nisim Mizrahi
Tal Brodezky
Rafael Ezra
Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation
Journal of Cannabis Research
Cannabinoid bioavailability
Self-Nanoemulsifying drug delivery systems
SNEDDS
Pharmacokinetics
Delta-9-tetrahydrocannabinol
THC
title Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation
title_full Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation
title_fullStr Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation
title_full_unstemmed Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation
title_short Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation
title_sort enhancing cannabinoid bioavailability a crossover study comparing a novel self nanoemulsifying drug delivery system and a commercial oil based formulation
topic Cannabinoid bioavailability
Self-Nanoemulsifying drug delivery systems
SNEDDS
Pharmacokinetics
Delta-9-tetrahydrocannabinol
THC
url https://doi.org/10.1186/s42238-025-00294-8
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