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

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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.

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Toennes

Geraths

Pogoda

et al. 2017

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“…The quantitative data were evaluated as described previously . For every subject the maximum concentration of the drug assayed (C max ) at the corresponding time (t max ) and the last concentration measured (C last ) were evaluated using the concentration‐time data.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Toennes

Schneider

Pogoda

et al. 2019

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Introduction Each year, synthetic drugs occur in high numbers on the illicit drug market. But data on their pharmacology and toxicology are scarce. Therefore, a controlled study was performed to evaluate pharmacokinetic parameters of 4‐fluoroamphetamine (4‐FA) in humans and to compare it with effects. Methods Twelve subjects ingested 100 mg and five subjects also received 150 mg 4‐FA in a bitter lemon drink. Blood and oral fluid samples were taken during the following 12 hours and analyzed for 4‐FA and traces of amphetamine as impurity by liquid chromatography−tandem mass spectrometry (LC–MS/MS). Results For 12 hours after ingestion, the concentration‐time course of 4‐FA was similar to that of amphetamine with maximal concentrations appearing in serum after about 2 hours (in median 195 ng/mL after the 100 mg dose, range 155–316 ng/mL). The elimination half‐life was approximately 8–9 hours and shorter than that of amphetamine but it exhibited a marked variation (5.5–16.8 hours). In oral fluid, 4‐FA could also be detected for 12 hours and concentrations were higher than in serum. During the first 3 hours after ingestion concentrations were higher, most probably due to oral contamination. Serum concentrations in forensic cases were in the range of those observed in the present study suggesting dosages in recreational use in the range of those tested here. Conclusions The pharmacokinetic properties of 4‐FA are similar to that of amphetamine including a marked variation in elimination. However, recreational dosages may already exhibit prominent adverse effects and may even have life‐threatening consequences.

Adding more “spice” to the pot: A review of the chemistry and pharmacology of newly emerging heterocyclic synthetic cannabinoid receptor agonists

Alam

Keating

2020

Synthetic cannabinoid receptor agonists (SCRAs) first appeared on the international recreational drug market in the early 2000s in the form of SCRA‐containing herbal blends. Due to the cannabimimetic effects associated with the consumption of SCRAs, they have acquired an ill‐informed reputation for being cheap, safe, and legal alternatives to illicit cannabis. Possessing high potency and affinity for the human cannabinoid receptor subtype‐1 (CB1) and ‐2 (CB2), it is now understood that the recreational use of SCRAs can have severe adverse health consequences. The major public health problem arising from SCRA use has pressed legislators around the world to employ various control strategies to curb their recreational use. To circumvent legislative control measures, SCRA manufacturers have created a wide range of SCRA analogs that contain, more recently, previously unencountered azaindole, γ‐carbolinone, or carbazole heterocyclic scaffolds. At present, little information is available regarding the chemical syntheses of these newly emerging classes of SCRA, from a clandestine perspective. When compared with previous generations of indole‐ and indazole‐type SCRAs, current research suggests that many of these heterocyclic SCRA analogs maintain high affinity and efficacy at both CB1 and CB2 but largely evade legislative control. This review highlights the importance of continued research in the field of SCRA chemistry and pharmacology, as recreational SCRA use remains a global public health issue and represents a serious control challenge for law enforcement agencies.