Development of a Preclinical Inhalation Model to Test Vaporized Cannabis Distillates

Summary

Cannabis distillate vape cartridges are battery-powered devices that aerosolize extracts containing high concentrations of cannabinoids. The absence of established preclinical models for these products creates challenges in studying their physiological effects. To address this gap, a standardized preclinical inhalation murine model for vaporized cannabis distillates has been developed.

Abstract

Despite their growing popularity, cannabis vape products remain understudied. Cannabis vape cartridges are used with battery-powered devices that aerosolize cannabis flower extracts containing high concentrations of cannabinoids such as THC. These types of products are commonly known as cannabis distillates. The potency of these products presents challenges in establishing effective dosing for preclinical studies. Currently, there are no established, standardized preclinical models for testing the safety and efficacy of these products in ways analogous to human use patterns. Thus, the in vivo cannabis distillate exposure regime required to achieve physiologically relevant doses in comparison to what is achieved in humans remains undetermined. To address this gap, a standardized preclinical murine model for inhalation of vaporized cannabis distillates has been developed using a computer-controlled delivery system. This protocol details procedures to administer cannabis vape distillates using a regimented puff topography to mice by a nose-only exposure tower. Methods to monitor mouse behavioral outcomes post-exposure and the utilization of a semi-quantitative ELISA to confirm THC delivery into the systemic circulation are also provided. This protocol will allow for the investigation of the pulmonary and systemic responses to cannabis vape distillate products by researchers interested in exploring the impact of cannabis vaping using real-world delivery protocols, thereby providing an opportunity for rigorous safety and therapeutic evaluation.

Introduction

With the legalization of cannabis occurring throughout the world, cannabis use is increasing. Significant changes in the retail cannabis market are not only boosting accessibility, but these changes are also driving the development and production of new types of cannabis products for consumption¹. Vaporizers, which heat cannabis products without combustion, are becoming an increasingly popular consumption method^2,3. Vaporizers include cannabis vape cartridges that utilize e-cigarette technology to heat and aerosolize cannabis distillates. These distillates are extracted from the Can....

Protocol

The procedures below were approved by the McGill University Institutional Animal Care Committee (Protocol Number 8087) in accordance with the guidelines of the Canadian Council on Animal Care (CCAC).

1. Equipment preparation

NOTE: The following protocol applies to the SCIREQ inExpose system supported by the flexiWare 8 software.

1. Ensure the correct assembly of all components of the system to resemble the example shown in Figure 1A. Ensure there is a closed tube inserted into the buffer chamber of the puffing pump to prevent system leakage, as shown in

Results

The initial objective was to determine an exposure regime that could deliver physiologically relevant levels of THC to the blood in comparison to humans. Thus, a key component to selecting exposure parameters was to use features that mimicked human use patterns^20,21. Male and female C57BL/6 mice were exposed to a Pineapple Express Pax Era Pod containing ~85% THC for 10 min, 20 min, and 30 min at 1 puff/min with a 78 mL puff volume.......

Discussion

Cannabis distillate vape products contain high concentrations of cannabinoids, including up to 85% THC for the product utilized in this protocol. As the cannabis flower currently reaches only as high as 36% THC⁷, the potency of cannabis distillate vape products provides challenges when developing a model for inhalation exposure. The objective was to determine an exposure regime that could effectively deliver relevant doses of cannabinoids to mice without causing adverse effects from excessive THC .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
2,2,2-Tribromoethanol	Sigma-Aldrich	T48402-5G	Avertin
inExpose	SCIREQ	sales@scireq.com	www.scireq.com
Microtainer Serum Separator Tubes	BD	365967
Pax Era Vape Pen	PAX		Purchased from Ontario Cannabis Store
Pineapple Express Pax Pod	Good Supply		Purchased from Ontario Cannabis Store
SoftRestraints	SCIREQ	IX-XN1-SR-AL	www.scireq.com
THC Forensic ELISA Kit	Neogen	131019