News from the Institute of Biomolecular Chemistry in Italy.
In a study published in the journal Molecules, researchers found that cannabimovone (CBM), a rare cannabinoid, can sensitize cells to insulin. CBM thus joins CBD, THC, THCV, and THCA as a potentially promising avenue of research for diabetes prevention.
What is diabetes?
Diabetes is a disease characterized by the presence of too much sugar in the blood. Untreated, it can lead to health issues like heart disease, stroke, and blindness, among others.
The disease takes two forms, named Type 1 diabetes and Type 2 diabetes.
Type 1 happens when the pancreas produces too little insulin, the hormone that regulates the amount of sugar in the blood. This type is fairly rare, generally genetic, and most often shows up during childhood. Treatment generally involves insulin injections to control blood sugar levels.
In Type 2, the body can’t process blood sugar normally, and results from a combination of genetics and lifestyle factors. People with Type 2 either don’t produce enough insulin to regulate sugar in the blood, or their cells are resistant to insulin.
Though now considered safe, administering insulin is often viewed as a last line of defense for these patients. Many people would rather not have to rely on injections to manage their condition, and so exhaust all other treatment options before turning to insulin.
Seeking better treatments
More than 34 million Americans live with Type 2 diabetes—roughly 10% of the population. As of 2017, diabetes cost Americans $327 billion a year in healthcare expenses and reduced productivity. It’s one of the costliest diseases for both individuals and the systems that care for them.
The National Institute of Health spent $1.1 billion on diabetes research in 2015. Given the prevalence and economic impact of the disease, novel treatment options are highly sought after.
Because Type 2 diabetes can be prevented, the first step in managing it often involves changes in diet and exercise. Drug treatments enter the picture when lifestyle changes aren’t cutting it. Those drugs most commonly work by lowering sugar levels, increasing insulin production, or sensitizing cells to insulin. While effective at managing the disease, the drugs can also come with some serious side effects.
Lower levels of insulin resistance
Despite marijuana’s well-known effect of stimulating the munchies, surveys have found that regular cannabis users generally have lower BMIs (body mass index) and smaller waists than those who don’t use cannabis.
Researchers have also associated cannabis use with lower levels of insulin resistance, which is great news for stoners at risk for diabetes. There have been many studies trying to break down exactly what cannabinoids have a positive impact on diabetes and how.
Many cannabinoids, like THC and CBD, can reduce specific types of inflammation associated with obesity and diabetes. Small doses of THC-V in humans have been shown to reduce blood sugar levels as well as increase insulin production.
THC-A, THC, and CBD have all shown promise in increasing insulin sensitization and decreasing blood sugar levels via activation of a specific receptor called PPARɣ. Cannabimovone, the focus of the Italian research, could potentially be an even more attractive option for PPARɣ activation.
PPARɣ is a receptor that plays a key role in regulating lipid and glucose metabolism. It’s widely distributed in fat tissues and increases insulin sensitivity in cells in a number of ways. Because of this, it’s been the target of many drugs developed to treat Type 2 diabetes. The largest group of these drugs, called thiazolidinediones (TZDs), work by sensitizing cells to insulin.
TZDs can be effective for long-term treatment, and, arguably, have a better treatment profile than more popular diabetes treatments. Unfortunately their side effects, including increased risk of heart attack and osteoporosis, have led to a decrease in their use. Because those side effects are associated with the potency at which they bind to PPARɣ, diabetes researchers are interested in discovering or developing a compound that is a less-potent activator of PPARɣ. They want to keep the positive insulin-sensitizing effects, while minimizing the negative effects by striking a balance in how the receptor is activated. That’s where cannabimovone could potentially come in.
What is cannabimovone (CBM)?
Cannabimovone (CBM) is a rare cannabinoid first isolated from a variety of Italian hemp Carmagnola in 2010. While CBM is rare in most strains of the plant, researchers have had little trouble synthesizing the molecule in the lab.
The Italians were interested in THC and CBD’s insulin-sensitizing effects and wondered if there were any other cannabinoids that might do the same with fewer side effects. Using computer modeling, they searched their cannabinoid database, and there it was: CBM fit into the model.
Seeking a narrow target
Before this, the only known biological target for CBM was TRPV1, the receptor that allows you to feel the heat of capsaicin, the active component in hot chili peppers. While it’s possible that there are many more biological targets for CBM, researchers are very interested in finding compounds that have a limited number of targets in the body. Many unwanted side effects from drugs come from interactions outside of those specifically targeted.
None of this matters, of course, if CBM kills healthy cells. That would mean CBM was toxic, and exclude it from further development. The Italian team evaluated how toxic CBM was by exposing a bunch of kidney cells in vitro to various concentrations of the compound. The cells did just fine at every concentration level, meaning that CBM passed its first test on its path towards potentially becoming a therapeutic treatment.
A long way to go still
The next step was figuring out how CBM compared to a commonly-used diabetes drug. On that front: So far, so good. CBM sensitized cells just as well as the pharmaceutical option, while also encouraging the expression of PPARɣ—something the pharma drug did not do.
Many in vitro studies show promise—but the human body is far more complex than a test tube.
There’s a long way to go before CBM becomes a treatment for diabetes, if it proves to be safe and effective. CBM hasn’t even been tested in lab animals yet, let alone humans. But the Italian study sheds a little more light on the potential uses of rare cannabinoids we’re just beginning to discover and understand.