Why is this area of research so important in general?
It’s two-fold. Number one, cardiovascular disease is a global epidemic. It’s the top killer in the United States, accounting for about one in every five deaths. About 19 million people die every year worldwide from some form of cardiovascular disease. And the numbers are going to increase as our population ages.
The average age of the cannabis consumer, in Colorado at least, is nearly 40 (38.5). And since cannabis has been legalized recreationally in Colorado, the group with the largest percentage increase in use are people over 60. It’s gone up almost 500% since legalization in that age group (mostly seeking medicinal aid).
So you have an aging population that’s going to have cardiovascular disease and an older population that wants to use cannabis. And we don’t understand the effects of cannabis on the cardiovascular system.
Some studies, including one highly publicized out of Harvard, suggest the risk of heart attack is several times higher in the hour after smoking marijuana than it would be normally. What can you tell us about that?
That was a prospective study in which anyone that came into the emergency room with an acute myocardial infarction (heart attack) was questioned about their cannabis use, and they found this association. I’ve read the study many times. I’ve read the follow-up study, and it does appear that cannabis can be a trigger for myocardial infarction.
Users (especially those who don’t use cannabis very often) have an increase in heart rate (and sometimes blood pressure) right after smoking that’s transient. It goes back to normal very rapidly.
Studies looking at marijuana smokers raise an important question: Is smoking contributing to the problems or the marijuana?
That’s a great question and one I actually wrote a grant for that has not been funded. We know that smoke itself has harmful chemicals in it. People are currently studying the smoke from cannabis because it doesn’t have the same additive chemicals as tobacco does. But introducing anything into the lungs can be harmful; everyone would agree with that. But we don’t know the safety profiles on edibles compared to smoked or inhaled cannabis yet.
What are the primary receptors cannabinoids act on in the body and what do they do?
THC (tetrahydrocannabinol) acting on the CB1 receptors in the brain seems to be the most significant contributor for the psychoactive effects of cannabis. Other cannabis components acting on CB2 receptors in the periphery – in the rest of your body, not in your brain – have significant effects, such as decreased inflammation and decreased gut motility. CB1 receptors in the periphery can be associated with changes in blood pressure and heart rate directly, stimulating receptors on the heart or the blood vessels.
Mechanistically, we’re still trying to understand all the receptor signaling (as there are other, less well-known cannabinoid receptors) and what it’s stimulating. If we can either harness that beneficial potential or inhibit that potential if it’s adverse, then we can make a safer product.
How does CBD signaling differ from THC?
CBD does not bind directly to the cannabinoid receptors. It seems to bind near the cannabinoid receptors, so they think it modulates cannabinoid signaling. That suggests, in order for CBD to be most effective, there needs to be a little bit of THC there to activate that receptor so CBD can change its effect: turn it up; turn it down. That type of interaction, or the cross talk between THC and CBD, is called the entourage effect. CBD is kind of the entourage for THC, and it modulates the effects.
What is your opinion on the safety of cannabis use?
That depends on a lot of things, including the product. I think that some of the cannabis products sold in stores and dispensaries today are absolutely dangerous. When I looked through the literature when I started getting involved in research, a lot of the primary research that is still referenced today was done in the 1970s, and the average amount of THC in the cannabis at that time was 2.7%. The lowest THC product I could find when going around to dispensaries now, and I’m talking about dry cannabis flower that you smoke, was about 14%. The average in Colorado is nearly 18% THC (dried flower).
However, they also make these things called waxes and shatters. People dab them; it’s called dabbing. You put it in a glass pipe and light it with a butane torch. I liken it to the crack of marijuana. It’s a very concentrated product and can have over 90% THC in it. And I believe those products are dangerous. It's not your Cheech and Chong weed from the ’70s. These products are completely different, and I don’t think we know their safety profile.
Talk about your research.
Trying to do this work on campus is very difficult. If you want to do direct studies, which means you give subjects product, you have to have a DEA (Drug Enforcement Administration) Schedule I license. So I’ve taken a different approach. I’ve been trying to study the receptor signaling on isolated tissues in muscles and in animal models.
I have a research project going on right now in which I fit animal models with instruments that monitor their heart rate, blood pressure and arrythmias for an extended period of time. Then I can give them chemicals that stimulate the cannabinoid receptors directly – so not whole cannabis, not inhaled or edibles, but direct stimulation of different cannabinoid receptors – in order to elucidate mechanisms.
And then I do more in-situ experiments in which I take out cardiac or vascular muscles and put them in a muscle bath. I stimulate the muscles with the cannabinoid receptor agonists to see how it changes contraction and contractility. This gives us direct mechanistic information regarding the effects of cannabinoids on the heart and blood vessels.
What are your goals?
The goal is to understand the direct effects of cannabinoids on the heart and blood vessels. I believe that stimulation of the CB1 receptor causes an increase in contraction of blood vessels and raises blood pressure. I have direct research that demonstrates that, so I’m writing a grant right now that I hope will be funded because I would like to try a cannabinoid receptor inhibitor as a drug that will allow us to treat hypertension.
I think in hypertension (and a lot of diseases), the endocannabinoid system is dysregulated, and you get up-regulation of the CB1 receptors on the blood vessels, so you get increased pressure. So we can use that endocannabinoid system and manipulate it to treat diseases without using cannabis. There’s really a multitude of things that can be done and need to be done. We need more research, and we need more funding.
Note: This interview was edited for clarity and length.
