You feel grass tickling your neck and arms. You open your eyes, but the people standing around you all of sudden seem about 10 feet tall as they lean over you. Something is not right, and you realize you are laying on the ground on your back. You have been hit.
Thinking back to the progression of your day, you got up and went to school in the morning, then got to PE class, where you all played soccer. Your head met your friend’s knee with an excessive force that sent you straight to the ground. Now you are being told the words “you got a concussion”… but what now?
A recent Gallop poll found 49% (up from 45% in 2017) of Americans have tried marijuana in some form at some point (Hubbard, 2021). Some are doing it for health benefits, others for recreation. Whatever reason people are using marijuana, it is clearly an important topic to discuss based on the sheer amount of people using it in the USA alone. To learn more about the stats and history of marijuana in the US, check out this link! There are some interesting health benefits to some of the compounds in marijuana called cannabinoids. The two most well known and studied are THC and CBD. At this point in time, these chemical abbreviations are nearly household names! In this post, we will explore some of the health benefits of CBD and THC are, as well as explaining the science behind why these chemicals can be so effective.
Is Cannabis Really “Naturally” Found in the Brain?
Yes. No. Well, sort of! The brain produces a class of chemicals called endocannabinoids. these have names like anandamide, arachidonylethanolamine, and 2-archidonoyl glyerol. These are endogenous cannabinoids, similar to form and function to THC and CBD. Fun fact, anandamide is derived from the Sanskrit word “ananda” which means internal bliss (Scherma, 2019). The Sanskrit meaning hints at some of its functions in modulating brain chemistry.
Interesting! But where do these endocannabinoids come from? Interestingly, they are modified from fat in your cell membranes. Neuronally, this occurs in the post-synaptic neuron, AKA the neuron being being stimulated. See figure 1 below for a nice visual.
Figure 1. Reproduced from Zou et al. This figure shows endocannabinoid signaling between the pre-synaptic neuron (blue) and the post-synaptic neuron (green).
So great. We know the names of several endocannabinoids, but they have to bind somewhere to exert any of their effects. Endocannabinoids bind primarily to two receptors: CB1 and CB2 (Kendall, 2017). CB2 receptors are mostly found in the immune system, and when activated by endocannabinoids, inflammation levels increase and drug self-administration frequency decreases (Kendall, 2017). On the other hand, CB1 receptors are expressed throughout the body (Kendall, 2017) and are responsible for many of the positive benefits and side effects of THC and CBD.
Health Benefits of THC and CBD
The claims made online about what THC and CBD can do to a person range anywhere from giving one brain damage, to curing any ailment. Unfortunately, because because marijuana is a schedule I drug, conducting research on it is very difficult and makes a lot of these claims unsubstantiated. Because of this, I will focus on only a few of the positives of cannabinoids that I feel are substantiated with at least some rigorous, scientific evidence.
Should Grandpa Be Toking Up?
An interesting study conducted in mice found that older mice given THC had improved memory (Sarne, 2018). Not only did these old THC mice have the memories that matched young mice, but so did the expression levels of genes involved with memory (Sarne, 2018). This suggests that THC administration could be a viable way to slow or even reverse aspects of aging in the brain (Sarne, 2018).
What About CBD?
When one reviews the literature on CBD, it becomes apparent that it’s anti-inflammatory properties are one of it’s greatest assets in treating disease. A randomized clinical trial (RCT) found CBD is effective at significantly reducing the pain caused by arthritis (Verrico, 2020). Another study found that CBD can help treat Chron’s disease, and even wean some people off of steroid therapy (Naftali, 2013). Yet another RCT found CBD to be effective in preventing inflammation driven hyperpermeability of the human gut (Couch, 2019). The connection between all these studies is the anti-inflammatory effect of CBD. Too much inflammation can lead to many different diseases, and CBD seems like an effective tool to combat excess inflammation.
Conclusion
The amount of Americans using marijuana has been increasing ever since the records began. Because it is a schedule 1 drug, research using marijuana is very difficult and there are many questions science can answer, but isn’t being allowed to do so. Nonetheless, some promising studies have been conducted and have found health benefits for both THC and CBD. From the memory enhancing and anti-aging effects of THC, to the anti-inflammatory benefits of CBD, cannabinoids offer hope for treating a variety of ailments.
Sources
Couch, D. G., Cook, H., Ortori, C., Barrett, D., Lund, J. N., & O’Sullivan, S. E. (2019). Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo-A Randomized, Placebo-controlled, Double-blind Controlled Trial. Inflammatory bowel diseases, 25(6), 1006–1018. https://doi.org/10.1093/ibd/izz017
Hubbard, K. (2021). Record high: More Americans are trying marijuana, Gallup … Record High: More Americans Are Trying Marijuana, Gallup Poll Finds. Retrieved December 9, 2021, from https://www.usnews.com/news/national-news/articles/2021-08-17/record-high-more-americans-are-trying-marijuana-gallup-poll-finds.
Kendall, D. A., & Yudowski, G. A. (2017). Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Frontiers in Cellular Neuroscience, 10, 294. https://doi.org/10.3389/FNCEL.2016.00294/BIBTEX
Sarne, Y., Toledano, R., Rachmany, L., Sasson, E., & Doron, R. (2018). Reversal of age-related cognitive impairments in mice by an extremely low dose of tetrahydrocannabinol. Neurobiology of aging, 61, 177–186. https://doi.org/10.1016/j.neurobiolaging.2017.09.025
Scherma, M., Masia, P., Satta, V., Fratta, W., Fadda, P., & Tanda, G. (2019). Brain activity of anandamide: a rewarding bliss?. Acta pharmacologica Sinica, 40(3), 309–323. https://doi.org/10.1038/s41401-018-0075-x
Naftali, T., Bar-Lev Schleider, L., Dotan, I., Lansky, E. P., Sklerovsky Benjaminov, F., & Konikoff, F. M. (2013). Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 11(10), 1276–1280.e1. https://doi.org/10.1016/j.cgh.2013.04.034
Verrico, C. D., Wesson, S., Konduri, V., Hofferek, C. J., Vazquez-Perez, J., Blair, E., Dunner, K., Jr, Salimpour, P., Decker, W. K., & Halpert, M. M. (2020). A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain, 161(9), 2191–2202. https://doi.org/10.1097/j.pain.0000000000001896
When I first signed up for neurochemistry, I was worried about my lack of knowledge in regard to chemistry, but I knew I had a love for neuroscience that I wanted to learn more about. Concordia has given me the opportunity to take what I love and learn about it in more ways than one. While taking other neuroscience classes here I have learned the basics and lightly touched on different pathways that are involved. However, it was never to the extent of what neurochemistry had to offer, which is understandable to have a class fully designated to looking at all different signaling pathways and their correlations to many different areas in the brain. I knew I would struggle with my lack of chemistry knowledge but with the help of many classmates I became more familiar with the information that was given during class. Having a good background in chemistry is important for this class but do not think that your lack of information will make your opinion less than that. Everyone comes into the class with knowledge about different topics and experiences that aid in conversations regarding every topic. When thinking about this struggle, Concordia’s motto of BREW was engraved into my mind. We as Concordia students base our four-year educational experience from our rooted value being BREW. Becoming responsibly engaged in the world is a way of life. It’s looking at the world and understanding the problems that each person may face, helping always, and stepping forward when everyone else might be afraid. The experiences and lessons I learned in this class taught me how to engage in my world, while also showing me how I could help others from the lessons I learned. This class has also deeply enforced my love for learning, especially when it comes to something that I may not feel the most confident in. It has made me reach out of my comfort zone when asking other students for clarification and well as showing me different study methods that are more beneficial than what I had been using previously. For example, previously I would look over the topic at hand and try and memorize what was being discussed. However, this was not the most efficient method for this class, instead, I found it better to draw out the different signaling pathways in order to see what exactly they followed and how different proteins interacted within that pathway. The types of learning that were involved in neurochemistry highly centered around group work/discussion. For this type of class I think this is the most beneficial way in which the subject can be taught. If we were to sit down and have the class purely lecture based, I feel as though it would not be as enjoyable. Though it is important to understand the baseline of what the differentarticles are talking about we would miss all the questions that we as individuals have on varying topics. This also teaches us how to question what we are reading and find ways to answer the questions we have through the use of published research. If I were to highlight a skill this class has provided me with would be critical thinking, how to ask questions and find the answers on your own.This way of learning is just another way in which liberal art institutions like Concordia College seek to benefit their student more than other institutions. We are able to ask questions and seek out different ways to solve them. Even more so, students that took part in this semester peak project were able to conduct research on a given topic and see how our local area is affected by this. Many of us were able to give back to the community in so many ways and help those that are in need. That is also something I love about Concordia College. We aren’t just a school focused on good grades and going through the motion of life, we are an institution focused on seeing problems within our community and reaching out a helping hand. This way of problem solving/helping will be instilled in all of us for years to come.
Childhood-onset schizophrenia (COS) is very rare. It is only considered to be COS when diagnosed in children under 13, but full onset of the disease often does not occur until late adolescence or early adulthood. Although, if a child is experiencing hallucinations, delusions, or psychosis (more of which we will get into later) this can definitely be a cause for concern. It is important to understand that many children display unusual behavior; their brains are not even near to being fully developed! Also, before jumping the gun on schizophrenia, these symptoms can point to other psychiatric disorders such as depression, anxiety, and autism. A common worry that I have seen for parents is a child’s development of an imaginary friend. Is it an hallucination, a delusion, or simply a child with a healthy imagination?
What are Imaginary Friends?
Imaginary friends, also known as imaginary companions (ICs), have been seen throughout adolescent’s lives for years. It is by far not an uncommon phenomenon. Research even goes so far as to show that 65% of children up to age 7 experience an IC (Taylor et al., 2004). There are multiple reasons why adolescents may develop an IC:
Each of these reasons may be considered beneficial to a child’s development, rather than detrimental (Figure 1). Research has shown that benefits may include advanced social cognition, healthy coping strategies, superior emotional intelligence, and especially heightened creativity (Majors & Baines, 2017)! Imaginary friends can take any form that may be important to the child, whether that be a person, animal, or stuffed animal. More likely than not, ICs are a healthy aspect of child development, and it is important to understand the difference between imaginary friends and schizophrenic hallucinations.
Hallucinations and Delusions in Schizophrenia
Often times, parents either disregard the presence of an imaginary friend, or discourage the act altogether, due to worries in their child’s perception of reality (Majors & Baines, 2017). Although, as described above, ICs differ greatly from symptoms seen in schizophrenia such as hallucinations and delusions. Hallucinations can come in many different forms, including visual (sight), auditory (hearing), olfactory (smell), and tactile (feelings). In the case of schizophrenia, the individual does not understand these hallucinations are fake, and they are not in control. In children with imaginary friends, they most often understand that their friends are not real, and the child is in control of them (Fritz, 2015). Delusions are beliefs that do not align with reality. These include beliefs that someone is planning to harm them, beliefs that one is ill, beliefs that someone is in love with them, or beliefs that one is superior to others. Again, this is far different from a child’s development of an imaginary friend, as they are not out of touch with reality.
When to Take Action
A parent should become concerned if their child beings displaying these types of behavior (Fig. 2).
Only speaks when spoken to; replying with short answers
Flat, monotonous facial expression
Beyond this, it is important to understand that schizophrenia in children is very rare. It is also a disorder of development, so major symptoms often do not show until late adolescence or teen years. Also, many of these symptoms correlate with other psychiatric illnesses that are not quite severe as schizophrenia, and often enough, they are just “symptoms” of being a developing kid. Although, if a parent is still concerned, it can never hurt to get a check-up!
Article Summary
Schizophrenia is a developmental disorder with a variety of positive and negative symptoms. The article focuses specifically on the role of the Wnt signaling, GSK3ß, and dopamine release. When there is an increase in dopamine, this inhibits Akt, leading to an increase in activation of GSK3ß. In regard to Wnt signaling, increases in dopamine also inhibit TCF/LEF-mediated transcription through the direct sequestering of ß-catenin. A primary treatment for schizophrenia, lithium, acts through the direct inhibition of GSK3ß, leading to an accumulation of ß-catenin and therefore, TCF/LEF-mediated transcription. There are also multiple genetic factors involved, primarily DISC1. DISC1 has been shown to inhibit GSK3ß, but it is dysfunctional in schizophrenia. Through this article, it appears as though the inhibition of GSK3ß, a decrease in dopamine release, and an upregulation of ß-catenin activation and TCF/LEF-mediated transcription are plausible targets for schizophrenia treatment (Singh, 2013).
References
Fritz, G. K. (2015). Imaginary friends . CABL, 31(5). https://doi.org/https://doi.org/10.1002/cbl.30041
Majors, K; Baines, E; (2017) Children’s play with their imaginary companions: Parent
experiences and perceptions of the characteristics of the imaginary companions and purposes served. Educational and Child Psychology , 34 (3).
Singh, K. K. (2013). An emerging role for Wnt and GSK3 signaling pathways in Schizophrenia.
Taylor, M., Carlson, S. M., Maring, B. L., Gerow, L., & Charley, C. M. (2004). The
Characteristics and Correlates of Fantasy in School-Age Children: Imaginary
Companions, Impersonation, and Social Understanding. Developmental Psychology, 40(6), 1173–1187. https://doi.org/10.1037/0012-1649.40.6.1173
Post-traumatic stress disorder (PTSD) is a mental health disorder that develops after witnessing or experiencing a traumatic event. It has been found that memories of these traumatic events are often much stronger than the formation of non-traumatic memories (Reul, 2014). During the experience of traumatic events, the body enters fight-or-flight mode in which many normal body functions are halted, including working (short-term) memory. Due to this, the body becomes extremely vigilant, absorbing as much as they can about their current surroundings. The brain attaches smells, feelings, visuals, sounds, etc. to this event, storing them in long-term memory. Since this event is unable to be fully processed, the brain may cause recurring bouts of anxiety, known as triggers. These triggers are due to a combination of three memory processes:
Strong perceptual priming (exposure to a specific stimulus evokes a strong response to another stimulus).
Strong associative learning (strong relationship between two stimuli).
Poor memory elaboration (decreased ability to enhance an existing memory with new information) (Ehlers, 2015).
All of these processes are manifestations of underlying genetic and molecular changes in response to stressful events. Some of these changes include activation of the MAPK signaling pathway in the brain and subsequent gene transcription (c-Fos and Egr-1) that enhance traumatic memory stability (Reul, 2014).
Types of PTSD Triggers
Triggers are reactions that make one act as if their body is in danger, even though they harmless themselves. These can be experienced in many different ways:
Panic attacks
Figure 1
Dreams or vivid memories
Violence or aggression
Increased startle response
Substance abuse
PTSD triggers may be either internal or external. Internal triggers are those that one experiences within their body such as anger, pain, increased heartrate, muscle tension, and loneliness. External triggers are people, places, or things that one may encounter throughout their day. These include an anniversary date, a certain place, a movie or television show, a specific smell, or a person that serves as a traumatic reminder. Essentially, anything that reminds an individual of their traumatic experience may serve as a trigger.
Recognizing PTSD Triggers
It is important for one with PTSD to identify what their triggers may be in order to seek proper treatment. Due to the various reactions one may have to their triggers, and the amount of possibly triggering experiences, identification may be very difficult. It becomes especially difficult with sensory triggers, such as taste, smell, or touch. In order to determine one’s triggers, it is important to ask questions such as, “Where and when was I when my symptoms flared up?” or, “What was my experience during this flareup?”. Although, the primary and most beneficial way to discover one’s triggers is discussion with mental health professional.
Interestingly enough, after identifying one’s triggers, repeated exposure to them is one of the most effective treatments, also known as prolonged exposure therapy. This allows one to remove that trigger from the traumatic experience, bringing it to the present where it no longer holds significance. Along with this, there are a variety of other coping mechanisms one may pursue:
It is also imperative to stray away from unhealthy coping mechanisms, such as alcohol and drug use. The experience of PTSD triggers is a difficult and challenging one to overcome, but understanding their development, recognizing one’s triggers, and seeking help are the most important steps one can take.
References
Ehlers, A. (2010). Understanding and treating unwanted trauma memories in posttraumatic stress disorder. Zeitschrift Für Psychologie / Journal of Psychology, 218(2), 141–145. https://doi.org/10.1027/0044-3409/a000021
Reul, J. M. (2014). Making memories of stressful events: A journey along epigenetic, gene transcription, and signaling pathways. Frontiers in Psychiatry, 5. https://doi.org/10.3389/fpsyt.2014.00005
The endocannabinoid system is a complex biological system that helps to regulate various processes in the central nervous system. The endocannabinoid system plays a role in pain, memory, neuroprotection, and modulation of synaptic plasticity. The endocannabinoids are endogenous ligands that bind to CB1 and CB2 receptors in the brain and are produced via enzymatic degradation of naturally-occurring molecules. In English, this basically means that the endocannabinoids are produced by molecular scissors that cut off certain pieces of molecules that are already existing in the body. These newly-cut molecules then bind to the same receptors that are activated when one ingests marijuana. The endocannabinoids are responsible for regulating many things throughout the body, so I think it is important to discuss how endocannabinoid signaling works.
Endocannabinoid Signaling:
Endocannabinoids operate as retrograde messengers, meaning they mediate function on the pre-synaptic cell, rather than the post-synaptic cell. Endocannabinoid signaling begins the same way all neuronal signaling does—an action potential is sent through the neuron and a neurotransmitter is released. The neurotransmitter then binds to the post-synaptic cell, which allows for the influx of calcium into the post-synaptic cell. This is where endocannabinoid signaling differs from most other types of signaling. When calcium enters the post synaptic cell, endocannabinoids are released into the back into the synapse and bind to the CA1 and CB2 receptors (higher affinity for CA1 receptor, though). Once the endocannabinoids bind to their receptors, they can induce one of two things: depolarization-induced suppression of inhibition (DSI) or depolarization-induced suppression of excitation (DSE). The endocannabinoids induce DSE and DSI the same way, but which is induced depends on the type of pre-synaptic cell.
Depolarization-Induced Suppression of Inhibition
DSI is one result of endocannabinoid signaling. The CB1 and CB2 receptors are G-protein-coupled receptors (GCPR), which means they are associated with a G-protein. When the endocannabinoids are released from the post-synaptic cell and bind to the CB1 receptor, a complex signaling cascade occurs. The GPCR becomes a substrate for another enzyme called G-protein-coupled receptor kinases (GRK). GRKs are then targeted by beta-arrestin, which decouples the G-protein from the GPCR. Because the G-protein is uncoupled from the receptor, adenylyl cyclase is not activated, which then correlates with a decrease the levels of cyclic AMP (cAMP). The lowered levels of cAMP the inhibit calcium channels, thus decreasing the levels of neurotransmitters that are released, which opens potassium channels and causes hyperpolarization of the cell. In order for DSI to occur, the pre-synaptic cell has to be an inhibitory neuron. So, when the cell is hyperpolarized by the binding of endocannabinoids to the receptor, it suppresses the inhibitory effect of the pre-synaptic cell. This is a lot of information with a lot of acronyms, so I know it is easy to get lost. To try to help you understand DIS, I have included an image below that hopefully clears up any confusion.
Fig. 1. An image that shows the different steps of the endocannabinoid signaling cascade, including a description of what is happening. Drawn by H. Almlie.
Depolarization-Induced Suppression of Excitation
DSE is not much different from DSI. The exact same signal cascade occurs both DSE and DSI, so I will not go through the entire signaling cascade in words. There is a difference in which ion enters the post-synaptic cell, but this is a minor difference that doesn’t affect the rest of the cascade. The only major difference is the result of the hyperpolarization. In the DSI signaling cascade, hyperpolarization of the pre-synaptic neuron suppresses its inhibitory effects. In DSE, the endocannabinoids are acting on an excitatory pre-synaptic cell. So, when the cell becomes hyperpolarized, the excitatory effects of the pre-synaptic neuron are suppressed. A summary image of the signaling cascade is shown below.
Fig. 2. An image of the various steps of the endocannabinoid signaling cascade, including descriptions of what is happening. Drawn by H. Almlie.
Synaptic Plasticity:
I have discussed the signaling pathway of the endocannabinoid system so that it is easier to visualize how synaptic plasticity is modulated by the system. So, I described in detail how depolarization-induced suppression of inhibition occurs, which we can then transfer to depolarization-induced suppression of excitation. Through these two mechanisms, the endocannabinoid system modulates synaptic plasticity. DSI helps to strengthen neural pathways decreasing the amount of inhibition that pathway experiences. DSE helps to weaken neural pathways by decreasing the amount of excitation experienced by neurons in that pathway. So, DSE and DSI help to modulate synaptic plasticity by essentially doing the opposite of what those neurons usually do. In this way, endocannabinoids play an essential role in modulating synaptic plasticity within the central nervous system.
What kinds of learning occurred for you during this semester?
I learned how to read, break down, and organize difficult scientific literature along with present to my classmates.
How do the skills, competencies, and knowledge gained in the experience (CAP, blogging) relate to your future goals?
During the Community Action Project, I learned how to connect with the elderly population and collaborate with a team and other companies. The skills that I strengthened and developed during this project will help me with my future goals as I work with co-workers, patients, and other companies. My patients will consist of all ages, however, I wish to especially work with the elderly population, so this experience has helped me learn how to connect with them virtually and over the phone rather than just in person. This skill is important as I envision the future will consist of more virtual appointments and communication.
What does learning at a liberal arts institution mean to you?
Learning at a liberal arts institution to me means that I have a well-rounded learning experience consisting of a diverse range of classes and topics taught. Smaller class sizes enable me to make connections with my professors and the majority of students within my area of study or interests. The liberal arts philosophy focuses not only on student success but student growth. Students at a liberal arts institution learn valuable skills within their area of study along with current and historical social justice issues.
If you were to highlight on your resume a skill or competency that you improved upon this semester, what would you be sure to include?
I would highlight on my resume that I learned how to work better with a team and connect with other businesses along with participants of our project virtually.
Describe an example of solving a problem using several disciplinary perspectives.
In this class, we learned how to solve the problem of not understanding concepts within scientific articles. To solve this problem, each student learned how to read, break up, and organize the article. The class then expressed their interpretations, questions, and misunderstandings to each other. These questions were collected and assigned to students to answer. After researching their assigned question each student would then present their findings to the class so other students could widen their understanding of the topic. Following the presentations, the students worked in small groups to work on remaining questions and misunderstandings together.
The endocannabinoid system (ECS) was a mysterious being for quite some time, considering its recent discovery in only 1988. Although it is still in its infancy from a research standpoint, it is now known to be a major regulator with one primary goal: maintaining homeostasis. Many researchers consider the ECS to be the most important physiological system in establishing and maintaining human health. This is due in large part to the extensive network of cannabinoid receptors (CBR) located throughout the central nervous system (CNS), from neurons to immune cells to glands to organs. The ECS has been shown to be involved in many imperative processes:
Appetite and digestion
Neuroprotective effects of CB1R activation through GSK-3 inhibition (Snitow, Bhansali, and Klein, 2021).
Due to the wide range of ECS functions and receptor activation, the use of endocannabinoids, specifically cannabis, have been implicated in the treatment of a variety of diseases. Some of these diseases include multiple sclerosis (MS), Alzheimer’s disease (AD), and Huntington’s disease (HD). This is due to the fact that activation of CB1R by endocannabinoids have been shown to promote neuroprotective effects (Kendall and Yudowski, 2017). It has been found that administration of THC increases phosphorylation of Akt in the hippocampus, striatum, and cerebellum, mediated by CB1R (as phosphorylation was blocked with CB1R antagonist). Along with this, THC was also shown to increase inhibitory phosphorylation of GSK3ß (Ozaita, Puighermanal, and Maldonado, 2007). GSK3ß inhibition is involved in the activation of Wnt signaling and its target genes, one of these genes being BDNF which is heavily involved in neuroprotection. Inhibition of GSK3ß is also involved cell proliferation and survival (Snitow, Bhansali, and Klein, 2021). The molecular underlying of CB1R activation through THC has shown to provide neuroprotective effects in battling neurodegenerative disease. Along with maintaining homeostasis, the ECS may be necessary for much more.
How does the ECS Work?
The ECS utilizes endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and enzymes to break down endocannabinoids. The endocannabinoids, 2-AG and anandamide (AEA), are retrograde ‘neurotransmitters,’ meaning they work from post to pre-synapse, rather than pre to post-synapse. Also, rather than being synthesized prior to use and stored in vesicles such as traditional neurotransmitters, endocannabinoids are rapidly synthesized upon demand. They are then released into extracellular space where they bind to a CBR on the pre-synaptic terminal (Lu and Mackie, 2016). There are two main types of cannabinoid receptors:
Crystal structure of the human cannabinoid receptor (Hua et al., 2016).
Cannabinoid Receptor 1 (CBR1) – a G-protein coupled receptor (Gi/o) abundant in neurons of the CNS (cortex, basal ganglia, cerebellum, and hippocampus)
Cannabinoid Receptor 2 (CBR2) – a G-protein coupled receptor (Gi/o) abundant in the immune system and associated structures
Some researchers hypothesize that there may be a third cannabinoid receptor as well. Although, these are likely widespread with each receptor having a specific function (Sallaberry and Astern, 2018). Lastly, the ECS has specific enzymes used to break down the endocannabinoids. AEA is primarily degraded by the enzyme fatty acid amino hydrolase (FAAH). A second degradation process may be through oxidation via cyclooxygenase-2 (COX-2) to form prostamides. 2-AG may be degraded by three hydrolytic enzymes: monoacylglycerol lipase (MGL) and alpha/beta domain hydrolases 6 and 12 (ABHD6 and 12). It may also be oxidized by COX-2, or under rare conditions, hydrolyzed by FAAH. MGL is the primary degrading enzyme for 2-AG (Lu and Mackie, 2017).
The ECS and Cannabis Use
The ECS interacts with both delta-9-tetrahydracannabinol (THC) and cannabidiol (CBD) in the marijuana plant, but in differing ways. THC is most similar to AEA, as they are both low-efficacy agonists of the CB1R (Lu and Mackie, 2017). Although, THC produces a high while AEA does not. This is due to the enzyme, FAAH, which breaks down AEA but is not able to break down THC. Therefore, THC acts as competitive inhibitor for the body’s natural endocannabinoids which produces a dramatic effect due to its psychoactive properties. Although, AEA has been shown to produce calming effects. Researchers believe CBD works through inhibiting the FAAH enzyme from breaking down AEA to produce a calm sensation without psychoactive side effects.
References
Kendall, D. A., & Yudowski, G. A. (2017). Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Frontiers in Cellular Neuroscience, 10. https://doi.org/10.3389/fncel.2016.00294
Ozaita, A., Puighermanal, E., & Maldonado, R. (2007). Regulation of PI3K/AKT/GSK-3 pathway by cannabinoids in the brain. Journal of Neurochemistry, 102(4), 1105–1114. https://doi.org/10.1111/j.1471-4159.2007.04642.x
Snitow, M. E., Bhansali, R. S., & Klein, P. S. (2021). Lithium and therapeutic targeting of GSK-3. Cells, 10(2), 255. https://doi.org/10.3390/cells10020255
Heart disease is the leading cause of death in the United States, with approximately 660,000 people dying of this condition every single year.[1] Heart disease is a very broad term that includes many different types of specific heart conditions. The most common type of heart disease is coronary artery disease, which is characterized by the build-up of plaque in your coronary arteries.[2] This cardiac disease is most commonly attributed to poor lifestyle habits including a lack of exercise, smoking, and a poor diet.[3] Obesity is also a major contributor to coronary artery disease (and is a potential consequence of the aforementioned lifestyle habits).[4] Obesity is a prevalent problem around the world, but it is considered an epidemic in the United States due to its prevalence. In 2018, 42.4% of adults were considered to be obese in the United States.[5]
Now that you have some basic information about obesity, I would like to use my social studies knowledge to compare and contrast obesity it two different countries: America and Mauritania. I will compare how obesity is perceived in these two countries and the prevalence of the condition, just because I think it is interesting to analyze and learn about. After delving into the social science aspect of obesity, I will then dive into the neuroscience. We will dip our toes into the water of Lake Obesity before diving head-first into the deeper waters of said lake.
Obesity in America
I already discussed some of the statistics regarding obesity in the United States, so I will not rehash those. I will, instead, discuss the general perceptions and representation of obesity in America. As I stated previously, obesity in American society is pretty common. A little under half of the population is considered to be obese. Despite its prevalence, there are a lot of negative stereotypes that accompany the image of obese individuals. Individuals who are obese are often thought to be lazy, unintelligent, and weak-willed.[6] Many individuals believe that weight is something that should be in a person’s control, but those who are obese have simply failed at remaining in control of how much they eat and exercise.[7] As I will discuss in a later section, this belief is not entirely true (hint: neurochemistry is involved).
Many people are fighting the stigma of obesity by promoting “body positivity,” which is a movement that encourages people to love their own body, no matter their weight. It also encourages others in society to embrace those who have more weight, rather than ostracizing them. The movement is not meant to promote obesity, but it is more focused on people accepting their body and not letting others judge them based on their size.[8] There are also television shows that spread awareness of the obesity problem—showing the struggles of those individuals who are obese (the television programs tend to show the extreme cases of obesity). Though there are many stigmas surrounding individuals who are obese, our society is progressing (albeit, slowly) to see obesity as more of a societal issue, rather than an issue of an individual not being able to control their eating and exercising habits.
Obesity in Mauritania
I have discussed how obesity is generally viewed in America, but I now want to discuss how obesity is viewed in a country located in West Africa. I learned about this country and some of its traditional practices in eleventh grade when I took geography. In the country of Mauritania, obesity is seen in a completely different light, compared to America. Obesity has a lot of positive stereotypes in Mauritania. In fact, women purposely become obese because of what it means for them. Obesity is equivalent to wealth in Mauritania because being obese implies you have enough money to purchase an excess of food. Women are encouraged to become obese in Mauritania because it makes the more desirable and beautiful in the eyes of potential husbands. Obesity has many positive connotations in this West African country, and I think it is an important contrast to note. If you want to learn more about Mauritania’s “fat camp” (where girls are sent to gain weight), I HIGHLY recommend watching this video. Start the video at 10:09 to skip to the part about Mauritania. I have also included a drawing below of the stereotypes associated with obesity in both countries, just as a summary.
Fig. 1. An image comparing perceptions of obesity in American and Mauritania. Drawn by H. Almlie.
Now that I have bored you to death by comparing how obesity is seen in two different countries, I want to give you whiplash and just talk a little bit about the neuroscience behind obesity. At the Thanksgiving dinner table, my dad asked a rhetorical question about why he feels full when he still wants to keep eating. Even though it was a rhetorical question, I answered his question. When you eat food, insulin and leptin receptors in your brain send signals to AgRP neurons and POMC neurons. AgRP neurons tell you to eat and POMC neurons tell you to not eat. So, when you are hungry, AgRP neurons are activated which encourages your body to intake food and limit energy expenditure. Meanwhile, the POMC neurons are inhibited, which means the signal to stop eating is not being sent. When you feel full, it is because the signals have switched so AgRP is being inhibited, while POMC is activated which is responsible for the “full” feeling you have after eating. In obesity, however, this signaling is altered. In obesity, the leptin and insulin receptors that are responsible for sending the signals to the AgRP and POMC neurons are resistant to their respective ligand. Because the receptors are resistant to their ligand, there is no regulation of the AgRP neuron, meaning your body is always receiving the signal to eat. This signaling cascade thus perpetuates the problem of obesity because you are not receiving the signal to stop eating. Jumping back to the section about obesity in America, this unregulated signaling is why obesity is not just simply a failure to control caloric intake—there are neurochemical changes going on in the brain that perpetuate the problem. The image below illustrates this neurochemical pathway and what is going on in obesity.
Fig. 2 An image that summarizes the neurochemical pathways of leptin/insulin signaling under normal conditions and obesity conditions. Image taken from https://moodle.cord.edu/pluginfile.php/1052912/mod_resource/content/2/inflammation%20and%20MD%202017.pdf
When sitting in class and finishing work many individuals look forward to a specific time of the day. This is the time in which we can snuggle into our beds and fall asleep. However, is sleep more important than we think? Sleep provides healing and restoration and promotes good health and recovery from illness. Sleep is a cyclical physiological process that alternates with long periods of wakefulness. It influences physiological function and behavioral responses. This is controlled by your internal clock called your circadian rhythm. The part of your brain that controls the circadian rhythm is the suprachiasmatic nucleus (SCN) nerve cells in the hypothalamus control the rhythm of the sleep-wake cycle and coordinate this cycle with other rhythms.
Sleep Disturbance
There are some symptoms of the sleep cycle that cause disturbances and result in lack of sleep. These include anxiety, restlessness, irritability, and impaired judgement. However, is lack of sleep really that big of a problem? Lack of sleep can have serious potential problems for one’s health including high blood pressure, diabetes, heart attacks, and heart failure. The previous list of health problems relates to that of physical health, but what about the physiological perspective of the brain? When making memories it is important to note that there are three types of ways in which something can become a memory. This includes acquisition-learning or experiencing something new, recall-having the ability to access the memory in the future, and consolidation-the memory becomes stable in the brain. The first two are through to be done while an individual is awake, however, consolidation requires an individual to be asleep. This is because adequate sleep aids in the health of your hippocamps and neocortex within the brain. These areas while sleeping are believed to replay the events of the day and review/process memories and move them into an area where they can be stored as long-term memories.
Are there medical ways to help insomnia?
GABA are inhibitory neurotransmitters of the central nervous system that aids in sleep. GABA inhibitors are broken down into three different generations of hypnotics based on the GABA receptor mediated inhibitory process. These include the first- and second-generation hypnotics being barbiturates and benzodiazepines, while the third generation of hypnotics being imidazopyridines and cyclopyrrolones. The first- and second-generation hypnotics decrease waking, increase slow-wave sleep and enhance paradoxical sleep. Slow-wave sleep is the third phase of sleep which is the deepest phase of non-rapid eye movement sleep. During this time dreaming and sleepwalking can occur. This stage is also important for memory consolidation, which is a process where recently learned experiences are transformed into long-term memory. When paradoxical sleep is reached intense brain activity in the forebrain and midbrain occur. It differs from slow wave sleep due to the absence of motor function except for eye muscles and the diaphragm. An individual is unable to sleepwalk but is still dreaming during this time. The third generation of hypnotics is like that of the first- and second-generation hypnotics on waking and slow wave sleep but has a decreased paradoxical sleep during the first few hours of sleep.
How do benzodiazepines work?
By Hannah P.
Benzodiazepines are a class of drugs named for their chemical structure that are commonly used to treat anxiety disorders and sleep-related disorders. They include well-known drugs like valium, Xanax, and klonopin. There are dozens of drugs in the benzodiazepine class, but the mechanism by which they all exert their effects is thought to be similar. The sedating and anxiety-reducing effects of benzodiazepines are believed to be attributable to the drugs’ actions at receptors for the neurotransmitter gamma-aminobutyric acid (GABA). In particular, benzodiazepines act at a subtype of GABA receptors called the GABAa receptor; GABAa receptors that also bind benzodiazepines are sometimes called benzodiazepine receptors. When benzodiazepines bind, or attach, to the GABA receptor, they bind at alocation separate from where GABA itself binds and exerts an influence over GABA binding. This type of action is called an allosteric effect, and in the case of benzodiazepines it results in increased action at the GABA receptor. There is not complete consensus on exactly how benzodiazepine binding affects activity at the GABA receptor but there is evidence to suggest that it increases the likelihood that GABA binding will activate the receptor and/or increases the effect that GABA has when it binds to the receptor. That effect is to open an ion channel and allow the passage of negatively charged chloride ions into the neuron. This influx of negatively charged ions pushes the membrane potential further from zero, or hyper polarizes it, and makes it less likely the neuron will fire an action potential.This type of neural inhibition is the basis for the effects of benzodiazepines, for by inhibiting the activity of neurons that make up networks involved with anxiety and arousal, the drugs are able to produce calming effects.
By Hannah P.