How Music Changes Your Brain

The brief second of stillness immediately before the first downbeat is my favorite part of an orchestra concert, both as a cellist and as an audience member. So much goes into creating this single moment, even discounting the months of preparation of the orchestra and years of training of each member. The anticipation that hangs in the hall thick enough to cut, every musician breathing together, the eyes of every player on the conductor, the feeling of resistance as my bow grips the strings of my cello, and the silence of the audience’s anticipation for great music create a beautiful, liminal transitory tension that is, quite frankly, nothing short of addicting, even if it only lasts for a moment. I’ve played cello for the past ten years and I have yet to tire of that feeling. Yet, as interesting as that moment is, what goes on in the brain once the music starts is even more complex.

What listening to music does to the brain

Music is really cool. I freely admit that, as a music lover and musician, I’m biased and unable to objectively assess my own claim, but I think that my assertion is true and that I can convince you of that.

Did you know that music can reduce pain by activating the dopaminergic reward pathway (figure 1)? In fact, this reward pathway involves endogenous opiate signaling, which helps explain the pleasurable feeling you get from listening to your favorite Taylor Swift album on repeat and helps explain why we return to our musical favorites. While I doubt that this can fully explain why I’ve listened to the same Dear Evan Hansen song 59 times this year or why I spent over 27 hours listening to Vance Joy in 2019, I do think it’s clear that dopaminergic reward pathway signaling plays a role in bringing us back to our favorites.

Figure 1. Graphic showing that music causes increased dopamine release in the brain, leading to decreased pain sensation. (Strickland, Artstract #3).

Did you also know that music can help reduce stress and even help reduce the amount of anesthetic needed in surgery? This is probably the most interesting effect of listening to music that I’ve learned about to date. This impact is mediated by reducing stress hormones released along the hypothalamic-pituitary-adrenal (HPA) axis. Research shows that listening to relaxing music helped lower cortisol levels more rapidly after exposure to stress and prevented stress-induced increases in blood pressure and heart rate.

Importantly, the experiences of listening to music and performing music are incredibly different in terms of their impacts on the brain. While listening to music has the effects discussed earlier, making that music is even more involved. As Barrett, Ashley, Strait & Kraus describe in their 2013 article Art and Science: How Musical Training Shapes the Brain, “To be a musician is to be a consummate multi-tasker. Music performance requires facility in sensory and cognitive domains, combining skills in auditory perception, kinesthetic control, visual perception, pattern recognition, and memory.”

So that begs the question: How does musical training change your brain?

Our brains are highly plastic. Not literally. What I mean by that is that our brains constantly change in response to our environment and choices and musical training, similar to how exercise builds muscle mass and endurance, creates a few very interesting functional and anatomical changes. Specifically, instrumental musicians have more gray matter in the somatosensory, premotor, superior parietal, and inferior temporal areas of the cortex that correlate with their level of skill. Additionally, musicians show increased corpus callosum volume. The corpus callosum functions as the bridge between the left and right hemispheres of the brain. This suggests that musicians may have increased connectivity between the left and right hemispheres. Interestingly these anatomical differences facilitate more advantages than mere musicality. Research has also demonstrated that musicians’ more efficient audio-motor learning ability enables them to more accurately pronounce foreign languages and improves their spatial tactile acuity.

So, what does this all mean?

First, taken together, these data indicate that music is incredibly powerful.

Second, because music can be learned and taught, it’s clear that the benefits of being a musician can be realized by all if people are given the opportunity to learn. This, of course, opens the much broader discussion of equity and access to music – especially at early ages in public education. I simply would not be the musician and human I am today without my music instructors.

Can Music Reduce Your Stress and Pain Perception?

artstract by C.Eisenschenk

Music seems to be everywhere these days and serves a variety of purposes from person to person. Some use music to quell their nerves, others use it for focus measures, some may use it for working out, etc. Music provides a variety of purposes, including simple enjoyment. So, what is music actually doing in the brain at these times? Could music serve even more purpose and be used in medical rehabilitation settings? To answer these questions, we first have to dive into the neurochemistry behind the brain. Two of the biggest theories surrounding on how music works neurochemically is the reward, motivation, and pleasure pathway and the stress and arousal response system.

Inside the Brain

The Reward Pathway

When we listen to music, it is referred to as the consummatory phase. During this time, music serves as a reward stimulus and activates the reward pathway, releasing dopamine and endogenous opioids.

As seen in the figure below, dopamine release in the ventral tegmentum area (VTA) function to regulate motivation and goal-directed behaviors when music is serving as a reward stimulus and is mediated by the mesocorticolimbic system. Endogenous opioids are also released with dopamine in the nucleus accumbens (NAc)of the brain and are what provide the feeling of pleasure in the reward system. Using music as a form of reward allows for those short-term behavioral changes of inhibiting stress and/or anxiety and increasing pleasure and motivation.

https://www.dreamstime.com/stock-illustration-dopamine-serotonin-pathways-brain-cross-section-showing-affection-mood-memory-sleep-pleasure-reward-image61090431

Stress & Arousal Response

We know that music can serve as a calming technique to decrease stress levels, and the reward pathway is involved in that by providing pleasure. What happens in a stress response? During a stress response, the neuroendocrine, autonomic, metabolic, and immune system are all affected. The HPA Axis is activated during high stress, releasing high levels of cortisol, which is the primary stress hormone. It’s been found that while listening to music, specifically slow tempo, low pitch, and no lyric music, HPA activation is actually reduced at cortisol markers, resulting in lower stress levels. This helps protect the body against the neurotoxicity that long-term stress and anxiety produce. Taking this into account that music helps reduce stress and anxiety by increasing dopamine and endogenous opioid release and decreasing cortisol production, could music possibly be used in high pain medical situations like physical rehabilitation for chronic pain and/or post-surgery?

Music Therapy with Physical Therapy

Music therapy being incorporated during physical therapy sessions is a rather common occurrence in many chronic pain cases and cases involving gait issues. Studies have found that using music in these cases increases the patient’s motivation during the session but also helps to reduce their pain perception and muscle tension, most likely due to music’s effect on stress response and dopamine release. Music is able to provide a distraction element along with these neurochemical aspects to subjectively reduce pain because the patient’s cognitive attention is elsewhere with the music. This component of the consummatory phase of music makes it a great option to help patients experience less pain, anxiety, and muscle tension. The rhythm and tempo patterns in music seem to benefit gait therapy especially, helping the body fall into walking/marching with the beat. Using music in these more severe physical therapy cases seems to be extremely beneficial and are promising when even looking at acute pain. Incorporating background music or music therapy in most physical therapy sessions could serve as a great distraction for patients and give them an overall more enjoyable, motivated, and less painful therapy session.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920463/

https://www.tandfonline.com/doi/full/10.1080/08098131.2010.485785?scroll=top&needAccess=true

https://pubmed.ncbi.nlm.nih.gov/20498613/

 

How Music is Raising the “Bar” in Brain Functioning

What’s your favorite song? Can you picture a specific time or place that makes that song so special? Music has been incorporated into the lives of humans for hundreds of years. We know how it can make us feel, whether it’s screaming in your ears as you push up on the bench press for your new personal record at the gym or as it’s gently swaying back and forth in the background as you are studying for an upcoming exam, music seems to be used in everyday life, and for good reason! Recent studies are beginning to specifically explore just why our brain likes music so much, so that is what we will find out below along with a brief analysis of if playing an instrument or listening to music seems to be more beneficial to your brain!

The Neurochemistry of Music

If someone has ever told you “music is medicine”, they might not be completely wrong! In recent years, there has continued to be additional amounts of information regarding the positive impacts that music has through neurochemical changes in the brain. One way music affects us is through reward, motivation and pleasure. Certain songs and/or noises can instantly evoke powerful emotions ranging from happiness to sadness to even a state of reminiscence. This has been stated as one of the main reasons as to why people even listen to music. Inside the brain, it has been shown that during this process, there is a dump off of dopamine at places such as the VTA and NAc that provide us with that pleasurable feeling that medication such as opioids do. This in part is why music has been shown to be capable of triggering short-term behavioral changes while also temporarily inhibiting feelings such as stress and/or anxiety. In fact, music that is non-lyrical with a low pitch and/or slow tempo (types that I personal enjoy listening to while studying) have been shown to be most effective at reducing stress and anxiety!

A few other areas that music has been shown in improve are immunity and social interactions. Having the ability to partake in creating music or simply just listening have both shown to decrease inflammation within the body as well as boosting the immune system overall! Social health has also seen an increase in those who listen to or create music together. Neurochemicals such as oxytocin and vasopressin are presented in the body which seems to establish and maintain positive feelings and reduce stress– so keep up with those weekly group-garage band sessions with your friends! There is still currently ongoing research in each of these areas, as we still cannot be certain that it is solely music alone causing these impacts on our emotions and body, so hold off on telling your mom that you only have to listen to music in order to feel better the next time you catch the flu!

Playing versus Listening

Okay, so whether you skipped down to this section of the post immediately after reading the final line of the introduction or have read the blog to its entirety up to this point, it is now time to see what benefits our brain the most: playing an instrument or listening to music. So, what do you think? Ultimately: playing an instrument has generally shown to be more beneficial to your brain than listening to music. Of course, there will be a select number of individuals who have more benefits through listening, but this is what covers the majority of individuals. There are two factors that this largely comes down to. The first being that playing an instrument is normally far more of an active process than is listening to music. Your fingers and hands are usually both doing different things at the same time while your eyes dart across the sheet music. Most of the time when music is on, the only “active” thing we do is sing along and that can be thought of as more of a pleasurable aspect versus “testing” your brain to see how accurate you can be on wording and pitch. Researchers have been quoted as saying how this process “engages every major part of your central nervous system”. It has also been shown to relieve stress and bring people together even more than just listening to music does. A short video description of the two can be found here!

The second factor is how playing an instrument can be thought of as engaging all parts of your brain versus listening to music only engaging specific areas. I like to think of this in reference as to going to the gym. Listening to music can be thought of as just working a specific area of your body, let’s say your arms, while playing an instrument compares to doing a full-body workout! This in turn demonstrates an increase in the fine motor skills, specific to playing an instrument, that results in both hemispheres of your brain working on a task simultaneously. This has your corpus callosum constantly bringing signals back and forth between the two hemispheres to communicate with one another and in turn both strengthens and increases the speed at which this is done. This ultimately results in an individual being more effective and efficient at other tasks that require both hemispheres of the brain to be working simultaneously!

The Coda

Over the last few years, much has been discovered with regards to just how beneficial music is to our brains, not only emotional or behavioral, but also through our interactions and abilities to perform other tasks. There are still many questions left to be answered, however, so future research is still necessary to explore specifically how music is impacting our body so much and if it will one day be able to compete with modern medicine through uses more than we have ever initially intended or imagined.

The Final Chapter of Neurochemistry

Neurochemistry has been a class I have feared since being a first-semester freshman. I struggled in Gen. Chemistry and Organic Chemistry. I started to find a liking for the subject when in Biochemistry, but I was still hesitant about this course.

Walk into first day of class and am greeted by faces I have grown with over the past three years and have considered to be my friends since Intro to Neuro freshman year. I am normally an uncomfortable person in regard to conversation-based courses, however, having a group that you already know really helps. This allowed me to communicate with peers openly and comfortably about heavy neuroscience topics. Also, this group allowed for a safe space during discussion days where individuals felt comfortable to share more personal stories that related to the topics at hand.

For the first six classes, we reviewed basic signaling molecules and pathways to refresh our brains and set us up for the rest of the weekly topics. For the first class, we examined excitatory signaling that is capable of stimulating an activity and/or response by a neuron. The primary excitatory neurotransmitter being glutamate with the primary receptors being NMDA, AMPA and Kainite. Then we discussed inhibitory and retrograde signaling with GABA being the primary inhibitory neurotransmitter. These receptors include ionotropic GABA-alpha and metabotropic GABA-beta. Glutamate and GABA work together to modulate immune and endocrine system responses.

Following the basic signaling molecules, we began looking into G-protein signaling and G-protein coupled receptors (GPCRs). Gi and Gs receptors help to regulate adenyl cyclase activity, whereas Gq helps to regulate movement of Ca2+ ions and PKC. These receptors are characterized by a seven-transmembrane alpha-helical fold. Following GPCRs we talked about RTK pathways. These pathways include insulin pathways and use tyrosine kinase activity. Then, with cytokine pathways we discussed the Jak/Stat pathway. These pathways can include autocrine, or activation of cell itself, paracrine, or signal activates nearby cell, and endocrine, or activation by signal in circulation that activates a cell further down. Lastly, we talked about wnt-b catenin signaling. This pathway regulates cell fate and stem cell differentiation during embryonic development.

The first six topics helped to solidify information that has been drilled into our brains for many classes. Coming from a semester that felt as though I retained nothing, it really helped to have a refresher and get me back on track with basic signaling. I tend to gravitate towards the psychological and neurobiological aspects of my major, but this class help to confront the parts of neuroscience that I have avoided for some time.

The first topic we discussed included making memories of stressful events. In this we discussed how stress effects memory retention. In particular, I looked into adjustment disorder, acute stress disorder, and PTSD. Adjustment disorders causes distress out of proportion to the event with behavioral and emotional within three months of the event. Acute stress disorder is any maladaptive response to a traumatic event with symptoms lasting three days to one month. Symptoms can include dissociative behaviors, steep disturbances, and severe anxiety. If symptoms persist past one month, the diagnosis changes to PTSD. This topic allowed me to connect information I had learned about symptoms in abnormal psychology to the neurochemistry in stressful events.

The next topic talked about was mental illness, specifically the role of wnt and GSK3 signaling in schizophrenia. Since schizophrenia is believed to be due to a lack of b-catenin transcription, overactive GSK3-beta, and an increase in dopamine, hallucinations are believed to be one of the most apparent symptoms of the disorder. Hallucinogens that bind to 5-HT2A receptors. Antipsychotics bind to specific serotonin receptors in the VTA and ventral striatum, this may be the area for psychosis. Since hallucinogens are able to evoke hallucinations that are easily to distinguish as fake, but hallucinations from psychosis evoke stimuli that appear real.

We talked about addiction and the cellular basis for it during for the third topic. For this week, I took time to look at the dual diagnosis between mental illness and substance use disorders. ¼ to ½ of all substance abusers also meet the criteria of a mental illness or have a diagnosis of a mental illness. The most common comorbidities including ADHD, depression, bipolar disorder, and schizophrenia.

For the fourth week, we talked about the metabolic cascade that follows a concussion. Though bilingualism is meant to be beneficial if taught during the “critical period” of neurodevelopment during childhood. During the critical period, children are able to gain a logical and emotional connection to the language being taught, whereas adults learn mostly from a logical standpoint. With higher executive functioning seen in bilinguals, following a mTBI the individual may suffer from a disproportionate return of language. Also, children have less myelin protecting axons, children are more likely to suffer axonal injury and executive function deficits. Even after learning about all of this, I managed to sustain a concussion myself and was able to use the SCAT-5 to go about making sure I do not impair my brain farther than I already had.

The fifth week we discussed the connection between Alzheimer’s and diabetes. Also, this topic was returned during the seventh week when discussing hypothalamic inflammation and obesity. Hypothalamic inflammation can result from poor diet and health. This continuation of inflammation in the brain can lead to innumerable complications, one potential complication is the increased risk for Alzheimer’s. Though Alzheimer’s can be hereditary, through the APOE-4 gene, if diet is not maintained, if the brain is not protected from injury, you are going to be at an increased risk no matter your family history.

During the sixth week, we discussed autism spectrum disorders. Now I am passionate about this topic and was very excited about this week. I discussed the benefit of sensory rooms in schools, but also the potential downfall of excluding children from mainstream rooms. I will say I was disappointed in some of my peers from their lack of awareness on some aspects of ASD and laws that protect vulnerable adults. It helped me to stand up later on in another one of my classes for something that was said that didn’t directly affect me, but I imagined it being said to one of my kiddos from work and was heartbroken.

During the eighth week, we discussed how the endocannabinoid receptors work on the CNS. This week I looked at if targeting the endocannabinoid system could help reduce the aggregates seen in Huntington’s Disease. ERK has to be phosphorylated to see any positive effect, but activation of CB1 receptors did allow for cell to be rescued from cell death. However, this also increased the total number of aggregates being produced.

Lastly, we discussed how music affects our brains neurochemically. For this week, I chose to look at if the genres we dislike changes how the neurochemistry plays out. It turns out that even if we hate a genre, our brain will still release dopamine and trigger the amygdala to evoke emotion.

Mainly, in all of these topics I was able to make a connection to psychology courses. By examining neurochemical changes in the brain, it helps make sense of why certain symptoms are present, thus allowing to make sense for different therapeutics that are being used to treat a variety of disorders. This class helped me to become more confident in my abilities to communicate with peers about topics and inform them on other topics. This skill will be heavily transferable as I progress beyond Concordia.  Discussion days really helped to make us feel as professionals and not just students. Also, even if we were all in a neurochemistry course together, we all come from different majors, have different life experiences, and interpret information differently. This is one of the cool things about a liberal arts education. We get to dive into and inspect a topic from a variety of disciplines and potentially gather a deeper understanding than a neuroscience-only education.

Photo Sourced From: https://www.brandeis.edu/psychology/neurochemistry-cognition/

Your brain may like a music genre even if you don’t

How many times have you heard someone complain when a country song comes on the radio, but will end up tapping their foot or humming along at some point during the song? Whether you are listening to your most played Spotify song of the year or passing by some street band at a subway station, your brain is responding in incredible ways.

The reason we like a certain genre derives from the personality characteristics and social groups we associate with the genre. For example, we may associate “heavy metal” with burly motorcycle guys covered with tattoos or we may see that same group when thinking about “country” music. It all comes down to our psychological perceptions. We choose to express certain characteristics of ourselves through the music we listen to. Even if you don’t actively listen to classical or show-tunes, if you perform it, it becomes part of who you are. Music may also bind us to a certain culture that makes up our identity. Lastly, music is very strongly linked to memories and may cause an emotional response or a sense of nostalgia.

Music can have a significant benefit to our brains, no matter the genre. Overall music carries the ability to trigger short-term feelings of anxiety and stress. Music helps to reduce the HPA axis activation for cortisol and beta-endorphin. Beyond that, simple music properties can affect neurotransmission associated with cardiovascular health, respiratory control, motor functioning, and potentially cognitive functioning. Some studies have even begun to show that music provided to healthy post-surgery patients helped decrease the need for pain medications.

However, these are heavily individualistic results, but what happens when we listen or perform music as a group? Calming music and performing music has been observed to increase oxytocin levels and immunoglobin A levels in males and females. One form of music performance, group drumming, has shown to increase the 5-DHA-to-cortisol ratio which has shown to enhance immune functioning and cell response buffering. This form of performance also showed to increase total number of lymphocytes, counteract age-related immune functioning declines, and increase NK cell activity.

Now after seeing music’s overall effect on the brain, how do different genres affect us? Pop, rap, country, and reggae are all genres that typically have repetitive beats and catchy tunes. This is meant to get our dopamine pumping and get us up singing and dancing. This can help explain why even if you outwardly hate a song, you are still tapping your foot to the beat. Certain slow-paced songs, typically 60-100 beats/min, can activate the amygdala to evoke emotion in response to the song. Though this emotion is not the same as the memory-associated emotion produced.

Metal is considered to be a relatively aggressive genre. Though these tempo and lyrics are aggressive in nature, they are actually known to make listeners calmer and comb out stressful and depressive thoughts. Though this may be not due to any neurochemical effect from dopamine, but rather an end result of getting your blood-pumping. Getting your blood-pumping, whether it be from exercise or metal music, can help drown out thoughts and provide a safe outlet for emotion.

Classical music has been heavily regarded in mainstream media as the perfect study music. This is relatively true. Classical music tends to lack repetition that helps to keep you attentive while still getting the dopamine rush to induce pleasure and calmness. The complexity and variety of notes used in classical pieces may also activate more areas of the brain than other genres, which may in turn help with focus in studying.

Lastly, jazz is a different type of genre. This genre is heavily improvised and provides a “call-and-response”. This allows musicians to communicate with one another through their beats. This “conversation” allows activation of the language syntax part of the brain. For the listener, the “talking” of jazz music allows for hyperactive neural stimulation which permits the listener to interpret the beats in their own way.

In conclusion, music interpretation is heavily individualistic and how one interprets a genre is going to be different from the next person. So if you listen to classical music while studying and your friend listens to low-fi rap, may I suggest headphones so you may both succeed.

 

A world of Music

 

Music, a universally understood and appreciated artistic form of expression. We use it to amplify or suppress emotions, share in creativity, empathize with others, and even to wreak havoc. Music is so important we find our own identity in many of the countless forms and genres. Music has the power to ignite rebellions, spark innovation, establish peace, and inspire love. So, let’s take a look at current research in an attempt to understand the neurochemistry of music and how music is so influential.

Reward, Motivation, Pleasure

Music is associated with countless emotions but is most commonly associated with sensations of joy, accomplishment, and determination. Because of this, initially, we will focus on music’s implications on the reward pathway. Music can trigger short-term behavioral changes and temporarily inhibit feelings such as stress and/or anxiety. While listening, music serves as a reward stimulus which ultimately amplifies the reward pathway triggering dopaminergic transmissions and the release of endogenous opioids (naturally produced within the organism). Dopamine in this case serves as a regulator of motivation and goal-directed behaviors in the reward system. The feelings that are associated with musical reward are mediated by a region of the brain called the mesocorticolimbic system. The actions of motivation, learning, and goal-directed behavior are mediated by the dopaminergic neurons in the specific brain region called the ventral tegmentum (VTA), which projects to another region called the Nucleus accumbens (NAc) and the prefrontal cortex (PFC). The endogenous opioids released during musical reward in the NAc are what provide the reward feeling of pleasure. The involved neurochemicals interact with receptors at different sites of action, so dopamine and opioid release can each affect various actions/behaviors.

Stress and Immune function

Many environmental triggers can stimulate stress responses in the body and when these responses are activated, they prompt short-term adaptive behaviors, physiological changes, and inhibit non-essential functions (sympathetic nervous system). It has been found that slow tempo, low pitch, non-lyrical music can reduce stress and anxiety in healthy subjects ultimately protecting against the neurotoxic effects of long-term stress. Listening to music or participating in music-making has been shown to decrease inflammation and have positive effects on the immune system. However, it remains uncertain if these effects are due to the mood-regulating function of music, the camaraderie of making music in a group atmosphere, or some other factor. What data has shown is that group music increased Natural killer cell (NK) activity, increased 5-DHA-to-cortisol ratio (reduces level of stress), enhanced immune functioning, decreased stress-induced cytokines (important factors in inflammation), counteracted age-related decline in immune function, and significantly increased the total number of lymphocytes (defensive cells of the immune system). Passively listening to music and group singing had similar effects.

Social Affiliations

Music has also been found to influence the neurochemicals oxytocin and vasopressin. Oxytocin is a vital neuropeptide involved in the establishment and maintenance of social health but can have contradicting effects. Oxytocin can facilitate increased social health and development of connections, but its levels also increase during periods of separation and social isolation. This facet demonstrates oxytocin’s additional role as a distress signal in social or nonsocial situations indicating that context matters. Vasopressin is a molecule that closely regulates social behavior (affiliative, social, & romantic behaviors) and whose gene regulates oxytocin activity. Endogenous opioids (b-endorphin) may also play a role in pain signaling in response to social isolation. Low levels of endogenous opioids or opioid antagonists promote separation distress behaviors and lead animals to seek out contact, while increased opioid levels reduce these behaviors. Music could potentially increase opioid production, leading to a sense of comfort. Through the increased actions of neurochemicals like oxytocin, vasopressin, and endogenous opioids stimulated by music, there is a potential link between music and the establishment and maintenance of social bonds in a variety of social and nonsocial contexts.

Conclusion

We understand music to have a significant impact on our lives, visible through our emotions, behaviors, and interactions. However, there remains much to learn about the exact mechanisms by which music influences our neurochemistry as many of the current studies exhibit significant limitations, therefore, continued future study is necessary to fully elucidate the profound influences of the phenomenon we call music.

Treating anxiety through the endocannabinoid system

The Endocannabinoid System

When a person speaks of cannabinoids, most people’s minds will automatically think of weed or CBD oil, but it is extremely important for people to understand that our bodies naturally create cannabinoids. More specifically, the body uses these

Physiological roles of the eCS.

endogenous cannabinoids in the endocannabinoid system (eCS). The eCS play important roles in regulating other systems and responses such immune responses, communication between cells, appetite, metabolism, memory, and even more. Since the eCS regulates so many physiological aspects, problems can arise when when the system gets disrupted, and one physiological dysfunction that dysregulates the eCS affecting millions of people around the world is that of stress and anxiety.

Treating anxiety now

Short-term anxiety or stress may help a person respond to danger or get a task done right before the due date, but long term stress and anxiety can have negative effects on a persons health including gastrointestinal issues, heart issues, headaches, migraines, sleeping problems, or depression. To treat anxiety caused symptoms, doctors prescribe medications such as selective serotonin reuptake inhibitors (antidepressants), benzodiazepines, or beta-blockers. Although these medications may help suppress anxiety and its effects, they all cause various side effects including drowsiness, memory problems, insomnia, stomach problems or pains, and quite a few others. Considering the high amount of negative side effects given by anti anxiety medications, it is becoming increasingly more popular for scientists and pharmaceutical companies to look into other possible anti anxiety treatments. An new, exciting approach involves medications that regulate the endocannabinoid system to treat anxiety.

Relating anxiety and the eCS

When functioning properly, the endocannabinoid system helps to regulate the release of glutamate (the main excitatory neurotransmitter in the

Normal function of the eCS.

brain) and GABA (the main inhibitory neurotransmitter in the brain). It inhibits the release of the neurotransmitters making it so they are not being released at too high of rates. It does this using the postsynaptic production of the endocannabinoids AEA and 2-AG. The endocannabinoids are released back into the synaptic cleft and the CB1 receptor reuptakes them which inhibits the release of glutamate and GABA. But, when the body is responding to stress and anxiety, there is an over production of FAAH and PTP1B which are enzymes that can breakdown endocannabinoids. In this scenario, the endocannabinoids are not being released to the synaptic cleft

Diagram showing the abnormal function of the eCS in response to stress and anxiety.

and therefore not activating the CB1 receptor. This allows for uncontrolled release of glutamate or GABA which can increase symptoms related to stress and anxiety. Since the eCS and anxiety are so closely related, introducing pharmaceutical forms of cannabinoids could be a potential treatment for anxiety.

Possible applications

Recently, there has been clinical trials that have shown promising treatments for anxiety using pharmaceuticals that affect the eCS. In the trials that have introduced drugs that have inhibited the breakdown of AEA by FAAH. There has also been promising research with using CB1 receptor agonists in helping with anxiety symptoms. Most likely, these medications could potentially be used in conjunction with currents anti anxiety medications or used as a starting treatment to treat acute anxiety disorders. Although the application of these medications affecting the eCS may be years away from being prescribed to patients, this is a promising and exciting science that may help to rid people with anxiety of the common symptoms caused by current anti anxiety medications.

 

A Safer Replacement for Delta-9 THC

Legalizing marijuana has been a pressing debate throughout the past decade. Our generation has been able to be front and center on this hot topic. Slowly, we are witnessing states legalize it both medically and recreationally. The legalization allows for many benefits along with consequences. In a recent class discussion, we were able to discuss the endocannabinoid system (ECS) and the possibility of using marijuana-based products to activate this system. Activation of ECS is useful because the system “plays key modulatory roles during synaptic plasticity and homeostatic processes in the brain.”

 

Within the ECS, there are cannabinoid receptors. The two receptors discussed in our research article were the CB1 and CB2 receptors. Throughout the rest of the blog, I will be mainly focusing on relationships dealing with the CB1 receptor. The CB1 receptor is found in the central nervous system and provides as a binding site to a marijuana most active ingredient which is delta-9 tetrahydrocannabinol (delta-9 THC). The binding of Delta-9 THC to the CB1 receptor allows for activation of the ECS. This allows in feelings that have been described as relaxing and pain reducing. Due to these effects, therapeutic conversations have been aroused. One use of therapy that has been discussed is using marijuana derivatives as a pain killer. The thought is to be used similarly to opioids. However, just like opioids, marijuana can have negative impacts as well. Addiction can still be present but said to be at a lesser extent in marijuana than opioids. Recreational use is used in many of the same reasons that opioids are used for which is a large part of the hold up on legalization. Delta-9 THC also provides users with paranoia and euphoria. This gives them anxious feelings along with sickness and not being able to function. Research continues to create products that will not being on these consequential feelings yet provide the consumer with beneficial effects.

 

 

 

Barstool Sports is a multi-media sports company and provides a podcast. On their podcast they heavily advertise for a different derivative of cannabis. They advertise 3-chi which is a delta-8 THC company. After discussing delta-9 THC in class I wanted to do more research on delta-8 THC and see what the differences are. On their website, 3-chi has a biochemist explain why the use of delta-8 THC is much more beneficial than delta-9 THC. Although this podcast and company advertises on the recreational side of things, relating this to potential medical use is relevant.

 

Delta-8 THC is also an ingredient in a cannabis plant but comes off as the least abundant. Through chemical reactions, scientist can make delta-8 THC out of delta-9 THC. The reaction process is what turns some researchers away due to safety concerns. When researchers get past the point of the chemical process of the THC derivative, they noticed that delta-8 does not bind as well to the CB1 receptor as the delta-9 receptor. The slight difference in the double bond as you can see below is the reason the binding is not as strong. The lower binding ability is what makes delta-8 THC a more effective product. When the CB1 does not get the perfect binding, activation is not as strong within the ECS. This has proven to provide similar benefits to delta-9 THC such as relaxation and pain reducer but does not give off the negative effects. Delta-8 users report that they do not need to use as much, and they don’t get the paranoia or the euphoria.

 

 

Whether or not recreational use of marijuana becomes legal, there is still a lot of research to be done with cannabis. Research has shown that the use of marijuana can provide medical benefits, but negative effects can come with it. The ability to derive delta-9 THC to delta-8 THC can be very significant if in further research does show the medical benefits. There is still a long ways to go, but it makes me more comfortable knowing that certain derivatives could possibly provide medical use without the negative impacts.

 

 

 

Miracle Drug?

 

Your family might not be like my family. At Thanksgiving, In between the catching up on how school and work is, an interesting conversation came up between us. My Aunt and Uncle began talking about CBD, and how it’s helped them for a variety of ailments, including one specific issue they’d been having. Turns out their dog has an intense fear of storms, and CBD lotion seems to alleviate that fear. I personally couldn’t imagine giving my dog CBD, but this example does speak to just how wide a range for use the general public see for CBD. Indeed, it has been suggested that CBD and medical marijuana can offer help in a variety of conditions, all the way from anxiety to pain.

Neurochemical Mechanisms

As it turns out, there is specific neurochemical evidence to support that the human endocannabinoid system, which is stimulated by things like medical marijuana and CBD, can be leveraged to alleviate all types of distressing symptoms. This is due, in part, to the fact that the endocannabinoid system is self-regulating. As a certain signal increases, pain for example, a neuron that receiving excessive pain signals, can signal to the neuron that sent the initial signal to just chill just a bit. This method of self-regulation can be extremely helpful, especially in situation where excessive cell signaling is taking place such as in anxiety and pain. The way this retroactive signaling takes place is only somewhat understood. We know the endocannabinoid systems activates a vast array of downstream signaling cascades within cells, but not all their functions are fully understood. Considering both the function and widespread availability of endocannabinoids, the science supports the proposed healing effects put forth by an abundance of experimental and anecdotal evidence. In fact, the CB1 endocannabinoid receptor is one of the most largely expressed in the entire central nervous system! It makes sense that it could help a variety of ailments, even those that seem they couldn’t possibly be related.

Miracle Drug?

When considering CBD and medical marijuana, I have even heard the term “miracle drug” thrown around due to both it’s efficacy, and range in use. Now, for the rest of this blog, I will make no attempt to hide my own biases and opinions. I’m a psych guy. I tend to view issues through a psychological perspective, one which involves avoiding the use of pharmacological options until it is absolutely clear their benefit outweighs their risk. Indeed, every intervention, in my opinion, should be viewed in this way. A provider should only pull out the pen to write the script when the dangers/discomfort of an ailment clearly less of a risk than the condition itself. Any pill or injection is an unnatural means for chemical agents to enter the body. Regarding taking Ibuprofen for a headache, the risk is low and the benefit can be great, so taking it makes all the sense in the world. When issuing chemotherapy for cancer, the risk of cancer far outweighs that of chemo in nearly all scenarios, despite the brutal side effects.  Now, the water begins to get murky when thinking of diseases typically associated with the treatment of medical marijuana and CBD. For the sake of this blog, I am going to focus on chronic pain and anxiety.

Artstract by Ben Swanson

As a society, we tend to look for the next drug to alleviate suffering, almost as if it is the only option. Alleviating suffering is indeed a positive thing, and every opportunity to research CBD and medical marijuana should be taken because the opportunities for replacing opioids and benzodiazepines for treatments are impressive. However, as with chronic pain and anxiety, and other disorders CBD and medical marijuana is typically used for, these things usually aren’t going to do serious bodily harm. Cause distress? Absolutely. Impact quality of life? Certainly. These things should certainly be addressed, but they should be done so when looking at the risks and benefits of taking CBD and weed. Now I can guess what you’re thinking…

”Come on Ben, this is a natural substance that comes from plants. This is a lot safer than other stuff we put in our bodies that get prescribed. You’re fear mongering about a relatively harmless drug that millions have found helpful.”

Word of Caution

What I would say is this; we don’t really know that. On initial inspection, it sure seems that way when CBD and marijuana is less harmful compared to other drugs used to treat anxiety and pain. However, the reality is that we do not have the scientific data to support that assumption. The exact mechanisms for CBD are not well understood, and because it is so widespread in the CNS, I fear we have jumped the gun on CBD and medical marijuana. What is someone going to look like after 20 years of taking CBD? What kind of effects will this have in the CNS and it’s ability to regulate itself? Could CBD be addictive long term? The fact is, there are no answers to these questions because the research does not yet exist. Should it exist? Absolutely. There will be a flood of research in coming years examining these very questions. But without this research, I hope providers and consumers alike are weighing the risk benefit of CBD and medical marijuana. I hope people ask themselves, is this something I really NEED? Or is this something that I think I need. Do the risks of not fully understanding this drug, truly outweigh the treatment benefits? The possibilities behind medical marijuana and CBD are exciting, and I’m going to be thrilled if they truly are a less harmful substituted for some common ailments. However, right now I am cautiously optimistic, and believe more research is needed before we can coin this the “miracle drug”.

How Endocannabinoids Change Your Brain: The Sneaky Role of Beta Arrestin

The first thing many people think of when someone starts talking about cannabinoid signaling likely isn’t how cannabinoid exposure can change how your brain processes signals by directly modulating the number of receptors on neurons but likely has something to do with how recreational marijuana has been talked about in media or in pop culture. While there’s certainly nothing wrong with thinking of marijuana’s recreational uses first, cannabinoids do so much more for the human brain than create the ‘high’ associated with recreational marijuana use. Cannabinoids, a wide family of molecules, have been used to treat pain, muscle aches, anxiety, and even reduce the risks of addiction development when used in place of opiate pain medications. However, I’m most fascinated by how they directly change the number of receptors present on individual axons, leading to the formation of drug tolerance.

This is where beta-arrestin comes in. Let’s dive inside the brain.

Inside the brain: How beta-arrestin alters receptor concentration on post-synaptic neurons

 

Figure 1. Graphic showing GPCR activation and eventual endocytosis via beta-arrestin signaling. (Ma L, Pei G. 2007. β-arrestin signaling and regulation of transcription. Journal of Cell Science. doi:10.1242/jcs.03338.)

Let’s break it down. First, a ligand (a small signaling molecule) will bind to the GPCR on the extracellular (outside) part of the neuron. This is what tells the GPCR to activate. Once the ligand binds, the g protein dissociates from the GPCR and its alpha subunit, an effector protein, goes off to trigger the response. After the alpha subunit leaves the GPCR, GRK2 binds to the beta-gamma subunits of the GPCR and removes them, phosphorylating the GPCR’s tail in the process. This leaves the phosphorylated tail open for beta-arrestin to bind to it. Once beta-arrestin binds to the tail of the GPCR, it triggers endocytosis, bringing the entire GPCR into the cell in a small bubble of the cell membrane. This leads to desensitization by reducing the number of receptors available to respond to a given signal.

“That’s great,” you might say, “I now understand beta arrestin’s impacts on GPCRs, but how do endocannabinoids activate beta-arrestin?”

Great question. I’m glad you asked it. Let’s talk about it.

It’s actually pretty simple. Repeated exposure to cannabinoids that function as ligands for CB1 receptors increases GRK2 activity, thereby also increasing both beta-arrestin signaling, and GPCR endocytosis. This helps explain why some individuals who use cannabinoids repeatedly build up a tolerance, requiring more of the cannabinoid to achieve the same feeling. For example, THC, the cannabinoid found in recreational marijuana responsible for the “high” associated with its use, is likely the most well-known example of this effect.

Conclusion

In closing, there are two things I think you should take from this.

  • Endocannabinoid signaling can be complicated. Beta arrestin’s role in changing receptor concentrations was only discovered in the last 20 years and its stimulation by endocannabinoids is still being understood.
  • There’s still so much that science does not understand about how the brain works. It’s both a daunting and highly exciting prospect.

 

 

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