Can cannabis help with type 2 diabetes mellitus? Research on the endocannabinoid system and diabetes shows a strong connection between an overactive endocannabinoid system and the incidence of diabetes and obesity, and using cannabinoids tends to stimulate this system. Despite this, study after study shows that cannabis users are less likely to experience diabetes or obesity than those who don’t use the drug. In addition studies on particular cannabinoids like THCV or CBD show these isolated compounds show promise for treating diabetes and its causes.
The Endocannabinoid System
Cannabis’ effects are primarily caused by the way it interacts with the endocannabinoid system, an important system in the human body that maintains internal balance. This system is made up of endocannabinoids (natural chemical molecules in the body), endocannabinoid receptors (which endocannabinoids bind to and activate), and enzymes (which clear endocannabinoids from the body). This crucial system maintains homeostasis for many functions like sleep, pain, energy metabolism, memory, inflammation, hunger, and mood.
When working normally, endocannabinoids bind to endocannabinoid receptors to activate a variety of different effects like reducing or increasing appetite, pain signaling, energy or hunger. Interestingly, the cannabinoids in cannabis, such as THC and CBD are also able to activate these receptors in a similar way to our internal endocannabinoids, and thus they can also cause this wide array of effects.
When it comes to diabetes mellitus, the endocannabinoid system also plays in important role. Specifically, an overactive endocannabinoid system can actually contribute to diabetes’ development in a number of ways. For one thing, obesity is a big risk factor for developing type 2 diabetes, and activation of the CB1 receptors is known for spurring on food intake, increasing appetite and a preference for highly palatable foods (such as fatty or sweet snacks). It can also lead to increased fat storage as it signals the body to reserve energy and store calories for later. In times when food supplies are low, which is common in our evolutionary history, this system is key for encouraging food intake when it is available and storing the energy for later on. But in diabetes, this system becomes dysregulated.
Unsurprisingly, we see overactive endocannabinoid systems in patients with abdominal obesity. To add to that, drugs that block CB1 activation have been shown to reduce food intake and weight, suggesting that too much CB1 activation may be related to the development of obesity.
In addition to leading to obesity, a dysregulated endocannabinoid system with too much CB1 activation can also negatively impact insulin sensitivity and glucose metabolism, ultimately increasing insulin sensitivity and creating the conditions for type 2 diabetes. Too much CB1 signaling may also be a factor in diabetic neuropathy, causing oxidative and inflammatory effects.
In clinical trials, a drug called rimonabant was found to be effective at reducing some of these CB1 related effects by blocking CB1 activity. It reduced body weight, and helped with lipid and glucose control. Unfortunately, it also led to severe psychological adverse effects like depression, anxiety and suicidal ideation so it was withdrawn from the market.
Later drugs were developed to block CB1 activity in the body but not in the central nervous system. These didn’t have the psychological side effects and did improve glucose tolerance, and insulin sensitivity, but didn’t reduce weight or food intake the way rimonabant did. Still, these new CB1 blockers give hope that blocking CB1 could be a viable treatment for diabetes and obesity.
While too much CB1 activity can be a problem, not enough CB2 activity can also negatively impact sufferers of diabetes. CB2 receptor activity actually seems to play a protective role in diabetic neuropathy, a common symptom of uncontrolled diabetes. Therefore, CB2 seems to counter the harmful effects from CB1 activity. Unfortunately, in patients with diabetes, this CB2 activity is diminished, furthering the imbalance. CB2 activation has also been found to provide an especially protective function for the kidneys, where we also see impaired CB2 receptors and overactive CB1 receptors. Diabetic nephropathy, or disease of the kidney secondary to diabetes is unfortunately all too common, and the therapeutic benefit of CB2 may be a promising therapeutic target in the future.
On the other hand, CB2 activation isn’t always beneficial. Studies have shown that CB2 agonists may actually potentiate obesity-associated inflammation, insulin resistance and hepatic steatosis. And deficiencies in CB2 receptors can improve insulin sensitivity. CB2 receptor overexpression can even induce hyperglycemia in adult mice.
There are so many ways that the ECS can impact the development and progression of diabetes. So unsurprisingly, it has been targeted by scientists looking for a new diabetes treatment. Cannabinoids from cannabis are one notable way to interact with and modulate this important system.
Can cannabis help with type 2 diabetes? While the research is still somewhat conflicted, there is evidence suggesting that cannabis can provide a protective effect against this condition.
Since cannabis is known for activating CB1, and we’ve seen how CB1 activity can have a negative impact on diabetes, many researchers expected that cannabis use would be tied to increased levels of obesity and diabetes. But surprisingly, this isn’t what the research found. Multiple large scale studies show the exact opposite. Individuals who chronically use cannabis are statistically less likely to be diabetic or obese.
This has left researchers puzzled. Why would cannabis protect against obesity and diabetes when CB1 activation seems to cause so many problems?
One suggestion is that cannabis, known for being an antiinflammatory plant, might be fighting against the low grade inflammation in diabetes.
Research has also found that cannabis users tend to have increased insulin sensitivity and lower fasting insulin levels. One study found that cannabis users’ insulin resistance levels were a full 17% lower on average than those who didn’t use cannabis, and fasting insulin levels were 16% lower. In this same study, researchers also noticed that cannabis use was associated with a smaller waist size.
These studies focus on cannabis in general, which suggests many respondents were consuming THC (cannabis’ most plentiful and popular active ingredient), in addition to lower levels of other cannabinoids and terpenes. So regular THC-heavy cannabis use may actually play a protective role in diabetes. Still, other studies have looked in depth at some different cannabinoids to find out whether they might be particularly helpful for diabetes.
For example, some researchers say CBD may play a role in treating diabetes. Studies have shown benefits for diabetes from using CBD, such as reducing retinopathy, cardiomyopathy and neuropathy, likely do to its antioxidant, anti‐inflammatory and tissue protective effects. Other studies have demonstrated CBD can improve mitochondrial function, reduce obesity, and protect against diabetic complications.
THCV is another cannabinoid that researchers are looking at as a diabetes treatment. In one
2016 study, people with type 2 diabetes who were not taking insulin were treated with this cannabinoid. The researchers found that THCV use caused significantly lower fasting blood glucose, improved production of insulin and increased levels of a protein that regulates blood sugar. They concluded that THCV could be a new therapeutic agent for glycemic control in those with type 2 diabetes.
A large pharmaceutical company with a CBD product called Epidiolex which is FDA approved for certain types of epilepsy, GW pharmaceuticals also believes THCV could be a helpful diabetes solution. GW is currently testing a THCV based medication for diabetes which may reduce fasting plasma glucose levels, increased fasting insulin, and increased insulin sensitivity, among other diabetes fighting effects.
Still, while the evidence points towards cannabis’ positive effects on diabetes – scientists caution there is no consensus as to why the clinical data conflicts with our understanding of how the ECS affects diabetes. Perhaps isolating individual components of the cannabis plant or certain combinations of different components may lead to an answer. Researchers agree that more research is needed in order to find out.
Potential side effects of cannabis use
Despite the positive potential for cannabis and diabetes, the side effects of cannabis can be a deterrent for some. Generally, cannabis can cause a wide array of side effects such as a temporary cognitive deficits, short term memory loss, anxiety or paranoia, impaired coordination and respiratory symptoms (such as coughing and increased phlegm production) when inhaled.
It can also have longer lasting risk factors for some — such as increasing risk of psychosis for schizophrenic patients, or increasing the risk of certain cardiac conditions. For a minority of patients, it can lead to addiction.
With diabetes, two side effects that might be particularly challenging are dry mouth (which is also associated with diabetes) and the appetite-inducing effects of cannabis (which can lead to craving foods that diabetic patients should avoid).
This article was originally published on The Cannigma, and shared here with permission.