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62 Exploration of Sex Differences in Cannabis Use Patterns, Driving Performance, and Subjective Intoxication Effects
- Kyle F. Mastropietro, Jeffrey M. Rogers, Dafna Paltin, Anya Umlauf, David J. Grelotti, Robert L. Fitzgerald, Igor Grant, Thomas D. Marcotte
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 847-848
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Objective:
Although some animal research suggests possible sex differences in response to THC exposure (e.g., Cooper & Craft, 2018), there are limited human studies. One study found that among individuals rarely using cannabis, when given similar amounts of oral and vaporized THC females report greater subjective intoxication compared to males (Sholler et al., 2020). However, in a study of daily users, females reported indistinguishable levels of intoxication compared to males after smoking similar amounts (Cooper & Haney, 2014), while males and females using 1–4x/week showed similar levels of intoxication, despite females having lower blood THC and metabolite concentrations (Matheson et al., 2020). It is important to elucidate sex differences in biological indicators of cannabis intoxication given potential driving/workplace implications as states increasingly legalize use. The current study examined if when closely matching males and females on cannabis use variables there are predictable sex differences in residual whole blood THC and metabolite concentrations, and THC/metabolites, subjective appraisals of intoxication, and driving performance following acute cannabis consumption.
Participants and Methods:The current study was part of a randomized clinical trial (Marcotte et al., 2022). Participants smoked ad libitum THC cigarettes and then completed driving simulations, blood draws, and subjective measures of intoxication. The main outcomes were the change in Composite Drive Score (CDS; global measure of driving performance) from baseline, whole blood THC, 11-OH-THC, and THC-COOH levels (ng/mL), and subjective ratings of how “high” participants felt (0 = not at all, 100 = extremely). For this analysis of participants receiving active THC, males were matched to females on 1) estimated THC exposure (g) in the last 6 months (24M, 24F) or 2) whole blood THC concentrations immediately post-smoking (23M, 23F).
Results:When matched on THC exposure in the past 6 months (overall mean of 46 grams; p = .99), there were no sex differences in any cannabinoid/metabolite concentrations at baseline (all p > .83) or after cannabis administration (all p > .72). Nor were there differences in the change in CDS from pre-to-post-smoking (p = .26) or subjective “highness” ratings (p = .53). When matched on whole blood THC concentrations immediately after smoking (mean of 34 ng/mL for both sexes, p = .99), no differences were found in CDS change from pre-to-post smoking (p = .81), THC metabolite concentrations (all p > .25), or subjective “highness” ratings (p = .56). For both analyses, males and females did not differ in BMI (both p > .7).
Conclusions:When male/female cannabis users are well-matched on use history, we find no significant differences in cannabinoid concentrations following a mean of 5 days of abstinence, suggesting that there are no clear biological differences in carryover residual effects. We also find no significant sex differences following ad libitum smoking in driving performance, subjective ratings of “highness,” nor whole blood THC and metabolite concentrations, indicating that there are no biological differences in acute response to THC. This improves upon previous research by closely matching participants over a wider range of use intensity variables, although the small sample size precludes definitive conclusions.
Optimal mixing in two-dimensional stratified plane Poiseuille flow at finite Péclet and Richardson numbers
- F. Marcotte, C. P. Caulfield
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- Journal:
- Journal of Fluid Mechanics / Volume 853 / 25 October 2018
- Published online by Cambridge University Press:
- 23 August 2018, pp. 359-385
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We consider the nonlinear optimisation of irreversible mixing induced by an initial finite amplitude perturbation of a statically stable density-stratified fluid with kinematic viscosity $\unicode[STIX]{x1D708}$ and density diffusivity $\unicode[STIX]{x1D705}$. The initial diffusive error function density distribution varies continuously so that $\unicode[STIX]{x1D70C}\in [\bar{\unicode[STIX]{x1D70C}}-\unicode[STIX]{x1D70C}_{0}/2,\bar{\unicode[STIX]{x1D70C}}+\unicode[STIX]{x1D70C}_{0}/2]$. A constant pressure gradient is imposed in a plane two-dimensional channel of depth $2h$. We consider flows with a finite Péclet number $Pe=U_{m}h/\unicode[STIX]{x1D705}=500$ and Prandtl number $Pr=\unicode[STIX]{x1D708}/\unicode[STIX]{x1D705}=1$, and a range of bulk Richardson numbers $Ri_{b}=g\unicode[STIX]{x1D70C}_{0}h/(\bar{\unicode[STIX]{x1D70C}}U^{2})\in [0,1]$ where $U_{m}$ is the maximum flow speed of the laminar parallel flow, and $g$ is the gravitational acceleration. We use the constrained variational direct-adjoint-looping (DAL) method to solve two optimisation problems, extending the optimal mixing results of Foures et al. (J. Fluid Mech., vol. 748, 2014, pp. 241–277) to stratified flows, where the irreversible mixing of the active scalar density leads to a conversion of kinetic energy into potential energy. We identify initial perturbations of fixed finite kinetic energy which maximise the time-averaged perturbation kinetic energy developed over a finite time interval, and initial perturbations that minimise the value (at a target time, chosen to be $T=10$) of a ‘mix-norm’ as first introduced by Mathew et al. (Physica D, vol. 211, 2005, pp. 23–46), further discussed by Thiffeault (Nonlinearity, vol. 25, 2012, pp. 1–44) and shown by Foures et al. (2014) to be a computationally efficient and robust proxy for identifying perturbations that minimise the long-time variance of a scalar distribution. We demonstrate, for all bulk Richardson numbers considered, that the time-averaged kinetic-energy maximising perturbations are significantly suboptimal at mixing compared to the mix-norm minimising perturbations, and also that minimising the mix-norm remains (for density-stratified flows) a good proxy for identifying perturbations which minimise the variance at long times. Although increasing stratification reduces the mixing in general, mix-norm minimising optimal perturbations can still trigger substantial mixing for $Ri_{b}\lesssim 0.3$. By considering the time evolution of the kinetic energy and potential energy reservoirs, we find that such perturbations lead to a flow which, through Taylor dispersion, very effectively converts perturbation kinetic energy into ‘available potential energy’, which in turn leads rapidly and irreversibly to thorough and efficient mixing, with little energy returned to the kinetic-energy reservoirs.