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

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Abstract

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 3 mg JWH-018. The drug and nine of its metabolites were analyzed in their blood samples taken during the following 12 h by liquid chromatography–mass spectrometry (LC–MSMS).

The maximum concentration of JWH-018 reached 2.9–9.9 ng/ml after inhalation and markedly decreased during the next 1.5 h, followed by a multiexponential decline (t1/2 in median 1.3 h and 5.7 h). 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.

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