Cannabis Smoke Impairs Endothelial Function Regardless of Cannabinoid Profile, Study Finds

Exposure to cannabis smoke or cannabis vapor can lead to problems with endothelial function, regardless of the cannabis’ previous drying treatment or its cannabinoid profile, suggests new research presented at the American Heart Association's Scientific Sessions 2022.

In this new work, researchers from the Division of Cardiology at the University of California San Francisco studied rats exposed to cannabis smoke and vape aerosol generated from different lots of cannabis material. They found that exposure to smoke and vapor from all materials led to significant impairments in endothelial function.

This may have important implications for the generalizability of previous research into cannabis and endothelial function, the researchers say, as past studies primarily worked with material from the University of Mississippi, supplied through the National Institute on Drug Abuse (NIDA).

Function impaired regardless of drying or cannabinoid content

For this study, the UCSF researchers used an automated smoking machine with a special nose cone to expose groups of laboratory rats to cannabis smoke or vaporizer aerosol, as if they had been directly using inhalable cannabis.

Five different batches of cannabis material were used in this study. Three batches were sourced from NIDA and included a cannabinoid-depleted “placebo” product, a medium-THC and medium-CBD product that had been dried aggressively under hot air, and a batch of similar composition that had been dried gently. The fourth batch was a high-THC low-CBD product from Biopharmaceutical Research Company (BRC), an alternative Drug Enforcement Administration-approved supplier. Commercially available hemp cigarettes were also included.

“For smoke, we used a cigarette smoking machine that pulls a preset user-defined volume of air through a lit marijuana cigarette over the desired duration (2 seconds per puff) meant to model how humans draw air through cigarettes, and passes the smoke through a tubing to a nose cone,” study author Dr. Matthew L. Springer told Analytical Cannabis.

“For aerosol from a Volcano vaporizer, the Volcano balloon was filled with aerosol as in normal use and then the smoking machine sucked aerosol directly out of the balloon instead of a cigarette, and passed the aerosol to the nose cone in a similar timing to that of the smoke.”

The researchers assessed the rats’ endothelial function using flow-mediated dilation (FMD) tests administered pre-exposure and 10 minutes following exposure.

They found that the rats’ performance in the FMD test was significantly impaired after exposure to cannabis smoke and vapor, regardless of the cannabis material being used. Additionally, no significant recovery of FMD was seen in the rats exposed to cannabis smoke 30 minutes post-exposure.

Based on these results, the researchers say that acute exposure to cannabis smoke or aerosol will impair endothelial function, regardless of the source of the cannabis material, its composition, or its drying regimen.

Real-world material

In recent years, concerns have been raised over the similarities – or rather, the lack thereof – between NIDA cannabis and the types of product being sold in regulated state markets. NIDA cannabis tends to be dried more aggressively, for example. The cannabinoid profile of this cannabis is also rather different; a 2017 study published in Scientific Reports found that the THC content of NIDA material is significantly lower than what is found in commercial cannabis products, while containing between 11-23 times more cannabinol (CBN) than those products.

“The two main criticisms of work that we have done previously with NIDA research marijuana from the University of Mississippi, have been that the UMiss material tops out at about 10% THC, whereas people use cannabis with up to 20% THC these days.” Springer explained. “And [commercial] cannabis is normally dried gently, whereas the UMiss material is dried more aggressively to prevent mold growth in storage.”

Researchers who work with the NIDA-supplied material from UMiss are normally instructed to re-humidify the material to ensure a realistic burning profile. But as Springer says, “once a volatile compound has been lost to aggressive drying techniques, it is gone for good.”

For many years, this single cultivation facility at UMiss was the sole approved source of cannabis for scientific studies in the United States. As a result, some began to question the research done on this material, and whether the findings were generalizable to the products actively being used by consumers.

“The different cannabinoid profile and different drying regimen have been viewed with suspicion as possible reasons that our [past] results may not be relevant to real-world cannabis,” Springer said. “These were reasonable concerns, but our results here show that these concerns are unfounded.”

The importance of endothelial function

The endothelium is a thin membrane lining that covers the walls of blood vessels and the inside of the heart. But the endothelium is more than a simple barrier between tissues and the blood; it is also an endocrine organ capable of releasing substances that control vascular relaxation and contraction and enzymes that control blood clotting and immune function.

“Endothelial function is viewed as a mark of a healthy vessel, in that various intrinsic properties of the cells that make up the blood vessel wall are all working properly,” Springer explained.

“Not only is poor endothelial function correlated with increased risk of coronary heart disease, but directly the reduction of endothelial function is a first step toward atherosclerosis later, and resulting from that, increased future risks of heart attacks and strokes, as well as more specialized problems such as erectile dysfunction.”

The idea that cannabis smoke and vape aerosol impairs endothelial function is then a serious concern. But this discovery is not new.

“It is important to note that we have previously shown that cannabis smoke and cannabis leaf vaporizer aerosol leads to impaired endothelial function, using NIDA research marijuana,” Springer said. “The goal of this study was to show whether this result held true even if the cannabis being used was more like real-world material, i.e., higher THC levels and more gentle drying conditions that don't risk losing as many volatile terpenes.”

Moving forward, Springer and his UCSF colleagues will be examining serum samples taken from the rats that were exposed to the different materials used in this study, to evaluate whether there are any differences in cardiovascular risk between the groups. If so, Springer says that the team will look to identify whether these changes are mediated by the CB1 or CB2 cannabinoid receptors. Another study looking at the differences in endothelial function after secondhand smoke exposure is also currently underway.