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Can Cannabis Help Type 2 Diabetes? Overview 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. Cannabis Treatment 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 statiscally 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. Side effects 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). About Type 2 Diabetes Overview Type 2 diabetes (DM2), also called adult onset diabetes or insulin resistant diabetes, is the most common type of diabetes, accounting for around 90% of all diabetes cases. Some 422 million people worldwide are diagnosed with diabetes, including 4.7 million people in the UK, which makes up for 10% of people over 40. In the US, it’s estimated that over 30 million people had diabetes in 2017, and 90-95% of them have type 2 diabetes. When you have diabetes, it means that your body is either not producing enough insulin, or is resisting the effects of insulin. Insulin is a hormone that your body produces naturally in order to control glucose levels in your bloodstream and move glucose into the cells, where it is used to produce energy, among other roles. If you have type 2 diabetes, glucose builds up in your bloodstream which, in excess, can have harmful consequences. As a matter of fact, diabetes is one of the biggest risk factors for what we most commonly die from in the western world; diseases like heart attacks, strokes, and even cancer. Unfortunately, uncontrolled diabetes is one of the biggest burdens in modern society and the problem is only growing. Symptoms One of the biggest problems with diabetes is that it is a “silent killer,” meaning it does not produce many symptoms, and can go undiagnosed for years. Once diagnosed, since people don’t feel symptoms at the earliest stages of the disease, they feel less of a need to treat it. The most common early symptoms for type 2 diabetes are: Feeling thirsty most of the time Needing to urinate unusually frequently Tiredness, fatigue, and a lack of energy As the disease progresses and the nerves become more affected, people begin to experience numbness, tingling and pain in their feet and then throughout their extremities. Furthermore, when people have diabetes their ability to heal is significantly impacted and they can have open wounds that never heal. As people begin to lose sensation in their toes and fingers, and cuts don’t heal, they can develop serious infections and may even need amputations of toes or fingers. Later onset symptoms of type 2 diabetes include: Numbness, tingling and pain in the extremities, starting with the toes Blurry vision which can lead to blindness Slower recovery from injury Wounds and infections that fail to heal Erectile dysfunction Complications Severe type 2 diabetes, or type 2 diabetes that is poorly managed, can quickly lead to serious and life-threatening complications. The complications of type 2 diabetes include: Diabetic ketoacidosis, when your body breaks down fat cells because it can’t get enough glucose, producing toxic acids called ketones. This can be acutely life threatening and requires hospitalization, often in the intensive care unit. Hyperglycemic hyperosmolar nonketotic syndrome (HHNS), which is when your blood sugar is so high that your blood turns thick and syrupy, and cannot move normally through your body. Hypoglycemia, or low blood sugar, causing dizziness, headaches, blurry vision, and confusion Loss of vision and total blindness Reduced circulation to the legs and extremities, which leads to the need to amputate the legs Kidney failure Infertility Digestive issues General difficulty recovering from infections and wounds Heart failure Stroke Cognitive decline Other serious and life threatening conditions Diagnosis If your doctor suspects that you might have type 2 diabetes, they will order a simple blood test to check your blood sugar level. Sugar in the blood can be checked easily, and to diagnose diabetes the doctor will want to see consistently elevated glucose levels. In addition, a test called Hemoglobin A1C can actually measure the average glucose level over 3 months, which is much better and diagnosing and monitoring overall sugar levels. The blood tests used to confirm type 2 diabetes are: HgB A1C, which is an average reading of blood glucose levels across the past 2 or 3 months. Fasting plasma glucose, which tests your blood sugar level after you haven’t eaten or drunk anything except water for at least 8 hours. Oral glucose tolerance test (OGTT), which tests your blood sugar levels before and 2 hours after you drink a sweet drink, in order to see how your body responds to the high sugar intake. Causes The primary cause of type 2 diabetes is that your body is resistant to insulin or is not producing enough insulin. Its cause is multifactorial, meaning it is a combination of genetic and multifactorial causes. Doctors and scientists agree about certain risk factors that raise the likelihood that you’ll develop insulin resistance, but people can also develop type 2 diabetes without the presence of any of these risk factors. Others have many risk factors, but still don’t develop insulin resistance. Type 2 diabetes is on the rise around the world, thanks to a global increase in calorie intake, particularly from unhealthy processed foods, worldwide drops in regular exercise and activity levels, and general changes in regional diets that replace healthy eating with empty calories and junk food. The risk factors for developing type 2 diabetes are: Being overweight or obese is the main risk factor for developing type 2 diabetes. The connection between obesity and type 2 diabetes has been well known for many years. Inactivity. When you live an active life, you burn up excess glucose as energy, so it doesn’t sit around in your bloodstream. The opposite is true if you lead a sedentary lifestyle. Excess stomach fat. Carrying a lot of excess fat around your abdomen (the “apple” body shape) rather than elsewhere on your body. Race. People with black, hispanic, American Indian, or Asian-American heritage are more likely to develop type 2 diabetes. Age. The older you are, the higher your risk. However, type 2 diabetes is now growing among children and youth, too. Family history. If you have a parent or sibling who has type 2 diabetes, your risk of developing it increases. Gestational diabetes. Women who developed gestational diabetes during pregnancy, and/or gave birth to a baby weighing more than 9 pounds (4kg), are at greater risk of getting type 2 diabetes. Polycystic ovarian syndrome. Women who have this condition are at greater risk of developing type 2 diabetes. Some people are diagnosed with prediabetes, which is when your blood sugar level is higher than normal, but not high enough to be diagnosed as type 2 diabetes. If you have prediabetes and you don’t take steps to treat it, you are likely to develop full type 2 diabetes, and intervention is indicated to try to prevent you from developing diabetes. Treatment With good medical care, most people with type 2 diabetes are able to control their glucose levels with proper diet, medication, and lifestyle changes. But this does require taking an active part in their care and adhering to doctors’ recommendations. Healthy lifestyle Many people with type 2 diabetes are able to manage it by making changes to their lifestyle, specifically to their diet and activity levels. Losing weight reduces the amount of fat in your body and decreases your blood sugar levels, easing the strain on your body’s insulin production. A loss of 5-10% of your body weight can sometimes be sufficient in reversing a diagnosis of type 2 diabetes. Eating a healthy diet is vital for managing type 2 diabetes successfully, regardless of weight loss. Excess carbohydrates, saturated fats, and processed sugars cause your blood sugar levels to spike and then drop dramatically, which can quickly exhaust your insulin levels. Stick to whole grains, fiber, lean protein, and vegetables, and monitor your carbohydrate intake carefully. Managing a healthy diet is a critical component of controlling and preventing diabetes. Exercise burns extra glucose, encourages weight loss, and helps make your cells more sensitive to insulin. Quitting smoking doesn’t directly improve type 2 diabetes. However, smoking when you have type 2 diabetes has a disastrous effect on your vascular health, preventing a healthy blood supply from reaching your legs, and drastically increasing your risk of amputation. Monitoring blood sugar levels Many people with type 2 diabetes need to regularly check their blood sugar levels to see whether they are within a normal range. Your doctor will guide you about how often to check your blood sugar levels, and what to do if they are too high or too low. Medication For some people, living a healthy lifestyle isn’t enough to control their blood sugar levels, and they need to take medication as well. The most common medications for type 2 diabetes are: Metformin. This prevents your liver from making too much glucose, and helps your body to respond better to the insulin it produces. It’s usually the first medication prescribed to treat type 2 diabetes. Sulfonylureas. This encourages your pancreas to produce more insulin in order to keep up with your blood sugar levels. Meglitinides. These are a class of medications that work like sulfonylureas to stimulate more insulin production, but they work faster and for a shorter period of time. Thiazolidinediones. These medications help your body respond better to the insulin it produces, but they can also increase your risk of heart failure, so it’s not a drug of first choice. GLP-1 receptor agonists. These are injected into the bloodstream to slow down digestion and lower blood sugar levels. SGLT2 inhibitors. These stop your kidneys from reabsorbing sugar into the bloodstream. Insulin injections If lifestyle changes and other medications aren’t successful, you might need to inject insulin into your body in order to manage your type 2 diabetes. Insulin has to be injected and can’t be taken by mouth, because the process of digestion destroys the active hormone. Depending on your situation, you might have just one long-acting insulin shot at night, generally Lantus or Levemir, or might need additional insulin shots at times during the day.

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