Tetrahydrocannabinol or THC is the active chemical in marijuana responsible for the mind-altering effects and has grabbed the attention of many Americans. In the United States, marijuana is legal for medicinal purposes in sixteen states and Washington D.C. With this growing popularity, a demand has been made for more effective and symptom specific strains of marijuana. The two most popular types are known as Cannabis sativa and Cannabis idica. Indica strains have been known to be more of a relaxant and are commonly used to treat symptoms such as chronic pain, anxiety, tremors, and muscle spasms. The sativa strains are stimulants and have been used to relieve chronic pain, increase appetite, and relieve depression.
Along with the strain, the potency of the plant plays an important role in the effectiveness of the treatment. Since the 1970’s, when marijuana averaged approximately one percent THC, marijuana of the twenty first century has reached an average of five percent. Some of the most potent strains have reached THC levels as high as eight to ten percent. As the demand for medical marijuana increases, the effectiveness of delivering THC to the body via the endocannabinoid system has become an area of interest. Thus, researchers and scientists, along with underground marijuana farmers, are seeking to maximize the beneficial effects of THC while minimizing the risks.
The two most popular methods of delivering the THC are through smoking and oral absorption. When marijuana is smoked, THC is inhaled and is passed through the lungs’ membrane. It then enters the bloodstream, which eventually makes its way to the brain’s cannabis receptors, the ultimate goal. In oral absorption, THC is delivered to the stomach, but the process of being absorbed by the bloodstream is relatively slow. A substantial percentage of the THC is often times degraded by metabolism in the liver before it even enters the bloodstream.
The most effective way seems to be smoking; however, many health concerns have been linked to smoking. From a scientific standpoint, it only seems right that a more effective delivery method is researched. If marijuana, or more specifically THC, is to be a legal commercial drug available to the United States as a whole, it must first be able to prove reliable in the medical community.
Frying Brain Tumors with Marijuana
Cannabinoids are a class of compounds including and related to marijuana’s active ingredient- tetrahydrocannabinol (THC), which have both psychoactive effects (the high or buzz) and neuroprotective effects such as antitumor function. The latter effect of cannabinoids has given rise to one of the most interesting areas in cancer treatment.
Specifically, naturally occurring cannabinoid anandamide has been shown to inhibit breast cancer growth. In addition it has been noted that the unnaturally occurring THC has the power to cause selective cell death of transformed neural cells, i.e. nervous cancer cells such as brain cancer.
Gliomas are among the most frequent class of primary brain tumors and are one of the most aggressive forms of cancer, which often results in death of affected patients within months. Currently treatments such as surgery, radiotherapy, and chemotherapy are only marginally successful, usually only serving as a palliative treatment to make better the remainder of the victim’s life. However, THC and other cannabinoids have been shown to selectively target and destroy glioma tumors in rat studies, while showing no deleterious effects to either the rats’ health or changes in their behavioral characteristics.1
This of course is a surprise, considering the characteristic that most people are familiar with regarding the properties of THC, is its high inducing effect. In fact, the reason these effects were not shown in clinical rat studies is because the dosing of THC to parts of the brain, which are linked with behavior change, is much less than that exhibited regarding normal recreational marijuana use. By directly dosing the tumor, the “high-effect” can be minimized and the destruction of the tumor can be maximized.
So THC is an exciting possibility to selectively target brain tumors, and not suffer the recreational influence of marijuana.
For more information on the study cited in this post go to: Anti-tumoral action of cannabinoids
Cannabinoids, the fear and perhaps, the promise.
The Fear
Cannabinoids have been making quite a stir in America long before the the active component, THC, was discovered in the 60’s. Reefer Madness has been the fear of parents and school teachers since the 30’s and hasn’t let up much since. However, it was not till the 90’s that researches discovered the reason for marijuana’s effects was due to natural cannabinoid pathways already working in our bodies and that these pathways have mechanisms that protect the brain. I have a feeling that many of the proponents supporting the fear of reefer madness would be shocked and disbelieving about the neuroprotective work done by endocannabinoids.
Cannabinoids, the Brain’s Knight in Shining Armor?
The review paper we read for this week listed a number of instances where endocannabinoids protect the brain from external and internal damage. Behavioral changes and memory loss may be prevented by increasing the duration endocannabinoids remain active in the brain., while THC administration has been shown to reduce neuron loss and brain damage in ischemia models. These are just a couple of examples and are both carried out by the action of endocannabinoids, but in very different ways.
Excitotoxicity protection
Endocannabinoids have the role of protecting the brain from its own chemicals. The brain uses chemicals released from brain cells, neurons, to process and pass on information about the body. One of these important chemicals is glutamate which excites the places in the brain where it is released in order to pass on information from neuron to neuron until it reaches the target area that will process the message and carry out the action to react to that message. However, when there is too much glutamate being released by neurons it creates a state of excitotoxicity, or basically brain hyperactivity, which can have results as severe as seisure. When cells process that there is too much glutamate being released, endocannabinoids are released to stop the release of glutamate. This can greatly curb the problems that may arise from excitotoxicity.
Endocannabinoids are Making the Microglia Lazy
In the event of a trauma or stoke in which bleeding takes place in the brain there is potential for huge brain damage. The endocannabinoid system also has a procedure for helping to protect and repair the cells within the brain. There are a certain type of cell, the microglia, that act to repair damaged cells. When an area of the brain is damaged, these microglia congregate in that area to repair the damage. Unfortunately, when these cells start working in large numbers for long periods of time they produce waste that can be as damaging as the problem they had congregated to fix. This is where endocannabinoids come into the picture. They connect to these microglia and stop some of them from working. This creates a balance so that there are enough microglia to do their work without overdoing it and causeing damage themselves.
If Endocannabinoids are so Great, What’s the Problem?
The problem is actually quite similar to the problem the microglia can cause in the brain. By overcompensating, it is easy to do more harm than good. If endocannibinoids are given free reign, they can likely cause as many problems as when glutamate isn’t controlled. In other words, it appears that balance is the ticket. Most humans naturally have a proper balance of cannabinoids without taking a huge amount THC in the form of marijuana or even supplements of natural endocannabinoids. In the same vein though, there are people with imbalances that may be helped by prescriptions that increases the action of cannabinoids in the brain. This is why further research into endocannabinoids is necessary, to help provide information about what a proper endocannabinoid system looks like. With this information, medications may be created that can help correct imbalances and improve people’s lives.
Tough Questions with Science: Marijuana’s THC vs. The Body’s Endocannabinoids
Some day it will happen, I just know it. As a future educator it is my job to get my students out of their seats and diving headfirst into science. WHY? WHY? WHY? This will be the question that I will have plastered all over my classroom, the fundamental question of science. I want to show my students how knowledge of chemistry can give them a new view on the world, as well as be a powerful tool at their disposal. So what happens the day I am asked about the pros and cons of Marijuana on a chemical level? Part of me hopes this day never comes, part of me (secretly) hopes that my students are engaged enough to ask real world questions like this. And the final part of me is glad that I don’t have to think about the red tape at the moment because I am not licensed or teaching.
So where would this discussion go? The first point I would make is the body is complicated. Well… MAJOR understatement the body is extremely complicated. We are made of little insignificant and seemingly inert atoms and molecules can come together to create indescribably impressive structures, which are called cells. These cells then must interact, communicate, and build upon each other to create the body, as we know it.
As mentioned these cells need to communicate complicated messages to the others. How is this done? I am glad (I can imply) that you asked. If a cell has a job to do a signaling molecule can be sent out, which would be comparable to a boss sending you an email. As soon as this signal is received the cell gets to work, the process happens when a signaling molecule attaching to a receptor (seen in the below figure). But this simplified analogy gets complicated fast, many of the receptors of the cells begin different tasks, and many receptors can accept different messengers. And that is where the fight between Marijuana’s THC, and The Body’s Endocannabinoids begins.
The Endocannabinoids (eCBs) are an essential part of the human body; in the situation above they would be the signaling molecules (aka the email). When they attach to receptors the effects can be lower levels of different chemicals in the body. Specifically GABA, and glutamate, including MSG, which influence motor activity, learning, and memory. eCBs also protect neurons from death during times of excitotoxic injuries. All of these are positive and important effects of eCBs. Now the interesting part of the story is that Marijuana’s THC is very good at mimicking the eCBs by attaching to the same receptors. Which would imply that THC is just as good for the body as eCBs, which would further imply that Marijuana is also good for the body. Well if your are making those implications STOP!!! There is still more to this story.
Endocannabinoids are not all good if they attach to the wrong receptor they can induce neurotoxicity inducing brain damage. Which means that THC could potentially do the same. Another negative of having marijuana’s THC in the body would be that the receptor interactions be different then normal, because you would have both THC and eCBs in the body. A third complication would be the delivery system, for the most part eCBs stay where they need to be in the body, but because the THC enters the body by inhalation there are many more places it can travel, messing with the delicate and complicated systems in ways we cannot yet understand. And finally there is the complication that THC isn’t the only chemical in Marijuana, which means that there is potential that other chemical problems may occur.
Morals of the story:
- The body is complicated.
- Marijuana has both positive and negative effects on the body.
- If a student ever asks me about marijuana, I am sending them to the biology teacher.
Cannabis: preventing brain damage instead of causing it?
Seizures are the physical changes in behavior that are observed after a period of abnormal electrical activity in the brain. Seizures can be caused by a variety of things including brain injury, brain tumor, high fever, certain infections, and illegal drug use. Behaviors exhibited during a seizure include mood changes, vision changes, loss of muscle control/falling, shaking of the body, and muscle twitching or tension. A seizure can last up to 15 minutes but generally no longer. There are many different categories of seizures varying in intensity, one of which is epilepsy. Epilepsy is a disorder in which individuals have multiple seizures throughout their lifetime even after the underlying cause is treated. For more information on seizures: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001714/
During seizures large amounts of a neurotransmitter (send signals in the brain), glutamate, are released in the brain. This build up of excess chemicals causes too many signals to be sent to the brain cells, resulting in cell death. Repeated cell death can cause lasting brain damage, possibly preventing individuals from learning new things or storing information. Endocannabinoids are molecules that bind to endocannabinoid receptors in the brain. Upon binding, endocannabinoids inhibit the binding of glutamate to its respective receptor. This function can directly relate to seizures. Endocannabinoids have the ability to block the excess release of glutamate produced during a seizure. If the excess glutamate is blocked then fewer brain cells are likely to die, preventing lasting brain damage.
This all sounds great however our brains do not naturally produce enough endocannabinoids to overpower the large amount of glutamate released. So the question is how do we get extra cannabinoids in our system? Some believe that cannabis, an exocannabinoid, could be the answer. THC, the active ingredient in marijuana, also binds to endocannabinoid receptors giving it the ability to inhibit glutamate binding as well. The problem with this is that marijuana has many unwanted side effects such as paranoia, short-term memory loss, memory and learning problems, distorted perception and loss of coordination (for more information: http://www.webmd.com/mental-health/marijuana-use-and-its-effects). It is possible that marijuana with a lower THC content could provide enough binding to prevent most of the glutamate binding and have decreased side effects. Another possibility is to synthesize molecules identical or very similar to the naturally occurring endocannabinoids in our brain. These synthesized molecules, if created successfully, would not have the negative side effects of THC and could prevent the lasting brain damage of a seizure.
Possible Role of Endocannabinoids in Reducing Post-Surgical Chronic Pain?
The article of discussion this week focused on the ability of endocannabinoids to aid in the protection of the brains’ neurons. Much of the evidence that was presented confirmed this neuroprotective role and even highlighted the endocannabinoid’s ability to promote the repair of damaged neurons and synthesize new neurons. Our class briefly discussed the implications of endocannabinoids as cognitive enhancers. In the future, could these be a part of our daily vitamin regimen? Could promoting healthy practices of brain protection and improvement be as simple as an endocannabinoid supplement?
Integrating this substance into our daily vitamins may be a bit extreme. However, there might be something to say about the endocannabinoid’s ability to aid in neuron repair after a surgical procedure. I came across an article during my research that talked about the levels of endocannabinoids aiding in the inflammation levels and recovery of individuals who had undergone a surgical procedure. http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0010891 Participants in this research had undergone various surgical procedures, and researchers found that increases in endocannabinoid signaling lead to a limitation of pro-inflammation signaling. They also concluded that increased levels of endocannabinoid signaling also reduced the patients’ chances of experiencing long lasting chronic pain following surgery.
If further research into this area was conducted, could this lead to a simple solution for the chronic pain that often plagues patients after surgeries? Not only could it decrease the likelihood of chronic pain, but if endocannabinoids reduce inflammation signaling, then perhaps an endocannabinoid dose after surgery could help to reduce the length of time needed for recovery and even aid in the success rates of recovery. Careful considerations would have to be made however, because too much of these endocannabinoids has been shown to have negative effects on neurons. Of course, there would need to be much more research conducted to see if these effects are possible, but nonetheless, the seed of idea has been planted.
This Is Your Brain On Cannabinoids
Ah, the feeling of bliss:
You feel yourself relax as tension oozes out of your body and worries, fears, and problems seem to fade away…
Life slows down measurably—from the week’s hurried, stressful pace to a deliciously calming crawl…
A feeling of happiness, even euphoria, evades your senses as you experience what can only be described as a high…
You unwind and take it all in…
Marijuana? Cannabis sativa? “Grass”? There’s another name that doesn’t get mentioned as often: cannabinoids. While marijuana is usually thought of as the pleasure substance of choice, in reality it is only a skilled mimic of cannabinoids, chemicals that already exist in our brains naturally. Marijuana only increases what we’ve already got.
What do cannabinoids do in the brain?
Although cannabinoids were discovered relatively recently in the 1990s, quite a bit of research has already been accomplished looking into these unique and mysterious brain compounds. Turns out, they’re involved in a lot of important functions.
The brain cells (neurons) are regularly very active, sending signals back and forth to each other in order to communicate.
Neurons communicate via electric and chemical signals
But in some medical conditions like stroke and traumatic brain injury, the neurons become extremely activated due to too much glutamate, a chemical that increases signaling in the brain. This can actually be harmful, because too much activity wears out the neurons and causes cell death. The good thing about cannabinoids is that they can decrease this activity, saving the neurons from wear and tear.
There’s also some evidence that cannabinoids are involved in the immune system. Immune cells in the brain called microglia are responsible for identifying enemy cells and other threats to the neurons.
Immune cells attack invading disease cells
Cannabinoids may increase the ability of immune cells to decrease disease and inflammation in the brain.
Potential treatment applications
Because of these benefits, researchers have been looking into using cannabinoids to treat brain diseases and inflammation. Medical researchers have already been investigating their effects in treating things like cancer and pain. Neurological illnesses like multiple sclerosis might benefit from cannabinoid treatments as well. In multiple sclerosis, immune cells attack the body’s own cells instead of targeting actual threats. The neurons become inflamed throughout the body, causing muscle dysfunction and eventually cognitive impairment and death.
Because of cannabinoids’ apparent ability to work in the immune system, some studies have investigated whether they do improve the lives of multiple sclerosis patients. While these brain systems are very complex and it will take much more research to really understand what is happening in the brain’s cannabinoid system, it appears that giving more cannabinoids may help reduce some of the symptoms of multiple sclerosis.
Cannabinoid drugs
How do people “take” cannabinoids? The easiest thing is to use the closest mimic of the brain’s cannabinoid chemicals—marijuana. In some research, marijuana has been shown to have health benefits. However, there are definitely some drawbacks to marijuana use as well—including obvious lung damage from smoking, muscle tremors and spasms from too much use over a long period, and possible memory problems as well.
There are some new drugs in development that deliver a small amount of cannabinoids orally and are quite effective at delivering the benefits of cannabinoids and marijuana without the added side effects and potential damage. One called dexanabinol is currently in drug trials for treating brain damage and inflammation in conditions like stroke and multiple sclerosis. It hasn’t been approved by the FDA yet, but it and other drugs are hopefully on their way to use.
John, a multiple sclerosis patient, found that cannabinoids (in the form of cannabis) effectively reduced some of his symptoms, allowing him to enjoy life a little longer. “Today I weigh 155 lbs. and use a wheelchair most of the time,” he says. “Cannabis has, no doubt, given me a better life than I would have had without it. I didn’t ask for this. I would gladly give up using cannabis and all the other drugs that are prescribed for me if I were miraculously cured.”
The potential cannabinoids have to improve suffering people’s lives spur researchers on to find a way to use them meaningfully.
Hope for new Alzheimer’s treatments
Alzheimer’s disease is a memory impairment mostly seen in elderly people. Alzheimer’s Foundation of America describes the disease as “a progressive, degenerative disorder that attacks the brain’s nerve cells, or neurons, resulting in loss of memory, thinking and language skills, and behavioral changes.” Alzheimer’s has become an increasing threat to the well-being of the growing elderly population in the United States. The Alzheimer’s Foundation estimates that as many as 5.1 million Americans suffering from the disease. The organization also predicts that the number of people above age 65 and older will be more than double between 2010 and 2050 to 88.5 million which is about 20 percent of the population, and age above 85 and older will increase three-fold, to 19 million. Plus, about a half million Americans younger than age 65 have some form of dementia, including Alzheimer’s disease. Looking at these statistics, we could imagine the enormous cost of health care for this aging population. However, there have been a large number of extensive researches being carried out for effective preventive measures and treatment of Alzheimer’s.
Lately, researchers from the Medical College of Wisconsin, Milwaukee, have found possible targets for new therapeutic approaches. They found out that some actions of Endocannabinoid, a substance similar to the active ingredient of marijuana, could protect Alzheimer’s-related neurodegeneration to an extent through cell receptor related interactions in the brain. Endocannabinoids can inhibit the inflammatory processes of Alzheimer’s in the brain. The researchers found reduced formation of Alzheimer’s plaques in the brain when one type of endocannabinoid receptor, CB2, is expressed in the brain slices of Alzheimer’s rats.
Endocannabinoids were also found to have neuroprotective properties in the brain, that is, they could protect the brain cells from dying due to the attack by inflammatory agents or from over-excitation, that is, neurons having to work harder than necessary because of some chemical imbalance. Endocannabinoids are also involved in production of new brain cells and hence they are believed to be protective against memory impairment. Another study at Complutense University in Madrid, Spain, looked at this neuro-prtotective property of endocannabinoids. The researchers found out that endocannabinoids can block the action of microglia, a cell that is responsible for releasing inflammatory agents when activated. Hence, researches are being carried out to look at potential therapeutic means for Alzheimer’s related neural cell death by inhibiting these microglia cells.
There are also researches that focus on the anti-oxidant properties of Endocannabinoids in Alzheimer’s related cell death. Anti-oxidants are agents that inhibit the release of free radicals in the brain. Free radicals can cause cell death through subsequent chain reactions. The anti-oxidant properties of endocannabinoids can protect the neurons from attacks of free radicals and hence increase the survival of neurons in most of the brain areas that are responsible for memory formation and storage.
Thanks to the increase research findings through the efforts of dedicated researchers, we are hopeful to counteract the increasing threat of cognitive decline of our large population of elderly populations in the coming decades. Research findings could help reduce millions for the health care cost that we are going to have to face in the near future.
Dear Dad, It's not all bad; the truth about cannabis and cannabanoids.
Cannabis, or commonly known as marijuana is a type of cannabinoid. Many of you know of it’s damaging side effects and have heard of the ongoing debate on whether to legalize marijuana. Some of the reasons to legalize marijuana is because of medicinal purposes; they have been shown to treat Parkinson’s disease, nausea and vomiting, anorexia, spasticity, movement disorders, pain, glaucoma, epilepsy, asthma, psychiatric symptoms, and autoimmune disease. For more information about how it helps treat these disorders you can click here, http://www.cannabis-med.org/english/patients-use.htm Even though cannabis may help treat some of the symptoms of the above disorders, it does not go without side effects, some of these side effects are as follows; impaired coordination, distorted perceptions, difficulty thinking and problem solving, impaired learning and memory capabilities. Follow this link for more information on side effects, http://www.nida.nih.gov/infofacts/marijuana.html.
However, not all forms of cannabinoids are bad and cause the side effects listed above. A form of cannabinoids that are naturally occurring in the brain, are called endocannabinoids and can actually be good for your brain. These chemicals can actually protect some of your brain cells from injury and inflammation if they are found in the right levels in the brain. Found in too low of levels and they don’t properly protect the cells from death, if they are in too high of levels it causes something called excitotoxicity. Excitotoxicity is also a form of cell death caused by over stimulation. Therefore we need to make sure that we remain in the right range for endocannabinoids.
Now people may be thinking that they could just raise their levels of cannabis in the brain with marijuana, however the levels of the chemical found in marijuana that actually help protect the brain are found in much too high of levels and cause the greater cell death.
Endocannabinoids…..what???
Cannabis, also known as marijuana, produces significant psychoactive effects in our brain through its active ingredient, THC. The actions of THC are a result of its binding and interaction with protein receptors on neurons called cannabinoid receptors. Why do our brains have these receptors? What naturally occurring molecules interact with these receptors? The answer to these questions is the endocannabinoids – the molecules our brains produce that interact with the cannabinoid receptors. The scientific community has been actively engaged in learning more about these molecules and what roles they play in a healthy brain. In this week’s literature article, we are looking at the involvement of the endocannabinoids in protecting neurons from injury and inflammation.
