Excretion of metabolites of the synthetic cannabinoid JWH-018 in urine after controlled inhalation.

Each year, synthetic cannabinoids are occurring in high numbers on the illicit drug market but data obtained after controlled application are rare. The present study on pharmacokinetics in urine is part of a pilot study on adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Six subjects inhaled smoke from 2 and 3mg JWH-018. The drug and ten potential metabolites were analyzed in urine samples collected during 12h after inhalation by liquid chromatography-mass spectrometry (LC-MS/MS) without and with conjugate cleavage. The parent compound was not detectable, but 13 of its metabolites, all of which were conjugated. Concentrations of the predominant metabolite, JWH-018 pentanoic acid, were less than 5ng/ml, but in two subjects it was still detected up to 4 weeks after ingestion. Other major metabolites were 5- and 4-HOpentyl-JWH-018, JWH-073 butanoic acid and a hypothetically dihydroxylated and dehydrogenated metabolite of JWH-018. Occasionally, further hydroxylated metabolites were found. Generally, hydroxylated metabolites were detected in concentrations lower than 1ng/ml already 10h after inhalation. All concentrations were much lower than reported for urine samples of authentic JWH-018 users. The formation of the metabolite JWH-018 pentanoic acid was found to be slightly delayed, but its rather high concentrations and detection over several weeks after single dosing makes it a useful target for urine analysis. The different excretion of carboxylic acid and hydroxylated metabolites may aid in evaluation of time of use.

Pharmacokinetic properties of the synthetic cannabinoid JWH-018 in oral fluid after inhalation.

Each year, synthetic cannabinoids occur in high numbers on the illicit drug market, but data on their detectability are rarely available. A pilot study was performed to assess adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Oral fluid has been evaluated as a specimen for drug monitoring. Six subjects inhaled smoke derived from 2 and 3 mg JWH-018. The drug and 10 of its metabolites were analyzed in oral fluid samples collected during the following 12 hours using the Quantisal collection device by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Maximum concentrations of JWH-018 reached 2.2-2036 (median 25.7) ng/mL after inhalation and decreased during the next hour to only 0.08-8.42 (median 0.89) ng/mL. Metabolites were not found. During the elimination phase (median half-life 1.69 hours), detection of the drug over 6-12 hours (median 8 hours) after inhalation was achieved (0.024 ng/mL limit of quantification). Oral fluid/serum ratios varied considerably intra- and inter-individually in a range of 0.05-555 (median 1.38). The detection of JWH-018 in oral fluid requires high analytical sensitivity even 1 hour after inhalation. The pharmacokinetic properties of inhaled JWH-018 are similar to those of THC. Times for detection are typically less than 12 hours. High variability of the oral fluid/serum ratio precludes extrapolation of oral fluid concentrations to blood.

Pharmacokinetic properties of the synthetic cannabinoid JWH-018 and of its metabolites in serum after inhalation.

Each year, synthetic cannabinoids are occurring in high numbers in the illicit drug market, but data on their pharmacology and toxicology are scarcely available. Therefore, a pilot study was performed to assess adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Six subjects inhaled smoke from 2 and 3mg JWH-018. The drug and nine of its metabolites were analyzed in their blood samples taken during the following 12h by liquid chromatography-mass spectrometry (LC-MSMS). The maximum concentration of JWH-018 reached 2.9-9.9ng/ml after inhalation and markedly decreased during the next 1.5h, followed by a multiexponential decline (t1/2 in median 1.3h and 5.7h). The concentration of the pentanoic acid metabolite was slightly higher than that of the 3-, 4- and 5-hydroxypentyl metabolites and of the 6-hydroxyindol metabolite. The data also suggest a multiexponential decline and slow terminal elimination of JWH-018 and all metabolites. The detection of JWH-018 and of its metabolites in serum requires high analytical sensitivity. The pharmacokinetic properties of inhaled JWH-018 are similar to that of THC. A slow terminal elimination of drug and metabolites may lead to accumulation in chronic users.