Scientists may be able to manipulate the human endocannabinoid system to create therapeutic cardiovascular benefits, and according to a review by the American Heart Association, medical cannabis could be a tool to help fight heart disease.

The review, “Cannabinoids, the Heart of the Matter,” published July 17, 2018, in the Journal of the American Heart Association, suggests that cannabinoids -- compounds derived from cannabis -- should be studied as a treatment for certain heart conditions.

“We wanted to bring attention to the potential life-saving applications of cannabinoids for the treatment of heart conditions through the manipulation of specific cannabinoid-sensitive receptors, and the review article format allowed us to thoroughly and rigorously examine all the published data from many individual studies in one article,” Andrea Small-Howard, Ph.D, co-author of the review article and chief science officer for Las Vegas-based GB Sciences, Inc., a cannabis company involved with biopharmaceutical research and development, wrote in an email.

“The human body has cannabinoid receptors, which are specific proteins embedded in the membranes of different cell types,” Small-Howard said. “The binding of cannabinoids to these cannabinoid receptors triggers specific reactions. Manipulating the reactions at these cannabinoid-sensitive receptors with externally-administered cannabinoids could possibly help people with specific heart conditions.”

For example, cannabinoid receptor type 1 (CB1) is known as a regulator of cellular regeneration and cell death, she said. CB1 can cause either of these outcomes depending on the signals it receives – particularly from internally produced cannabinoids or externally-ingested cannabinoids.

“On the one hand, CB1 activity is associated with heart failure and the death of heart cells in heart failure,” she said. “However, CB1 activity can be changed by administering different levels and types of cannabinoids. This makes CB1 an important target for developing heart disease therapies due to CB1's involvement in multiple disease processes, including coronary artery disease, heart attacks, high blood pressure and heart failure.”

Another receptor known as TRPV1 -- or the transient receptor potential cation channel subfamily V, member 1 -- is involved in sensing pain, heat, and chemical and mechanical stimuli. In the heart, TRPV1 receptors in certain spinal nerves sense both pain and damage to the heart. TRPV1 is also implicated in cardiac hypertrophy, or an enlarged heart, which happens as heart disease progresses, she said.

“Studies by our co-authors have demonstrated that manipulating TRPV1 receptors can shrink the enlarged hearts in a rodent model of cardiac hypertrophy,” Small-Howard said. “The treatment can also be used to prevent this advanced symptom of heart disease.”

Using cannabinoids as a therapy for heart conditions comes with challenges, including as-yet-unknown side effects throughout the body. Researchers also have safety concerns about using synthetic cannabinoids, and struggle with obtaining active ingredients from plant sources, according to Small-Howard.

“The delivery method is critical to the success of these programs,” she said. “The levels of the cannabinoids in the body need to be tightly controlled over time – and space – to treat heart diseases. It seems unlikely that the full benefits of cannabinoids for the heart will be obtained using dispensary-level administration like smoking or edibles. True pharmacological delivery systems will likely be necessary to achieve the control required over the dosing for heart disease patients.”

She said additional research is needed to learn more about how cannabinoid-sensitive receptors contribute to heart disease processes, as well as controlled clinical trials on the use of cannabis plant extracts.

Dr. Joe Goldstrich, a retired cardiologist who is now on the board of the Society of Cannabis Clinicians, said the review article didn't go into great detail about the cannabinoid he believes holds the true potential benefits for the heart – cannabidiol (CBD). He said CBD has antioxidant and anti-inflammatory properties, which could be significant in treating atherosclerosis, an inflammatory process by which plaque accumulates in the arteries.

Goldstrich said CBD may be useful to the heart, “but they don't really deal with that [in the review]. That is one of the things that I see as the most promising uses of cannabinoids in the treatment of cardiovascular disease, CBD.” On the other hand, the cannabinoid THC should be treated with extreme caution in heart patients, he said.

“If you were going to find a chink in the armor … they frequently say cannabis has never killed anybody,” Goldstrich said. “Well, that may not be true.”

He said THC has the potential to trigger an arrhythmia or irregular heartbeat, and increase or decrease blood pressure. And in someone with cardiovascular disease, a drop in blood pressure could cause a heart attack, he added. “It's a powerful agent when it comes to the cardiovascular system and you have to be very cautious and careful,” he said.

Goldstrich said much more research is needed to discover the medical potential of cannabis. But for that to happen, marijuana's federal status as a Schedule I controlled substance with no potential medical value has to change, he said.

“We need to de-schedule so we can do clinical trials and meaningful research,” he said. “As long as we have this absurd scheduling of cannabis as Schedule I, we're living the lie and it's an obstruction. People who might benefit from the medicine are not able to because we don't have the needed research.”