Nasal Accumulation and Metabolism of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration in an Adolescent Rat Model

Authors

Alexa Torrens, University of California
Christina M Ruiz, University of California
Maricela X Martinez, University of California
Alex Mabou Tagne, University of California
Pritam Roy, University of Illinois at Urbana-Champaign
Dakota Grimes, University of California
Faizy Ahmed, University of California
Valeria Lallai, University of California
Victoria Inshishian, University of California
Malia Bautista, University of California
Yen-Chu Chen, University of California
Marilyn A. Huestis, Thomas Jefferson UniversityFollow
Aditi Das, University of California
Christie D Fowler, University of California
Stephen V Mahler, University of California
Daniele Piomelli, University of California

Document Type

Article

Publication Date

1-1-2023

Comments

This article is the author’s final published version in Pharmacological Research, Volume 187, January 2023, Article number 106600.

The published version is available at https://doi.org/10.1016/j.phrs.2022.106600. Copyright © Torrens et al.

Abstract

Passive aerosol exposure to Δ9-tetrahydrocannabinol (THC) in laboratory animals results in faster onset of action and less extensive liver metabolism compared to most other administration routes and might thus provide an ecologically relevant model of human cannabis inhalation. Previous studies have, however, overlooked the possibility that rodents, as obligate nose breathers, may accumulate aerosolized THC in the nasal cavity, from where the drug might directly diffuse to the brain. To test this, we administered THC (ten 5-s puffs of 100 mg/mL of THC) to adolescent (31-day-old) Sprague-Dawley rats of both sexes. We used liquid chromatography/tandem mass spectrometry to quantify the drug and its first-pass metabolites – 11-hydroxy-Δ9-THC (11-OH-THC) and 11-nor-9-carboxy-Δ9-THC (11-COOH-THC) – in nasal mucosa, lungs, plasma, and brain (olfactory bulb and cerebellum) at various time points after exposure. Apparent maximal THC concentration and area under the curve were ∼5 times higher in nasal mucosa than in lungs and 50–80 times higher than in plasma. Concentrations of 11-OH-THC were also greater in nasal mucosa and lungs than other tissues, whereas 11-COOH-THC was consistently undetectable. Experiments with microsomal preparations confirmed local metabolism of THC into 11-OH-THC (not 11-COOH-THC) in nasal mucosa and lungs. Finally, whole-body exposure to THC deposited substantial amounts of THC (∼150 mg/g) on fur but suppressed post-exposure grooming in rats of both sexes. The results indicate that THC absorption and metabolism in nasal mucosa and lungs, but probably not gastrointestinal tract, contribute to the pharmacological effects of aerosolized THC in male and female rats.

Recommended Citation

Torrens, Alexa; Ruiz, Christina M; Martinez, Maricela X; Tagne, Alex Mabou; Roy, Pritam; Grimes, Dakota; Ahmed, Faizy; Lallai, Valeria; Inshishian, Victoria; Bautista, Malia; Chen, Yen-Chu; Huestis, Marilyn A.; Das, Aditi; Fowler, Christie D; Mahler, Stephen V; and Piomelli, Daniele, "Nasal Accumulation and Metabolism of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration in an Adolescent Rat Model" (2023). Institute of Emerging Health Professions Faculty Papers. Paper 20.
https://jdc.jefferson.edu/iehpfp/20

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Language

English