Department of Bioengineering, Northeastern University, Boston, MA, USA.
Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA.
Inhal Toxicol. 2020 Apr;32(5):200-217. doi: 10.1080/08958378.2020.1767237. Epub 2020 Jun 1.
The rapid increase of cannabis consumption reinforces the need to elucidate the health hazards of this practice. The presence of fine particulate matter in cannabis smoke and vapor poses a major concern, as it may contribute to cardiopulmonary disease. To facilitate the assessment of risks associated with cannabis inhalation, we developed and characterized a method for exposing mice to cannabis in a way that mimics the delivery of the drug to the airways of smokers. Cannabis (10.3% THC, 0.05% CBD) was vaporized to generate aerosols with a reproducible particle profile. Aerosols were acutely delivered to male, adult C57BL/6 mice via a nose-only exposure system. Serum THC levels were measured for increasing cannabis doses. Blood pressure and heart rate were recorded at baseline and following exposure. Behavioral response to cannabis inhalation in the open field was documented. Awake neurological activity upon cannabis exposure was monitored using BOLD fMRI. Cannabis aerosols contained particles with count median diameter of 243 ± 39 nm and geometric standard deviation of 1.56 ± 0.06. Blood serum THC levels increased linearly with aerosolized mass and peaked at 136 ± 5 ng/mL. Cannabis inhalation decreased heart rate and blood pressure but promoted anxiety-like behavior. Observed differences in BOLD activation volumes linked cannabis to increased awareness to sensory stimuli and reduced behavioral arousal. Quantified physiological, behavioral, and neurological responses served as validation for our mouse model of cannabis inhalation. Animal models of aerosol exposure will be instrumental for uncovering the health outcomes of chronic cannabis use.
大麻消费的迅速增加，突显了阐明这种做法对健康危害的必要性。大麻烟雾和蒸气中存在的细颗粒物是一个主要关注点，因为它可能导致心肺疾病。为了便于评估与大麻吸入相关的风险，我们开发并描述了一种使小鼠模拟吸烟者气道吸入大麻的方法。大麻（10.3%THC，0.05%CBD）被蒸发以产生具有可重复颗粒特征的气溶胶。通过鼻内暴露系统，将气溶胶急性递送至雄性成年 C57BL/6 小鼠。为递增的大麻剂量测量血清 THC 水平。在基线和暴露后记录血压和心率。记录在开放场中对大麻吸入的行为反应。使用 BOLD fMRI 监测大麻暴露时的清醒神经活动。大麻气溶胶中包含计数中位直径为 243±39nm 且几何标准偏差为 1.56±0.06 的颗粒。血清 THC 水平随气溶胶质量呈线性增加，峰值为 136±5ng/mL。大麻吸入降低了心率和血压，但促进了焦虑样行为。观察到的 BOLD 激活体积差异将大麻与增加对感官刺激的意识和减少行为唤醒联系起来。量化的生理、行为和神经反应为我们的大麻吸入小鼠模型提供了验证。气溶胶暴露动物模型将有助于揭示慢性大麻使用的健康结果。
