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Effect of cannabidiol pretreatment on the kinetics of tetrahydrocannabinol metabolites in mouse brain.
Drug Metab Dispos 1995; 23(8):825-31DM

Abstract

Tetrahydrocannabinol (THC), a major constituent of marijuana, and several of its metabolites are psychoactive in humans. Cannabidiol (CBD), a nonpsychoactive cannabinoid, inhibits hepatic microsomal THC metabolism and also modulates subjective psychological responses to THC in humans. Treatment of mice with CBD markedly decreased the hepatic microsomal in vitro formation of the major THC metabolites, 6 alpha-OH-THC and 7-OH-THC and increased formation of the minor metabolite 6 beta-OH-THC. THC blood levels were modestly elevated after CBD pretreatment and THC administration, compared with untreated controls, and area under the curve (AUC) of THC increased 50% as a function of decreased clearance. CBD pretreatment modestly increased the Cmax, AUC, or t1/2 of the major THC metabolites in the blood, whereas those kinetic parameters for 6 beta-OH-THC were dramatically increased. Changes in brain concentrations and kinetic parameters of the major THC metabolites did not reflect the relatively modest changes found in blood levels after CBD pretreatment, but exhibited large increases in AUC (7- to 15-fold) and t1/2 (2- to 4-fold), as well as in tmax. Changes in brain concentrations and kinetic parameters for 6 beta-OH-THC reflected the marked changes observed in blood levels after CBD pretreatment. Thus, CBD pretreatment resulted in large increases in AUC and t1/2 of all THC metabolites in brain, with a modest increase in AUC of THC. These changes in THC metabolite brain pharmacokinetics may contribute to the modulation of psychological responses to THC observed after CBD treatment.

Authors+Show Affiliations

Department of Pharmacology, University of California-San Francisco 94143-0450, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7493549

Citation

Bornheim, L M., et al. "Effect of Cannabidiol Pretreatment On the Kinetics of Tetrahydrocannabinol Metabolites in Mouse Brain." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 23, no. 8, 1995, pp. 825-31.
Bornheim LM, Kim KY, Li J, et al. Effect of cannabidiol pretreatment on the kinetics of tetrahydrocannabinol metabolites in mouse brain. Drug Metab Dispos. 1995;23(8):825-31.
Bornheim, L. M., Kim, K. Y., Li, J., Perotti, B. Y., & Benet, L. Z. (1995). Effect of cannabidiol pretreatment on the kinetics of tetrahydrocannabinol metabolites in mouse brain. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 23(8), pp. 825-31.
Bornheim LM, et al. Effect of Cannabidiol Pretreatment On the Kinetics of Tetrahydrocannabinol Metabolites in Mouse Brain. Drug Metab Dispos. 1995;23(8):825-31. PubMed PMID: 7493549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of cannabidiol pretreatment on the kinetics of tetrahydrocannabinol metabolites in mouse brain. AU - Bornheim,L M, AU - Kim,K Y, AU - Li,J, AU - Perotti,B Y, AU - Benet,L Z, PY - 1995/8/1/pubmed PY - 1995/8/1/medline PY - 1995/8/1/entrez SP - 825 EP - 31 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab. Dispos. VL - 23 IS - 8 N2 - Tetrahydrocannabinol (THC), a major constituent of marijuana, and several of its metabolites are psychoactive in humans. Cannabidiol (CBD), a nonpsychoactive cannabinoid, inhibits hepatic microsomal THC metabolism and also modulates subjective psychological responses to THC in humans. Treatment of mice with CBD markedly decreased the hepatic microsomal in vitro formation of the major THC metabolites, 6 alpha-OH-THC and 7-OH-THC and increased formation of the minor metabolite 6 beta-OH-THC. THC blood levels were modestly elevated after CBD pretreatment and THC administration, compared with untreated controls, and area under the curve (AUC) of THC increased 50% as a function of decreased clearance. CBD pretreatment modestly increased the Cmax, AUC, or t1/2 of the major THC metabolites in the blood, whereas those kinetic parameters for 6 beta-OH-THC were dramatically increased. Changes in brain concentrations and kinetic parameters of the major THC metabolites did not reflect the relatively modest changes found in blood levels after CBD pretreatment, but exhibited large increases in AUC (7- to 15-fold) and t1/2 (2- to 4-fold), as well as in tmax. Changes in brain concentrations and kinetic parameters for 6 beta-OH-THC reflected the marked changes observed in blood levels after CBD pretreatment. Thus, CBD pretreatment resulted in large increases in AUC and t1/2 of all THC metabolites in brain, with a modest increase in AUC of THC. These changes in THC metabolite brain pharmacokinetics may contribute to the modulation of psychological responses to THC observed after CBD treatment. SN - 0090-9556 UR - https://www.unboundmedicine.com/medline/citation/7493549/Effect_of_cannabidiol_pretreatment_on_the_kinetics_of_tetrahydrocannabinol_metabolites_in_mouse_brain_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7493549 DB - PRIME DP - Unbound Medicine ER -