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Metabolic and respiratory alterations following acute exposure to high-THC and high-CBD cannabis smoke in female mice

Ario Safaeian, Kaylen M. Young, John G. Howland, Catherine M. Ivy

Journal of Cannabis Research August 26, 2026 DOI: 10.1186/s42238-026-00490-0 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled laboratory experiment in mice Peer reviewed
Population Mice
Interventions Placebo smoke high-CBD cannabis smoke
Duration 20-minute smoke treatment; 20-minute normoxia and 20-minute acute hypoxia challenges before and after treatment
Measures Plethysmography, respirometry, rectal temperature
Topics Cannabis CBD
Key findings Body temperature dropped after placebo, high-CBD, and high-THC smoke, with placebo and high-CBD smoke appearing to add to the high-THC effect, while increases in total ventilation and tidal volume were mainly attributable to THC. Recovery of body temperature, breathing, and metabolism after acute hypoxia was unaffected by CBD exposure.

Abstract

Abstract Background Cannabis use has increased in recent years due to legalization. Smoking cannabis leads to inhalation of ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in addition to other particles and gas in the smoke matrix as a result of combustion. The effect of THC on breathing pattern and metabolism has been characterized, but the influence of CBD and the smoke matrix on breathing pattern and metabolism has not been documented. In our study, we investigated the effects of placebo smoke, high-CBD smoke, and high-THC smoke on body temperature, breathing pattern, and metabolism. We also assessed whether there were latent effects of cannabidiol exposure on respiratory control and recovery dynamics by using an acute hypoxia breathing challenge.

Methods: Acute hypoxia challenges were conducted on each mouse before and after smoke treatment (20 min), with mice exposed to normoxia (21% O 2 ) and acute hypoxia (16% O 2 ) for 20 min each. Plethysmography and respirometry were used to assess breathing pattern and metabolism, with rectal temperature measured at the beginning and end of each hypoxia challenge.

Results: We found that body temperature depression was influenced by all treatments, suggesting that placebo smoke and high-CBD smoke have additive effects on top of the high-THC smoke treatment. In contrast, the increases in total ventilation and tidal volume with high-THC smoke appeared to be predominantly modulated by high-THC smoke, with a small effect of placebo smoke. We also found that body temperature, breathing pattern, and metabolism recovery was not impacted by cannabidiol exposure, as these measurements returned to similar levels as in the control mice.

Conclusions: Not all physiological responses of high-THC smoke were strictly due to THC itself, as the smoke matrix and CBD also contribute.