The Endocannabinoid System

The endocannabinoid system is a regulatory system in our bodies that has effects on many functions such as mood, pain, learning and memory, inflammatory response, and eating. There has also been evidence that the endocannabinoid system plays a neuroprotective role following injury (1).

There has been a lot of interest lately in the utilization of this system as a therapeutic target for many diseases. Drugs that act on the endocannabinoid system to increase appetite and to help treat seizures caused by epilepsy have been approved, and utilize both CBD and THC to do so.

Endocannabinoids

Our bodies naturally produce molecules that activate this system, called endocannabinoids. These molecules are produced on-demand in response to the state our body is in. The receptors endocannabinoids act on are two types of CB receptors.

1. 

   CB1 receptors are primarily found in the central nervous system, and are mainly on presynaptic neurons.

2. CB2 receptors are found commonly on cells and tissues in the immune system, and are mainly activated in response to inflammation.

There are also exogenous materials that will act on the endocannabinoid system. Most commonly known and used are cannabis and THC.

Cannabis and THC

While you may have heard the terms marijuana and cannabis used interchangeable there are different meanings to each. The word ‘cannabis’ refers to all products derived from the plant Cannabis sativa. ‘Marijuana” refers to parts or products from the Cannabis sativa plant that contain a significant amount of tetrahydrocannabinol (THC).

All natural (non-synthetic) marijuana is cannabis, but not all cannabis is marijuana. Hemp is the term used for cannabis compounds that contain less than .3% of THC or less (2).

• THC: the main psychoactive molecule found in cannabis plants. This is the molecule that produces the ‘high’ sensation.
• CBD: cannabidiol is a molecule found in cannabis and is an activator of the endocannabinoid system. This molecule however doesn’t give the high that THC does.

Throughout the 1900s it became illegal in most of the world to grow cannabis plants for sale or personal use. But why?

Drug Scheduling in the US

To talk about the illegality of cannabis and THC, we need to have some basic understanding of how drug classification works in the United States. Under the Controlled Substances Act the government allowed the Drug Enforcement Administration (DEA) to classify drugs into 5 categories depending on the drugs accepted medical uses and it’s potential for abuse and addiction.

The higher the schedule, the more potential for abuse and addiction. Schedule 1 drugs are substances or chemicals that are defined as “drugs with no currently accepted medical use and a high potential for abuse” (3). Examples include LSD, ecstasy, and marijuana.

Woah wait! Why is marijuana included in that list when we already mentioned drugs that use THC?  That’s where it gets tricky.

Medical Uses for CBD and THC

It’s commonly known that THC can induce hunger, or ‘the muchies’. Dronabinol is a capsule form of synthetic THC that is used as an appetite stimulant. It was approved in 1985 by the FDA, and was classified as a schedule 2 medication. However in 1991 it was rescheduled to schedule 3 based on evidence that it has low potential for abuse (4). So how is THC as dronabinol considered less addictive than the THC in marijuana? There has been lots of push to reschedule cannabis and marijuana down from schedule 1 based on this.

Benefits to Rescheduling Cannabis

THC is an approved an appetite stimulant medication and is often given to people undergoing chemotherapy to combat weight loss. However recently there has been research on the potential effects that THC can have for obstructive sleep apnea, chronic neuropathic pain, glaucoma, arthritis, and many others (5). CBD has recently been a topic of interest for the treatment of seizures, inflammation, migraines, and psychosis and other mental disorders (6).

Cannabis being a schedule 1 drug makes further research into the use of THC to treat these conditions rather difficult, requiring lengthy petitions and government approval. Rescheduling cannabis into a lower drug class would make researching and developing medications involving THC and CBD an easier process.

References:

1. https://www.health.harvard.edu/blog/the-endocannabinoid-system-essential-and-mysterious-202108112569

2. https://www.nccih.nih.gov/health/cannabis-marijuana-and-cannabinoids-what-you-need-to-know

3. https://www.dea.gov/drug-information/drug-scheduling

4. https://www.pharmacytimes.com/view/dea-denial-of-petition-to-reschedule-marijuana

5. https://www.ncbi.nlm.nih.gov/books/NBK563174/

6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966847/

Addiction is a significant issue in today’s society. Addiction is defined as a compulsive and persistent dependence on a substance or behavior that has negative consequences. Some of the most common types of addiction are substance addiction (addiction to drugs, alcohol, and tobacco), natural addiction (addiction to food, binge eating disorder) and behavioral addiction (addiction to gambling, video games, and social media).

Addiction can have a significant impact on an individual’s life as well as the lives of those close to them. It can result in physical and mental health issues, financial difficulties, social isolation, and legal complications. Addiction can also have a negative impact on the larger community by causing crime, violence, and other social problems.

Addiction is particularly problematic in today’s society due to a number of factors. For starters, addictive substances and behaviors are more widely available, thanks to the proliferation of online gaming and social media platforms. Second, there is less social stigma attached to addiction, which may make it easier for people to engage in addictive behaviors without fear of being judged. Finally, many people lack access to effective addiction treatment and support services, making it difficult for them to overcome their addiction and live a healthy life.

Drug abuse can activate several signaling pathways in the brain, leading to the development of addiction. The following are some of the most common signaling pathways involved in drug abuse:

1. Dopamine pathway:The mesolimbic dopamine pathway, which is a circuit of brain regions involved in reward and motivation, is one of the key pathways identified by Dr. Nestler and his colleagues. This pathway is activated when a person engages in rewarding behavior or takes an addictive drug, and dopamine is released in the nucleus accumbens, a key region of the brain’s reward circuitry. This dopamine release reinforces and motivates the individual to repeat the behavior.
2. Glutamate pathway: The glutamate pathway is responsible for learning and memory. Drugs of abuse can activate this pathway, leading to changes in synaptic plasticity, which can lead to drug cravings and addiction.
3. GABA pathway: The gamma-aminobutyric acid (GABA) pathway is responsible for the brain’s inhibitory system. Drugs of abuse can disrupt the balance of GABA signaling, leading to an increase in excitatory signaling, which can lead to drug cravings and addiction.
4. Endocannabinoid pathway: The endocannabinoid system is responsible for regulating appetite, pain, and mood. Drugs of abuse can activate the endocannabinoid pathway, leading to changes in appetite and mood.

Moreover, repeated drug use or addictive behavior causes the brain to adapt, resulting in long-term changes in gene expression and synaptic plasticity. Dr. Nestler has identified a number of specific molecular pathways involved in these adaptations, such as changes in gene expression of various transcription factors, epigenetic DNA modifications, and changes in synaptic plasticity and neuroplasticity.

While there may not be a single common molecular pathway for addiction, Dr. Nestler’s research has contributed to the identification of some of the key molecular and cellular mechanisms that underpin addictive behavior. This understanding is critical for the development of new treatments and interventions to assist individuals in overcoming addiction and leading healthy, fulfilling lives.

Artstract created by Kailee Vigen

The Obesity Crisis 

41.9 percent of American adults have obesity as of 2022. This obesity rate is due to many contributing factors such as race, genetics, environmental, and biological. Since 2021, nineteen states have announced a population obesity rate of 35% or higher. A decade ago, none of the fifty states were even near 35% obese. What has caused this increase, and what can be done to help the obesity crisis? With numbers as such, it is safe to say that this is not an individual problem – this is the nations, and even the world’s problem.

The only explanation for such an increase in obesity is, simply, increased caloric intake and decreased exercise causing weight gain. As treatment, it is advised to eat healthier and exercise more, which is attainable for some individuals, but not all. At such a large scale of obesity, our only hope for a “cure” is market changes and policy. One policy that has been proposed and is now implemented in Philadelphia, PA, Boulder, CO, and Berkeley, CA is a sweetened beverage tax. In Berkeley, this tax caused a 21% drop in sugary drink consumption. This is one promising example that such policies can help with the obesity crisis. It is discouraging seeing the healthy food priced at least two times more as the processed and fatty snack aisle in grocery stores. If healthier food costs were lowered and unhealthy foods were taxed, the obesity epidemic would see the end of its climb and plummet. 

The Science

Biologically, obesity is more than just a bigger waist and greater amounts of adipose tissue built up throughout the body, it actually affects brain function as well. Altered brain function also contributes to obesity in individuals, but it all begins with diet – a high fat diet.

What is a High Fat Diet (HFD)?

HFD is the consumption of 35% of total caloric intake coming from fats, both saturated and unsaturated. These high-fat foods include the beloved and cheap processed foods we all know and love, animal fats, chocolate, butter, and oils. To put this diet into perspective, if one consumes 2,000 calories in a day, and 700 calories of that came from fats, equivalent to half a normal sized bag of Doritos, then this would be considered a HFD. Unfortunately, just this one day of poor eating can cause detrimental change to the brain and thus the body as a whole. 

A HFD has been found to activate pathways causing leptin and insulin resistance – preventing individuals from feeling satiated and increasing blood sugar levels. This nutrient excess through overconsumption drives inflammation of the hypothalamus. This hypothalamic inflammation occurs even before weight gain. This inflammation alters the brain’s homeostatic and metabolic functions, contributing to obesity through such imbalanced energy and insulin resistance, as shown in the figure below. It has also been shown that HFD reduces synaptic plasticity, the body’s way of making new pathways for things learned and the formation of new memories. 

Conclusion

The obesity epidemic is one of the largest problems in the US and in the world. Obesity is not only gaining weight, it also alters brain function and creates different neuronal pathways from a HFD. Obesity effects an individual much more than one would think, and that is alarming. Taxes on unhealthy foods are a strong start to deterring individuals from buying such cheap, fat-filled  foods. Obesity is much more than an individual problem – the weight is truly in the country’s and world’s hands. 

References

Farberman, R. (2022). State of Obesity 2022: Better Policies for a Healthier America. Trust for America’s Help. Retrieved April 12, 2023, from https://www.tfah.org/report-details/state-of-obesity-2022/#:~:text=Nationally%2C%2041.9%20percent%20of%20adults,obesity%20rate%20of%2045.6%20percent.

Blumenthal, D.; Seervai, S. (2018). Rising Obesity in the United States Is a Public Health Crisis. The Commonwealth Fund. Retrieved April 13, 2023, from https://www.commonwealthfund.org/blog/2018/rising-obesity-united-states-public-health-crisis

Kristantis, B.; Turner, D. (2020). High-Fat Diet. Advances in Cancer Research. Retrieved April 11, 2023, from https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/high-fat-diet#:~:text=A%20high%2Dfat%20diet%20(HFD,%2C%20butter%2C%20and%20oily%20fish.

Jais, A., & Brüning, J. C. (2017). Hypothalamic inflammation in obesity and metabolic disease. The Journal of Clinical Investigation, 127(1), 24–32. https://doi.org/10.1172/JCI88878

What is Obesity?

Obesity is a condition characterized by excessive accumulation of body fat to the extent that it impairs health. It is commonly defined by body mass index (BMI), a measure of weight in relation to height, with a BMI of 30 or higher considered obese. Obesity and metabolic diseases such as type 2 diabetes are major public health challenges that have reached epidemic proportions globally. While the exact mechanisms underlying these diseases are complex, recent research has pointed to the role of hypothalamic inflammation in their development.

A paper titled “Hypothalamic inflammation in obesity and metabolic disease” by Alexander Jais and Jens C. Brüning provides an in-depth review of the current understanding of this phenomenon. The authors explain that the hypothalamus, a brain region that plays a crucial role in regulating energy balance and glucose homeostasis, is particularly vulnerable to inflammation due to its high sensitivity to changes in nutrient and hormonal signals.

One section of the paper discusses the mechanisms that contribute to hypothalamic inflammation in obesity and metabolic disease. It also discuss the role of the immune system and how chronic low-grade inflammation can lead to hypothalamic dysfunction.

Fatty Acids

Another interesting aspect of the paper is the discussion of how certain dietary components can influence hypothalamic inflammation. For example, saturated fatty acids, which are commonly found in animal products and many processed foods, can activate inflammatory pathways in the hypothalamus. On the other hand, consumption of omega-3 fatty acids, which are found in foods like fatty fish and flaxseed, has been shown to have anti-inflammatory effects in the hypothalamus.

Neural Networks

Inflammation can affect the neural circuits that regulate feeding behaviour and energy expenditure, leading to alterations in appetite, physical activity, and metabolic rate. Activation of pro-opiomelanocortin (POMC) neurons and inhibition of agouti-related peptide (AgRP) neurons by adipostatic signals leads to the activation of melanocortin 4 receptor (MC4R) expressing neurons in the paraventricular nucleus (PVN) of the hypothalamus. This results in satiety and stimulation of energy expenditure. In contrast, during fasting, AgRP expression increases while POMC expression decreases, leading to decreased MC4R signaling.

Hypothalamic Inflammation

The figure above shows how the consumption of a high fat diet can lead to hypothalamic dysfunction, a condition associated with an increase in oxidative stress. When the hypothalamus becomes inflamed due to the consumption of a high-fat diet, it can lead to a disruption of insulin and Leptin hormones (appetite regulators) and contribute to the development of obesity. Insulin and leptin act directly on specific subsets of neurons in the arcuate nucleus (ARC) of the hypothalamus to control energy balance. The authors describe several approaches, including anti-inflammatory drugs, lifestyle interventions, and dietary modifications, that have shown promise in preclinical and clinical studies.

Overall, this blogpost highlights the importance of understanding the role of hypothalamic inflammation in the development of obesity and metabolic disease. By identifying the underlying mechanisms and consequences of this process, researchers may be able to develop more effective strategies for preventing and treating these conditions.

Sleep and Memory Consolidation

Sleep is an essential component of our daily lives, and it plays a critical role in our cognitive and emotional functioning. One important aspect of sleep is its role in memory consolidation – the process by which new information is transferred from short-term to long-term memory. In recent years, researchers have made significant advances in understanding the relationship between sleep, circadian rhythms, and memory consolidation. One particularly insightful paper on this topic is “Role of circadian rhythm and REM sleep for memory consolidation” by Zhengui Xia and Dan Storm.

The paper explores the complex relationship between sleep, circadian rhythms, and memory consolidation. The authors suggest that the circadian rhythm, which regulates the sleep-wake cycle, plays a critical role in memory consolidation. They propose that the timing of learning and memory consolidation can impact the effectiveness of memory formation, and that the circadian rhythm affects various aspects of brain function, including synaptic plasticity, gene expression, and neurotransmitter release.

CRE-Mediated Signaling

The paper referenced in this blogpost discusses the role of signaling pathways in hippocampus-dependent memory consolidation. The following paragraph summarises the section of the paper that discusses the role of CRE-mediated signaling in LTM consolidation: The process of memory consolidation is initiated by Ca2+ signals generated by NMDA receptors and is dependent on de novo transcription and translation. CRE-mediated transcription is strongly implicated in the consolidation of long-term memory (LTM) and integrates Ca2+ and cAMP signals. The CREB-binding protein, CREB, is implicated in LTM and other forms of neuroplasticity in mice and drosophila. Studies on mice show that stimulation of CRE-mediated transcription during training depends on activation of NMDA receptors and MAPK. Inhibition of CRE-mediated transcription by administration of CRE inhibitors to the hippocampus blocks memory formation, indicating the involvement of CRE-mediated transcription in memory consolidation.

REM Sleep

REM (Rapid Eye Movement) sleep is a stage of sleep characterized by rapid eye movements, low muscle tone, and vivid dreaming. It is one of the four stages of sleep, along with non-REM (NREM) sleep stages 1, 2, and 3. REM sleep is typically associated with heightened brain activity and increased heart rate and blood pressure. The authors delve into the role of REM sleep in memory consolidation. They suggest that REM sleep plays a critical role in the consolidation of emotional memories, procedural memories, and declarative memories. They propose that this may be due to increased activity in brain regions involved in memory consolidation, as well as increased levels of neurotransmitters such as acetylcholine.

The implications of this research are significant. A better understanding of the relationship between sleep, circadian rhythms, and memory consolidation could ultimately lead to more effective treatments for sleep disorders and cognitive impairments. For example, individuals with sleep disorders or cognitive impairments may benefit from interventions that target the timing and quality of sleep, or that enhance the activity of neurotransmitters involved in memory consolidation.

In conclusion, “Role of circadian rhythm and REM sleep for memory consolidation” provides valuable insights into the complex relationship between sleep, circadian rhythms, and memory consolidation. By understanding the neurobiological mechanisms underlying this relationship, researchers and healthcare professionals may be able to develop more effective interventions for individuals with sleep disorders or cognitive impairments.

What is Psychopathy?
Psychopathy is a personality disorder that is often characterized by a lack of empathy, impulsivity, and manipulative behavior. While there is still much to learn about the disorder, recent research has shed light on its neurobiological roots. In a paper published in the journal Molecular Psychiatry, researchers explore the genetic and environmental factors, brain regions, and neurotransmitters that may be implicated in psychopathy. They also suggest potential directions for future research and highlight the importance of better understanding the neurobiological mechanisms underlying the disorder.

The authors suggest that genetics may account for a significant portion of the variance in psychopathy, but that environmental factors such as childhood abuse and neglect may also play a role. They suggest that gene-environment interactions may be particularly important in the development of psychopathy. This highlights the need for continued research into both genetic and environmental factors that may contribute to the disorder.

Biology of Psychopathy

The researchers also discuss the brain regions and neurotransmitters that may be involved in psychopathy. Their results concluded that expression of ZNF132 and RPL10P9 is greatly reduced in neurons and astrocytes of habitually violent offenders. They also suggest that dysfunction in the prefrontal cortex, amygdala, and other brain regions may be implicated, as well as imbalances in neurotransmitters such as serotonin and dopamine. They also introduce a theory that states that a deficient opioid system may be implicated in psychopathy, which would explain why psychopaths tend to engage in drug abuse; to satisfy their reward system. This suggests that further research on the neurobiological basis of psychopathy could lead to a better understanding of the brain mechanisms involved in the disorder.

The authors highlight several potential directions for future research, including the need for more precise measurements of psychopathy, the use of animal models to study the disorder, and the development of more effective treatments. They suggest that identifying specific biomarkers of psychopathy could be particularly useful in developing more targeted treatments. Additionally, the authors suggest that a better understanding of the neurobiological mechanisms underlying psychopathy may have broader implications for understanding other psychiatric disorders.

Research on the neurobiological roots of psychopathy could ultimately have implications for reducing crime rates by identifying effective treatments for individuals who exhibit psychopathic traits and who are at higher risk of engaging in criminal behavior. Additionally, a better understanding of the neurobiological mechanisms underlying psychopathy could lead to more targeted interventions aimed at preventing the development of psychopathic traits in the first place, potentially reducing the number of individuals who engage in criminal behaviour.

In conclusion, the research on the neurobiological roots of psychopathy provides a valuable framework for understanding the disorder and may lead to new treatments and diagnostic tools in the future. Continued research in this area is critical to further our understanding of this disorder and to improve outcomes for individuals affected by it.

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It’s fairly well known that obesity can lead to an increased risk for numerous different health outcomes, such as type 2 diabetes and cardiovascular diseases. Obesity also causes a state of constant low-grade inflammation in the body, which in turn has it’s effects on the brain as well that people often don’t realize. Many thing’s go wrong in the body and brain that contribute to obesity, primarily an imbalance of energy homeostasis and hunger cues.

What’s Happening in the Brain

The hypothalamus region of the brain controls several endocrine functions that take metabolic feedback and regulate energy homeostasis. Basically, the hypothalamus will give signals to either increase or decrease hunger and energy use in response to the signals the body sends to the hypothalamus. Obesity can occur due to disorders of the hypothalamus, such as Prader-Willi syndrome. This is an inherited disorder that causes the hypothalamus to not recognize the sensation of being full when eating. This causes a constant urge to eat, and puts you are risk for obesity.

The Melanocortin System

The main player in this regulatory function is the melanocortin system. Insulin and leptin circulate the body in levels that are proportionate to the amount of adipose (fat) tissues, and the nutritional status of the body. These molecules bind to receptors in the melanocortin system and will decrease food intake, and increase energy usage.

In a healthy brain these cues are in balance, leading to a balance of energy usage and food intake. In obesity it’s been studied that there is a dysfunctional melanocortin system, leading to an increase of food intake and decreased energy usage.

Dietary Fats

Surely you’ve been told to eat the ‘right’ foods, and that fats usually aren’t those right foods. And maybe you’ve heard of ‘good’ fats and ‘bad’ fats, but what makes those different? The main two groups are saturated fatty acids (SFAa), and unsaturated fatty acids.

Saturated fats the ‘bad’ fats. They are typically solid at room temperature, meat and dairy products are the main dietary sources of these. Their structure consists of only single bonds, and have the maximum amount of hydrogen atoms in their structure. These fats are known to raise both good and bad cholesterol in the body, raising the risk of cardiovascular and other diseases.

Unsaturated fatty acids are the ‘good’ fats. These are more complex molecules, consisting of double bonds that cause bends in their chain. These fats are typically liquid or fluid like at room temperature. Common sources of these are oils such as vegetable or canola oil, nuts, and fish. These fats typically raise the level of good cholesterol in our body.

Effects of Fats in the Body and Brain

Studies have been done in rodents about the effects of certain fats on the hypothalamus. A diet with high amounts of SFAs have been shown to increase hypothalamic inflammation in days, while mono-unsaturated fatty acids did not compromise and hypothalamic function. SFAs have also been shown in these studies to cross into the brain and accumulate in the hypothalamus, where they block insulin and leptin signaling, and will disrupt the melanocortin system. It’s recommended that about 10-30% of our calorie intake should be fats, although only about 5-10% of caloric intake should be saturated fats.

References

1. https://my.clevelandclinic.org/health/articles/22566-hypothalamus
2. https://www.sciencedirect.com/science/article/pii/S2212877821000466
3. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/fat/art-20045550
4. “Hypothalamic Inflammation in Obesity and Metabolic Disease” A. Jais

What Are Endocannabinoids?

Endocannabinoids are naturally occurring molecules that are similar in structure to the active compounds in cannabis. These molecules are produced by the body and interact with the same receptors as THC, the main psychoactive compound in cannabis.

Structure

There are two main endocannabinoids: anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Anandamide has a chemical structure consisting of an ethanolamine head group, an arachidonic acid chain, and an amide bond linking them together. 2-AG, on the other hand, consists of a glycerol backbone with two arachidonic acid chains attached to it via ester bonds. Both endocannabinoids are synthesized on demand from membrane phospholipids and are rapidly metabolized to terminate their signaling effects.

Receptors

The two main receptors that are relevant to endocannabinoids are CB1 receptors and CB2 receptors. CB1 receptors are primarily found in the brain and central nervous system, while CB2 receptors are primarily found in immune cells and peripheral tissues.

Endocannabinoids, such as anandamide and 2-arachidonoylglycerol (2-AG), bind to these receptors to regulate various physiological processes, including pain, appetite, mood, and inflammation. CB1 receptor activation is associated with the psychoactive effects of cannabis, while CB2 receptor activation is associated with anti-inflammatory effects.

Research has also shown that there are other receptors that can interact with endocannabinoids, such as TRPV1 receptors and GPR55 receptors. These receptors may have additional roles in mediating the effects of endocannabinoids in the body.

Signaling Pathways

CB1 and CB2, are G protein-coupled receptors (GPCRs) that are located throughout the body. When endocannabinoids bind to these receptors, they initiate a signaling cascade that leads to various physiological effects.

When an endocannabinoid binds to a CB1 receptor, it activates a G protein that can lead to the inhibition of adenylyl cyclase, which in turn reduces the production of cyclic adenosine monophosphate (cAMP). This leads to a decrease in the activity of intracellular enzymes such as protein kinase A (PKA) and mitogen-activated protein kinases (MAPKs), which ultimately results in the inhibition of neurotransmitter release from presynaptic neurons.

In addition, CB1 receptor activation can also lead to the activation of ion channels such as inwardly rectifying potassium (K+) channels and voltage-gated calcium (Ca2+) channels. This can result in the hyperpolarization of the postsynaptic membrane and a decrease in the excitability of neurons.

On the other hand, when an endocannabinoid binds to a CB2 receptor, it can activate several signaling pathways, including the inhibition of adenylyl cyclase and the activation of PI3K/Akt and MAPK signaling cascades. CB2 receptor activation can also lead to the inhibition of intracellular calcium release and the activation of potassium channels, which can contribute to the anti-inflammatory and immunomodulatory effects of endocannabinoids.

Endocannabinoids in Neurodegenerative Disease

The paper discussed in class highlights the potential roles of cannabinoid receptors in various diseases of the central nervous system (CNS). The authors describe the potential therapeutic benefits of targeting these receptors for the treatment of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

The authors describe the endocannabinoid system as a key regulator of neurotransmitter release, synaptic plasticity, and immune function in the CNS. They discuss the role of CB1 receptors in regulating the release of neurotransmitters such as glutamate, GABA, and dopamine, and the potential therapeutic benefits of CB1 agonists in modulating these pathways.

The authors also describe the potential therapeutic benefits of CB2 receptor activation in the treatment of neuroinflammatory and neurodegenerative diseases, as well as pain and psychiatric disorders. They discuss the anti-inflammatory and immunomodulatory effects of CB2 receptor activation, as well as its potential role in regulating microglial activation and neurogenesis.