title: Quantification of anandamide and 2-arachidonoylglycerol plasma levels to examine potential influences of tetrahydrocannabinol application on the endocannabinoid system in humans.
abstract: The effects of tetrahydrocannabinol (THC) and endogenous cannabinoids (endocannabinoids, ECs) are both mediated by activation of the cannabinoid receptors CB1 and CB2. Exogenous activation of these receptors by THC could therefore alter EC levels. We tested this hypothesis in healthy volunteers (n = 25) who received a large intravenous dose of THC (0.10 mg/kg). Effects on the EC system were quantified by serial measurements of plasma ECs after THC administration. Eleven blood samples were drawn during the first 5 h after THC administration and two more samples after 24 and 48 h. THC, its metabolites THC-OH (biologically active) and THC-COOH (non-active), and the ECs anandamide and 2-arachidonoylglycerol (2-AG) were quantified by liquid chromatography-mass spectrometry. EC-plasma levels showed a biphasic response after THC injection reaching maximal values at 30 min. Anandamide increased slightly from 0.58 ± 0.21 ng/ml at baseline to 0.64 ± 0.24 ng/ml (p < 0.05) and 2-AG from 7.60 ± 4.30 ng/ml to 9.50 ± 5.90 ng/ml (p < 0.05). After reaching maximal concentrations, EC plasma levels decreased markedly to a nadir of 300 min after THC administration (to 0.32 ± 0.15 ng/ml for anandamide and to 5.50 ± 3.01 ng/ml for 2-AG, p < 0.05). EC plasma concentrations returned to near baseline levels until 48 h after the experiment. THC (0.76 ± 0.16 ng/ml) and THC-OH (0.36 ± 0.17 ng/ml) were still measurable at 24 h and remained detectible until 48 h after THC administration. Although the underlying mechanism is not clear, high doses of intravenous THC appear to influence endogenous cannabinoid concentrations and presumably EC-signalling.
authors.affiliation: Department of Anaesthesiology, Ludwig - Maximilians University of Munich, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Thieme
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
authors.forename: Daniela
authors.initials: D
authors.lastname: Hauer
authors.forename: Robert
authors.initials: R
authors.lastname: Greif
authors.forename: Torsten
authors.initials: T
authors.lastname: Dame
authors.forename: Ruediger Paul
authors.initials: RP
authors.lastname: Laubender
authors.forename: Werner
authors.initials: W
authors.lastname: Bernhard
authors.forename: Detlef
authors.initials: D
authors.lastname: Thieme
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.forename: Lorenz
authors.initials: L
authors.lastname: Theiler
mesh_terms: D000328:Adult; D001095:Arachidonic Acids / Q000097:blood*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D013759:Dronabinol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D063388:Endocannabinoids / Q000097:blood*; D005260:Female; D005989:Glycerides / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D013058:Mass Spectrometry; D053284:Polyunsaturated Alkamides / Q000097:blood*; D055815:Young Adult
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D013759:Dronabinol; C094503:glyceryl 2-arachidonate; C078814:anandamide; D006854:Hydrocortisone
keywords: 2-Arachidonoylglycerol; Anandamide; Endocannabinoids; HPLC; Mass spectrometry; Plasma concentrations; Tetrahydrocannabinol