Cobbers on the Brain – Page 2 – Student Commentary on the Neurological Sciences

Cells to Circuits: Understanding Schizophrenia from Early Development

Posted on March 21, 2026 by kleppke / 0 Comment

Artstact created by K. Leppke with help of ChatGPT

Neural Stem Cells and Development

The development of your brain was an extremely complex process, which was critical to the way your brain is structured and functions today. At the center of this process early on are neural stem cells, NSCs. NSCs helps neurons develop, get organized, and form synapses. They follow a very specific set of biological rules to create the brain’s complicated structure. If development strays from these rules, the alterations to the brain can lead to consequences can last a lifetime.

But unfortunately, NSCs are influenced by both genetic factors and environmental impacts. Small errors in this early stage of brain development can cause a ripple, effecting more major changes downstream. Early environmental factors, like prenatal infection, stress, inflammation, or poor nutrition, can effect NSC processes. If specific genes don’t function properly, their instructions for the brain can cause poor neuron structure. The RELN and DISC1 genes typically help guide how stem cells grow, divide, connect, but their deletion or nonfunction has been linked with schizophrenia (1).

The Schizophrenic Brain

Signaling pathways in the brain, like Wnt and GSK3, play a crucial role in regulating NSC survival and function. These pathways help neurons form correctly and establish strong synaptic connections, supporting cognition and behavior. Abnormalities in Wnt signaling and GSK3 activity can interfere with NSC survival and differentiation (2). This can lead to fewer neurons or non-functioning neurons, with weaker or less organized connections. These changes in Wnt and GSK3 activity ultimately affect essential processes for major brain functions, like thinking, memory, and perception.

Dopamine signaling is closely linked to the Wnt and GSK3 pathways. Dopamine typically aids neuron signaling, learning, habits, and behavior. In its interactions with signaling, dopamine can influence how neurons grow and connect. In schizophrenia, dopamine regulation is disrupted by pathways like GSK3 (2). This can lead to excessive dopamine, which contributes to hallucinations and disorganized thinking. These dopamine abnormalities stem from earlier developmental issues in NSCs and signaling pathways. While dopamine directly contributes to symptoms, it is also influenced by deeper development problems.

Several genetic factors associated with Schizophrenia can alter the behavior of NSCs and disrupt the formation of neural circuits. Therefore, researchers have been experimenting with how these genes impact early development with NSCs. Genes such as RELN and DISC1, and others involved in Wnt and GSK3, help regulate NSC processes. When these genes are altered or mutated, NSCs may divide improperly or fail to generate functional neurons, leading to reduced synapse formation and weaker connectivity (1). An experiment was done to see how the RELN gene impacts stem cells becoming functional neurons. This experiment, and this figure, identifies RELN as a key contributor to poor neuronal connections (3).

Figure 1: This diagram shows how stem cells were reprogramed into induced pluripotent stem cells (iPSCs), which act like early NSCs and can develop into many types of brain cells. These iPSCs are then directed to become glutamatergic neurons and GABAergic neurons. Neurons derived from schizophrenia patients, with a RELN deletion, showed neuron abnormalities, indicating poor neuronal connectivity. To confirm that these changes are genetic, researchers deleted the same genes in healthy stem cells, which partially reproduced the same neuronal defects. This shows how genetic factors effect neural development and synaptic structure in schizophrenia (3).

Conclusion

Disruptions in early developmental pathways, specifically Wnt and GSK3, have lifetime effects on brain structure and function, which can contribute to the development of Schizophrenia. These pathways regulate NSC growth, differentiation, and connectivity, meaning that slight alterations during early brain development can lead to poor synaptic networks and neural communication. Therefore, understanding and potentially targeting these pathways offers a promising direction for earlier intervention and more effective treatments that address the underlying biological causes.

References

[1] Ono T., Hashimoto E., Ukai W., Ishii T., Saito T. 2010. The role of neural stem cells for in vitro models of schizophrenia: Neuroprotection via Akt/ERK signal regulation. Schizophrenia Research, vol 122, issues 1–3, pgs 239-247. https://doi.org/10.1016/j.schres.2010.05.008.

[2] Singh K. 2013. An emerging role for Wnt and GSK3 signaling pathways in schizophrenia. Developmental Biology: Frontiers for Clinical Genetics. Blackwell Publishing; 83: 511-517.

[3] Ishii T., Ishikawa M., Fujimori K., Maeda T., Kushima I., Arioka Y., Mori D., Nakatake Y., Yamagata B., Nio S., Kato T., Yang N., Wernig M., Kanba S., Mimura M., Ozaki N., Okano H. 2019. In Vitro Modeling of the Bipolar Disorder and Schizophrenia Using Patient-Derived Induced Pluripotent Stem Cells with Copy Number Variations of PCDH15 and RELN. ENEURO.0403-18.2019; DOI: 10.1523/ENEURO.0403-18.2019

Community/Health

The Burden of Adapting to a Society That Wasn’t Built With You In Mind: Autism Spectrum Disorder

Posted on March 18, 2026 by cborrud / 0 Comment

The burden of adaptation is often placed on the Autistic individual, not the environment.

How Autistic People Experience the World

People with Autism Spectrum Disorder are affected in many ways such as the way they communicate and socialize with others. They can become easily overwhelmed by aspects of the environment such as bright lights and loud noises that are hard to avoid in our society. They can also seek out some types of sensory stimulation like rocking that might not be accepted in social situations [1].

Those with autism also face challenges when taking the literal meaning of words. With our society using more slang, sarcasm and symbolic language, it’s important that as a society there are more steps taken to create a more inclusive world for Autistic people.

Unfortunately, society isn’t naturally designed with these differences in mind. Therefore, many forms of therapies exist to help autistic individuals navigate it.

Image 1 sourced from synlab.com. Image 2 sourced from simplypsychology.org.

Therapies

Since there is no cure for the disorder itself, therapies are given to help people navigate a world that wasn’t built for them.

Applied behavior analysis (ABA) is one of the most common types of treatment. The goal of ABA is to increase communication skills, increase helpful behaviors, decrease harmful behaviors, and improve attention. [2] The Early Start Denver Model (ESDM) is an applied behavior analysis therapy focused towards 1–2-year-olds [3]. These techniques are great at improving their skills but, they often center on shaping behavior to better align with social expetaions.

Speech and Language Therapy are used to improve the individual’s communication whether it’s verbal, gestured or through an electronic device [4].

Occupational Therapy is also commonly used to help the person improve their sensory input in turn reducing their anxiety [3]. A focus of this is to help those with ASD tolerate loud noises and bright spaces. It is vital that society creates more inclusive spaces rather than just creating an expectation that neurodivergent people just tolerate their environment.

Image sourced from usa.edu

These therapies do a great job with helping the autistic individuals adapt however, it still reflects the broader problem of placing the responsibility on the individual not the environment.

Medications are often prescribed to manage high energy levels as 81.2% of children with ASD also have ADHD [5]. Often, these medications are prescribed to improve their attention and productivity. This shows how schools and work environments prioritize sustained attention and controlled behavior. The most commonly prescribed ADHD medications are Vyvanse, Concerta, and Adderall [6]. These 3 medications all affect dopamine signaling in the brain which is what regulates motivation, reward and attention [7].

Two other medications, Risperidone and Aripiprazole, are the only FDA-approved medications for treating irritability and aggression in children (5 and older) with autism. They also involve dopamine signaling but, they are also prescribed for mood and psychotic disorders [8].

This poses the question, how much of what is being treated is a symptom of autism spectrum disorder or a symptom of living in environments that weren’t built with them in mind?

Neurodiversity offers valuable perspectives and insights that benefit in society greatly. While therapies offer important support, there is still a lack of understanding and inclusivity of autistic individuals. This is why autism advocacy is so important.

Sources:

Featured image sourced from ChatGPT

1. How do autistic people see the world? | above and beyond therapy. (n.d.). Retrieved March 18, 2026, from https://www.abtaba.com/blog/autistic-people-see-the-world

2. Applied Behavior Analysis (ABA). (n.d.). Retrieved March 18, 2026, from https://www.autismspeaks.org/applied-behavior-analysis

3. CDC. (2024, July 18). Treatment and intervention for autism spectrum disorder. Autism Spectrum Disorder (ASD). https://www.cdc.gov/autism/treatment/index.html

4. Speech Therapy. (n.d.). Retrieved March 18, 2026, from https://www.autismspeaks.org/speech-therapy

5. DiCarlo, G. E., & Wallace, M. T. (2022). Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates. Neuroscience and Biobehavioral Reviews, 133, 104494. https://doi.org/10.1016/j.neubiorev.2021.12.017

6. Medications for attention-deficit hyperactivity disorder. (n.d.). Retrieved March 18, 2026, from https://caringforkids.cps.ca/handouts/behavior-and-development/medications-for-attention-deficit-hyperactivity-disorder

7. Baik, J.-H. (2013). Dopamine Signaling in reward-related behaviors. Frontiers in Neural Circuits, 7. https://doi.org/10.3389/fncir.2013.00152

8. Alsayouf, H. A., Talo, H., Biddappa, M. L., & De Los Reyes, E. (2021). Risperidone or aripiprazole can resolve autism core signs and symptoms in young children: Case study. Children, 8(5), 318. https://doi.org/10.3390/children8050318

Health

Diving into the Brain of Autism Spectrum Disorder

Posted on March 18, 2026 by agriffi1 / 0 Comment

Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is characterized by deficits in social communication and interaction, restricted interest, and/or repetitive behaviors. ASD is a wide spectrum that is diagnostically it is broken into three levels. Biologically ASD also varies, and it is theorized that there are many subtypes within this classification. Individuals with ASD are also more likely to be diagnosed with psychiatric disorders (especially ADHD, ODD, and anxiety disorders), multisystem disorders (especially Gastrointestinal disorders), and seizures (specifically epilepsy). [1,2]

Genetic and Environmental factors

There is no single cause of ASD. It is more of a label for a group of symptoms that seems to be more likely to occur with certain factors. Just as there is not a single cause, there is not a single gene that results in ASD, but rather many genes that seem to contribute to the likelihood of developing this disorder. Different gene mutations are thought to partially be responsible for the subtypes within ASD – two genetic mutations that result in ASD are fragile X syndrome and Rett syndrome. Environmental factors, especially during pregnancy, are also involved in the development of ASD. For example, maternal infection and exposure to toxins, such as anticonvulsant valproic acid (VPA), seem to also contribute to the development of ASD. [1]

Fragile X syndrome and Rett syndrome

Fragile X is a genetic mutation. It is the leading cause of inherited intellectual disability; symptoms include physical abnormalities, behavioral issues, developmental delays, intellectual and learning disabilities, anxiety, ADHD, and ASD. It has no cure, but medications and therapies are used to treat symptoms. The protein affected by this genetic mutation is important in the development of synapses and modulation of dopamine in the forebrain. [3,4]

Rett syndrome is also a genetic mutation; however, unlike Fragile X syndrome, it is not inherited but rather a genetic change that occurs spontaneously . It affects movement, communication, behavior, cognitive abilities, and brain development. Similarly to Fragile X syndrome, there is not cure, but medications and therapies are used to treat symptoms. [5] There is a decrease in dopamine that is seen in this disorder. [6]

Dopamine

Dopamine is a neurotransmitter involved in learning, motivation, attention, and social and repetitive behaviors. The brain produces dopamine in the substantia nigra, ventral tegmental, and a small amount in the hypothalamus. Dopamine dysfunction is thought to be the main cause of one of these subtypes of ASD. [1] The idea that dopamine dysfunction is a contributor to ASD is Supported by the fact that it effects aspects of many theories as to the development of autism: it impacts how neurons communicate and connect with one another and is hypothesized to be involved in sensory processing – many children with autism have sensory issues and sensitivities. [1,7]

[1] DiCarlo, G. E., & Wallace, M. T. (2022). Modeling Dopamine Dysfunction in Autism Spectrum Disorder: From Invertebrates to Vertebrates. Neuroscience and Biobehavioral Reviews, 133, 104494. https://doi.org/10.1016/j.neubiorev.2021.12.017

[2] Autism spectrum disorder (ASD) | Autism Speaks. (n.d.). Retrieved March 17, 2026, from https://www.autismspeaks.org/what-autism

[3] What Is Fragile X Syndrome (FXS)? (n.d.). Cleveland Clinic. Retrieved March 17, 2026, from https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome

[4] Wang, H., Kim, S. S., & Zhuo, M. (2010). Roles of Fragile X Mental Retardation Protein in Dopaminergic Stimulation-induced Synapse-associated Protein Synthesis and Subsequent α-Amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) Receptor Internalization. The Journal of Biological Chemistry, 285(28), 21888–21901. https://doi.org/10.1074/jbc.M110.116293

[5] What Is Rett Syndrome? (n.d.). Cleveland Clinic. Retrieved March 17, 2026, from https://my.clevelandclinic.org/health/diseases/6089-rett-syndrome

[6] Wenk, G. L. (1995). Alterations in Dopaminergic Function in Rett Syndrome. Neuropediatrics, 26(2), 123–125. https://doi.org/10.1055/s-2007-979741

[7] Sensory issues | Autism Speaks. (n.d.). Retrieved March 17, 2026, from https://www.autismspeaks.org/sensory-issues

[8] What Is Dopamine In The Brain. (2025, June 6). https://www.simplypsychology.org/the-role-of-dopamine-as-a-neurotransmitter-in-the-human-brain.html

Uncategorized

Autism Spectrum Disorder: On the Rise?

Posted on March 18, 2026 by gkuehn / 0 Comment

For anyone paying attention to our modern day political atmosphere, it would seem that autism gets mentioned quite regularly. Stemming back from the initial 1998 retracted publication in the Lancet linking MMR vaccines to autism, the disease and its prevalence are used by grifters to foment anti-science narratives among the scientifically uninformed. Despite there being no evidence whatsoever connecting autism with vaccines, the precipitous rise in diagnoses is enough to question what might be causing it – if anything. To do that, we need to talk about the cause of autism.

What is it?

For those unfamiliar with autism and its symptoms, autism is classified as a neurodevelopmental disease, largely impacting communication and behavior. Understood to be genetic in origin, finding what exactly about that origin leads to autism is quite the difficult task, since as of today over 800 genes have been implicated in autism (1). Given this staggering genetic complexity, researchers have increasingly turned to studying the underlying biological systems that these genes influence, hoping to find common threads that might explain how such varied genetic changes produce similar behavioral outcomes. One such system that has garnered significant attention is the dopamine signaling pathway.

Dopamine

For the layperson, dopamine is known as the molecule that makes you feel good when you complete a task, or the molecule that keeps you beholden to your phone and its incessant notifications. The unacquainted will find its structure herein enclosed (2).

For our purposes, however, dopamine is the neurotransmitter that enforces feelings of motivation and reward. Interestingly, in a review published in 2022, researchers DiCarlo and Wallace investigated the various studies looking at dopamine signaling in autism spectrum disorder (ASD). The authors found that dopamine dysfunction may underlie a distinct subtype of ASD. Brain imaging studies have consistently shown structural and connectivity abnormalities in dopamine-rich regions like the caudate nucleus, and genetic animal models repeatedly demonstrate that ASD-associated mutations disrupt dopamine signaling while simultaneously producing hallmark ASD behaviors (3). Rather than suggesting dopamine is the singular cause of autism, the authors propose it as one of likely several neurobiological subtypes, and argue that identifying individuals with this dopaminergic form of ASD through genetic testing or clinical biomarkers could allow for more targeted, personalized treatment approaches. This conclusion has interesting implications for the question posed earlier. With the prominence of cell phones and iPad kids, is our increased exposure to screens causing dopamine dysfunction? Could this be the cause of the increase in autism throughout the years? Hard to say. To better understand the rise in autism cases, it’s crucial to look at how clinicians diagnose autism.

Diagnosing Autism

The history of autism diagnosis is really a history of evolving understanding. When Leo Kanner first described the condition in 1943, it was poorly understood and spent decades misclassified as childhood schizophrenia, with parents — particularly mothers — even blamed for causing it through cold parenting. It wasn’t until 1980 that autism was formally recognized as a distinct developmental disorder with specific diagnostic criteria, and by 1994 it had expanded into a spectrum encompassing subtypes like Asperger’s. As the DSM continues to be revised, the individuals diagnosed has increased from roughly 1 in 2,000 in the late 1960s to 1 in 36 today (4).

Conclusion

So, is autism on the rise? The honest answer is: it’s complicated. What we can say is that a large part of the increase we see is best explained by an increase in diagnostic criteria (5). As we continue to lump more and more neurological disorders under the same umbrella, an increase in overall cases is completely natural. Furthermore, as our society gets better about destigmatizing therapy and treatment of all kinds while increasing clinical awareness, an increase makes complete sense. At the same time, ongoing research into the neurobiological underpinnings of ASD, including the role of dopamine signaling, suggests that autism is not one thing but many, a spectrum of distinct subtypes with distinct biological fingerprints. What we should not be doing is entertaining debunked vaccine theories or chasing politically motivated narratives that distort public understanding of a genuinely complex condition. The path forward lies not in fear, but in continued research, nuanced diagnosis, and personalized treatment for the individuals and families navigating life on the spectrum.

(1) Genovese, A.; Butler, M. G. The Autism Spectrum: Behavioral, Psychiatric and Genetic Associations. Genes 2023, 14 (3), 677. https://doi.org/10.3390/genes14030677.

(2) The Brain’s Dopamine Neurotransmitter. https://www.psychologistworld.com/biological/neurotransmitters/dopamine (accessed 2026-03-17).

(3) DiCarlo, G. E.; Wallace, M. T. Modeling Dopamine Dysfunction in Autism Spectrum Disorder: From Invertebrates to Vertebrates. Neurosci. Biobehav. Rev. 2022, 133, 104494. https://doi.org/10.1016/j.neubiorev.2021.12.017.

(4) Newschaffer, C. J.; Croen, L. A.; Daniels, J.; Giarelli, E.; Grether, J. K.; Levy, S. E.; Mandell, D. S.; Miller, L. A.; Pinto-Martin, J.; Reaven, J.; Reynolds, A. M.; Rice, C. E.; Schendel, D.; Windham, G. C. The Epidemiology of Autism Spectrum Disorders. Annu. Rev. Public Health 2007, 28 (1), 235–258. https://doi.org/10.1146/annurev.publhealth.28.021406.144007.

(5) Is There an Autism Epidemic? | Johns Hopkins | Bloomberg School of Public Health. https://publichealth.jhu.edu/2025/is-there-an-autism-epidemic (accessed 2026-03-17).

Disease/Health

From Dopamine to Digestion: Understanding Autism Beyond the Brain

Posted on March 17, 2026 by jwolf6 / 0 Comment

Imagine the brain as the body’s control center, constantly processing signals that shape how we think, feel, and behave. For a long time, it was believed that these signals were controlled almost entirely within the brain itself. But new research suggests that something much smaller, like microbes living in the gut, may also influence how the brain communicates. These discoveries are changing how scientists think about brain development and the signaling systems that shape behavior.

Dopamine and the Brain in Autism

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects communication, social interaction, and patterns of behavior. Scientists now understand that autism does not have a single biological cause. Instead, hundreds of different genetic and environmental factors can influence how the brain develops, meaning that ASD likely involves several different biological pathways rather than a single mechanism. One system researchers are increasingly interested in is the brain’s dopamine signaling system and how it impacts ASD [1].

Dopamine is a neurotransmitter that helps regulate motivation, learning, and reward. It plays a major role in how the brain determines what experiences are rewarding and which behaviors should be repeated. Dopamine signaling is especially important in brain regions involved in the reward system, such as the basal ganglia and striatum, which help guide learning and motivation. When dopamine signals function normally, they help individuals learn from rewarding experiences and motivate behaviors such as goal-directed actions and social interaction.

Research suggests that changes in dopamine signaling may contribute to some of the behavioral changes seen in ASD. Rather than proposing that dopamine alone causes autism, scientists suggest that dopamine dysfunction may represent a subtype within the autism spectrum. Genetic studies have identified mutations in proteins involved in dopamine signaling, including the dopamine transporter that helps regulate dopamine levels at synapses. Brain imaging also shows differences in dopamine circuits in the striatum and basal ganglia, which were discussed earlier as they help regulate reward processing and repetitive behaviors. Since dopamine plays a large role in motivation and learning, disruptions in this system could influence how the brain processes rewards, which can affect social motivation, attention, and repetitive behavioral patterns seen in individuals with ASD [1].

Figure 1. Simplified overview of dopamine signaling at a synapse, showing how dopamine is produced, released, and binds to receptors to influence brain communication [1].

To learn more about dopamine and its connection to ASD, click here.

The Gut Microbiome

In years of research, scientists have discovered that the brain does not work in isolation. Instead, it constantly communicates with other systems in the body through networks such as the Gut-Brain Axis. This bidirectional communication system links the brain and digestive system through neural, immune, and metabolic signaling [2]. A major part of this system is the gut microbiome, the community of trillions of microorganisms that live in the digestive tract.

Research has found that many individuals with ASD have different gut microbial communities compared to neurotypical individuals. These differences often include reduced microbial diversity, lower levels of beneficial bacteria like Bifidobacterium and Prevotella, and higher levels of bacteria associated with inflammation, including Clostridium and Klebsiella. Some studies suggest that the microbiome differences can appear early in life, even before the behavioral symptoms of autism are fully expressed. This has led researchers to look at whether changes in the gut microbiome can influence brain development [3].

Gut microbes can affect the brain in several ways. They produce molecules known as microbial metabolites, including short-chain fatty acids (SCFAs), which help in immune responses, maintain the intestinal barrier, and influence brain signaling. Changes in these metabolites, particularly lower levels of butyrate, which helps protect the intestinal barrier, have been seen in individuals with ASD [4]. Gut microbes also influence the metabolism of tryptophan, an amino acid that helps in making neurotransmitters such as serotonin [5]. Also, imbalances in the microbiome may increase intestinal permeability (also known as “leaky gut”) and trigger immune responses that release inflammation molecules, which researchers think could influence brain development and signaling [3] .

Figure 2. The Gut Brain Axis showing how the brain and the gut microbiome communicate through nerves, immune signals, and molecules from microbes [6].

Why This Connection Matters

Understanding how the gut microbiome interacts with the brain may help researchers better understand the biological complexity of ASD. Because gut microbes can influence immune signaling, metabolic pathways, and neurotransmitter systems, including those involved in reward and motivation, changes in the microbiome could potentially affect brain circuits related to behavior. Scientists are also interested in the fact that the microbiome is modifiable. Unlike many genetic factors, gut bacteria can change in response to diet, environment, and medical treatments.

For this reason, researchers are looking into whether microbiome-based approaches such as dietary changes, probiotics, or fecal microbiota transplantation could help improve the gastrointestinal symptoms and possibly influence some behavioral outcomes in individuals with ASD [3]. This area of research is still developing but studying the brain and the microbiome together gives new insight into how different systems in the body interact in ASD and develop future treatment options. To learn more about the various treatment options and the research going into it, click here.

References

[1] G. E. DiCarlo and M. T. Wallace, “Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates,” Neuroscience & Biobehavioral Reviews, vol. 133, p. 104494, Feb. 2022, doi: https://doi.org/10.1016/j.neubiorev.2021.12.017.

[2] M. A. Taniya et al., “Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation,” Frontiers in Cellular and Infection Microbiology, vol. 12, p. 915701, Jul. 2022, doi: https://doi.org/10.3389/fcimb.2022.915701.

[3] Y. Wan, Q. Su, and S. C. Ng, “New insights on gut microbiome and autism,” Trends in Molecular Medicine, Jul. 2024, doi: https://doi.org/10.1016/j.molmed.2024.06.010.

[4] E. Młynarska et al., “The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders,” Nutrients, vol. 17, no. 7, p. 1135, Mar. 2025, doi: https://doi.org/10.3390/nu17071135.

[5] “Kids with autism show altered gut microbiome-brain interactions, researchers find,” Uclahealth.org, Jun. 18, 2025. https://www.uclahealth.org/news/article/kids-with-autism-gut-microbiome-brain

[6] M. A. Taniya et al., “Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation,” Frontiers in Cellular and Infection Microbiology, vol. 12, p. 915701, Jul. 2022, doi: https://doi.org/10.3389/fcimb.2022.915701.

Featured image created by Julia Wolf and Microsoft CoPilot.

Disease/Health/Uncategorized

Dopamine in Action: Mapping the Brain Circuits with Potential Roles in Autism Spectrum Disorder

Posted on March 15, 2026 by edoty / 0 Comment

Dopamine is a neurotransmitter that plays a central role in motivation, learning, cognition, and movement. With increasing research summarized in the article by DiCarlo and Wallace, disruptions in dopamine signaling are thought to contribute to the symptoms seen in Autism Spectrum Disorder (ASD). ASD is highly complex and influenced by over 1,000 genes, so this paper focused on the link between dopamine dysfunction and the specific subtype of ASD that shows comorbidity with Attention Deficit Hyperactivity Disorder (ADHD). Since dopamine regulates reward processing, motivation, cognition, and motor control, abnormalities in dopaminergic circuits may alter how individuals with ASD experience social rewards, process information, and regulate behavior.[1]

Dopamine Production in the Brain:

Most dopamine in the brain originates from two regions in the midbrain: the Ventral Tegmental Area (VTA) and the Substantia Nigra (SN). The VTA is the primary source of dopaminergic neurons and is involved in reward processing and motivation. These neurons increase their firing after rewarding experiences, helping the brain associate certain behaviors with positive outcomes, thus forming habits.[2] The substantia nigra, particularly the pars compacta region, also produces dopamine, but its major function is motor control.[3] From these areas, dopamine interacts with other regions of the brain through several key signaling pathways.

Dopamine Pathways in the Brain:

One of the most important dopamine circuits discussed in relation to autism is the mesolimbic pathway. This pathway originates in the VTA and spans to various structures such as the nucleus accumbens, amygdala, and hippocampus. The mesolimbic pathway is responsible for reward processing and reinforcement learning. It does so by strengthening connections between certain behaviors and positive outcomes.[4] The review article highlights that disruptions in dopamine signaling within this pathway may affect how rewarding social interactions feel for individuals with autism.[5]

Another pathway that originates from the VTA is the mesocortical pathway. This circuit reaches the prefrontal cortex and is involved in cognitive functions such as attention, working memory, decision-making, and impulse control.[6] In ASD, these functions are often altered. The paper suggests that disruptions in dopamine signaling within the mesocortical pathway may contribute to cognitive differences associated with ASD, including challenges in adapting to new information, maintaining attention, or regulating behavior.[7] Because the prefrontal cortex is critical for complex decision-making, even small changes in dopamine signaling in this pathway could influence how individuals process and respond to environmental stimuli.

The nigrostriatal pathway is the third major dopaminergic circuit. This pathway originates in the substantia nigra and projects to the dorsal striatum. Dopamine signaling along this pathway ensures smooth and controlled voluntary motor activity. Dysfunction of the nigrostriatal pathway is most famously associated with Parkinson’s Disease, where dopamine dysregulation leads to tremors and slowed movement.[8] However, dopamine abnormalities in this pathway may also be relevant to ASD.

Source of Photo: Theory of Addiction | Encyclopedia MDPI

Final Thoughts:

Together, these dopamine pathways illustrate how a single neurotransmitter can influence a wide range of behaviors depending on where it acts in the brain. The review article argues that examining these circuits and the role of dopamine may help researchers better understand the biological diversity within autism. By identifying specific patterns of dopaminergic dysfunction, scientists may eventually be able to classify specific subtypes of ASD and develop more targeted treatments.

Acknowledgments:

Feature Image created by me using AI generation

[1] Gabriella E. DiCarlo and Mark T. Wallace, “Modeling Dopamine Dysfunction in Autism Spectrum Disorder: From Invertebrates to Vertebrates,” Neuroscience & Biobehavioral Reviews 133 (February 2022): 104494, https://doi.org/10.1016/j.neubiorev.2021.12.017.

[2] “Ventral Tegmental Area: Location and Core Functions,” Biology Insights, July 24, 2025, https://biologyinsights.com/ventral-tegmental-area-location-and-core-functions/.

[3] “Substantia Nigra (SN): What It Is, Function & Anatomy,” Cleveland Clinic, accessed March 9, 2026, https://my.clevelandclinic.org/health/body/23010-substantia-nigra-sn.

[4] “Dopamine Chart: Pathways, Receptors, and Role in Brain,” Biology Insights, April 29, 2025, https://biologyinsights.com/dopamine-chart-pathways-receptors-and-role-in-brain/.

[5] DiCarlo and Wallace, “Modeling Dopamine Dysfunction in Autism Spectrum Disorder.”

[6] Biology Insights, “Dopamine Chart.”

[7] DiCarlo and Wallace, “Modeling Dopamine Dysfunction in Autism Spectrum Disorder.”

[8] Biology Insights, “Dopamine Chart.”

Uncategorized

Marijuana: Medical Miracle Plant or Myth?

Posted on February 25, 2026 by ehunt4 / 0 Comment

In the last couple decades, feelings about marijuana have changed drastically nationally and internationally. In the USA, forty states have legalized medical marijuana and twenty-four of them have fully legalized it for adults to partake in. Despite this, marijuana remains illegal for recreation and medical use by the federal government. Therefore, marijuana is technically illegal in all fifty states with no medical uses.

A common argument for those that are for legalization of marijuana is that it has lots of health benefits, and up until recently many people thought marijuana was non-addictive or much less addictive than other drugs. So, is there any benefits to marijuana? Well, this is a complex question. Marijuana has multiple compounds that have an effect on your body, the most well known ones are THC and CBD (1). Many of these compounds have been found to effect certain areas of your body in a good way. So the question is not whether marijuana has benefits to it, but what in marijuana can be good for you and how much of an impact do these compounds really have on your health?

How does marijuana affect you?

The endocannabinoid system keeps your central nervous system in check by letting neurons know what to do next. Basically, when a presynaptic neuron releases neurotransmitters these bind to receptors on the postsynaptic neuron and either excite or inhibit the neuron. Following the binding of neurotransmitters is when the endocannabinoid system kicks into gear. The postsynaptic neuron will form endocannabinoids on demand which then act as a neurotransmitter in their own respect. These endocannabinoids travel back to the presynaptic neuron and bind to cannabinoid receptors which starts a chain reaction that leads to depolarization in the neuron which prevents further neurotransmitter release. Basically, it acts as a messenger from the postsynaptic neuron to tell the presynaptic neuron “we’re good, we don’t need anymore neurotransmitters”. This is a simplified version of this article that explains the endocannabinoid system in great detail, so if you are looking for a more in depth explanation this is a great place to start.

As mentioned earlier, marijuana has multiple compounds that can affect you. These compounds are known as cannabinoids. So to understand how marijuana affects you, you must understand what these compounds do individually. The cannabinoids in marijuana that will be discussed are THC, CBD, CBN, and CBC.

THC

The most dominant of these compounds is THC, more specifically Delta-9 THC. This is the main psychoactive compound in marijuana, or in other words, it is the compound that produces the high people experience when they use marijuana. While strains can make the percentage of all these compounds vary extremely widely, typically Delta-9 THC can range from 13-40% of the dry weight of the plant, but the average percentage of illicit marijuana was found to be 27% (2). For more details on how THC rates have changed over the years, check this article out.

Out of all the compounds in marijuana, this is the most problematic one. For your average person, THC is more harmful than it is good. Regular use can lead to reduced cardiovascular functioning, an increased risk of anxiety and depression, abnormal brain development, and a myriad of other things you don’t want to happen to you (3). For people experiencing extremely debilitating diseases such as Parkinson’s, THC can do wonders. For people experiencing these diseases, the benefits far outweigh the adverse health risks. THC has been found to be a cure for the motor symptoms of Parkinson’s and improved symptoms of tremors, rigidity, pain and sleep problems, but the research into this is extremely limited so do not take this as gospel (4). Currently medical THC is used for managing symptoms of chemotherapy such as nausea, chronic pain relief and muscle spasms. For a more in depth look at THC as a medical treatment, check out this article.

CBD

CBD is probably the second most well known compound of marijuana and it has gotten a great amount of attention in the last decade or so. CBD is non-psychoactive, which is one of the reasons it has gotten so popular. Those who are looking to reap some of the benefits of marijuana but don’t want to get high have turned to various forms of ingesting CBD. The best thing about CBD products is you do not need a prescription to obtain them and they are legal in all fifty states as well as federally.

CBD can have benefits for your overall health, giving it potential for use as a supplement. One of its main properties is its anti-inflammatory potential. CBD stimulates the release of anti-inflammatory cytokines which then diminishes the level of pro-inflammatory cytokines. This has made CBD a viable treatment for inflammatory diseases in the intestines, brain and skin (5). Inflammation in your body is beneficial in the short term as that’s how our bodies repair damage and fight disease. But long term inflammation can cause pain and damage to tissues and can increase your risk for neurodegenerative diseases such as Alzheimer’s, Multiple Sclerosis, and Parkinson’s (6). For more information on inflammation look here. For more in depth information and more benefits of CBD check out this article.

CBN

CBN is another cannabinoid in marijuana. This develops from THC as the plant ages and is one of the lesser known cannabinoids by the general public. CBN is another cannabinoid that is legal nationwide and is sold as a supplement either independently or in conjunction with CBD. It is mildly psychoactive, it doesn’t get you high like THC but those who take it report a relaxing or sleepy effect. Therefore, a reason people take CBN is to fall asleep better and to wake up less during the night.

CBN is similar to CBD in the sense that they both have anti-inflammatory properties, but the main advertised use for it is for a sleep medication. This can be very misleading though. Contrary to the other cannabinoids talked about here, there is absolutely zero evidence that CBN provides any benefits to sleep (7). While there is some evidence showing its anti-inflammatory properties, this evidence is very limited. CBN is a lesson in the misleading advertising of cannabinoids with the liberalization of views on marijuana and that many of these companies can claim things that are not true.

CBC

CBC is another lesser known compound in marijuana. Similarly to other cannabinoids, CBC has anti-inflammatory properties. But the thing that makes it special is it’s role in pain relief. Most other cannabinoids bind to cannabinoid receptors know as CB1 and CB2, but CBC has a very weak affinity to both of these, meaning it does not really bind well to either of these receptors. Conversely, CBC has a high affinity for TRPA1 and TRPV1 receptors.

TRPA1 and TRPV1 receptors play a large role in pain perception. When your body experiences a damaging stimuli, say you stub your toe, that release little messengers in your body which bind to both of these receptors. This causes them to activate and send a signal to your brain saying something is wrong, and that signal is what causes us to feel pain. CBC activates both of these receptors, which one would assume causes more pain and not pain relief. But the thing is, when these receptors become activated many times, they become desensitized or become inactivated. So when CBC activates these receptors, they become desensitized or inactivated, leading to a relief in pain (8).

What does all this information mean?

What all this information shows is that marijuana has the potential to be used as a treatment for certain diseases and that the information is quite limited, making its potential unknown. This also means the information on how effective it is and how bad it can be for you is also quite limited. When you consider the current information, your average person doesn’t have much benefit to consuming these compounds. There is much more research to be done into the effects, good and bad, and anything claimed by companies should be taken with a grain of salt. In all, marijuana isn’t going to be a miracle cure or sure fire prevention for diseases, but it won’t do you much harm if you partake every now and again. With anything, approach it with caution and educate yourself before you fully plunge into the world of marijuana.

Atakan Z. (2012). Cannabis, a complex plant: different compounds and different effects on individuals. Therapeutic advances in psychopharmacology, 2(6), 241–254. https://doi.org/10.1177/2045125312457586
Vernich, F., Stefani, L., Fiorelli, D., Mineo, F., Pallocci, M., Treglia, M., Marsella, L. T., & Tittarelli, R. (2023). Trends in Illicit Cannabis Potency based on the Analysis of Law Enforcement Seizures in the Southern Area of Rome. Toxics, 11(8), 648. https://doi.org/10.3390/toxics11080648
Volkow, N. D., Baler, R. D., Compton, W. M., & Weiss, S. R. (2014). Adverse health effects of marijuana use. The New England journal of medicine, 370(23), 2219–2227. https://doi.org/10.1056/NEJMra1402309
Patel, R. S., Kamil, S., Shah, M. R., Bhimanadham, N. N., & Imran, S. (2019). Pros and cons of marijuana in treatment of Parkinson’s disease. Cureus, 11(6), e4813. https://doi.org/10.7759/cureus.4813
Leinen, Z. J., Mohan, R., Premadasa, L. S., Acharya, A., Mohan, M., & Byrareddy, S. N. (2023). Therapeutic potential of cannabis: A comprehensive review of current and future applications. Biomedicines, 11(10), 2630. https://doi.org/10.3390/biomedicines11102630\
Singh, K., Bhushan, B., Chanchal, D. K., Sharma, S. K., Rani, K., Yadav, M. K., Porwal, P., Kumar, S., Sharma, A., Virmani, T., Kumar, G., & Noman, A. A. (2023). Emerging therapeutic potential of cannabidiol (CBD) in neurological disorders: A comprehensive review. Behavioural neurology, 2023, 8825358. https://doi.org/10.1155/2023/8825358
Maioli, C., Mattoteia, D., Amin, H. I. M., Minassi, A., & Caprioglio, D. (2022). Cannabinol: History, Syntheses, and Biological Profile of the Greatest “Minor” Cannabinoid. Plants (Basel, Switzerland), 11(21), 2896. https://doi.org/10.3390/plants11212896
Lowin, T., & Straub, R. H. (2015). Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis. Arthritis research & therapy, 17(1), 226. https://doi.org/10.1186/s13075-015-0743-x

Legality of Cannabis by Jurisdiction map is custom made by Wikipedia user Lokal_Profil –Derived from Blank USA, w territories 2.svg by Heitordp

The photo in THC section retrieved from https://www.henryford.com/blog/2023/01/what-you-should-know-about-marijuana

The photo in the CBD section retrieved from https://www.stbernarddrugs.com/post/whats-the-hype-over-cbd

The photo in the CBN section retrieved from https://www.extractlabs.com/product/cbn-gummies/

Featured image retrieved from https://www.cdc.gov/cannabis/faq/index.html

Health

Is Cannabis an Effective Treatment?

Posted on February 25, 2026 by agriffi1 / 0 Comment

The Endocannabinoid System

The endocannabinoid system (ECS) is involved in many functions of the brain, including modulating synaptic plasticity, learning and memory, homeostatic processes, mood, pain, perception, gene expression, neuroprotection, and making new proteins. Research has shown that the ECS is a promising target for many diseases, including neurodegenerative diseases, epilepsy, cognitive deficits, drug abuse and dependence, and potentially traumatic brain injuries (TBI). However, treatment through the ECS has a lot of complexities and additional understanding through continued research is essential. [1]

The Cannabis Plant

There are sixty active ingredients in the cannabis plant. Delta-9 THC is the major psychoactive ingredient which causes the effects we often think about in relation to cannabis. In research involving cannabis, a specific synthetic ingredient is usually studied rather than the whole plant. [1]

Cannabis as a Potential Treatment

Cannabis has been shown to have neuroprotective effects and show positive improvements related to numerous diseases. Treatment of cannabis in multiple sclerosis, which is characterized by demyelination of axons and death of neurons, has shown better motor function, decreased pain, and improvements in spasticity, spasms, and pain. In Alzheimer’s disease, cannabis has shown improvements in behaviors and dementia symptoms. Additionally, Huntington’s disease, traumatic brain injury, and epilepsy have shown promising results with treatment involving marijuana derivatives. [1]

A possible approach for taking advantage of the benefits and trying to limit the risks of cannabis being investigated, is to isolate specific active ingredients. A main ingredient being investigated for its therapeutic effects is Cannabidiol (CBD). CBD has been shown to benefit anxiety, inflammation, nerve-pain, arthritis, and seizures. [3,4] The FDA has not approved cannabis for any medical uses; however, synthetic derivatives of marijuana have been approved, including CBD in certain forms for specific ailments. [5]

Challenges

The ECS works throughout the body, which means receptors that will be affected by cannabinoids are also widespread. This makes targeting this system and developing effective therapies challenging since it is hard to predict exactly what will be effected and where. A cannabinoid binding to a receptor in one area seems to have different effects than if it binds in another area, making it hard to develop generalizable, consistent treatments. [1]

Cannabis has many potential therapeutic effects, but there are also many potential drawbacks to consider. Thinking, attention, memory, coordination, movement, decision making, and perception of time can all be negatively impacted, especially in younger individuals. Brain development, especially from repeated exposure to THC can be permanently impacted. [6] Repeated use of cannabis can result in tolerance and dependence. [1] Additional research is important to understand cannabis, the effects of its isolated active ingredients as well as when interacting together, long-term effects of cannabis use, and its potential therapeutic benefits.

Footnotes

[1] Kendall, D. A., & Yudowski, G. A. (2017). Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Frontiers in Cellular Neuroscience, 10, 294. https://doi.org/10.3389/fncel.2016.00294

[2] What you need to know (and what we’re working to find out) about products containing cannabis or cannabis-derived compounds, including CBD. (2023). FDA. https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis

[3] DiLonardo, M. J., & Walker-Journey, J. (n.d.). CBD vs. THC: What’s the Difference? WebMD. Retrieved February 25, 2026, from https://www.webmd.com/pain-management/cbd-thc-difference

[4] What Is Cannabidiol (CBD)? Uses, Benefits, and More. (2018, August 3). Healthline. https://www.healthline.com/health/your-cbd-guide

[5] Medical Marijuana. (n.d.). Cleveland Clinic. Retrieved February 25, 2026, from https://my.clevelandclinic.org/health/articles/medical-marijuana

[6] CDC. (2025, July 24). Cannabis and Brain Health. Cannabis and Public Health. https://www.cdc.gov/cannabis/health-effects/brain-health.html

Health/Hot topics

Seizures, Synapses, and the Science behind THC

Posted on February 24, 2026 by kleppke / 0 Comment

The Brain’s Endocannabinoid System

The brain is constantly sending an receiving signals that keep our whole body functioning properly, but it needs help staying regulated. One main system in that brain that helps with regulation is one that many people have never heard of before, the endocannabinoid system (ECS).

The ECS is a network that helps regulate neurotransmitter release and neuronal signaling. When neurons become too active, the cell can produce molecules called endocannabinoids. These molecules activate CB1 receptors, which slow the release of neurotransmitters. The main two neurotransmitters it regulates are glutamate and GABA, with the goal of equilibrium of their levels [2].

If the neuron is releasing too much glutamate (an excitatory neurotransmitter, increasing activity), CB1 activation reduces that release. This is called depolarization-induced suppression of excitation.
If the neuron is releasing too much GABA (an inhibitory neurotransmitter, relaxing activity), CB1 can reduce its release as well. This is called depolarization-induced suppression of inhibition.

More about the ESC can be found here: https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2016.00294/full

Triggering Seizures- The Problem

Epilepsy is a condition commonly characterized by seizures. Seizures are bursts of abnormal electrical activity in the brain, typically caused by an imbalance between excitatory and inhibitory neurotransmitters (figure 1) in the brain can cause these unstable electrical surges. When excitation is occurring significantly more than inhibition, increased activity causes neuron to fire uncontrollably, triggering a seizure. These can occur more often when the ESC can’t stabilize balance (figure 2), which happens most often in people with low amounts of CB1 receptors, or endocannabinoid levels and enzymes that produce and break down these molecules are abnormal[3].

Figure 1: Here is a helpful visual of how balance in the brain determines seizures. When unbalanced, impulses in the brain receive a “green light,” leading to abnormal bursts of electricity, causing the seizure [1].

Figure 2: This diagram shows the imbalance between excitatory and inhibitory neurotransmission and how it contributes to seizure activation. Excitatory neurons release glutamate, increasing neuronal excitability. Inhibitory neurons release GABA, reducing excitability [4].

Therapeutic THC- A Solution?

THC is the primary psychoactive compound in cannabis, which partially activates the CB1 receptors, meaning it can bind to the same receptors used by the brain’s own endocannabinoids and activate them[3]. Since CB1 activation reduces glutamate release, THC can reduce neuronal over excitability, helping to control seizures[2]. Therefore, THC can function as an anticonvulsant by:

Reducing excitatory glutamate signaling
Enhancing inhibitory GABA pathways
Regulating ion channels that control neuronal firing

These mechanisms can lower seizure frequency or intensity in some individuals. THC also comes with psychoactive risks. At high doses, especially containing more than 15% THC, risks outweigh potential therapeutic benefits [5]. Side effects can include anxiety, cognitive impairment, and increased risk of dependence. Researchers are still working to determine the optimal THC dose, concentration, and cannabinoid combination to maximize anti-seizure effects while minimizing unwanted psychoactive outcomes[6].

This video has some additional information on THC’s interaction with CB1 receptors: https://youtu.be/ISUXrjBXHsE?si=OAVJVSV78OxVnVV-&t=41

Conclusion

Seizures occur when the balance between excitation and inhibition breaks down. The endocannabinoid system plays a central role in trying to maintain that balance. When it functions properly, it acts by suppressing inhibition or excitation to bring neural firing to equilibrium. Cannabinoids, like THC, activate this system, which can reduce seizure activity. However, dosing, safety, and long-term effects remain active areas of research.

Key Takeaways:

Epilepsy involves an imbalance between excitatory (glutamate) and inhibitory (GABA) signaling.
The endocannabinoid system regulates the balance of this signaling through CB1 receptors.
THC activates CB1 receptors to restore balance and reduce excessive neuronal firing.
Cannabinoids can act as anticonvulsants, but high THC concentrations pose psychoactive risks, making dosing important.
Ongoing research aims to refine cannabis-based therapies for safer, more effective seizure control.

References

*Featured image/ artstract created by AI.

[1] Devinsky, O., Jones, N. A., Cunningham, M. O., Jayasekera, B. A. P., Devore, S., & Whalley, B. J. 2024. Cannabinoid treatments in epilepsy and seizure disorders. Physiological Reviews, 104(2), 591–649. https://doi.org/10.1152/physrev.00049.2021

[2] Kendall DA and Yudowski GA. 2017. Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Front. Cell. Neurosci. 10:294. doi: 10.3389/fncel.2016.00294

[3] Springer C, Nappe TM. 2023. Anticonvulsants Toxicity. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK537206/

[4] Chudai Zeng & Chu Chen. 2025. Endocannabinoid signaling in epilepsy, Neurobiology of Disease. Volume 215, 107074, ISSN 0969-9961, https://doi.org/10.1016/j.nbd.2025.107074.

[5] Santiago Philibert-Rosas, Cameron J. Brace, Sanaa Semia, Barry E. Gidal, Bradley T. Nix, Anne F. Josiah, Melanie Boly, Aaron F. Struck. 2025. The role of cannabis in epilepsy illustrated by two case reports. Epilepsy & Behavior Reports. Volume 32, 100804, ISSN 2589-9864. https://doi.org/10.1016/j.ebr.2025.100804.

[6] Gómez-Nieto, R., López D. E., Garcia-Cairasco N. 2021. Challenges and Conundrums in Cannabinoid-Based Treatments for Epilepsy Syndromes and Associated Neurobehavioral Comorbidities. Frontiers in Behavioral Neuroscience. Volume 15. https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2021.781852

Uncategorized

The Brain’s Hidden Barcode

Posted on February 24, 2026 by jwolf6 / 0 Comment

Imagine scanning a barcode at the grocery store. That pattern of lines tells the scanner exactly what the product is, how much it costs, and where it came from. Now imagine your brain doing something similar, using tiny chemical “barcodes” to decide how cells respond to various signals like cannabis, stress, or pain. Researchers have found that receptors in the brain use a system called phosphorylation barcoding to control how signals are processed. Understanding this hidden barcode system in cannabinoid receptors could change how we think about cannabis, brain signaling, and future medical treatments.

The Endocannabinoid System

Your brain has a unique signaling system called the endocannabinoid system (ECS). This system helps keep brain activity in balance in plays a major role in memory, mood, pain, and neuroplasticity. It works through cannabinoid receptors, especially CB1 receptors, which are some of the most abundant receptors in the brain. When neurons become active, they release endocannabinoids, mainly anandamide (AEA) and 2-arachinonoglycerol (2-AG). These molecules travel backward across the synapse and bind to CB1 receptors on the presynaptic neuron. The backward signaling reduces neurotransmitter release, acting like a brake that prevents neurons from becoming overactive.

CB1 receptors are a type of GPCR, which means they translate chemical signals into cell responses. When activated, they typically use G proteins for signaling, but they can also be phosphorylated and recruit other proteins, which leads to long term changes in brain function. Since CB1 receptors are so widespread, the ECS in involved in many neurological conditions like epilepsy, neurodegeneration, traumatic brain injury, and psychiatric disorders [1].

Figure 1. Endocannabinoids travel backward across synapses to calm brain cells. Repeated activation changes endocannabinoid receptors and impacts multiple signaling routes inside neurons [1].

To learn more about the endocannabinoid system, click here.

The Creation of Brain “Barcodes”

Neurons communicate using receptors on their surface. One of the largest and most important receptor families is called G protein-coupled receptors (GPCRs). These receptors detect neurotransmitters, hormones, and drugs and turn those signals into actions inside of the cell. GPCRs act as decision making sites, rather than simple on/off switches. When a GPCR is activated, enzymes called G-protein coupled receptor kinases (GRKs) add small chemical tags called phosphate groups to the receptor. Instead of just one tag, multiple spots can be tagged in different combinations. This pattern is known as the phosphorylation barcode. These barcodes are read by proteins called β-arrestins, which decide what happens next [2]. Some barcodes shut the receptor down, some pull it into the cell, and others activate new signaling pathways that can change how the neuron acts. Different molecules can create different barcodes on the same receptor, this means that the same receptor can send different messages depending on what binds to it, this is called biased signaling [3].

Figure 2. GPCR phosphorylation barcoding. Multiple phosphate tags create unique patterns that determine how the receptor signals inside the cell [4].

Phosphorylation Barcoding and the Endocannabinoid System

In the ECS, phosphorylation barcoding allows CB1 receptors to fine tune how cannabinoid signals are processed. Different phosphorylation patterns on CB1 receptors influence whether signaling continues at the cell surface or shifts to other pathways inside the neuron. These differences help explain how cannabinoid signaling can produce both rapid changes in neurotransmission and longer-term effects on brain function [2]. Different phosphorylation barcodes at CB1 receptors can lead to changes in gene expression and protein synthesis [1]. Also, barcodes explain why THC and cannabis affect people in different ways, since individuals and brain regions can generate distinct phosphorylation patterns in response to the same drug [5].

Why This Matters for the Public and Brain Health

Understanding phosphorylation barcoding in the ECS could help scientists develop better cannabinoid based treatments. Since cannabinoid receptors can send different messages based on their “barcode”, researchers may be able to design drugs that keep the helpful effects of cannabinoids, like pain relief and calming cells, while reducing unwanted side effects like memory problems or dependence. This could improve treatment for conditions such as chronic pain, epilepsy, neurodegenerative diseases, and mental health disorders.

To learn more about how endocannabinoids and cannabis are being studied as medical treatments, click here.

References

[1] D. A. Kendall and G. A. Yudowski, “Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease,” Frontiers in Cellular Neuroscience, vol. 10, no. 294, Jan. 2017, doi: https://doi.org/10.3389/fncel.2016.00294.

[2] N. R. Latorraca et al., “How GPCR Phosphorylation Patterns Orchestrate Arrestin-Mediated Signaling,” Cell, vol. 183, no. 7, pp. 1813-1825.e18, Dec. 2020, doi: https://doi.org/10.1016/j.cell.2020.11.014.

[3] S. B. Liggett, “Phosphorylation Barcoding as a Mechanism of Directing GPCR Signaling,” Science Signaling, vol. 4, no. 185, pp. pe36–pe36, Aug. 2011, doi: https://doi.org/10.1126/scisignal.2002331.

[4] H. Chen, S. Zhang, X. Zhang, and H. Liu, “QR code model: a new possibility for GPCR phosphorylation recognition,” Cell Communication and Signaling, vol. 20, no. 1, Mar. 2022, doi: https://doi.org/10.1186/s12964-022-00832-4.

[5] M. S. Ibsen, D. B. Finlay, M. Patel, J. A. Javitch, M. Glass, and N. L. Grimsey, “Cannabinoid CB1 and CB2 Receptor-Mediated Arrestin Translocation: Species, Subtype, and Agonist-Dependence,” Frontiers in Pharmacology, vol. 10, Apr. 2019, doi: https://doi.org/10.3389/fphar.2019.00350.

Featured image was created by Julia Wolf and Microsoft CoPilot