The debate of whether or not cannabis should be used for recreation has been raging for well over a decade now, and there are strong arguments on both sides. People in favor of recreational marijuana point to research that shows the extensive benefits of the plant, while those opposed call cannabis a “gateway drug” and point to the conflicting data in the scientific community surrounding the substance. With the topic being so prominent, the fact that the sciences can display cannabis as a cure and poison is extremely interesting.

This is conflicting representation is most likely due the lack of scientific research regarding the substance. Cannabis interacts with receptors of the endocannabinoid system which has several important functions in the body. The most widely studied receptors of this system are the CB1 receptor and CB2 receptors, which can be found both in the brain and in peripheral nervous tissues and cells.

The abundance of these receptors throughout the body are one of the major obstacles when determining the effect of Cannabis on the human body. For example the CB1 receptor has been found in the brain, cardiovascular system, liver, GI tract, and reproductive systems. Therefore administration of cannabis affects the body in several ways simultaneously making it difficult to study. Recent studies have attempted to demonstrate the effects of marijuana on several diseases.

The CB1 receptor has been found to inhibit GABA and Glutamate release in which directly impacts neurotransmission. This is proposed as a plausible underlying mechanism of CB1-mediated neuroprotection against excitotoxicity, a prominent pathological process of many disorders such as epilepsy, Alzheimer’s disease, Parkinson’s disease.

In Parkinson’s disease the up regulation of  the CB1R and endocannabinoid system  activity which could be a mechanism to compensate the degenerated dopaminergic neurons, or a pathological process that contributes to the worsening of the disease. In addition, the activation of the CB1 receptor has been shown to be beneficial in Alzheimer disorder animal models with memory deficits and cognitive disorders. However, results from these models are still debated in the scientific community.

The conflicting data is not the only problem however. Marijuana is currently considered a schedule 1 drug. This means that in the eyes of the law and the government, cannabis is in the same class as heroin, LSD, and ecstasy. This classification has several impacts on the scientific communities ability to research the effects of the drug. For instance, in order to perform research on a schedule 1 drug, there are mountains of paperwork and regulations which must be addressed. This makes the already expensive research even more expensive and time consuming. This leads to limited research on a drug that has the several possibilities in regards to several crippling diseases.

The effects of cannabis on the human body is still uncertain. Several studies have shown remarkable effects of the drug , while other studies have shown the drugs potential to exacerbate several diseases.  This uncertainty is a product of conflicting experiments as well as limited research. In order to determine whether or not cannabis is a miracle drug or a potent poison, further research is needed.

Sources:

https://www.ncbi.nlm.nih.gov/pubmed/28827089

Many of us wonder where we will be in ten, maybe twenty years from now regarding our health. What will the health care system look like? Will it be improved? What advancements will be made that prolong life as well as improve quality of life?

Let’s take a look through the crystal ball to see what the future has in store…

Congrats! I see cannabis in your future!

That’s right. Cannabis. You might be surprised, maybe even unhappy with these results, but the truth is that there are some pretty neat findings involving cannabis and the endocannabinoid system that may be beneficial to your health.

Cannabidiol (CBD) is an essential component of medical marijuana/cannabis. The CBD industry is growing at exponential rates and will continue to grow. It is your choice if you are going to jump on board with these products that are rapidly growing in popularity.

Cannabis has been used throughout history and has been used for a diverse range of medical purposes. However, although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice.

Understanding the Crystal Ball

The science described below will help explain the reason for the wide range of effects associated with the endocannabinoid system.

The Cannabinoid Receptor (CB1): CB1 receptors are members of the G_i/G_o – linked GPCR family. This means they inhibit voltage sensitive calcium channels and adenylyl cyclase. On the other hand, CB1 receptors regulate the activity of G-protein coupled inwardly rectifying potassium channels and stimulate the MAPK signaling pathway. The figure below shows the activating and inhibiting roles of the CB1 receptor.

Fig. 1

Inhibition: adenylyl cyclase (AC), formation of cyclic adenosine monophosphate (cAMP), activity of protein kinase A (PKA), calcium influx via voltage-gated calcium channels (VGCC).

Activation: MAPK signaling pathway and PI3K/Akt pathway

The CB1 receptors are widely spread throughout the body, thus giving reason to the broad spectrum of physiological roles these receptors can play. With this being said, research has shown the endocannabinoid system to be largely involved in various central neural activities and disorders including appetite, learning and memory, anxiety, depression, schizophrenia, stroke, multiple sclerosis, neurodegeneration, epilepsy, and addiction. The figure below shows the different regions the CB1 receptor is involved in throughout the human body.

Fig. 2

The widespread expression and versatile functions of CB1 receptors support its potential as a drug target for various diseases. However, the undesired effects that arise immediately or later on in life should not be ignored.

The Future is in Your Hands

Nobody can know for sure what the future will bring from these findings, but we can always be optimistic. Ultimately, if individuals are using cannabis for health related reasons and it is improving their quality of life, then there is no point in judgement.

With the growing CBD industry, there are many questions that arise. There are so many different directions to go with the endocannabinoid system that can potentially lead to finding drugs that benefit human health and, of course, improving human health is the ultimate goal. I hope we all go on to live healthy lives. If that life involves drugs targeting the endocannabinoid system, then so be it.  The future is in your hands!

For more information on the research presented on the endocannabinoid system follow this link:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/

There are a number of active ingredients in cannabis aka marijuana and THC is the most prevalent, CBD comes in second. CBD stands for cannabinol which is part of the larger category of phytocannabinoids that make up the complex, naturally occurring compounds in the marijuana plant. CBD seems to be used by everyone from retirees who are struggling with arthritis pain to dogs who have some anxiety while going on car rides. Everyone knows of a success story due to CBD, but how does it really work and why is it different than marijuana?

There are naturally occurring receptors in our body specifically made for cannabinoids like CBD and THC and endocannabinoids produced in our body. The most commonly mentioned are CBR1 and CBR2. CB1 is more prevalent in the brain while CB2 is more commonly seen in other peripheral tissues. Two important endocannabinoids produced by our bodies are AEA and 2-AG that will activate CB1 receptors by crossing the membrane and then suppressing neurotransmitter release through the suppression of calcium channels. This is often why people are warry of using THC and marijuana in general as a treatment because there are a larger number of downstream effects that can occur after the activation of these receptors because CBR1 is literally all over our body and the most prevalent GPCR in our brain!

Therefore, people turn to CBD as a treatment option. CBD has a low affinity for these receptors meaning the side effects of its usage are not at worrisome. They likely work through adenosine reuptake on the antagonism of some GPCRs. Below is a figure that lists some receptors or targets in the brain that CBD is known to interact with.

One important interaction to note is that CBD is an agonist of 5-HT which is another name for serotonin which is important in reducing depression and regulating anxiety.

In summary, you would have some of the same positive effects on your body if you were to ingest marijuana but using just CBD seems to be a way to reduce the negatives, like the psychoactive component, and still get the beneficial results. However, the research on CBD is somewhat confusing as the federal government is not quite sure how it wants to regulate it yet. Marijuana and therefore THC is still illegal at a federal level and the FDA claims it isn’t sure about the efficacy of CBD even though numerous studies have supported the benefits. Until marijuana is legal, it won’t be an easy subject to study and without studying it, we have no idea the true effects, positive or negative, it can have on our bodies.

https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis

https://www.healthline.com/health/mental-health/serotonin#functions

Metabolic syndrome is the name for collective disorders caused by overnutrition. Some symptoms associated with metabolic syndrome include:

• Obesity
• Insulin resistance
• Impaired glucose tolerance
• Dyslipidemia
• High blood pressure

These symptoms on their own are predictors of development of more serious disorders such as type two diabetes and cardiovascular disease. New research suggests possible mechanisms for development of metabolic syndrome through brain inflammation, especially inflammation of the hypothalamus. Overnutrition activates an inflammatory pathway that alters signaling for leptin and insulin. Leptin and insulin are largely responsible for hunger cues and glucose tolerance. There are several different molecules and pathways impacted by overnutrition and leading to long term changes in the brain. These underlying mechanisms are not yet well understood, though the relationships are rather complex as shown by the image.

Prenatal impacts

When a mother has a high fat diet, consistent with the standard American diet, there can be long term impacts on the child. These changes are due to changes in the way the brain is “wired.” These changes occur when a mother breastfeeds her child and can lead to problems with a child’s eating and an endless cycle of obesity and metabolic syndrome.

Treatment

Treatment of obesity and metabolic disorders is complex and multi-faceted. Treatment possibilities have been explored in mice. The most promising treatment involves inhibition of NFKB/IKKB pathway. This can be accomplished through brain specific deletion of certain transcription factors. Thus far these treatments have only been applied in mice. More common treatments revolve around weight loss. Programs like Weight Watchers and Profile by Sanford are designed to help people navigate diet and nutrition to live healthier lifestyles. Treatment for obesity often requires a reframing of lifestyle choices as well as counseling to treat underling mental illness.

Culture

The United States is ranked #1 in obesity rates across the word at 36.2%. This statistic requires some questioning as other developed nations have much lower rates of obesity. Culture is likely one of the biggest causes of this ranking. According to the USDA, portion sizes are one important aspect to this ranking. In 2000, Americans ate an average of 20% more calories than in 1983. In addition, consumption of fats has increased approximately 45% since 1970. Overconsumption of saturated fats is an important risk factor for triggering inflammatory pathways that lead to metabolic syndrome. One of the most interesting aspects of culture differences is the impact it has on the way people eat in different areas. In the United States, we move fast. We eat fast, work fast, and aim to accomplish as much in the day as possible. In European countries, things move more slowly. People will sit down for hours over a meal while enjoying each other’s company. Government regulations on food in different countries are also vastly different. Countries in Europe often require higher standards and result in food with greater nutrition. Additives are common in food in the United States while they are often outlawed in other countries. Portion sizes are also significantly larger in the US than they are in other countries.

If you have ever had trouble sleeping, you most likely watched late-night television in order to fall asleep.  The commercials televised in the wee hours of the morning often display miracle products, several being diets and weight loss supplements. These products often fail as obesity is a complex disorder caused by several factors. Recent studies have shown a correlation between the inflammation of the hypothalamus and obesity. The cause of this inflammation is still being examined, but one leading cause seems to be the impairment of leptin and insulin signaling.

Understanding the function of the hypothalamus in obesity is crucial for the development of a cure. Early lesion experiments revealed that alteration in the hypothalamic region of the brain resulted in changes in feeding behavior and energy expenditure. Two types of neurons are responsible for this regulation. AgRP neurons control food intake while POMC neurons decrease food intake and increase energy expenditure. Leptin and insulin play major roles in the homeostasis of both neurons. An improper balance of leptin and insulin or ineffective leptin and insulin signaling corresponds to an increase in food consumption and simultaneous decrease in energy expenditure. Studies have shown diets rich in saturated fatty acids cause activation of cytokines and inflammatory pathways, which disrupt leptin and insulin signaling in the hypothalamus. The activation inflammatory pathways lead to transcription of genes like SOCS3, leading to more cytokines and inflammatory signaling. This leads to the chemical hardwiring of the brain to eat more food, making losing weight a massive challenge. The figure  below demonstrates some of the neurochemistry of obesity.

This research does however lead to several possible treatments of obesity. Administering medication that prevents the transcription of inflammatory genes and hinders cytokine and inflammatory pathway signaling are two viable treatment options. Several studies have shown using anti-inflammatory medication such as Tylenol can decrease weight gain.  The simple solution would be to prevent over nutrition or limit saturated fatty acids. However, this may not be as simple as it appears. Currently cheapest and affordable foods, those purchased most frequently by the public, are high in sugars, carbohydrates, and fatty acids. Only individuals with money can afford to purchase fresh fruits and vegetables. This leads to a social and economic dilemma regarding weight gain and obesity. Furthermore, the human body was designed from an evolutionary standpoint. In other words, the ease at which food can be obtained and consumed today, compared to the hunter-gatherer lifestyle, raises the risk for obesity.

The issue of obesity is complex. Studies have shown a correlation between hypothalamus inflammation and the disease. It is hypothesized that inflammation occurs because of an imbalance or impaired signaling of leptin and insulin, leading to inflammatory responses. Treatments of obesity vary in their approach; however, mediation of inflammatory genes and pathways has shown promising results. Factors outside the physiologic domain must also be examined. Several economic and societal facto directly impact obesity. Understanding the complexity of the disease is imperative for one day finding a cure.

Sources

https://moodle.cord.edu/pluginfile.php/798963/mod_resource/content/2/inflammation%20and%20MD%202017.pdf

Most people know that the initiative of former First Lady Michelle Obama was Let’s Move. One of her goals was to help a new generation of kids grow up knowing the benefits of exercise and a healthy diet and how to apply it to their lives. Instilling such habits when young and being consistent into adulthood can be very beneficial and a vital part of people’s fitness (being fit is not the same as being “skinny” though). However, many people don’t start exercising and eating healthy foods until later in life, specifically as a means to lose weight. This can be an oversimplified understanding of the way obesity works because while these adjustments can definitely help with weight loss, they do not necessarily work for everyone. (Nor should people be expected to lose weight simply because they do not fall into the “Normal” BMI range, but issues with this categorization are a separate topic.) Regardless, a possible explanation for difficulties with losing weight can be found in the brain.

The Science

Within the brain region of the hypothalamus exists a neuronal circuit called the melanocortin system with two subsets of neurons: AgRP and POMC. At homeostatic functioning, insulin and leptin inhibit AgRP neurons within this system to decrease energy intake and instead activate POMC neurons to increase energy expenditure. However, an HFD (high fat diet) can significantly reduce hypothalamic sensitivity to insulin (even after only three days) and may contribute to the development of insulin and leptin resistance. This resistance may be restored by unsaturated fatty acids like omega-3. 

However, saturated fatty acids can trigger inflammatory signaling which, when prolonged, can lead to cell death in the hypothalamus, specifically in POMC neurons. HFDs and overnutrition can also cause oxidative stress in neuronal cells and consequently metabolic syndrome. An interesting fact is that hypothalamic inflammation, and thus possibly metabolic dysregulation, occurs before significant weight gain, meaning that once weight gain does occur, it might already be very difficult to lose it again and restore the original homeostasis in the brain.

Other Issues

This science explains why it may be more difficult for some people to lose weight. But if overnutrition or high fat diets can induce metabolic dysregulation and issues surrounding obesity, why do we consume “unhealthy” foods anyway? 

Well, there are a number of possible reasons… Sometimes we indulge in unhealthy food simply because it tastes good and we crave it. Sometimes we are in a rush and only have twenty minutes to eat, so we buy fast food. But oftentimes, there is more to it than that, especially in different segments of the population. 

Food availability and financial insecurity are two factors that can influence what types of food a person ends up consuming. Many people in the United States live in poverty or financial insecurity, and when unhealthy processed food is cheaper than healthy fresh food, people are more likely to purchase the box of mac-‘n-cheese or canned beef stew instead of fruits and vegetables or chicken breast. A further issue we encounter in connection to this, is that impoverished areas are often considered to be “food deserts”, meaning that there is less access to fresh foods because it is less available compared to urban or suburban settings. Therefore, even if people wanted to make healthy choices in terms of their diets, it may simply not be possible or feasible for them. This is where policies, incentives, or government-run programs may be beneficial. Let’s Move was a first step (the program also attempted to improve accessibility and affordability of healthy foods), but there is more to be done.