Endocannabinoid System: Marijuana as Treatment for Disease?

Endocannabinoids and the endocannabinoid system are a fairly recent area of study in the science world. When one just looks at the word “endocannabinoid,” probably one of the first things that comes to mind is “weed” or cannabis. This thought is valid and partially correct as the cannabinoids found in cannabis are incredibly similar to the ones naturally produced by our bodies, the endocannabinoids. Endocannabinoids are neurotransmitters that are released in the body as necessary, and they assist with multiple bodily functions. The two main endocannabinoids are arachidonyl ethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). Hydrolases and lipases break these endocannabinoids down after carrying out a response. 

The Endocannabinoid System (ECS)

The ECS is a biological system that contributes to the regulation of various bodily functions: 

  • Metabolism
  • Sleep
  • Pain
  • Immune responses
  • Homeostasis

These responses are triggered when an endocannabinoid binds to cannabinoid receptors on the surface of cells. Depending on the type of receptor and where in the body the endocannabinoid is binding to such a receptor, a variety of responses can be carried out. The two primary receptors are CB1 and CB2 receptors which are G-protein coupled receptors with endocannabinoids as their agonists.

CB1: Present in the central nervous system (brain and spinal cord). Binding to CB1 can result in pain relief.

CB2: Present in the peripheral nervous system and immune system. Binding to CB2 can result in anti-inflammatory responses. 

 

ECS and Neurodegenerative Disease

Recent studies have found potential therapeutic targets of the ECS in neurodegenerative diseases such as Huntington’s disease, Alzheimer’s disease, and Multiple Sclerosis. No, this does not involve smoking marijuana as a treatment for these diseases. In general for these diseases, it was found that increased expression of CB1 and CB2 creates neuroprotective effects and increases synaptic plasticity. In the case of Alzheimer’s, activation of these receptors even prevented amyloid beta plaque buildup, characteristic of the onset of Alzheimer’s disease! Although these findings are quite promising, there are still many challenges to concur before these treatments are put into practice. Due to the widespread expression of endocannabinoids and their variable role in excitatory and inhibitory processes, there is still much to learn about this vast system. 

ECS and Drug Abuse

The ECS plays a key role in our bodies reward pathways, both natural and drug-related. Endocannabinoids and cannabinoid receptors are highly expressed in the mesocorticolimbic system which houses most of the body’s dopamine pathways. With drug addiction, endocannabinoids and their receptors participate in compulsion, maintenance of drug consumption, and the loss of control seen with addicted individuals. The ECS is modified by drug consumption and even further modified with addiction, contributing to such addiction. 

On a brighter note, research is currently being done to target the ECS to treat addiction. A negative allosteric modulator for the CB1 receptor and inhibitor of the CB2 receptor are being studied as a hopeful treatment of the overactive ECS we see in addicted individuals! There are even studies that show the use of CBD or marijuana as a potential treatment for drug addiction as it has a power to reduce cravings and increase the feeling of reward without the drug of addiction. Basically, using other drugs to treat drug addiction! Makes sense, right? That is the beauty of the endocannabinoid system!

References

De Pietro, M. (2021). “What to know about endocannabinoids and the endocannabinoid system.” Medical News Today. https://www.medicalnewstoday.com/articles/endocannabinoid#production.

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

Manzanares, J. et al.  Role of the endocannabinoid system in drug addiction. Biochem Pharmacol 2018, 157:108-121. https://pubmed.ncbi.nlm.nih.gov/30217570/.

Navarrete, F.; García-Gutiérrez, M.S.; Gasparyan, A.; Navarro, D.; López-Picón, F.; Morcuende, Á.; Femenía, T.; Manzanares, J. Biomarkers of the Endocannabinoid System in Substance Use Disorders. Biomolecules 2022, 12, 396. https://www.mdpi.com/2218-273X/12/3/396.

Breaking Down Metabolic Syndrome: The Silent Threat to Our Health

 

 

Artstract on DALL.E

Metabolic syndrome, a cluster of conditions including obesity, high blood pressure, high blood sugar, and abnormal cholesterol levels, has been shown to have significant effects on the gut microbiome. Studies have found that individuals with metabolic syndrome have a less diverse microbiome, with decreased abundance of beneficial bacteria and increased abundance of harmful bacteria. These changes in the microbiome have been linked to increased inflammation, insulin resistance, and other aspects of metabolic syndrome. Additionally, some research suggests that alterations in the microbiome may contribute to the development of metabolic syndrome. Further studies are needed to fully elucidate the complex relationship between metabolic syndrome and the gut microbiome but targeting the microbiome may offer new avenues for treatment and prevention of metabolic syndrome [1].

 

Hypothalamic Microglia and Metabolic Syndrome

Hypothalamic microglia are a type of immune cell found in the hypothalamus region of the brain, which plays a crucial role in regulating metabolism and energy balance. In Metabolic syndrome, chronic low-grade inflammation can occur in the hypothalamus, leading to dysfunction of hypothalamic microglia, and subsequently, metabolic dysregulation. These activated microglia can release pro-inflammatory cytokines and reactive oxygen species, which impair the function of hypothalamic neurons and promote insulin resistance, obesity, and other components of Metabolic syndrome. Modulating the function of hypothalamic microglia could potentially be a therapeutic target for treating Metabolic syndrome and associated diseases [2].

Figure 1. Factors impacting myeloid cells in the MBH to regulate hypothalamic control of energy homeostasis


Social and Environmental Factors

Metabolic syndrome is influenced by a variety of social and environmental factors. Lifestyle factors such as physical inactivity, unhealthy diet, and stress can contribute to the development of metabolic syndrome. In addition, social determinants of health such as low socioeconomic status and limited access to healthcare can also increase the risk of metabolic syndrome. Environmental factors such as pollution and exposure to endocrine-disrupting chemicals may also play a role in the development of metabolic syndrome. Addressing these social and environmental factors through public health policies, community-based interventions, and individual behavior change may help reduce the burden of metabolic syndrome and related health complications [3].

Vegetable oils, such as corn, soybean, and canola oil, have been linked to an increased risk of obesity. These oils are high in omega-6 fatty acids, which are pro-inflammatory and can promote insulin resistance, a key factor in the development of obesity and metabolic syndrome. Additionally, these oils are often used in processed and fried foods, which are high in calories and may contribute to overconsumption. Replacing these oils with healthier fats, such as olive oil or avocado oil, may have beneficial effects on weight and overall health. Reducing the intake of processed and fried foods, in general, can also promote a healthier diet and lower the risk of obesity.

Processed sugar is a major contributor to the obesity epidemic. Consuming large amounts of sugar, particularly in the form of sugary drinks and processed foods, can lead to weight gain and other health complications. Excess sugar intake can contribute to insulin resistance, a key factor in the development of obesity and metabolic syndrome. Sugar also lacks important nutrients and can displace more nutrient-dense foods in the diet, leading to overall poor dietary quality. Reducing the intake of processed sugar is an important step in preventing and managing obesity, and can have numerous other health benefits.

[4]

Figure 2. Social and Environmental Factors


Interventions

Lifestyle interventions such as diet modification, regular exercise, and weight loss are the first-line treatments for metabolic syndrome. Medications may also be used to control blood pressure, blood sugar, and cholesterol levels. In addition, some studies have shown that certain supplements and herbs, such as omega-3 fatty acids, probiotics, and green tea, may have potential benefits in managing metabolic syndrome. Bariatric surgery may also be considered in individuals with severe obesity and metabolic complications. Overall, the treatment of metabolic syndrome requires a multifaceted approach that addresses both lifestyle factors and medical management [5].

 

Resources

[1] Jais, A., & Brüning, J. C. (2017, January 3). Hypothalamic inflammation in obesity and metabolic disease. The Journal of Clinical Investigation. Retrieved May 1, 2023, from https://doi.org/10.1172/JCI88878

[2] Folick, A., Cheang, R. T., Valdearcos, M., & Koliwad, S. K. (2022, April). Metabolic factors in the regulation of hypothalamic innate immune responses in obesity. Experimental & molecular medicine. Retrieved May 1, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076660/

[3] Ghosh, S., Dhar, S., Bhattacharjee, S., & Bhattacharjee, P. (2023, April 11). Contribution of environmental, genetic and epigenetic factors to obesity-related metabolic syndrome – the nucleus. SpringerLink. Retrieved May 1, 2023, from https://link.springer.com/article/10.1007/s13237-023-00420-y

[4] Beulens, J. W. J., Pinho, M. G. M., Abreu, T. C., den Braver, N. R., Lam, T. M., Huss, A., Vlaanderen, J., Sonnenschein, T., Siddiqui, N. Z., Yuan, Z., Kerckhoffs, J., Zhernakova, A., Brandao Gois, M. F., & Vermeulen, R. C. H. (2021, November 18). Environmental risk factors of type 2 diabetes-an exposome approach – diabetologia. SpringerLink. Retrieved May 1, 2023, from https://link.springer.com/article/10.1007/s00125-021-05618-w

[5] Saboya, P. P., Bodanese, L. C., Zimmermann, P. R., Gustavo, A. da S., Macagnan, F. E., Feoli, A. P., & Oliveira, M. da S. (2017, January). Lifestyle intervention on metabolic syndrome and its impact on quality of life: A randomized controlled trial. Arquivos brasileiros de cardiologia. Retrieved May 1, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5245849/

How Neurochemistry Shaped My Future

Welcome to my final blog post of the semester! As an international student from Rwanda studying at Concordia, my experiences in the neurochemistry class have been unique and have allowed me to integrate and apply the skills and competencies that I have gained throughout my education here.

At Concordia, the emphasis on liberal learning and becoming responsibly engaged in the world has been a guiding principle for me. In particular, the five goals for liberal learning have been instrumental in shaping my educational experience. As an international student, I have found that these goals have been especially important in helping me develop a better understanding of American culture and its connections to my own culture.

Over the course of the semester, I have gained a deeper understanding of neurochemistry and its connections to other disciplines such as biology, psychology, and pharmacology. By examining neurochemistry from these interdisciplinary perspectives, I have developed a more comprehensive and nuanced understanding of this field. This learning has allowed me to apply my foundational skills and transferable intellectual capacities in new and exciting ways.

In addition to enhancing my understanding of neurochemistry, the skills and competencies I have gained in this class are highly applicable to my future aspirations of becoming a healthcare professional. As an international student from Rwanda, I am well aware of the challenges that lie ahead in pursuing a career in medicine. However, instead of being discouraged by these barriers, I feel more determined than ever to overcome them and make a positive impact in the healthcare industry. The insights gained from studying neurochemistry have given me the confidence to tackle complex problems and approach patient care from a holistic perspective. With a deep understanding of how the human body and mind function, I am confident that I can provide excellent care to patients from all backgrounds. Ultimately, I believe that the skills and competencies I have gained through this course will be instrumental in achieving my long-term goals of becoming a compassionate and competent healthcare professional.

To me, learning at a liberal arts institution like Concordia means developing a well-rounded understanding of the world that prepares me to be a responsible and engaged citizen, not just in the United States but also in my home country of Rwanda. It means approaching problems from multiple perspectives, cultivating my own sense of self-awareness and ethical responsibility, and developing the skills and competencies necessary to be successful in a rapidly changing world.

One of the skills that I have improved upon this semester is my ability to think critically and solve problems using multiple disciplinary perspectives. As an international student, I have had to navigate cultural differences and overcome language barriers to succeed in this class. Having a supportive professor and a positive classroom environment played a crucial role in my success.

Overall, I am grateful for the opportunity to study neurochemistry at Concordia and to apply the skills and competencies that I have gained throughout my education here. As an international student with aspirations of going to medical school, I know that the journey ahead will be challenging. However, I am confident that my experiences at Concordia have prepared me well for this journey, and I look forward to applying these skills and competencies as I pursue my future goals in healthcare.

Reference:

https://catalog.concordiacollege.edu/core-curriculum/goals-liberal-learning/

Psychopathy EXPLAINED

What is Psychopathy?

Psychopathy can be characterized as an individual who has shallow emotional response, lack of empathy, impulsivity and an increased likelihood for antisocial behavior. No this does not mean that one day of being emotionless or not wanting to have emotions makes you a psychopath. There are a lot of components going into a psychopathic diagnosis. One interesting statistic is that by Hare’s psychopathy checklist-revised, psychopaths make up around 20% of the prison population in North America.[1] Considering this statistic, psychopaths are prone to violence and usually have increased aggressive behavior therefore commit a greater number of violent attacks compared to non-psychopaths.[1]

There is a possible relation to having a certain gene increasing susceptibility to psychopathy. An individual could inherit a specific genetic pathway toward psychopathy which is associated with low-expression variant of Monoamine Oxidase (MAO-A) gene. The MAO-A gene functions to encode an enzyme that degrade dopamine, norepinephrine, and serotonin. There has been research on the MAO-A polymorphisms tied to short allele and psychopathic and antisocial traits.[2]

 

Psychopathy versus Antisocial Personality Disorder

Psychopathy: psychopaths characterized as selfish, domineering, irresponsible, impulsive, fearless, shallow, as well as lacking empathy and remorse. Not restricted to people showing criminal or deviant behavior, therefore may also be found in “socially well-adjusted and successful individuals”.[4]

Antisocial personality Disorder: characterized as lack of self-control (prefrontal cortex), low avoidance of punishment and negative stimuli (amygdala), and heightened sensitivity to rewarding stimuli (striatum).[4]

Figure 1: Comparison of antisocial personality disorder and psychopathy as they relate to Dis-social behaviors and personality disorders.[4]

 

What is going on in the brain?

In psychopathy it was found that there are deficits in frontal, temporal, and subcortical limbic structures of the brain. Overall, there was reduced amygdala function found in adult psychopaths and a failure of top-down regulatory control of ventral PFC. Therefore, emotional blunting was found in those diagnosed as psychopaths. Along with this the amygdala, commonly known for control of processing fear, plays a role in the emergence of aggressive behaviors sometimes associated with psychopathy as it has been found that the amygdala is smaller in those with psychopathy. For violent or aggressive behaviors, there could also be a correlation to reduced glucose metabolism in the corpus callosum. Interestingly enough, the striatum which consists of caudate, putamen, nucleus accumbent, and globus pallidus is found to be enlarged by 9.6% in psychopaths.[3] Lastly, psychopathy is associated with substance abuse, or that sensation-seeking behavior, which could produce orbitofrontal impairments.

Possible correlations to alcohol…

During the in-womb development it has been noted that consumption of alcohol could be associated to increased childhood aggression. This as evidenced by a “longitudinal study of over 100,000 men documented that prenatal nutritional deficiency is associated with a 2.5 fold increased risk for Antisocial Personality Disorder in adulthood”. Interestingly enough, certain nutrient deficiencies have been associated with aggressive and antisocial behavior including low levels of omega-3 and zinc which play a role in building up omega-3 fatty acids critical for neural development. Early brain maldevelopment could be due to reduced zinc levels which involves the amygdala and hippocampus.[3]

Overall, there are a lot of components that go into how to screen for psychopathy. With around 1-2% of the adult general population with this diagnosis, psychopathy is a prominent mental health disorder compared to other psychological diagnoses.[1]

Work Cited

  1. Anderson NE, Kiehl KA. Psychopathy: developmental perspectives and their implications for treatment. Restor Neurol Neurosci. 2014;32(1):103-17. doi: 10.3233/RNN-139001. PMID: 23542910; PMCID: PMC4321752.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321752/#:~:text=Psychopathy%20is%20a%20neuropsychiatric%20disorder,antisocial%20deviance%20and%20criminal%20behavior
  2. Frazier A, Ferreira PA, Gonzales JE. Born this way? A review of neurobiological and environmental evidence for the etiology of psychopathy. Personal Neurosci. 2019 Oct 23;2:e8. doi: 10.1017/pen.2019.7. PMID: 32435743; PMCID: PMC7219694.
  3. Raine A. (2018). Antisocial Personality as a Neurodevelopmental Disorder. Annual review of clinical psychology, 14, 259-289. https://doi.org/10.1146/annurev-clinpsy-050817-084819
  4. Weber, S. Habel, U., Amunts, K., Schneider, F. (2008). Structural brain abnormalities in psychopaths – a review. Behavioral Sciences & the Law, 26(1), 7-28. https://doi-org.cordproxy.mnpals.net/10.1002/bsl.802.

Eating…More Complex than it Appears

What is obesity?

Obesity is considered to be an excessive or abnormal buildup of fat that causes risk to one’s health. Body mass index is how this is normally determined with people over 25 being labeled as overweight (Fig. 1). However, BMI is not always the most accurate representation because body mass can also be muscle weight instead of fat. For example, a body builder will obviously weigh more because of their muscle, but this does not mean they are obese. Society seems to have a stigma associated with the term “obese”, but the brain functioning behind this need to eat is important to understand. Furthermore, the problems with obesity do not stop there; the after-effects of the condition can include type 2 diabetes, dyslipidemia, cardiovascular diseases, and neurodegenerative disorders.

Fig 1. This graph shows how BMI is calculated. (3)

The hypothalamus and Obesity

One of the main components that plays a role in obesity relates to the hypothalamus, which is known for its role in homeostasis. The hypothalamus controls metabolic feedback and regulates energy homeostasis, so it has important influences on feeding behavior and energy spending. How does the hypothalamus do this? It is able to sense and integrate feedback from adipostatic hormones that are responsible for circulation of nutrients to adipose tissue. Specifically, leptin and insulin directly affect the ARC of the hypothalamus that works with energy homeostasis. However, neuronal inflammation and insulin and leptin resistance of the ARC neurons disrupts the metabolic feedback loop, which causes an increase food intake and body weight gain. Overconsumption of fat-rich diets changes the feedback sent to leptin and insulin, causing hypothalamus inflammation.

Further Inflammation caused by Saturated Fatty Acids

Inflammation can be worsened with other factors as well. One factor that plays a role in this are cytokines; they are small proteins that are vital in controlling the growth and activity of other cells. However, during diet-induced obesity, cytokines are overactivated, which farther leads to more hypothalamic inflammation. Saturated fatty acids can modulate neuronal control of energetic homeostasis as well. These fatty acids can cross the blood brain barrier, accumulating in the hypothalamus and triggering inflammatory signaling cascades.

Other eating Disorders- Serotonin and Dopamine

We know the background on the homeostasis imbalance that occurs for irregular feeding. Then, what are the eating disorders that can occur from different brain imbalances? First of all, eating disorders are serious health conditions that affect both your physical and mental health. These conditions include problems in how you think about food, eating, weight and shape, and in your eating behaviors (Fig. 2). These symptoms can affect your health, your emotions, and your ability to function in important areas of life.

Dopamine and serotonin also have been linked to eating disorders like anorexia. Dopamine is a chemical involved in weight, feeding behaviors, reinforcement, and reward. Since serotonin is involved with satiety and dopamine is associated with the brain’s reward system, altered receptor activity may explain why people with Anorexia have reduced hunger signals and alterations in their food reward system. Dopamine has also been linked with binge eating because it has a role in food cravings, decision making, executive function, and impulsivity, as well as its functional associations with these risk factors.

Fig 2. This figure summarizes the different types of common eating disorders. (4)

Conclusion

Obesity has a negative connotation often associated with it in society. However, it is important to understand the complexity behind what causes obesity. Obesity is not the only eating disorder that impacts so many lives; rather, there are many others as well that are caused by the changes in our brains. The hypothalamus, specifically, is often affected because of its role in homeostasis. The reward system is also crucial in how we eat and see food. The complexity behind eating is great and not an easy obstacle to overcome.

Citations:

  • Jais, A., & Brüning, J. C. (2017). Hypothalamic inflammation in obesity and metabolic disease. Journal of Clinical Investigation, 127(1), 24–32. https://doi.org/10.1172/jci88878
  • Steiger, H. (2004). Eating disorders and the serotonin connection: State, trait and developmental effects. Journal of Psychiatry and Neuroscience, 29(1).
  • The Editors of Encyclopaedia Britannica. (2008, December 3). Body mass index (BMI). Encyclopedia Britannica. https://www.britannica.com/science/body-mass-index
  • Ward-Zaragoza, M. (n.d.). Eating Disorder Awareness Week explained: Support, resources, symptoms. Buena Speaks. Retrieved April 29, 2023, from https://buenaspeaks.org/6407/features/eating-disorder-awareness-week-explained-support-resources-symptoms/
  • WHO, W. H. O. (2020, February 21). Obesity. World Health Organization: WHO. https://www.who.int/health-topics/obesity

 

 

 

 

A Bittersweet Goodbye to Concordia – My Capstone Experience

With graduation just a short 8 days away, this is my last assignment for a class ever! I am sitting in a Starbucks sipping on an iced chai tea reminiscing on how much I have grown as a student and as a person over the last four years thanks to Concordia and the liberal arts curriculum.

If I am being honest, I only applied to Concordia because the mascot was a corn cob and I love corn. I later found out that it was a liberal arts college, and being a first-generation student, I had no idea what that meant. I took the time to look up exactly what that meant and I really loved that Concordia was going to give me this well-rounded education that isn’t offered at other universities around Fargo-Moorhead.

When I began taking classes that didn’t fully align with my major, I was a little upset because all I wanted to do was learn about psychology and neuroscience. My mind completely changed the more I took classes such as Spanish, religion, English, philosophy, and many more. These classes showed me a new perspective on life and I will forever be grateful for that.

Neurochemistry was the final class I needed to complete my neuroscience major and to be honest I was scared that I wasn’t going to be good at this class. I thought that I wasn’t going to be smart enough to understand all the signaling pathways, but I was wrong! Neurochemistry turned out to be in my top 3 favorite classes ever taken at Concordia. The structure of this class has been life changing. Being able to read articles about real life things, research something I am interested in each week, and getting to have discussions with my classmates has made this class more beneficial that I could’ve ever imagined.

Concordia College has five goals for liberal arts learning and I truly believe I have met every single one of these goals throughout my four years here.

  1. Instill a Love for Learning:
    • I have always loved school but making the choice to go to college and commit to another four years of learning is a huge deal. I was excited to continue my education and learn things that I never knew existed, which is what I did in each class I took at Concordia. Learning is a life-long process and I am more than happy to continue learning in any I can whether that be in a classroom or through societal connections in the world around me. I have treated my classes as opportunities to learn and not just assignments and tests that I have to do. I am able to learn new information everyday and use it to understand the world around me.
  2. Develop Foundational Skills and Transferable Intellectual Capacities: 
    • People have always said that the skills you learn in school will be skills you need for the rest of your life, and boy were they right! I have learned how to problem solve, critically think, make decisions, acknowledge other perspectives, assess all kinds of information, and more. Throughout the many classes I have taken, I have learned and used one of more of the skills listed above. These skills are going to follow me into my career and even in my everyday life. Being able to use critical thinking to work through a problem is the skill I value most. I will fully admit I was not a good critical thinker until I came here and was constantly challenged (in a good way) by my professors to work through problems and use all of the knowledge I have and different perspectives to try and solve it, and I will appreciate that forever.
  3. Develop an Understanding of Disciplinary, Interdisciplinary, and Intercultural Perspectives and their Connections:
    • Something that I learned pretty early on was the fact that you can use the things you learn in your major and apply it to almost any other class you take or even just your life. Neuroscience is one of the biggest interdisciplinary majors because of how applicable it is to every aspect of life, which is why I love it so much! Everything I have learned in my neuroscience classes I have been able to use in other classes I take, even Spanish! By being proficient in neuroscience and psychology I am able to expand the things I learn to other areas to help me understand those areas as well, creating a well-rounded education.
  4. Cultivate an Examined Cultural, Ethical, Physical, and Spiritual Self-Understanding:
    • I have learned so much about myself and other people throughout my time here. There are many factors that make someone who they are and I didn’t even pay attention to this until I started taking classes here. Without this well-rounded education, I truly don’t think I would be able to understand myself and others as much as I do right now. I have learned about religion, culture, spirituality, social, and many more factors that make people who they are. This has allowed me to shut down any preconceived notions about people because I do not know everything about someone and how these factors are affecting them on a daily basis.
  5. Encourage Responsible Participation in the World: 
    • BREW! One of the many acronyms used at Concordia. I wish I would’ve kept track of how many times I have said BREW over the past four years because it would definitely be in the triple digits. Once I learned what BREW meant, I saw it applying to my life almost daily! I have loved being able to take what I learn in school and use it to influence the outside world. I love seeing my school world and my outside world collide – it makes me light up with joy. I love learning and I love sharing what I learn with everyone! I love introducing people to new ideas and new perspectives of thinking.

Over the past four months, neurochemistry has allowed me the space to think about all of these goals. I have hit all of them in my four years at Concordia, but also in the last four months taking this class. Dr. Mach provides a great environment for learning and for thinking about things that aren’t found in a textbook. This class has  made me learn in new ways, such as trying to understand a complex disease, trying to figure out the connections between the topics we talk about and the outside world, and so many more ways that I can’t even explain them. My critical thinking has grown exponentially the past four months and that is 100% because of this class and the way it is structured. This skill and many more will forever follow me.

Concordia College has been my home away from home for the past four years and it is time to say see you later. I will forever be grateful for the experiences that were  offered to me, the friends I made, the professors who believed in me when I didn’t believe in myself, and the turkeys for making me smile everyday.

Soli Deo Gloria

Olivia Pederson, Class of 2023.

 

 

Endocannabinoids with Cannabis

 

Cannabis on the Brain

The Endocannabinoid system regulates and controls many of our critical bodily functions such as learning, memory, emotional processing, sleep, temperature control, pain control, inflammatory and immune response, along with eating. [3] Therefore, the Endocannabinoid system has a major role in homeostasis and neuroplasticity of the brain and increased signaling is associated with reduced stress response, improved emotion regulation, and increased reward signaling.[1]

 

In the brain, the most populated receptors are the CB1 receptors as they function to regulate the levels and activity of most of the other neurotransmitters such as those that control hunger, temperature, or alertness. To stimulate the CB1 receptors there are molecules called Endocannabinoids that have a structural similarity to molecules of the cannabis plant. Interestingly enough, the first Endocannabinoid was named anandamide after the Sanskrit word ananda which means bliss. Therefore, with structural similarity to Endocannabinoids intake of cannabis can hijack the Endocannabinoid system.

As related to the Endocannabinoid system, THC in cannabis is a partial agonist with high affinities for both CB1 and CB2 receptors along with psychotropic effects. Overall THC has been shown to activate CB1 receptors in the cerebral cortex, hippocampus, caudate/putamen, globes pall idus, substantial nigra, and cerebellum. Whereas, CBD is non-psychotropic effects and inhibits drug-seeking and self-administration in animal models. CBD does not bind to CB1 and CB2 receptors with high affinity. [1]

Fun fact: As we know that the hunger signal mainly comes from the hippocampus of the brain, cannabis intake stimulates CB1 receptors, which are high in the hippocampus, eliciting the “munchies” or need to consume more food for the consumer.

Positives for certain treatments

Two different components in cannabis are CBD and THC. CBD has been shown to be beneficial for Alzheimer’s disease, cerebral ischemia, multiple sclerosis, and other neurological disorders. THC has been approved for certain medical diagnoses usually including cancer or those individuals going through chemo treatment to elicit a hunger response and get them to eat more during treatment. Some examples of the pill form of THC offered are dronabinol, nabilone, and pure THC which is marketed as Marinol.

With the THC pill there is slow absorption that depends on the rate of gastric emptying before it has any psychoactive effects on the consumer whereas smoking there is direct entrance to the brain and the bloodstream. Along with this there is a higher risk of fatal overdose by swallowing too many THC pills.

As for the benefits of cannabis as a whole is that there is alleviation of chronic pain, inflammation, spasticity, and other conditions see in physical therapy practice. [1]

Negatives from long term usage

THC use in low doses may relieve anxiety however in higher doses can provoke anxiety and paranoia as responses are exacerbated by inhalation of cannabis. [4] Overall, THC has been shown to have adverse effects on executive functioning in the brain short-term therefore, effecting planning, reasoning, interference control, and problem solving. As for effects of chronic use of cannabis it has been found to negatively effect executive functioning and working memory along with processing speed. Certain parts of memory are impaired includes verbal learning, encoding, recall, and recognition. Some other notable impairments from cannabis use include effects on inhibition, impulsivity, and decision-making.

Why research is limited

Cannabis usage was at 183 million past year users in 2017 [1], however it is distributed at the local level depending on the state regulations it has been challenging for research companies to get ahold of the drug without going through a lot of barriers to obtain the substance. To research potential therapeutic cannabis usage researchers must obtain approval from a range of federal, state, or local agencies, institutions, or organizations along with applying for grant funding which goes with other barriers to research. In this last resource there is a more in-detail description of what process researchers need to go through. [5]

Cannabis intake can help to up-regulate the Endocannabinoid system through substance, however there are certain costs as previously talked about with usage. Other more natural ways to elicit the endocannabinoid system could be just as simple as exercise.

Brain Enhancement

Abstract by Anna Dekkenga

What are nootropics?

Nootropics can be defined as “natural, semi-synthetic and synthetic molecules that claim to enhance cognitive function.” Often, they are consumed in the form of supplements. However, these supplements have yet to be approved by the FDA for the general population.

Figure 1. Do drugs really enhance the brain? Nootropics_1682517407.jpg

Intellectual Disability

Intellectual disability, or ID, affects 1 in 20 people in the United States. Those who suffer from ID also suffer from emotional and financial burdens along with “direct impairments on the individual and their ability to function in society.” [1] As such, there have been many attempts to improve the everyday lives of these people. However, all these therapies can be challenging because one size doesn’t fit all in this case. For example, a medication that targets gene defects may work for a person who develops ID because of a gene mutation, but it will not work for someone who develops ID because of disease. It’s clear that a one size fits all therapy would be the best outcome for everyone. Therapies that generalize to many types of disorders or conditions that are associated with cognitive dysfunction may be useful. There are a total of six neurocognitive domains, pictured below, that are assessed when addressing ID: perceptual and motor function, language and memory, social cognition, attention, and executive function. All these domains function together, and they do not and cannot operate in an isolated form. Knowing this, scientists have been working on multiple strategies that would help to enhance cognitive functioning. The two that will be addressed are environmental enrichment and pharmacological strategies that target signaling pathways.

Figure 1. Six neurocognitive domains. brain-more-than-memory-cognitive-functions-cerveau-plus-memoire-fonctions-cognitives-graph-en.png

Environmental Enrichment

   When talking about animals in this sense, it is easy to control their environment, but less so when talking about humans. Experimenting with rats, for example, researchers can control whether they are in an environment that enriches the rat or one that causes stress. Environmental enrichment is “the stimulation of the brain by its physical and social surroundings.” [2] It isn’t as easy to control our own environment, but we can avoid things that cause stress, as well as indulge ourselves in things that lead to happiness. Some examples that give us enrichment are mental stimulation, light, social partners, the birth of a baby, developing a hobby, etc. All these examples add value to our lives. [3]

Figure 3. Environmental enrichment for humans. 523670_Thumb_400.jpg

Pharmacological Strategies

   Before addressing that pharmacological strategies that can be used to treat ID, we first need to address BDNF. Brain-derived neurotropic factor, BDNF, plays an important role in survival and growth of neurons. It also plays a role in neuroplasticity which aids in memory and learning. BDNF is released in response to neuronal activity and binds to specific receptors on neuron surfaces which promotes their survival and growth. Too much or too little BDNF in the brain causes problems, everything in moderation. Too much may cause seizures, while too little is associated with ID. For those of us who do not suffer from ID, there are natural remedies to increase BDNF: coffee, blueberries, omega-3, zinc, and so much more. [4] Although supplements may not be FDA-approved, there are plenty of safe, healthy, and natural ways to increase BDNF levels. On the other hand, for those who do suffer from ID, ampakines seem to be a very promising remedy. Ampakines are drugs that directly increase the levels of BDNF, and support neuronal survival and differentiation.

So, what?

BDNF levels are decreased in the brains of those diagnosed with ID. There are non-pharmacological and pharmacological strategies to address this, and combining both is the most promising. Do not use this information as a diagnosis, or treatment for yourself or someone you may know. It’s important to know that these strategies may not work for everyone. All this information is just the basis to ID and what is going on in the brain. There still needs to be more development and research to help improve the lives of those with ID. But the information that has known is a great start.

 

[1] Morè, L., Lauterborn, J. C., Papaleo, F., & Brambilla, R. (2020). Enhancing cognition through pharmacological and environmental interventions: Examples from preclinical models of neurodevelopmental disorders. Neuroscience & Biobehavioral Reviews, 110, 28–45. https://doi.org/10.1016/j.neubiorev.2019.02.003

[2] McDonald, M. W., Hayward, K. S., Rosbergen, I. C. M., Jeffers, M. S., & Corbett, D. (2018, June 14). Is environmental enrichment ready for clinical application in human post-stroke rehabilitation? Frontiers. Retrieved April 27, 2023, from https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00135/full

[3] McDonald, M. W., Hayward, K. S., Rosbergen, I. C. M., Jeffers, M. S., & Corbett, D. (2018, June 14). Is environmental enrichment ready for clinical application in human post-stroke rehabilitation? Frontiers. Retrieved April 27, 2023, from https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00135/full

[4] How to increase BDNF: 10 Ways To Rescue Your Brain. Strong Coffee Company. (n.d.). Retrieved April 27, 2023, from https://strongcoffeecompany.com/blogs/strong-words/how-to-increase-bdnf-10-ways-to-rescue-your-brain

 

 

 

Barcode Hypothesis: GPCR phosphorylation patterns code their actions

When people hear anything about the endocannabinoid system their minds often go right to thinking about marijuana. Which isn’t surprising as marijuana use is increasing. According to the National Council of State Legislature, as of now 38 states in the US has approved medical marijuana use. It is not often that you get to see such a mass use, and approval of a schedule 1 class substance. In my opinion in all seems like it should be and is a touch and go process. With marijuana being a schedule 1 substance it very hard to study. There is very limited amount facilities able to study it and then limitations on the type of studies that are able to be done.

In 2019 the CDC reported that 18% of Americans had used marijuana that year. This is both medically and recreationally. The basis of marijuana’s effects on the endocannabinoid system is pretty mapped out. Yet, red flags do pop up for long term effects, effects on other system, etc. G protein coupled receptors (GPCRs) are the causes the activation of endocannabinoid system.  One of the most common note mentioned about activating endocannabinoid system (mostly by marijuana use) for treatment is the widespread effects, expression and many complex cascades that happen.

https://www.sciencedirect.com/science/article/pii/S0092867420315312The barcode hypothesis is often brought up. A unique characteristic about GPCRs is that phosphorylation occurs and that determines their roles downstream. It also gives the guide for how or which beta arrestin binds to the GPCR. Phosphorylation can cause the GPCR to be inhibited, it can cause activation of other membrane receptors, one article 2017 even mentions that a certain pattern can cause the GCPR’s to detach from the membrane. That is where the term barcode hypothesis comes from.

 

Yet, now think other than the phosphorylation pattern there is no control on the role that the GCPR is going to take. That certain barcodes cause certain cascades to occur causing a mass range of possibilities of expression.

Another article goes in to great detail cataloging all the different kinases and beta arrestins that can bind to GPCRs in the Endocannabinoid system. They also looked at the downstream effects that they had on the GPCR pathway. Phosphorylation effects if it binds on its side or in the middle. Even the affinity of the binding was all looked at. They found that the pattern of the phosphorylation mattered more than that number of phosphates. Which if you have been in the biochemistry world, you know structure equals function. Certain binding would even cause a conformational change for either the whole arrestin, but also only parts of the arrestin. This can directly effect binding of proteins downstream to the tail of the arrestin.

Why would this matter?

Well as mentioned earlier, studying the endocannabinoid system in regarding to marijuana’s effects is very hard. Yet it is legally allowed to be used and instructed as a treatment. Yet the truth is, it may cause benefits especially in the short term, but what about the long term? In my opinion makes me wonder why research restrictions couldn’t be lifted. That there are great possibilities that could from targeting the endocannabinoid system, but more precision would be nice to cut out any possible risks.

Nootropics

Nootropics

Nootropics, also known as “smart drugs” or cognitive enhancers, are substances that are believed to enhance cognitive function, memory, creativity, and motivation. Nootropics can include natural substances such as herbs and botanicals, as well as synthetic substances like prescription drugs and supplements.

While the use of nootropics is not new, interest in them has grown in recent years as people look for ways to optimize their mental performance. However, it is important to note that the effectiveness and safety of nootropics can vary widely, and some are not well-researched or regulated.

Potential Benefits of Nootropics

The potential benefits of nootropics are varied and depend on the specific substance being used. Some of the most commonly reported benefits include:

  1. Improved focus and concentration
  2. Increased memory and learning capacity
  3. Enhanced creativity and problem-solving abilities
  4. Reduced anxiety and stress levels
  5. Increased motivation and productivity

However, it is important to note that not all nootropics are created equal, and the effectiveness of these substances can vary widely based on individual factors like genetics, diet, and lifestyle.

BDNF

Brain-derived neurotrophic factor (BDNF) is a protein that plays a crucial role in the growth and survival of neurons in the brain. BDNF also plays an important role in the formation of new neural connections, which is key for learning and memory. Studies have shown that some nootropics may be able to increase BDNF levels in the brain, which could have potential benefits for cognitive function.

BDNF Signaling Pathway

BDNF, NGF, NT-3 Signaling Pathways
Ras-ERK Pathway

BDNF activates the Ras-ERK pathway. The Ras-ERK pathway is involved in a variety of cellular processes that are important for cognitive function, including neuronal growth and differentiation, synaptic plasticity, and long-term potentiation (LTP), which is a cellular mechanism thought to underlie learning and memory. Studies have shown that inhibiting the Ras-ERK pathway can impair LTP and cognitive function, while activating this pathway can enhance LTP and cognitive function.

One of the most well-known nootropics that may increase BDNF levels is exercise. Regular physical activity has been shown to increase BDNF levels in the brain, which may help improve cognitive function and reduce the risk of age-related cognitive decline.

In addition to exercise, certain dietary supplements have also been shown to increase BDNF levels. For example, omega-3 fatty acids found in fish oil have been shown to increase BDNF levels in the brain, which may help improve cognitive function and reduce the risk of depression.

As the paper for this week mentioned, combining environmental enrichment therapies with those that promote neuronal activity and signaling, such as selective activation of the Ras-ERK pathway, and/or facilitate brain-derived neurotrophic factor (BDNF) through the use of ampakines, may be a promising strategy for improving learning and memory in various forms of cognitive impairment, including those that occur during early development and aging. However, more research is needed to determine the extent to which these therapies can improve cognitive/behavioral impairments in different disorders or conditions of impairment, as well as the most effective treatment regimens.

References:

https://www.sciencedirect.com/science/article/pii/S0149763418302926?via%3Dihub

https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.frontiersin.org%2Farticles%2F10.3389%2Ffnins.2019.00790%2Ffull&psig=AOvVaw0Y1JZ9hwMRf9An4uAusnT0&ust=1682616000287000&source=images&cd=vfe&ved=0CBIQjhxqFwoTCICP4JmHyP4CFQAAAAAdAAAAABAD

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