Cobbers on the Brain

Use of marijuana for recreational or medicinal purposes has become a significant topic of discussion over the past decade. While the push for legalization has become increasingly ‘trendy’, as some would say, the physiological systems this drug affects have been helping our bodies thrive throughout our entire lifetime. The endocannabinoid system (ECS) in particular is a direct recipient of THC, the compound in marijuana responsible for its psychoactive, and possibly medicinal effects. Given the ECS’s wide variety of roles in the brain, impaired signaling to this system may contribute to development of several neurological diseases.

Although THC does bind to endocannabinoid receptors, our body produces endogenous endocannabinoids (eCBs) that bind to these receptors as part of our body’s normal functioning. These receptors, the CB1 receptor and CB2 receptor, are located in many areas of the brain, and one of the unique things about the ECS signaling process is the fact that endocannabinoid receptors on neurons are located presynaptically or on the axonal segments, instead of postsynaptically like many receptors. This allows for retrograde signaling, where communication between neurons occurs in the opposite direction that it normally does.

The binding of eCBs to these receptors through this retrograde signaling is now understood to regulate several everyday processes in the brain, including mood regulation, synaptic plasticity (involved with learning an memory), and pain perception. There’s a decent chance you’ve heard about cannabinoid receptors in the brain prior to reading this blog, but did you know that in addition to their CNS locations, cannabinoid receptors are also found within the rest of the body? Researchers have discovered these receptors in a plethora of PNS locations such as the spleen, heart, liver, male and female reproductive systems, sympathetic nerve terminals and immune cells, where they serve many diverse functions.  

Dysregulation of the ECS has been implicated in several neurological diseases and conditions. In Huntington’s disease, for example, expression of the CB1 receptor is reduced, and impaired ECS signaling has also been implicated for Alzheimer’s disease and Multiple Sclerosis. Conversely, enhancement of ECS signaling has been shown to improve symptoms of these diseases, as well as symptoms of Traumatic Brain Injury. These improvements are thought to be through the ECS’s mechanisms of neuroprotection against the cytotoxic factors such as nitric oxide seen in Multiple Sclerosis, the degeneration of the striatum seen in Huntington’s disease, AB toxicity seen in Alzheimer’s disease, and excitotoxicity and inflammation seen in Traumatic Brain injury.

While marijuana use is linked to some side effects, evidence seems to suggest that the potential benefits of THC, through interaction with the eCB system, outweigh the risks. And yet, marijuana continues to be labelled a schedule 1 drug (the most restricted level of controlled substances), while cocaine and methamphetamine are less restricted as schedule 2 drugs. The order of these drugs’ rankings don’t make logical sense in the context of their respective addictive and lethal properties, but they do reflect the stigma toward marijuana (and groups of people that have been associated with its use) throughout the decades.

This high level of restriction can additionally create difficulties for conducting research with marijuana. On the bright side, however, the recent election does offer insight into how benefits of marijuana are slowly becoming more valued; all 5 states that held a vote to either legalize marijuana either medically or recreationally, overwhelmingly passed it. There is still much to discover surrounding marijuana and the ECS, but with the rising interest and support, I feel confident that we will.

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.

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/

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.

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.