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

Stefan W Toennes, Anna Geraths, Werner Pogoda, Alexander Paulke, Cora Wunder, Eef L Theunissen, Johannes G Ramaekers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)162-168
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume150
Early online date9 Dec 2017
DOIs
Publication statusPublished - 20 Feb 2018

Keywords

  • Pharmacokinetics
  • Synthetic cannabinoids
  • JWH-018
  • Metabolism
  • Urine
  • Liquid chromatography-mass spectrometry
  • TANDEM MASS-SPECTROMETRY
  • QUANTITATIVE MEASUREMENT
  • MS/MS
  • SPECIMENS
  • Urinalysis
  • Humans
  • Male
  • Naphthalenes/administration & dosage
  • Indoles/administration & dosage
  • Young Adult
  • Tandem Mass Spectrometry
  • Biomarkers/urine
  • Biotransformation
  • Inhalation Exposure
  • Chromatography, Liquid
  • Female
  • Butyrates/urine
  • Hydroxylation
  • Pentanoic Acids/urine
  • Smoking, Non-Tobacco Products
  • Cannabinoids/administration & dosage
  • Renal Elimination
  • Cross-Over Studies
  • Pilot Projects

Cite this

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title = "Excretion of metabolites of the synthetic cannabinoid JWH-018 in urine after controlled inhalation",
abstract = "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.",
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author = "Toennes, {Stefan W} and Anna Geraths and Werner Pogoda and Alexander Paulke and Cora Wunder and Theunissen, {Eef L} and Ramaekers, {Johannes G}",
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year = "2018",
month = "2",
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language = "English",
volume = "150",
pages = "162--168",
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Excretion of metabolites of the synthetic cannabinoid JWH-018 in urine after controlled inhalation. / Toennes, Stefan W; Geraths, Anna; Pogoda, Werner; Paulke, Alexander; Wunder, Cora; Theunissen, Eef L; Ramaekers, Johannes G.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 150, 20.02.2018, p. 162-168.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Excretion of metabolites of the synthetic cannabinoid JWH-018 in urine after controlled inhalation

AU - Toennes, Stefan W

AU - Geraths, Anna

AU - Pogoda, Werner

AU - Paulke, Alexander

AU - Wunder, Cora

AU - Theunissen, Eef L

AU - Ramaekers, Johannes G

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2018/2/20

Y1 - 2018/2/20

N2 - 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.

AB - 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.

KW - Pharmacokinetics

KW - Synthetic cannabinoids

KW - JWH-018

KW - Metabolism

KW - Urine

KW - Liquid chromatography-mass spectrometry

KW - TANDEM MASS-SPECTROMETRY

KW - QUANTITATIVE MEASUREMENT

KW - MS/MS

KW - SPECIMENS

KW - Urinalysis

KW - Humans

KW - Male

KW - Naphthalenes/administration & dosage

KW - Indoles/administration & dosage

KW - Young Adult

KW - Tandem Mass Spectrometry

KW - Biomarkers/urine

KW - Biotransformation

KW - Inhalation Exposure

KW - Chromatography, Liquid

KW - Female

KW - Butyrates/urine

KW - Hydroxylation

KW - Pentanoic Acids/urine

KW - Smoking, Non-Tobacco Products

KW - Cannabinoids/administration & dosage

KW - Renal Elimination

KW - Cross-Over Studies

KW - Pilot Projects

U2 - 10.1016/j.jpba.2017.12.016

DO - 10.1016/j.jpba.2017.12.016

M3 - Article

C2 - 29245085

VL - 150

SP - 162

EP - 168

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

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