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

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
• Cannabis particle profile
• Serum THC levels
• BOLD functional MRI
• Open field test

Authors’ contribution

YMF, CFF, JMO, and CB contributed to the research design; YMF, MJE, JRC, and PK collected experimental data. All Authors contributed to the analysis and interpretation of the experimental results. YMF, MJE, PK, CFF, JMO, and CB drafted and revised the manuscript. All Authors reviewed the manuscript and approved the submission.

Acknowledgements

The authors would like to thank Dongyang Yi, Andrew Szendrey, Chris Le, and Tom Morrison for their distinct efforts in data collection for this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported, in part, by Northeastern University (NEU) Tier 1 Grant to CB, JMO, and CFF, NEU startup funding to CB and JMO, and the NSF GRFP fellowship [1451070] to YMF. The funding sources did not play any role in the design of the study, the acquisition and analysis of the data, nor in the preparation and submission of the manuscript.