Bornheim L M, Kim K Y, Li J, Perotti B Y, Benet L Z
Department of Pharmacology, University of California-San Francisco 94143-0450, USA.
Drug Metab Dispos. 1995 Aug;23(8):825-31.
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.
四氢大麻酚（THC）是大麻的主要成分，其多种代谢产物对人体具有精神活性。大麻二酚（CBD）是一种无精神活性的大麻素，可抑制肝脏微粒体中THC的代谢，还能调节人体对THC的主观心理反应。用CBD处理小鼠后，肝脏微粒体体外生成主要THC代谢产物6α-羟基-THC和7-羟基-THC的量显著减少，而次要代谢产物6β-羟基-THC的生成量增加。与未处理的对照组相比，CBD预处理后再给予THC，THC的血药浓度适度升高，THC的曲线下面积（AUC）因清除率降低而增加了50%。CBD预处理适度增加了血液中主要THC代谢产物的Cmax、AUC或t1/2，而6β-羟基-THC的这些动力学参数则显著增加。主要THC代谢产物在脑内的浓度和动力学参数变化并未反映出CBD预处理后血药浓度相对较小的变化，而是表现出AUC（7至15倍）和t1/2（2至4倍）以及tmax大幅增加。6β-羟基-THC在脑内的浓度和动力学参数变化反映了CBD预处理后血药浓度的显著变化。因此，CBD预处理导致脑内所有THC代谢产物的AUC和t1/2大幅增加，而THC的AUC适度增加。THC代谢产物脑内药代动力学的这些变化可能有助于调节CBD治疗后观察到的对THC的心理反应。
