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Development of a Standardized Mouse Model for Nose-Only Inhaled Cannabis

Cannabis is one of the most popular recreational drugs used worldwide. Since the recent legalization of marijuana across several countries and states, there is an increased interest in research into both the potential health risks and the therapeutic value of the biologically active compounds found in cannabis.

A recent pre-clinical study published in Inhalation Toxicology developed and standardized a novel mouse model of nose-only inhaled vaporized cannabis, investigating the neuroradiological, behavioural and physiological effects1. The researchers chose inhalation for this model as it is the most common route of administration in humans and has been shown to produce quantitatively different behavioural effects pre-clinically when compared to the intravenous or intraperitoneal route2.

In this study, male C57BL/6 mice were exposed to Cannabis sativa (10.3% THC, 0.05% CBD) for three sessions over the duration of four weeks using the nose-only inExpose exposure system. Inhalation exposure sessions were performed at a minimum of 72 hours apart. Cannabis sativa was aerosolized using the Volcano® vaporizer, producing a quality and consistent vapour, with temperature control. A 450mg mass point of cannabis leaf was used in the vapour as it was deemed an effective dose required to produce a target THC concentration of 75 to 165 ng/mL.

Mouse Model for Inhaled cannabis

Immediately following cannabis exposure, behavioural, physiological, and neurological measurements were collected. For behavioural assessment of locomotion and anxiolytic tendencies, the researchers used an open field maze. Following an acute cannabis exposure, mice displayed an increased aversion to the inner zone of the open field maze, indicative of an anxiogenic response.

A non-invasive tail cuff measured blood pressure and heart rate before and after cannabis exposures. The mice were found to have a decrease in heart rate along with diastolic and mean blood pressures immediately following exposure, compared to their baseline.

Blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) measured brain activity following cannabis exposure. An MRI-safe configuration was used to give cumulatively identical puff volumes per minute at a matched flow rate compared to the nose-only inExpose studies. Findings from the neuroradiological work reveal an increased awareness of sensory stimuli after cannabis exposure, as reflected by positive BOLD patterns in the somatosensory, visual, and primary olfactory cortex. The negative BOLD pattern revealed a potential reduction in behavioural arousal as reflected in the amygdala, brainstem, and pons.

Ultimately, the standardized mouse model for nose-only inhaled vaporized cannabis developed with the inExpose will help researchers further understand the cardiopulmonary health impacts that result from chronic cannabis use.

Learn what the authors of this paper have to say about the state of cannabis related cardiopulmonary research in our interview!

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