Antioxidant compound from soybeans may prevent marijuana-induced blood vessel damage

July 30, 2019

Science Daily/American Heart Association

Marijuana exposure damages cells of the inner lining of blood vessels throughout the heart and vascular system. In studies with human cells and arteries from mice, a compound found in soybeans blocked the damage and may have potential in preventing cardiovascular side effects of marijuana use.

In laboratory tests, a compound found in soybeans blocked damage to the lining of blood vessels in the heart and circulatory system and may someday provide a way to prevent the cardiovascular side effects of recreational and medical marijuana use, according to preliminary research presented at the American Heart Association's Basic Cardiovascular Sciences 2019 Scientific Sessions.

Marijuana is the most widely used illicit drug worldwide and is increasingly being made legal for recreational and medicinal purposes. However, there have been studies that link marijuana smoking to an increased risk of heart attack and stroke.

There can also be cardiovascular side effects, including changes in heart rate and blood pressure, when people take FDA-approved medications containing a synthetic version of delta-9-tetrahydrocannabinol (THC) -- the main compound in marijuana that gives the sensation of being high.

"These medications are prescribed to reduce the nausea and vomiting induced by chemotherapy and to increase appetite in certain people with acquired immune deficiency syndrome," said Tzu-Tan "Thomas" Wei, Ph.D., the study's lead author and assistant professor of pharmacology in the College of Medicine at National Taiwan University in Taipei City. "The goal of our studies is to investigate the mechanisms of marijuana-induced damage and discover new drugs to prevent those side effects."

The effects of THC occur after it binds to one of two cannabinoid receptors (CB1 and CB2) that are found throughout the brain and body and are also acted on by naturally occurring cannabinoids.

In the current study, the researchers used endothelial cells (like those that line blood vessels) derived from the stem cells of five healthy people. Exposing the cells to THC, they found that:

THC exposure induced inflammation and oxidative stress, which are known to affect the inner linings of blood vessels and are associated with the development of heart disease.

Lab techniques that block access to the CB1 receptor by THC eliminated the effects of THC exposure on endothelial cells.

Treatment with JW-1, an antioxidant compound found in soybeans, eliminated the effects of THC exposure.

In addition, the researchers used a laboratory technique called wire myography to examine the response of mouse arteries to THC, finding that JW-1 blocked THC's negative effects on the function of the inner lining.

An earlier attempt to gain health benefits from blocking the CB1 receptor proved problematic.

"Previously, a drug that blocked CB1 was approved in Europe for the treatment of obesity, but it had to be withdrawn because of severe psychiatric side effects," Wei said. "In contrast, as an antioxidant, JW-1 may have neuroprotective effects. Discovering a new way to protect blood vessels without psychiatric side effects would be clinically important with the rapid growth of cannabis use worldwide."

The researchers are currently extending their research by testing cells derived from regular marijuana users and those who smoke both cigarettes and marijuana. In addition, they are looking at the impact of THC along with the other main component of marijuana, cannabidiol.

"Meanwhile, if you have heart disease, talk to your doctor before you use marijuana or one of the synthetic THC-containing medications," Wei said. "Marijuana may cause more severe effects on the cardiovascular system in those with pre-existing heart disease."

https://www.sciencedaily.com/releases/2019/07/190730182430.htm

Bodyguard for the brain: Researchers identify mechanism that seems to protect brain from aging

July 13, 2011

Science Daily/University of Bonn

Researchers from the Universities of Bonn and Mainz have discovered a mechanism that seems to protect the brain from aging. In experiments with mice, they switched off the cannabinoid-1 receptor. As a consequence, the animals showed signs of degeneration -- as seen in people with dementia -- much faster.

The research results are presented in a current issue of the Proceedings of the National Academy of Sciences (PNAS).

Humans are getting older and older, and the number of people with dementia is increasing. The factors controlling degeneration of the brain are still mostly unknown. However, researchers assume that factors such as stress, accumulation of toxic waste products as well as inflammation accelerate aging. But, vice versa, there are also mechanisms that can -- like a bodyguard -- protect the brain from degenerating, or repair defective structures.

Researchers from the Universities of Bonn and Mainz have now discovered a hitherto unknown function of the cannabinoid-1 receptor (CB1). A receptor is a protein that can bind to other substances, triggering a chain of signals. Cannabinoids such as THC -- the active agent in cannabis sativa -- and endocannabinoids formed by the body bind to the CB1 receptors. The existence of this receptor is also the reason for the intoxicating effect of hashish and marijuana.

Not only does the CB1 receptor have an addictive potential, but it also plays a role in the degeneration of the brain. "If we switch off the receptor using gene technology, mouse brains age much faster," said Önder Albayram, principal author of the publication and a doctoral student on the team of Professor Dr. Andreas Zimmer from the Institut für Molekulare Psychiatrie at the University of Bonn. "This means that the CB1 signal system has a protective effect for nerve cells."

Mice prove their brain power in a pool

The researchers studied mice in different age categories -- young six week old animals, middle-aged ones at five months, and those of an advanced age at 12 months. The animals had to master various tasks -- first, they had to find a submerged platform in the pool. Once the mice knew its location, the platform was moved, and the animals had to find it again. This was how the researchers tested how well the rodents learned and remembered.

The animals in which the CB1 receptor had been switched off (the knock-out mice) clearly differed from their kind. "The knock-out mice showed clearly diminished learning and memory capacity," said Privatdozent Dr. Andras Bilkei-Gorzo from Professor Zimmer's team, who led the study. So, animals that did not have the receptor were less successful in their search for the platform. "In addition, they showed a clear loss of nerve cells in the hippocampus," he explained further. This part of the brain is the central area for forming and storing information. In addition, the researchers found inflammation processes in the brain. As the mice advanced in age, the degenerative processes became increasingly noticeable.

Amazing parallels with the human brain

The animals with the intact CB1 receptor, to the contrary, did clearly better with regard to their learning and memory capabilities, as well as the health of their nerve cells. "The root cause of aging is one of the secrets of life," commented Albayram. This study has begun to open the door to solving this enigma. The processes in the mouse brains have a surprising number of parallels with age-related changes in human brains. So, the endocannabinoid system may also present a protective mechanism in the aging of the human brain.

The principal author cautioned, "This will require additional research." The scientists would like to better understand the mechanism by which CB1 receptors protect the brain from inflammation processes. And based on these signal chains, it might then be possible to develop substances for new therapies.

https://www.sciencedaily.com/releases/2011/07/110712093856.htm