Historique
Article de Périodique
Effect of smoked cannabis on vigilance and accident risk using simulated driving in occasional and chronic users and the pharmacokinetic-pharmacodynamic relationship (2019)
Auteur(s) :
HARTLEY, S. ;
SIMON, N. ;
LARABI, A. ;
VAUGIER, I. ;
BARBOT, F. ;
QUERA-SALVA, M. A. ;
ALVAREZ, J. C.
Année
2019
Page(s) :
684-693
Langue(s) :
Anglais
Refs biblio. :
42
Domaine :
Drogues illicites / Illicit drugs
Discipline :
PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods)
Thésaurus mots-clés
CANNABIS
;
CONDUITE DE VEHICULE
;
ACCIDENT
;
VIGILANCE
;
PHARMACOCINETIQUE
;
TETRAHYDROCANNABINOL
;
ETUDE RANDOMISEE
;
SANG
;
PERFORMANCE
;
TEST
Thésaurus géographique
FRANCE
Résumé :
BACKGROUND: The pharmacokinetic-pharmacodynamic relationship between whole blood delta-9-tetrahydrocannabinol (THC) and driving risk is poorly understood.
METHODS: Fifteen chronic cannabis consumers (1-2 joints/day; CC) and 15 occasional cannabis consumers (1-2 joints/week; OC) of 18 to 34 years of age were included. A pharmacokinetic study was conducted with 12 blood samplings over a 24-h period before and after controlled random inhalation of placebo or 10 mg or 30 mg of THC. THC and metabolites were quantified using LC-MS/MS. Effects on reaction time by psychomotor vigilance tests and driving performance through a York driving simulator were evaluated 7 times. A pharmacokinetic-pharmacodynamic analysis was performed using R software.
RESULTS: Whole blood peak THC was 2 times higher in CC than in OC for a same dose and occurred 5 min after the end of consumption. THC remained detectable only in CC after 24 h. Despite standardized consumption, CC consumed more available THC from each cigarette regardless of dose. Maximal effect for reaction time was dose-and group-dependent and only group-dependent for driving performance, both being decreased and more marked in OC than in CC. These effects were maximal around 5 h after administration, and the duration was longer in OC than in CC. A significant pharmacokinetic-pharmacodynamic relationship was observed only between T-max for blood THC and the duration effect on mean reciprocal reaction time.
CONCLUSIONS: Inhalation from cannabis joints leads to a rapid increase in blood THC with a delayed decrease in vigilance and driving performance, more pronounced and lasting longer in OC than in CC.
ClinicalTrials.gov Identifier: NCT02061020 (c) 2019 American Association for Clinical Chemistry
METHODS: Fifteen chronic cannabis consumers (1-2 joints/day; CC) and 15 occasional cannabis consumers (1-2 joints/week; OC) of 18 to 34 years of age were included. A pharmacokinetic study was conducted with 12 blood samplings over a 24-h period before and after controlled random inhalation of placebo or 10 mg or 30 mg of THC. THC and metabolites were quantified using LC-MS/MS. Effects on reaction time by psychomotor vigilance tests and driving performance through a York driving simulator were evaluated 7 times. A pharmacokinetic-pharmacodynamic analysis was performed using R software.
RESULTS: Whole blood peak THC was 2 times higher in CC than in OC for a same dose and occurred 5 min after the end of consumption. THC remained detectable only in CC after 24 h. Despite standardized consumption, CC consumed more available THC from each cigarette regardless of dose. Maximal effect for reaction time was dose-and group-dependent and only group-dependent for driving performance, both being decreased and more marked in OC than in CC. These effects were maximal around 5 h after administration, and the duration was longer in OC than in CC. A significant pharmacokinetic-pharmacodynamic relationship was observed only between T-max for blood THC and the duration effect on mean reciprocal reaction time.
CONCLUSIONS: Inhalation from cannabis joints leads to a rapid increase in blood THC with a delayed decrease in vigilance and driving performance, more pronounced and lasting longer in OC than in CC.
ClinicalTrials.gov Identifier: NCT02061020 (c) 2019 American Association for Clinical Chemistry
Affiliation :
AP-HP, Hôpital Raymond Poincaré, Sleep Centre, Service d'Explorations Fonctionnelles, Garches, Université de Versailles-St. Quentin, France