Tags

Type your tag names separated by a space and hit enter

Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract.
Ther Drug Monit 2005; 27(6):799-810TD

Abstract

Cannabidiol (CBD) is known to modify the effects of Delta-tetrahydrocannabinol (THC) by decreasing anxiety and antagonizing other THC-effects. As a reason, pharmacodynamic as well as pharmacokinetic mechanisms were suggested. In context of the use of cannabis-based medicine extracts for therapeutic purposes, a study was performed in a double-blind and placebo-controlled cross-over design in which each of 24 volunteers (12 male and 12 female, age 18-45 years) obtained soft-gelatin capsules with 10 mg THC (THC-set), cannabis extract containing 10 mg THC +5.4 mg CBD (CAN-set) or placebo in weekly intervals. Blood samples were taken 30 minutes before and 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours and 24 hours after the intake. The concentrations of THC, of its metabolites 11-OH-THC, THC-COOH and of CBD in the plasma samples were determined by automatic solid phase extraction, derivatization with N,O-bis(trimethylsilyl)triflouroacetamide and gas chromatography-mass spectrometry. The concentration versus time curves (maximum concentrations Cmax, corresponding time tmax and areas under the curves AUC) were evaluated by statistical methods with respect to equivalence or differences between the CAN-set and the THC-set. Furthermore, the intra-individual ratios of Cmax and AUC for 11-OH-THC/THC, THC-COOH/THC and THC-COOH/11-OH-THC were compared between the THC-set and the CAN-set. Despite the large variation of the data, evidence emerged from the total of the results that CBD partially inhibits the CYP 2C catalyzed hydroxylation of THC to 11-OH-THC. The probability for this inhibition is particularly high for oral intake because THC and CBD attain relatively high concentrations in the liver and because of the high first-pass metabolism of THC. However, the effect of CBD is small in comparison to the variability caused by other factors. Therefore, a pharmacokinetic reason for the differences determined between pure THC and cannabis extract is improbable at the doses chosen in this study. Significantly higher AUC and Cmax and shorter tmax were found for females as compared with males.

Authors+Show Affiliations

Institute of Legal Medicine and Department of Psychiatry, University Hospital Charité, Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16306858

Citation

Nadulski, Thomas, et al. "Randomized, Double-blind, Placebo-controlled Study About the Effects of Cannabidiol (CBD) On the Pharmacokinetics of Delta9-tetrahydrocannabinol (THC) After Oral Application of THC Verses Standardized Cannabis Extract." Therapeutic Drug Monitoring, vol. 27, no. 6, 2005, pp. 799-810.
Nadulski T, Pragst F, Weinberg G, et al. Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. Ther Drug Monit. 2005;27(6):799-810.
Nadulski, T., Pragst, F., Weinberg, G., Roser, P., Schnelle, M., Fronk, E. M., & Stadelmann, A. M. (2005). Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. Therapeutic Drug Monitoring, 27(6), pp. 799-810.
Nadulski T, et al. Randomized, Double-blind, Placebo-controlled Study About the Effects of Cannabidiol (CBD) On the Pharmacokinetics of Delta9-tetrahydrocannabinol (THC) After Oral Application of THC Verses Standardized Cannabis Extract. Ther Drug Monit. 2005;27(6):799-810. PubMed PMID: 16306858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. AU - Nadulski,Thomas, AU - Pragst,Fritz, AU - Weinberg,Gordon, AU - Roser,Patrik, AU - Schnelle,Martin, AU - Fronk,Eva-Maria, AU - Stadelmann,Andreas Michael, PY - 2005/11/25/pubmed PY - 2006/5/25/medline PY - 2005/11/25/entrez SP - 799 EP - 810 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 27 IS - 6 N2 - Cannabidiol (CBD) is known to modify the effects of Delta-tetrahydrocannabinol (THC) by decreasing anxiety and antagonizing other THC-effects. As a reason, pharmacodynamic as well as pharmacokinetic mechanisms were suggested. In context of the use of cannabis-based medicine extracts for therapeutic purposes, a study was performed in a double-blind and placebo-controlled cross-over design in which each of 24 volunteers (12 male and 12 female, age 18-45 years) obtained soft-gelatin capsules with 10 mg THC (THC-set), cannabis extract containing 10 mg THC +5.4 mg CBD (CAN-set) or placebo in weekly intervals. Blood samples were taken 30 minutes before and 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours and 24 hours after the intake. The concentrations of THC, of its metabolites 11-OH-THC, THC-COOH and of CBD in the plasma samples were determined by automatic solid phase extraction, derivatization with N,O-bis(trimethylsilyl)triflouroacetamide and gas chromatography-mass spectrometry. The concentration versus time curves (maximum concentrations Cmax, corresponding time tmax and areas under the curves AUC) were evaluated by statistical methods with respect to equivalence or differences between the CAN-set and the THC-set. Furthermore, the intra-individual ratios of Cmax and AUC for 11-OH-THC/THC, THC-COOH/THC and THC-COOH/11-OH-THC were compared between the THC-set and the CAN-set. Despite the large variation of the data, evidence emerged from the total of the results that CBD partially inhibits the CYP 2C catalyzed hydroxylation of THC to 11-OH-THC. The probability for this inhibition is particularly high for oral intake because THC and CBD attain relatively high concentrations in the liver and because of the high first-pass metabolism of THC. However, the effect of CBD is small in comparison to the variability caused by other factors. Therefore, a pharmacokinetic reason for the differences determined between pure THC and cannabis extract is improbable at the doses chosen in this study. Significantly higher AUC and Cmax and shorter tmax were found for females as compared with males. SN - 0163-4356 UR - https://www.unboundmedicine.com/medline/citation/16306858/Randomized_double_blind_placebo_controlled_study_about_the_effects_of_cannabidiol__CBD__on_the_pharmacokinetics_of_Delta9_tetrahydrocannabinol__THC__after_oral_application_of_THC_verses_standardized_cannabis_extract_ L2 - http://Insights.ovid.com/pubmed?pmid=16306858 DB - PRIME DP - Unbound Medicine ER -