Dr. Oakes and Dr. Bellini are PIs for the Integrated Cardiovascular and Pulmonary team at Northeastern University. Their research focuses on the pulmonary and cardiovascular consequences of inhaled cannabis. This group is at the forefront of preclinical respiratory research for cannabis. We were lucky enough to sit down with them and get their thoughts on the current state and future of cannabis-related cardiopulmonary research.
There are several preclinical cannabis groups in the USA and Canada (e.g. Virginia Commonwealth University in Richmond, Wilfrid Laurier University in Waterloo, ON, and the University of Florida in Gainesville). Presently, preclinical cannabis research is mainly focused on neurophysiology, behavioral effects, and aerosol characterization. Many studies focus on the acute effects of cannabis smoke, and future studies are required to deepen our understanding of the chronic effects of cannabis inhalation.
Surprisingly, one area that needs further exploration includes the respiratory and cardio effects in preclinical cannabis exposure models, along with the overall long-term effects of cannabis use.
More research is absolutely needed for developing mouse models of inhaled cannabis exposure to better understand the underlying mechanisms of the endocannabinoid system.
The licensing process is extremely difficult, getting plant materials requires as much work as a mini-grant proposal. Once licensed, the cannabis must be kept under high security and requires multiple people to maintain and control the inventory.
Currently Novartis is the primary group supplying cannabis in the US.
We standardized our protocol by using the inExpose to generate a reproducible puff shape and size. We decided to deliver three 3-second puffs of cannabis smoke from the tabletop Volcano® vaporizer, followed by 20 s of fresh air. The vaporized was packed with an equal density of leaf each time. The three 3-second puffs were chosen to balance desired delivered aerosol concentration while providing the mice with breaks of fresh air.
Another important factor for standardization includes correlating the input weighed mass with the aerosolized mass.
Correlation of the input mass to the THC in the blood is also essential. The THC concentration is measured immediately after exposure by cardiac puncture of the right ventricle, as the THC half-life in mice is extremely short, much shorter than cotinine, which is the biomarker from cigarette smoke. Cardiac puncture is preferred over the trunk blood method, as it is more easily reproducible in mice.
Establishing a target delivery dose concentration range is another key factor for standardization. This is very difficult to achieve, even with the cotinine target for cigarettes. In clinical studies with humans, a 750mg dose is required to yield a “high”. We set our pre-clinical target for mice at 300-450mg.
It is also crucial to report the supplier and the concentration of cannabis, including the THC content and strain.
Some factors we look to include
How cannabis is delivered will heavily change the dosing and effects.
This area of research is becoming increasingly important. According to the literature, smoking joints is still the most common route of cannabis inhalation, however most of these statistics and literature were published prior to this year’s spike in THC pods. Following the spike, NHLBI encouraged people who are studying tobacco to shift their focus to vaping.
Additionally, there is a misconception among the public that if something is food safe, like the propylene glycol and vegetable glycerin in vape e-liquids, it’s safe to inhale. However, it’s evident that this isn’t the case.
Cannabis use in a clinical setting is quantified by joints per day, however the size and constituents of the joint are not taken into consideration at all. Variabilities in joint constituents includes black market or regulated cannabis, smoked with or without a filter, or the addition of tobacco. It’s very difficult to take these variabilities into consideration in a preclinical or clinical context.
The nose-only method allows for control of the exposure route, as it limits the ingestion opportunities that are present with whole body exposure. This results in a more translatable model, including better dosimetry calculations.
For our chronic cannabis studies, we plan on using the flexiVent to obtain lung function measurements including detailed and overall respiratory mechanics and lung volumes.
Dr. Jessica Oakes is an Assistant Professor in the Department of Bioengineering at Northeastern University. Her research area is quite diverse and includes pulmonary physiology, e-cigarettes, marijuana, computational biomechanics, MRI, and multi-scale airflow and aerosol modeling.
Dr. Chiara Bellini is also an Assistant Professor in the Department of Bioengineering at Northeastern University. Her primary research focus is on diseases of the cardiovascular system, effects of cell mediated growth and remodeling process on tissue and organ mechanics, and impact of inhaled aerosols (e.g. e-cigarettes, marijuana, fore smoke) on the vascular system.
Check out their recently published paper on the effects of nose-only exposure to vaporized cannabis in mice here:
Farra, Y. M., Eden, M. J., Coleman, J. R., Kulkarni, P., Ferris, C. F., Oakes, J. M., & Bellini, C. (2020). Acute neuroradiological, behavioral, and physiological effects of nose-only exposure to vaporized cannabis in C57BL/6 mice. Inhalation Toxicology, 1-18.