In Europe and the United States, the recreational use of gammahydroxy butyric acid (GHB) at dance clubs and “rave” parties has increased substantially. In addition, GHB is used to assist in the commission of sexual assaults. The aim of this controlled clinical study was to acquire pharmacokinetic profiles, detection times, and excretion rates in human subjects. Eight GHB-naïve volunteers were administered a single 25-mg/kg body weight oral dose of GHB, and plasma, urine, and oral fluid specimens were analyzed by using gas chromatography-mass spectrometry (GC-MS). Liquid-liquid extraction was performed after acid conversion of GHB to gamma-butyrolactone. Limits of quantitation of 0.1 (oral fluid), 0.2 (urine), and 0.5 µg/mL (plasma) could be achieved in the selected ion monitoring mode. GHB plasma peaks of 39.4 ± 25.2 µg/mL (mean ± SEM) occurred 20–45 min after administration. The terminal plasma elimination half-life was 30.4 ± 2.45 min, the distribution volume 52.7 ± 15.0 L, and the total clearance 1228 ± 233 µL/min. In oral fluid, GHB could be detected up to 360 min, with peak concentrations of 203 ± 92.4 µg/mL in the 10-min samples. In urine, 200 ± 71.8 and 230 ± 86.3 µg/mL, were the highest GHB levels measured at 30 and 60 min, respectively. Only 1.2 ± 0.2% of the dose was excreted, resulting in a detection window of 720 min. Common side-effects were confusion, sleepiness, and dizziness; euphoria and change of vital functions were not observed. GHB is extensively metabolized and rapidly eliminated in urine and oral fluid. Consequently, samples should be collected as soon as possible after ingestion.
Inhalation by vaporization is a promising application mode for cannabis in medicine. An in vitro validation of 5 commercial vaporizers was performed with THC-type and CBD-type cannabis. Gas chromatography/mass spectrometry was used to determine recoveries of total THC (THCtot) and total CBD (CBDtot) in the vapor. High-performance liquid chromatography with photodiode array detection was used for the quantitation of acidic cannabinoids in the residue and to calculate decarboxylation efficiencies. Recoveries of THCtot and CBDtot in the vapor of 4 electrically-driven vaporizers were 58.4 and 51.4%, 66.8 and 56.1%, 82.7 and 70.0% and 54.6 and 56.7% for Volcano Medic®, Plenty Vaporizer®, Arizer Solo® and DaVinci Vaporizer®, respectively. Decarboxylation efficiency was excellent for THC (≥ 97.3%) and CBD (≥ 94.6%). The gas-powered Vape-or-Smoke™ showed recoveries of THCtot and CBDtot in the vapor of 55.9 and 45.9%, respectively, and a decarboxylation efficiency of ≥ 87.7 for both cannabinoids. However, combustion of cannabis was observed with this device. Temperature-controlled, electrically-driven vaporizers efficiently decarboxylate inactive acidic cannabinoids and reliably release their corresponding neutral, active cannabinoids. Thus, they offer a promising application mode for the safe and efficient administration of medicinal cannabis.
30 January 2010 in Analytical and Bioanalytical Chemistry
The endocannabinoid (EC) system is implicated in many chronic liver diseases, including hepatitis C viral (HCV) infection. Cannabis consumption is associated with fibrosis progression in patients with chronic hepatitis C (CHC), however, the role of ECs in the development of CHC has never been explored. To study this question, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were quantified in samples of HCV patients and healthy controls by gas and liquid chromatography mass spectrometry. Fatty acid amide hydrolase (FAAH) and monoaclyglycerol lipase (MAGL) activity was assessed by [3H]AEA and [3H]2-AG hydrolysis, respectively. Gene expression and cytokine release were assayed by TaqMan PCR and ELISpot, respectively. AEA and 2-AG levels were increased in plasma of HCV patients, but not in liver tissues. Hepatic FAAH and MAGL activity was not changed. In peripheral blood mononuclear cells (PBMC), ECs inhibited IFN-γ, TNF-α, and IL-2 secretion. Inhibition of IL-2 by endogenous AEA was stronger in PBMC from HCV patients. In hepatocytes, 2-AG induced the expression of IL-6, -17A, -32 and COX-2, and enhanced activation of hepatic stellate cells (HSC) co-cultivated with PBMC from subjects with CHC. In conclusion, ECs are increased in plasma of patients with CHC and might reveal immunosuppressive and profibrogenic effects.