Cobbers on the Brain

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.

1. 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
2. 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
3. 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
4. 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
5. 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\
6. 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
7. 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
8. 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

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].

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].

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

The brain has its own cannabis system, and long before humans cultivated marijuana, our neurons were already communicating using cannabis-like molecules called endocannabinoids.

These molecules help regulate mood, memory, appetite, pain, and synaptic plasticity.  They act as a kind of neural “volume control”, fine-tuning communication between neurons. This internal system, called the endocannabinoid system (ECS), is essential for maintaining balance in the brain.[1] Under normal conditions, it works beautifully. But what happens when that carefully balanced system is repeatedly overstimulated by external THC? This question sits at the center of current cannabinoid research.

CB1 Receptors and Neural Signaling

In their review, Kendal & Yudowski (2017) describe how CB1 receptors – the primary receptors activated by THC – are among the most abundant G-protein-coupled receptors (GPCRs) in the brain.[1] These receptors are densely expressed in the hippocampus, prefrontal cortex, basal ganglia, and cerebellum – regions responsible for memory, executive function, reward, and movement.

Under normal conditions, endocannabinoids are produced on demand. They briefly suppress neurotransmitter release to fine-tune synaptic signaling. THC, however, is not produced on demand. It persistently activates CB1 receptors.

Figure 1 (left): Mechanism of retrograde endocannabinoid (eCB) signaling via CB1 receptors in a neural synapse [1]

Kendall & Yudowski explain that repeated THC exposure leads to CB1 receptor desensitization – meaning the receptors become less responsive over time.[1] This contributes to tolerance. The brain adapts by reducing signaling efficiency, shifting intracellular signaling pathways, and altering neural communication. In other words, the brain compensates.

How THC Changes Brain Function

In the short-term, THC exposure is associated with a plethora of cognitive changes, including impaired short-term memory, reduced attention, slower reaction times, altered motor coordination, as well as anxiety. These effects are largely explained by CB1 receptor activation in the hippocampus and prefrontal cortex. For most users, these impairments are temporary, but intoxication can increase risky behavior like impaired driving.[2]

On the other hand, chronic overstimulation of CB1 receptors with repeated or early exposure can produce tolerance, increase the risk of heart disease or stroke, alter reward circuitry, and disrupt executive function.[3]

Adolescent exposure may be particularly concerning. The ECS plays a role in synaptic pruning and cortical maturation during development. Introducing THC during this window may interfere with normal circuit refinement.

Figure 2: The progression of prefrontal cortical maturation and synaptic refinement during adolescence. [4]

Epidemiological studies have linked heavy adolescent cannabis use to increased risk of cognitive impairment and psychiatric vulnerability. [5]

What This Means for Us

While cannabis legalization is expanding, the perception of harm is decreasing, and THC potency has increased dramatically over the past few decades. We now know that the ECS system is not just another neurotransmitter pathway – it is a central regulator of synaptic balance. Repeated exogenous stimulation, however, may shift that system away from homeostasis. So understanding how THC interacts with CB1 receptors is not about morals; it is about informed decision-making. Science does not suggest that all cannabis use leads to irreversible harm. It does suggest that timing, frequency, dose, and developmental stage matter. The ECS system evolved to maintain balance, but the real question remains, “What happens when balance becomes overstimulation?”

References

[1]

D. A. Kendall and G. A. Yudowski, “Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease,” Front. Cell. Neurosci., vol. 10, Jan. 2017, doi: 10.3389/fncel.2016.00294.

[2]

“Marijuana,” Cleveland Clinic. Accessed: Feb. 24, 2026. [Online]. Available: https://my.clevelandclinic.org/health/articles/4392-marijuana-cannabis

[3]

N. D. Volkow, R. D. Baler, W. M. Compton, and S. R. B. Weiss, “Adverse Health Effects of Marijuana Use,” N Engl J Med, vol. 370, no. 23, pp. 2219–2227, Jun. 2014, doi: 10.1056/NEJMra1402309.

[4]

B. C. Meyer Heidi, “Brain Science Has Discovered New Drug-Free Approaches for the Anxious Adolescent,” Scientific American. Accessed: Feb. 24, 2026. [Online]. Available: https://www.scientificamerican.com/article/adolescent-anxiety-is-hard-to-treat-new-drug-free-approaches-may-help/

[5]

M. Arain et al., “Maturation of the adolescent brain,” Neuropsychiatr Dis Treat, vol. 9, pp. 449–461, 2013, doi: 10.2147/NDT.S39776.

Why should I care about this?

When you eat, your body needs a hormone called insulin in order for your body to utilize the energy in the food. Recent evidence suggests that insulin plays a very important role in the mechanisms behind Alzheimer’s and other neurodegenerative diseases. Often, the foods that taste so good to us, such as ultra-processed foods with large amounts of sugar and unhealthy fats, are not so great for insulin pathways. Therefore, if something that we can control like our diet can influence our risk for a disease as terrible as Alzheimer’s, we should do what we can to avoid developing it.

How insulin can affect Alzheimer’s

Alzheimer’s is characterized by two things, the first thing being NFTs that are formed through abnormal phosphorylation of a protein called tau, and the formation of something called Amyloid-beta plaques which will be referred to as AB plaques from this point forward (1). For a more detailed explanation of the ins and outs of Alzheimer’s, check out this article. Insulin pathways are what we call the chain of events that occur after the introduction or removal of insulin. Some components of these pathways can contribute to the formation of NFTs and AB plaques. One of these components involves an enzyme called GSK-3B, which is essential for metabolism of glucose but it also plays a role in tau phosphorylation. When insulin is not bound to a receptor, GSK-3B is activated, and when GSK-3B is activated, it promotes tau phosphorylation and deposition of AB plaques (2). Therefore, we want insulin to bind and deactivate GSK-3B in order to help prevent the formation and accumulation of NFTs and AB plaques. Another component worth talking about is another enzyme called PI3K. When PI3K is active, it inhibits GSK-3B. When PI3K is not functioning properly, it can lead to overactivation of GSK-3B, causing an excess of tau phosphorylation and AB plaque deposition (2). This is another reason why we want our insulin pathways to be working properly.

How does your diet affect insulin signaling?

Insulin binds to receptors that start the chain reactions of insulin pathways and without them, insulin would simply float there and do nothing. Insulin resistance refers to the ease at which insulin can bind to these receptors, meaning a higher insulin resistance makes it more difficult for insulin to bind properly. Type 2 diabetes is the development of high resistance to insulin, a disease that is characterized by unhealthy diets in those who develop it.

Interestingly, 80% of Alzheimer’s patients also have type 2 diabetes. When we eat an excess amount of calories, our cells adjust the amount of receptors in order to avoid overactivation of insulin pathways caused by the high levels of insulin released. Highly processed foods are characterized by high levels of sugar and unhealthy fats which are extremely calorically potent and therefore they increase insulin resistance (3). By increasing insulin resistance, we make it more difficult for insulin to do its job, which consequently results in less activation of PI3K and therefore less deactivation of GSK-3B. Additionally, diets that are high in fat can result in chronic neuroinflammation, which also contributes to AB plaque accumulation and NFT formation (4).

What should you do now?

You don’t need to necessarily follow a strict diet to prevent Alzheimer’s, nor will following one make you immune to Alzheimer’s. AB plaque accumulation and NFT formation are heavily influenced by insulin signaling, but they are also influenced by other things as well. Chances are, other consequences of an unhealthy diet are more likely to kill a person much before they start to develop Alzheimer’s, such as high blood pressure, diabetes, heart failure and a higher risk of cancer. If anything, these should be a much more compelling reason to change your diet. Being more aware of what you are eating, like how much sugar is in something and how many calories, can go a long way in changing eating habits. Changing your diet doesn’t mean following a well-known diet or only eating healthy foods, it can simply involve reducing the amount of unhealthy things you eat. As with everything in life, moderation is key. So maybe next time you get some candy, get the normal sized package instead of the share size. Or before you upgrade your meal at McDonald’s to a large, think about if paying an extra thirty cents for more food is really needed or if you simply want to do it because it is a better deal.

1. Breijyeh, Z., & Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules (Basel, Switzerland), 25(24), 5789. https://doi.org/10.3390/molecules25245789
2. Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry international, 135, 104707. https://doi.org/10.1016/j.neuint.2020.104707
3. Ede, G. (2016). Avoiding Alzheimer’s Disease Could Be Easier Than You Think. Psychology Today. https://www.psychologytoday.com/us/blog/diagnosis-diet/201609/avoiding-alzheimer-s-disease-could-be-easier-you-think\
4. Song, M., Bai, Y., & Song, F. (2025). High-fat diet and neuroinflammation: The role of mitochondria. Pharmacological research, 212, 107615. https://doi.org/10.1016/j.phrs.2025.107615