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18. Δ9-Tetrahydrocannabinol Effects on Respiration and Heart Rate Across Route of Administration in Female and Male Mice.

Author

Laudermilk, Lucas T., Marusich, Julie A., and Wiley, Jenny L.

Subjects
HEART beat, RESPIRATION, CANNABINOID receptors, HEART rate monitors, PHOTOPLETHYSMOGRAPHY, HEART rate monitoring, MICE
Abstract

The physiological impact of cannabinoid receptor agonists is of great public health interest due to their increased use in recreational and therapeutic contexts. However, the body of literature on cannabinoid receptor agonists includes multiple confounding variables that complicate comparisons across studies, including route of administration, timeline across which phenotypes are observed, agonist dose, and sex of the study cohort. In this study, we characterized the impact of sex and route of administration on Δ9-tetrahydrocannabinol (THC)-induced changes in cardiopulmonary phenotypes in mice. Using noninvasive plethysmography and telemetry, we monitored heart rate and respiration in the same cohort of animals across aerosol, oral gavage, subcutaneous, and intraperitoneal administrations of THC (0–30 mg/kg THC for oral gavage, subcutaneous, and intraperitoneal, and 0-300 mg/ml THC for aerosol). All routes of THC administration altered respiratory minute volume and heart rate, with the direction of effects typically being consistent across dependent measures. THC primarily decreased respiration and heart rate, but females given oral gavage THC showed increased heart rate. Intraperitoneal and subcutaneous THC produced the longest-lasting effects, including THC-induced alterations in physiological parameters for up to 10 h, whereas effects of aerosolized THC were short lived. The fastest onset of effects of THC occurred for aerosolized and intraperitoneal THC. Altogether, the work herein establishes the impact of dosing route on THC-induced heart rate and respiratory alteration in male and female mice. This study highlights important differences in the timeline of cardiopulmonary response to THC following the most common preclinical routes of administration. [ABSTRACT FROM AUTHOR]

Published
2023
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19. The piperazine analogue para-fluorophenylpiperazine alters timing of the physiological effects of the synthetic cannabinoid receptor agonist AMB-FUBINACA, without changing its discriminative stimulus, signalling effects, or metabolism

Author

Finlay, David B., primary, Mackie, Warwick, additional, Webb, Hunter D.J., additional, Thomsen, Lucy R., additional, Nimick, Mhairi, additional, Rosengren, Rhonda J., additional, Marusich, Julie A., additional, Glass, Michelle, additional, and Wiley, Jenny L., additional

Published
2023
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46. Thermal Degradants Identified from the Vaping of Vitamin E Acetate.

Author

Kovach, Alexander L, Carter, Randi R, Thornburg, Jonathan W, Wiethe, Robert, Fennell, Timothy R, and Wiley, Jenny L

Subjects
VITAMIN E, ELECTRONIC cigarettes, NUCLEAR magnetic resonance, ACETATES, MASS spectrometry, QUINONE
Abstract

Studies have suggested that vitamin E acetate (VEA), when used in an electronic vaping device, undergoes thermal degradation and is considered one of the main contributors in e-cigarette or vaping product use-associated lung injury (EVALI). Using a Borgwaldt 5.1 linear smoker, a SVS250 Electronic Vaporizer and two types of tank systems, VEA was analyzed for degradation products produced via the Cooperation Centre for Scientific Research Relative to Tobacco method 81 when the filter containing vaporized VEA was extracted using acetonitrile. Two of the major products identified were 2,3,5,6-tetramethyl-1,4-benzoquinone and 2,6,10,14-tetramethyl-1-pentadecene, which were confirmed using analytical standards and gas chromatography–high-resolution mass spectrometry (GC–HRMS). Additional synthesis of 4-acetoxy-2,3,5,6-tetramethyl-2,4-cyclohexadienone and subsequent characterization using nuclear magnetic resonance and GC–HRMS suggested that this is not one of the products produced. Identification of these degradants will allow future studies to quantify and examine the degradants in vivo and in vitro as biomarkers for exposure and toxicity assessment. [ABSTRACT FROM AUTHOR]

Published
2022
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