To study the brain apart from the mind, or to study the mind apart from the brain is a paramount mistake, both academically and personally. Yet there are people who do this. The guilty studiers of the brain wonder incredulously at the mind, treating it like it’s beyond the purview science. The guilty studiers of the mind are perhaps the guiltier party. They are usually altogether ignorant of the brain, or treat it offhandedly, as some organ that’s workings only correlate with those of the mind; the thing of real importance.
I held a brain in my Behavioral Neuroscience class the other day. I knew I was studying me. It knew it was studying it. I imagined at that moment the neural pattern in my brain that corresponded to my knowledge of my brain. I made note of the irony. There was at first an aversive reflex away from that knowledge. But this hardly stopped me from learning. I wasn’t going to let some intuition of mine keep me from knowing me. But I’m convinced that the brain has a secret it doesn’t want itself knowing, and it doesn’t seem like the studiers of the brain have fully grasped exactly what this secret is.
Neuroscience has a burden that no other field of science has right now. It has to deal directly with this secret. This secret will force us to redefine ourselves. Our identity, our soul, whatever we value about our precious egos, neuroscience can manipulate, change, break apart, better, worsen, and destroy. “Identity recreation,” “perspective alteration,” “mind transplant,” “thought control” will all be a new words used in the way, “mood alteration” is used now. People either see this as implausible, or too far in the future to attend to. But neither is true, this technology will arrive in our lifetimes. And humanity doesn’t have the time to brace itself for this blow. Can we properly engage in neuroscience class without understanding the risk we take in studying this material? Can we sit naively back studying something we should all be afraid of? Can we reconcile ourselves? Can we give up our egos?
Despite these concerns, no one is going to give up knowledge. Perhaps we do know what we’re up against and are just choosing to ignore it. I for one won’t preserve the secret. I’ll do just what every other good neuroscientist will do: learn the brain. There is no split any more. Mind/Brain. There is just our control over it. Neuroscience could just as easily be defined as the science of controlling ourselves. In 30 years, 50 years, anyone’s free to estimate, it will be the neuroscientist who has more power than anyone. The dexterous neuroscientist will have a better argument than anyone’s ever had. Feel free to think of an argument for something. Make it an argument that convinces everyone. Make it an argument so logically sound, so intuitively obvious, that someone would have to be crazy to deny it. The neuroscientist will have the power to make you doubt it; to make you change your mind. It’s not about right or wrong; it’s about power.
Marijuana, THC, and Medicine
The endocannibinoids play a vital role in regulation most of your brain and body functions. Without endocannibinoids, we are unable to function properly. Endocannibinoids are a family of molecules synthesized in your body that are found in the nervous system. The most common are anandamide and 2-arachidonoyl glycerol (2-AG). But they are not the only chemicals that can activate signaling in the brain, so can Marijuana.
Tetrahydrocannabinol, or THC, is commonly known for being the active ingredient found in marijuana. (Click to see the structure for those who are organically inclined)
Despite it the bad reputation it gets (not pointing any fingers), THC is useful for more than just getting high. A recent study in the Journal of Clinical Investigation by Salazar et al. shows that “Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy.” Glioma is a type of cancer specific to the brain and spinal cord. It’s named after the cells that cause it, glial cells. Glial cells are found primarily in the brain, and it is their irrational growth that causes the tumors to form. Basically, the THC gets into the signaling pathway of the cancer cells and tells them to destroy themselves. It is very cool stuff and great for the future of treating deadly cancers.
Another study from Scripps Research Institute, shows that THC is helpful in the treatment of Alzheimer’s Disease. THC stops the formation of protein buildup (amyloid plaque), by inhibiting acetylcholinesterase (AChE). AChE fosters the development of the protein buildup which causes inflammation of neurons in the brain. This is believed to be how Alzheimer’s disease is caused. This research is very interesting, and can lead to studies of novel new treatments.
If you want further information on the recent developments on THC and the endocannibinoid system, the Society for Neuroscience put out a great article on cannabis, and its applications for future research and the treatment of disease, obesity, cancer, pain, and anxiety. (http://www.sfn.org/skins/main/pdf/brainbriefings/BrainBriefings_Dec2007.pdf)
MS's new treatment?
Multiple sclerosis (MS) is an autoimmune disease that attacks the central nervous system and is often a disabling disease. The body begins to attack the fatty layer that surrounds and protects the nerve fibers in the central nervous system known as myelin and it can also damage the nerve fibers themselves. Symptoms range from numbing of limbs, fatigue, motor and coordination problems, vision problems, pain, and unusual muscle tension known as spasticity just to name a few.
There are many different types of treatment for MS including interferon, a type of chemotherapy, massage therapy, acupuncture, and chiropractic therapy. But there is a new type of treatment that is still in the “development” stage, it’s marijuana. Cannabis sativa (marijuana) is still in the study stage but it is thought to manage symptoms like pain, tremors, and spasticity. Early studies used tetrahydrocannabinol, THC, in its oral form because they could control the dose. What they wanted to see was how THC managed spasticity, tremor, and balance. The results of these studies however did not give any definitive answer. Each patient reported different results and different side effects for each symptom that was being studied.
For spasticity, mixed results were found because some patients reported feeling less spasticity, unfortunately these results could not always be confirmed by testing done by physicians. Also the effects of the THC lasted at the most three hours and came with multiple side effects including weakness, dizziness, mental clouding, coordination problems, short-term memory impairment. For tremor, a small study was done with eight severely disabled patients. Five of the eight patients reported improvement in their tremor and all eight reported experiencing a “high”. Unfortunately, in the balance category, a study found that THC actually worsened the person’s control of their posture and balance in both people with MS and people without MS.
These studies show both the good and the bad sides of marijuana use in the treatment of multiple sclerosis. But what it shows most is that much more research needs to be done. Cannabis could be a strong treatment for people suffering from MS symptoms or it could be another “treatment” that offers more side effects than results. Only time will tell.
1) http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/treatments/complementary–alternative-medicine/marijuana/index.aspx
Anorexia and Cannibinoids
You know what really grinds my gears? Anorexia nervosa. Anorexia nervosa is a widely known eating disorder that afflicts around 8 million Americans a year. Anorexia results from a low appetite or a strong fear to lose weight. A possible way to cure this problem is to stimulate the appetite of those afflicted.
Enter cannabinoids. Endocannabinoids are natural occurring chemicals that occur within our body that play key roles in the body, including blocking pain, modulating motor function, and other neuroprotective roles. You may recognize the root “cannabi” from the plant genus cannabis, also known as marijuana, pot, or ganja, which is an external source of cannabinoids for the body. The active ingredient of marijuana is tetrahydrocannibinol (THC). The THC content of marijuana determines how potent a certain species/hybrid of marijuana is. THC binds to cannabinoids receptors, which can result in the properties listed above.
Another way cannabinoids affect the body is through the stimulation of appetite. I am sure you are aware of the “munchies”, the tendency of marijuana smokers to get hungry when they are high. This is at least partially due to the received cannabinoids activating the natural endocannabinoids receptors in the brain, which stimulates appetite and stabilizes body weight. Endocannabinoids also stimulate the liver into increased fat synthesis. By stimulating appetite and converting food into fat at a higher rate, cannabinoids can allow users to gain more weight.
Now, I’m not necessarily saying that the best cure for anorexia is lighting up. THC can be created synthetically and taken alone. There can be drawbacks to taking too much cannabinoids. Higher levels of cannabinoids can induce euphoria, tolerance, or neurotoxicity. However, if taken moderately, cannabinoids can effectively treat anorexia.
1) http://www.macalester.edu/psychology/whathap/UBNRP/cannabinoid06/index.html
Canninbinoids: Saving the Brain
The endocannibinoid system has very complicated interactions within the brain. A very important role of this system is to control the rate of synaptic transmissions. They are the resistors of the brain, just like in an electrical circuit. Neurotransmissions can’t go at max speed all the time, the neurons will burn out, plus it is not necessary to constantly be transmitting at max speed. The endocannibinoid system saves on the resources that can be limited in the body and saves the neurons from the wear and tear of synapses. Marijuana tunes these resistors, by adding different concentrations of different cannibinoids into the cleft. Since all cannibinoids have similar properties to a certain extent, they will all react with the CB1 receptors in some way, and can activate G-proteins, which can lead to different activations or inhibitions of pathways.
I think that if we could study the processes and connections of this system and understand it better, we could be able to enhance the productivity of this system. This could lead to advancements in the treatment of different diseases and help in the full recovery of head injuries like concussions.
Athletes and Marijuana?
From high school to professional sports, it seems like we are hearing more and more about concussions these days. But what actually is a concussion? According to WebMD, a concussion is “any type of brain injury that is caused by a blow to the head or body, a fall, or another injury that jars or shakes the brain inside the skull.”1 Indeed, the reason we are hearing more about concussions from our favorite sports teams is because they are becoming more and more common. According to Saint Clare’s Concussion Center for Children and Adolescents, “From 1997 to 2007, ER visits for concussions doubled for ages 8-13 and tripled for ages 4-19”2. Furthermore, “Each year, an estimated 3.8 million concussions related to sports/recreation occur in the United States.” That’s a lot of brain injury! And with so many injuries, athletes are itching to get back into the game. Are there any potential treatments to decrease healing time?
Marijuana?
Yeah. Marijuana. According to a recent paper published in Current Pharmaceutical Design3, endocannabinoids, or molecules in our body similar to an ingredient in marijuana, may have neuroprotective effects. THC, marijuana’s pseudo-endocannabinoid, can bind to receptors in our nervous systems, stimulating many different outcomes.
Endocannabinoids have been shown to decrease over-stimulation of brain neurons. This is important because they can enhance neuron survival in a situation of traumatic brain injury. Furthermore, the endocannabinoid system seems to have an effect on neurogenesis, or the creation of new neurons. This could potentially shorten concussion-related healing time. Additionally, the endocannabinoid system seems to be neuroprotective through signal transduction systems. This means certain molecules are turned on and off inside the cell to promote neuron survival. Lastly, endocannabinoids may be neuroprotective through their effect on another brain cell, microglia. Microglia induce inflammation which, in some cases, can further damage neurons. By blocking microglial activation, endocannabinoids, or marijuana’s active ingredient THC, could protect the injured neurons.
Of course, this is just one side of the story. Understanding of medical marijuana and its involvement in the nervous system is still unclear. While it shows promise in some instances of nervous system impairment, it shows potential deleterious effects in others. However, these findings suggest that we may someday think of marijuana in a new light.
1. http://www.webmd.com/brain/tc/traumatic-brain-injury-concussion-overview.
2. www.saintclares.org/concussions
3. Galve-Roperh, I., Aguado, T., Palazuelos, J., Guzman, M. Mechanisms of control of neuron survival by the endocannabinoid system. Current Pharmaceutical Design 2008; 14: 1-10.
An Unorthodox Treatment
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.