Effect of Smoked Cannabis on Vigilance and Accident Risk Using Simulated Driving in Occasional and Chronic Users and the Pharmacokinetic–Pharmacodynamic Relationship

Hartley, Sarah; Simon, Nicolas; Larabi, Islam Amine; Vaugier, Isabelle; Barbot, Frédéric; Quera-Salva, Maria-Antonia; Alvarez, Jean‐Claude

doi:10.1373/clinchem.2018.299727

Cited by 39 publications

(45 citation statements)

References 40 publications

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“…The present study also demonstrated that cannabis increased subjective high and decreased performance on a sustained attention task in OUs, outcome variables previously found to be affected by cannabis (10, 31, 32). Furthermore, behavioral outcomes correlated with striatal functional connectivity to other areas of the reward circuit.…”

Section: Discussionsupporting

confidence: 81%

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Reduced responsiveness of the reward system underlies tolerance to cannabis impairment in chronic users

Mason

Theunissen

Hutten

et al. 2019

Preprint

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words)Cannabis is the most commonly used illicit drug in the world. However due to a changing legal landscape, and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly, cannabis impairment. Importantly, a growing body of evidence suggests regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug.However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo controlled, cross-over study assessed the acute influence of cannabis on brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional (OUs) and 12 chronic (CUs) cannabis users received acute doses of cannabis (300 μg/kg THC) and placebo, and underwent ultra-high field functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS). In OUs, cannabis induced significant neurometabolic alterations in reward circuitry, namely decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in CUs. The finding that cannabis altered circuitry and distorted behavior in OUs, but not CUs, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment. regions of interest (ROI) in the NAc and remote cortical areas, as an indirect measure of dopaminergic stimulation (10, 29, 30). Furthermore a priori ROI-to-ROI analysis assessed differences in connectivity strength between areas of the reward circuit. Finally, subjective high and sustained attention, two outcome variables shown to be modulated by (acute) cannabis exposure (10, 31, 32), were assessed.The second goal was exploratory in nature, to evaluate long-term effects of repeated cannabis exposure, by comparing the placebo condition of each group. Overall, we hypothesized that THC would induce behavioral, functional, and metabolic changes in the OUs, but not the CUs, indicative of (neuroadaptive) tolerance. Furthermore, based on previous studies with chronic cannabis users, we hypothesized that during placebo, CUs would show decreased concentrations of metabolites compared to OUs. MethodsParticipants. In total, 27 healthy cannabis users entered the study. Three participants were excluded due to poor fMRI data, resulting in a total of 12 occasional and 12 chronic users (male N= 14, female N= 10). For further details see SI Methods.This study was conducted according to the code of ethics on human experimentation established by the declaration of Helsinki (1964) and amended in Fortaleza (Brazil, October 2013) and in accordance with the Medical Research Involving Human Subjects Act (WMO) and was approved by the Academic Hospital and University's Medical Ethics committee. All participants were full...

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Section: Discussionsupporting

confidence: 81%

“…Furthermore a priori ROI-to-ROI analysis assessed differences in connectivity strength between areas of the reward circuit. Finally, subjective high and sustained attention, two outcome variables shown to be modulated by (acute) cannabis exposure (10, 31, 32), were assessed.…”

Section: Introductionmentioning

confidence: 99%

Reduced responsiveness of the reward system underlies tolerance to cannabis impairment in chronic users

Mason

Theunissen

Hutten

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…10,29,30 Furthermore a priori ROI-to-ROI analysis assessed differences in connectivity strength between areas of the reward circuit. Finally, subjective high and sustained attention, two outcome variables shown to be modulated by (acute) cannabis exposure, 10,31,32 were assessed.…”

Section: Introductionmentioning

confidence: 99%

Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users

et al. 2019

View full text Add to dashboard Cite

Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo-controlled, cross-over study assessed the acute influence of cannabis on the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300-μg/kg delta-9-tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, cannabis induced significant neurometabolic alterations in reward circuitry, namely, decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users. Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment, of which is important to understand in the context of the long-term therapeutic use of cannabis-based medications, as well as in the context of public health and safety of cannabis use when performing day-today operations.

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“…They also agreed that lowering the legal limits of blood alcohol concentration (BAC) would lower the likelihood of accidents. Newest studies were similarly performed for cannabis in [92] and [93].…”

Section: A Driver Studiesmentioning

confidence: 99%

A Review of Driving Simulation Technology and Applications

Bruck

Haycock

Emadi

2021

IEEE Open J. Veh. Technol.

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Driving simulation has become a very useful tool for vehicle design and research in industry and educational institutes. This paper provides a review of driving simulator components, including the vehicle dynamics model, the motion system, and the virtual environment, and how they interact with the human perceptual system in order to create the illusion of the driving. In addition, a sample of current state-of-the-art vehicle simulators and algorithms are described. Finally, current applications are discussed, such as driver-centered studies, chassis and powertrain design, and autonomous systems development.

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Effect of Smoked Cannabis on Vigilance and Accident Risk Using Simulated Driving in Occasional and Chronic Users and the Pharmacokinetic–Pharmacodynamic Relationship

Cited by 39 publications

References 40 publications

Reduced responsiveness of the reward system underlies tolerance to cannabis impairment in chronic users

Reduced responsiveness of the reward system underlies tolerance to cannabis impairment in chronic users

Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users

A Review of Driving Simulation Technology and Applications

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