Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes

Watanabe, Kazuhito; Yamaori, Satoshi; Funahashi, Tatsuya; Kimura, Toshiyuki; Yamamoto, Ikuo

doi:10.1016/j.lfs.2006.12.032

Cited by 194 publications

(168 citation statements)

References 22 publications

(21 reference statements)

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“…Strychnine, a highly toxic alkaloid, was mainly metabolized by CYP3A (Han et al, 2009). Most of the primary metabolites of the cannabinoids indicate CYP3A4 as a major enzyme that is involved in metabolic deactivation by human hepatic microsomes (Watanabe et al, 2007). Codeine is activated by CYP2D6 and leads to the production of morphine and morphine-6-glucuronide, which are pharmacologically more potent than codeine (Gasche et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Thunbergia laurifolia extract minimizes the adverse effects of toxicants by regulating P-glycoprotein activity, CYP450, and lipid metabolism gene expression in HepG2 cells

2014

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ABSTRACT. Thunbergia laurifolia (TL) is widely used as an antidote in Thai traditional medicine against toxic substances such as alcohol, pesticides, arsenic, and strychnine. We found that the lyophilized form of TL in 80% ethanol possessed the antioxidant levels within the range 23,163.9 ± 1457.4 Trolox equivalents mM/kg dry mass and 899.8 ± 14.5 gallic acid equivalents mM/kg dry mass using the oxygen radical absorbance capacity assay and the Folin Ciocalteu phenol assay, respectively. TL extract (TLE) at a high dose (3000 mg/L) induced cytotoxicity according to the neutral red assay and the MTT assay. However, TLE doses of 800-3000 mg/L could reduce intracellular oxidative stress in a dose-dependent manner (P < 0.05) using the dichlorodihydrofluorescein diacetate assay. TLE significantly enhanced the mRNA expression of CYP1A1, CYP1A2, CYP2B6, CYP3A4, and PPARg, but it significantly inhibited the mRNA expression of CYP3A7, CYP2D6, and CYP2E1 (P < 0.05) by reverse transcription-polymerase chain reaction. Moreover, TLE could increase the activity of a multidrug transporter, P-glycoprotein, which accelerated the excretion of toxic substances from HepG2 cells. It is suggested that TLE may be beneficial for detoxification by reducing oxidative stress, minimizing toxicity by regulating the expression CYP450 mRNAs for suitable production of CYP450 isoenzymes, and increasing PPARg mRNA expression and P-glycoprotein activity in HepG2 cells, thereby maintaining xenobiotic biotransformation balance.

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Section: Discussionmentioning

confidence: 99%

Thunbergia laurifolia extract minimizes the adverse effects of toxicants by regulating P-glycoprotein activity, CYP450, and lipid metabolism gene expression in HepG2 cells

2014

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“…Systemic inhaled bioavailability is between 10% in light users, and 23% in heavy users [5]. THC is mainly metabolized in the liver, by cytochrome P450 enzymes such as CYP2C9, CYP2C19 and CYP3A [6,7] which, in turn, is rapidly oxidized to an active metabolite, 11-hydroxy-THC (11-OH-THC) and further to THC-COOH [8]. ________________________________________ The primary metabolite 11-OH-THC is at least as potent as THC, has a similar pharmacokinetic profile, and probably contributes significantly to the effects observed after THC administration whereas THC-COOH is an inactive metabolite [4,9].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Cannabinoid Concentrations in Plasma, Oral Fluid and Urine in Occasional Cannabis Smokers After Smoking Cannabis Cigarette

et al. 2016

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-Purpose. A randomized cross-over, double blind placebo controlled study of smoked cannabis was carried out on occasional cannabis smokers. The objective of this research was to describe the pharmacokinetic parameters of THC and its metabolites in plasma, oral fluid and urine, from samples obtained simultaneously to provide estimations of THC and metabolites concentrations after smoking a cannabis cigarette. Methods. Blood, oral fluid and urine samples were collected until up to 72 h after smoking the cannabis cigarette (4% of delta-9-tetrathydrocannabinol (THC)). THC, 11-OH-THC and THC-COOH were analyzed by gas-chromatography-mass spectrometry. Pharmacokinetic parameters were estimated from these data. Results. Eighteen male healthy adults participated in the study. In total, 560 plasma, 288 oral fluid and 448 urine samples were quantified for cannabinoids. Plasma, oral fluid and urine pharmacokinetic parameters were calculated. A wide range of median THC Cmax (1.6-160.0 µg/L and 55.4-123120.0 µg/L in plasma and oral fluid, respectively), 11-OH-THC Cmax (0-11.1 µg/L in plasma) and THC-COOH Cmax (1.0-56.3 µg/L in plasma) was observed. When expressed as a percentage of the total available THC dose, and corrected for molar equivalents, mean percentage of total THC dose excreted was 1.9 +/-2.5 % with range of 0.2-7.5%. This high inter-individual variability was also observed on other calculated pharmacokinetic parameters. Conclusion. Prediction of plasma THC concentration from THC oral fluid concentration or from THC-COOH urinary concentrations is not feasible due to the large variations observed. The results from this study support the assumption that a positive oral fluid THC result or a positive urine fluid result are indicative of a recent cannabis exposure.

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“…Absorption of both thc and cbd from the gastrointestinal tract is good, but both molecules undergo extensive first-pass metabolism. The bioavailability of orally administered thc and cbd is in the range of only 2%-20% 5,[17][18][19][20][21][22] . Table i summarizes the pharmacokinetic profiles of the various forms of cannabinoid therapies 5,[17][18][19][20][21][22] .…”

Section: Cannabinoid Pharmacologymentioning

confidence: 99%

“…The bioavailability of smoked or vaporized thc is 10%-25% and depends on the duration of breath hold and depth of inhalation 5,[17][18][19][20][21][22] . Peak serum concentrations occur within 2-10 minutes.…”

Section: Cannabinoid Pharmacologymentioning

confidence: 99%

A User’s Guide to Cannabinoid Therapies in Oncology

Maida

Daeninck

2016

Current Oncology

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ABSTRACT"Cannabinoid" is the collective term for a group of chemical compounds that either are derived from the Cannabis plant, are synthetic analogues, or occur endogenously. Although cannabinoids interact mostly at the level of the currently recognized cannabinoid receptors, they might have cross reactivity, such as at opioid receptors.Patients with malignant disease represent a cohort within health care that have some of the greatest unmet needs despite the availability of a plethora of guideline-driven disease-modulating treatments and pain and symptom management options. Cannabinoid therapies are varied and versatile, and can be offered as pharmaceuticals (nabilone, dronabinol, and nabiximols), dried botanical material, and edible organic oils infused with cannabis extracts. Cannabinoid therapy regimens can be creative, involving combinations of all of the aforementioned modalities. Patients with malignant disease, at all points of their disease trajectory, could be candidates for cannabinoid therapies whether as monotherapies or as adjuvants.The most studied and established roles for cannabinoid therapies include pain, chemotherapy-induced nausea and vomiting, and anorexia. Moreover, given their breadth of activity, cannabinoids could be used to concurrently optimize the management of multiple symptoms, thereby reducing overall polypharmacy. The use of cannabinoid therapies could be effective in improving quality of life and possibly modifying malignancy by virtue of direct effects and in improving compliance or adherence with disease-modulating treatments such as chemotherapy and radiation therapy.

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Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes

Cited by 194 publications

References 22 publications

Thunbergia laurifolia extract minimizes the adverse effects of toxicants by regulating P-glycoprotein activity, CYP450, and lipid metabolism gene expression in HepG2 cells

Thunbergia laurifolia extract minimizes the adverse effects of toxicants by regulating P-glycoprotein activity, CYP450, and lipid metabolism gene expression in HepG2 cells

Comparison of Cannabinoid Concentrations in Plasma, Oral Fluid and Urine in Occasional Cannabis Smokers After Smoking Cannabis Cigarette

A User’s Guide to Cannabinoid Therapies in Oncology

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