Acute neuroradiological, behavioral, and physiological effects of nose-only exposure to vaporized cannabis in C57BL/6 mice

Inhal Toxicol. 2020 Apr;32(5):200-217. doi: 10.1080/08958378.2020.1767237. Epub 2020 Jun 1.

Abstract

Objective: 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. Materials and Methods: 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.Results and Discussion: 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.Conclusions: 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.

Keywords: Aerosol inhalation; BOLD functional MRI; Cannabis particle profile; Open field test; Serum THC levels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Administration, Intranasal
  • Aerosols
  • Animals
  • Anxiety / chemically induced*
  • Behavior, Animal / drug effects*
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Cannabis*
  • Dronabinol / blood*
  • Humans
  • Male
  • Marijuana Smoking*
  • Mice, Inbred C57BL
  • Models, Animal*
  • Models, Biological
  • Particle Size
  • Respiratory System / metabolism
  • Volatilization

Substances

  • Aerosols
  • Dronabinol