Cannabis consumption and cardiovascular risk: the mechanism elucidated

Regular cannabis use — more than once a month — increases the risk of cardiovascular disease. A new publication has highlighted the molecular mechanism involved in this biological process. THC increases cardiovascular risk via a receptor located on blood vessels called CB1.

It is already known and recognized that the cannabis increases consumers’ risk of cardiovascular disease. In contrast, little is properly understood regarding the underlying pathophysiological mechanisms. A research team wanted to know more about the link between exposure to the psychoactive substance of cannabis, the THC or tetrahydrocannabinol, and the cardiovascular risk for patients. Their work has been published in the prestigious journal Cell April 29, 2022.

An antagonist derived from soy, genistein

Smoking cannabis activates the production of cytokines pro-inflammatories implicated in the occurrence of cardiovascular illnesses. In addition, THC has the ability to bind to the receptor cannabinoid 1 (CB1/CNR1) located on blood vessels. To better understand the underlying mechanisms, the authors identified a antagonist of the CB1 receptor: genistein, an isoflavone from the soy.

Blocking the CB1 receptor in a cellular model

A cellular model mimicking theinflammation and the oxidative stress induced by exposure to THC was used. The NF-κB signaling pathway is involved. To study the effects of CB1 receptor silencing, three systems were used: RNA silent, theinterference Crisp and the molecule genistein antagonist. The silent RNA technique makes it possible to stop the translation of RNA by protein and thus extinguish the expression of a embarrassed, here that of the CB1 receptor. Crispr interference cuts a piece ofDNA to prevent his transcription into RNA and then its translation into protein. The use of antagonist molecules of a receptor, here genistein, makes it possible to block the underlying signaling pathways. In all three cases, the extinction of the CB1 receptor has attenuated the deleterious effects of THC in the cellular model.

Blocking the CB1 receptor in a mouse model

To go further, the authors used a model murine. Mice exposed to THC from cannabis were developing larger patches ofatherosclerosis compared to control mice. Mice that received THC then either obtained genistein or not. This made it possible to reduce the plaques ofatherosclerosis induced by THC and to limit the presence of THC in the central nervous system. These results confirm that the cardiovascular risk of THC is indeed linked to the activity of the CB1 receptor.

While many countries have legalized the use of recreational cannabis or plan to do soand that others are studying the use of medical cannabisthis work provides elements calling for caution.