Quantification of anandamide and 2‐arachidonoylglycerol plasma levels to examine potential influences of tetrahydrocannabinol application on the endocannabinoid system in humans. Issue 1 (28th October 2013)

• Record Type: Journal Article
• Authors: Thieme, Ulrike; Schelling, Gustav; Hauer, Daniela; Greif, Robert; Dame, Torsten; Laubender, Ruediger Paul; Bernhard, Werner; Thieme, Detlef; Campolongo, Patrizia; Theiler, Lorenz
• Other Names: Kicman Andrew T. guestEditor.; King Leslie A. guestEditor.
• Is Part Of: Drug testing and analysis. Volume 6:Issue 1/2(2014:Jan./Feb.)
• Page Start: 17
• Page End: 23
• Publication Date: 2013-10-28
• Subjects: Tetrahydrocannabinol -- Endocannabinoids -- Plasma concentrations -- HPLC -- Mass spectrometry -- Anandamide -- 2‐Arachidonoylglycerol; Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.1561
• Languages: English
• ISSNs: 1942-7603

Abstract

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. Copyright © 2013 John Wiley & Sons, Ltd. Abstract : The intravenous administration of tetrahydrocannabinol (THC) to volunteers resulted in s biphasic response of plasma endocannabinoids with an initial increase followed by a significant decline between 6 and 24 h after injection and a gradual return to baseline levels over the following 24 h. Although the underlying machanism is not clear, this observation indicates that THC have may prolonged effects on endogenous cannabinoid signalling with possible impliacations for cannabis dependency or the devepolment of mental disorders after chronic use.