Image of Smiling Girl with her hair swinging 

<h2 id="understanding-2-ag">Understanding 2-AG</h2>If you’re familiar with endocannabinoids, it’s likely you’ve heard of the most well known one—anandamide (AEA or N-arachidonoylethanolamine). This notorious endocannabinoid has a name that means “bliss molecule” and is known for its involvement in pleasure and reward processes within the brain.There’s another endocannabinoid that doesn’t get as much attention, but it’s equally as important as AEA and can be hundreds of times more abundant in the brain. It goes by the name of 2-arachidonoylglycerol (2-AG).1Like most of the endocannabinoid system (ECS), the discovery of 2-AG can be traced back to Israeli scientist Dr. Raphael Mechoulam. He and his PhD student Dr. Ben-Shabat first isolated 2-AG from the intestines of canines in 19952. They also identified that 2-AG has THC-like properties in mice, thus establishing 2-AG’s place within the ECS.Similar to anandamide, 2-AG is essential to maintaining homeostasis (balance) in the body. It does this in many complex ways, but similar to THC and anandamide, most of 2-AG’s actions are mediated through actions at the CB1 and CB2 receptors. Its abundance suggests that 2-AG is one of the most important endocannabinoids, regulating numerous important processes throughout the body. These processes include a number of important physiologic functions3 including:<ul class="list-disc mx-5"><li>regulating hunger</li><li>mediating inflammation</li><li>moderating mood</li><li>reducing pain</li></ul><h2 id="2-ag-and-food-intake">2-AG and food intake</h2>Anyone who has ever experienced the munchies can attest that the ECS has a well-established role in moderating food intake. In fact, numerous animal studies have shown a significant relationship between 2-AG levels, hunger and metabolism. Researchers have found that 2-AG levels in certain parts of the brain are increased during fasting, where it is responsible for mediating the feeling of hunger and the compulsion to eat. Once fed, the 2-AG levels in parts of the brain decrease back to normal.4It’s not hard to see how a dysregulated ECS could lead to problems with appetite and metabolism. 2-AG is an important part of a balanced ECS, and when it is pushed out of balance, there can be significant consequences. In the case of food intake, too much 2-AG could lead to excessive hunger, and too little could lead to a lack of appetite.Some scientists speculate that 2-AG is a contributing factor to the global obesity problem. Overconsumption of omega-6 fats, like those from corn or canola oil, may be leading to an ECS imbalance for much of the modern world. Because 2-AG is made from omega-6 fats, overconsuming them may be leading to increases in appetite via the ECS, contributing to a vicious cycle of gaining weight and overeating.5 These speculations, like much of our knowledge of cannabis, are based primarily on rodent studies and have yet to be confirmed by human clinical investigations.<h2 id="2-ag-and-nervous-system-inflammation">2-AG and nervous system inflammation</h2>Scientists have found in recent years that diseases of the nervous system often have an inflammatory component, which means treatments may have therapeutic benefits. Cannabinoids have been shown to have anti-inflammatory properties6 and may be helpful in treating some neurodegenerative diseases. Furthermore, scientists are very interested in how the ECS, and 2-AG specifically, is involved in the development of certain neurologic diseases.Neurodegenerative diseases like Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease are very burdensome, and finding an effective treatment for these diseases is a priority for scientists. Animal models have shown that by manipulating the levels of 2-AG and turning on or off the enzymes responsible for its production and degradation, scientists may be able to improve clinical outcomes.7It’s true that 2-AG itself has anti-inflammatory actions within the brain, especially by interacting with CB1 and CB2 receptors. However, that isn’t the only role it plays in the inflammatory pathway. 2-AG has now been found to serve as a reserve of an important fatty acid in the body called arachidonic acid (AA). Common anti-inflammatory medications like ibuprofen(Advil), naproxen(Aleve), and acetaminophen(Tylenol) all target parts of the AA cascade.The problem is that AA serves as the precursor for both pro-inflammatory and anti-inflammatory signaling in the body. In other words, 2-AG serves as one mediator in a complex system and its role is not one dimensional–it can be both pro-inflammatory and anti-inflammatory.8<h2 id="2-ag-and-anxiety">2-AG and anxiety</h2>Everyone experiences anxiety from time to time, but when that feeling becomes too intense or too frequent, it may become intrusive and develop into generalized anxiety disorder. It is not yet clear what exactly the role of 2-AG in anxiety is, but there is no doubt that it is involved.Generally speaking, 2-AG appears to reduce anxiety. However, the ECS is not that simple of a system. If 2-AG levels remain elevated for an extended period of time, down-regulation of CB1 and CB2 receptors could occur, which could induce changes to baseline mood and anxiety.9 This is likely due to the CB1 receptor playing a major role in regulating anxious and depressive behaviors.2-AG also plays a major role in mediating the stress hormone known as cortisol. When under stress, be it physical, mental or emotional stress, the body releases hormones to help protect itself. Scientists have figured out that 2-AG levels follow closely behind rising cortisol levels during times of stress.10 It’s not entirely clear why the body releases 2-AG along with cortisol, but a leading theory is that while stress signalling is important, too much of it is a bad thing. The body releases 2-AG at the same time as cortisol to help create balance, sending the signal back to the brain to turn off the cortisol.<h2 id="2-ag-and-depression">2-AG and depression</h2>Stress is one of the main causes of depression, and 2-AG is intimately and complexly involved with the stress response. Therefore 2-AG and depression have a relationship that is connected through the stress response. As per usual, the ECS plays a homeostatic role, helping to regulate the release of stress hormones like cortisol.11There are numerous animal models showing abnormal 2-AG levels associated with depression. It is not yet clear if these abnormalities are the cause or symptom of the depression. In either case, animal studies have also found that numerous antidepressants can alter 2-AG levels in certain parts of the brain, suggesting that actions within ECS may be responsible for their antidepressant effects.12Leveraging the endocannabinoid system for the treatment of depression makes sense, because the ECS has a well-established role in neuroplasticity and neurogenesis. 2-AG, through complex cellular mechanisms, can mediate the adaptability of the brain and body. In other words, the ECS helps humans respond to the world around them, helping them master a new skill, and new language, or a new movement. The nervous system is a dynamic system and the ECS helps to keep it agile and able to adjust to the changes of life. Modifying 2-AG levels could be helpful to those having difficulty adjusting to stress, thereby reducing symptoms of depression.<h2 id="2-ag-and-addiction">2-AG and addiction</h2>Given 2-AG’s broad actions in the brain noted above and AEA’s involvement in pleasure and reward processes, it comes as little surprise that this endocannabinoid plays a critical role in mediating reward and addiction. In the case of ethanol, drinking appears to cause a release of 2-AG which eventually leads to a release of dopamine, the reward chemical in the brain. Early rodent studies suggest that in the brain, reducing the amount of 2-AG that is produced reduces alcohol consumption.13 It isn’t just alcohol, though. Endocannabinoid levels (both 2-AG and anandamide) have been found to be altered by numerous addictive substances including nicotine, THC, ethanol, and opioids.14 Modifying levels of 2-AG may be beneficial to those who struggle with substance use disorders.Similar to anandamide, 2-AG is a pain mediator. Numerous studies manipulating 2-AG levels have shown it plays an important role in all types of pain, especially inflammatory pain. It has been shown that local administration of 2-AG causes pain-relieving effects. In all the studies that found 2-AG benefited pain, it was a diminishing effect. 2-AG plays an important role in pain signaling and pain desensitization, and it does so by interacting directly or indirectly with receptors CB1, CB2, and/or TRPV1 in numerous parts of the body.15 Through this two-fold mechanism, 2-AG is a critical regulator of both inflammatory and neuropathic pain.<h2 id="2-ag-vs-aea-vs-thc">2-AG vs AEA vs THC</h2>When you look at the full name of the endocannabinoids, you can see they are quite similar: N-arachidonoylethanolamine (anandamide) VS 2-arachidonoylglycerol (2-AG).But those small name changes correlate to significant molecular changes and different functions within the body. That’s what really sets 2-AG apart from anandamide; the actions at the receptor site in the body. You see, each endocannabinoid is a unique key that opens the lock (aka the receptor) in a specific way.In the case of anandamide and THC, they act remarkably similar in the body and open the lock similarly—they are both known as partial agonists (activators) at CB1 and CB2 receptors. If you think of activating the receptor like turning on a light bulb, THC and AEA both act similar to a dimmer switch, where the light is only partially turned on. This is different from 2-AG, which is considered a full agonist at both of these receptors which would be the equivalent of turning the light fully on.16 This means 2-AG produces a more robust biological response than partial agonists like anandamide.This type of agonist can be useful, but regular exposure to full agonists can increase the risk of adverse effects and can also lead to tolerance development. This difference in agonism is very important pharmacologically and is one of the biggest distinguishing factors between 2-AG and anandamide.There are numerous other nuances between these endocannabinoids, with one of the most important being affinity. Anandamide is very strongly attracted to the CB1 receptors, whereas 2-AG is not nearly as compelled to engage with CB1. Another primary difference is general abundance in the body. 2-AG can be found at significantly higher levels than anandamide within most tissues throughout the body.The difference in affinity means that, despite being much more abundant throughout the body, anandamide can out-compete 2-AG at the CB1 receptor site. This type of endocannabinoid competition could help to explain the complex and dynamic actions of the ECS.If 2-AG is so important, why haven’t you heard of it? Well, it’s unclear why 2-AG has not been talked about as much about anandamide. Perhaps it’s because anandamide was discovered first. Perhaps it’s the name—2-AG can’t compete with a name like “bliss molecule.” It is also possible that because anandamide functions almost exactly like THC in the body, people feel drawn towards it. In any case, 2-AG plays a crucial role throughout the body and brain and it shouldn’t be overlooked.<h2 id="how-can-you-increasedecrease-2-ag-levels">How can you increase/decrease 2-AG levels?</h2>Some food can contain 2-AG; in particular, milk may contain significant amounts.17 But chugging a bunch of milk would not be a good way to directly increase your 2-AG levels, as most of it would be broken by the body before it can be absorbed. It is also unclear how pasteurization, a mandatory process for most milk sold in stores, would affect the endocannabinoids present in milk.Some natural products may also contain molecules that can modify endocannabinoid breakdown. In fact, there are probably numerous plant molecules that interact with the ECS without even realizing it because they haven’t been studied from this perspective.Flavonoids like kaempferol from fruits and vegetables may be able to inhibit an enzyme in the body known as FAAH18, which could reduce breakdown of anandamide, and therefore provide a mood enhancing effect. And while not yet studied at any length, there are other plants and herbs that produce molecules that interfere with the breakdown of 2-AG, by inhibiting an enzyme known as MAGL.19<h2 id="2-ag-and-the-entourage-effect">2-AG and the entourage effect</h2>Long before cannabis was being sold in legal dispensaries, in 1999 Israeli scientists looked at how certain lipids produced in the body may help to prevent the breakdown of 2-AG. These co-produced endocannabinoid-like lipids help to protect the endocannabinoid from enzymes that would attempt to metabolize them; somewhat similar to how an entourage would surround and protect their celebrity from swarming fans. This was the original description of the entourage effect before the term was later applied to whole plant cannabis.An interesting fact about 2-AG is that it was one of the first molecules to be associated with the “entourage effect”. Those Israli scientists, in that same paper in 1999, made one of the earliest mentions of the modern definition of entourage effect that has been ascribed to cannabis saying that plant synergy “may play a role in the widely held (but not experimentally based) view that in some cases plants are better drugs than the natural products isolated from them.”20Explore a wide variety of <a target="_blank" rel="noopener noreferrer nofollow" href="https://savikalpa.com/collections/shunyata">plant based medicines</a> here.Sources:<ol class="list-decimal mx-5"><li>Justinová Z, Yasar S, Redhi GH, Goldberg SR. The endogenous cannabinoid 2-arachidonoylglycerol is intravenously self-administered by squirrel monkeys. J Neurosci. 2011;31(19):7043-7048. doi:10.1523/JNEUROSCI.6058-10.2011</li><li>Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 1995;50(1):83-90. doi:10.1016/0006-2952(95)00109-d</li><li>Baggelaar MP, Maccarrone M, van der Stelt M. 2-Arachidonoylglycerol: A signaling lipid with manifold actions in the brain. Prog Lipid Res. 2018;71:1-17. doi:10.1016/j.plipres.2018.05.002</li><li>Kirkham TC, Williams CM, Fezza F, Di Marzo V. Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol. 2002;136(4):550-557. doi:10.1038/sj.bjp.0704767</li><li>Izzo AA, Piscitelli F, Capasso R, et al. Peripheral endocannabinoid dysregulation in obesity: relation to intestinal motility and energy processing induced by food deprivation and re-feeding. Br J Pharmacol. 2009;158(2):451-461. doi:10.1111/j.1476-5381.2009.00183.x</li><li>Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333-1349. doi:10.4155/fmc.09.93</li><li>Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17</li><li>Turcotte C, Chouinard F, Lefebvre JS, Flamand N. Regulation of inflammation by cannabinoids, the endocannabinoids 2-arachidonoyl-glycerol and arachidonoyl-ethanolamide, and their metabolites. J Leukoc Biol. 2015;97(6):1049-1070. doi:10.1189/jlb.3RU0115-021R</li><li>Imperatore R, Morello G, Luongo L, et al. Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor CB₁R signaling and anxiety-like behavior. J Neurochem. 2015;135(4):799-813. doi:10.1111/jnc.13267</li><li>Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17</li><li>Silveira KM, Wegener G, Joca SRL. Targeting 2-arachidonoylglycerol signalling in the neurobiology and treatment of depression. Basic Clin Pharmacol Toxicol. 2021;129(1):3-14. doi:10.1111/bcpt.13595</li><li>Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17</li><li>Winters ND, Bedse G, Astafyev AA, et al. Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models [published online ahead of print, 2021 Jul 22]. J Clin Invest. 2021;146861. doi:10.1172/JCI146861</li><li>Serrano A, Parsons LH. Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol Ther. 2011;132(3):215-241. doi:10.1016/j.pharmthera.2011.06.005</li><li>Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17</li><li>Ueda N, Tsuboi K. Discrimination between Two Endocannabinoids. Chemistry &amp; Biology. 2012;19(5):545-547. doi:10.1016/j.chembiol.2012.05.001</li><li>Di Marzo V, Sepe N, De Petrocellis L, et al. Trick or treat from food endocannabinoids?. Nature. 1998;396(6712):636-637. doi:10.1038/25267</li><li>Thors L, Belghiti M, Fowler CJ. Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring flavonoids. Br J Pharmacol. 2008;155(2):244-252. doi:10.1038/bjp.2008.237</li><li>Yang, R., Lu, Y., &amp; Liu, J. (2014). Identification of tanshinone IIA as a natural monoacylglycerol lipase inhibitor by combined in silico and in vitro approach. MedChemComm, 5(10), 1528–1532.</li><li>Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat Prod Rep. 1999;16(2):131-143. doi:10.1039/a703973e</li></ol>&nbsp;&nbsp;This article was originally published on The Cannigma, and shared here with permission.

If you’re familiar with endocannabinoids, it’s likely you’ve heard of the most well known one—anandamide (AEA or N-arachidonoylethanolamine). This notorious endocannabinoid has a name that means “bliss molecule” and is known for its involvement in pleasure and reward processes within the brain.

There’s another endocannabinoid that doesn’t get as much attention, but it’s equally as important as AEA and can be hundreds of times more abundant in the brain. It goes by the name of 2-arachidonoylglycerol (2-AG).1

Like most of the endocannabinoid system (ECS), the discovery of 2-AG can be traced back to Israeli scientist Dr. Raphael Mechoulam. He and his PhD student Dr. Ben-Shabat first isolated 2-AG from the intestines of canines in 19952. They also identified that 2-AG has THC-like properties in mice, thus establishing 2-AG’s place within the ECS.

Similar to anandamide, 2-AG is essential to maintaining homeostasis (balance) in the body. It does this in many complex ways, but similar to THC and anandamide, most of 2-AG’s actions are mediated through actions at the CB1 and CB2 receptors. Its abundance suggests that 2-AG is one of the most important endocannabinoids, regulating numerous important processes throughout the body. These processes include a number of important physiologic functions3 including:

Anyone who has ever experienced the munchies can attest that the ECS has a well-established role in moderating food intake. In fact, numerous animal studies have shown a significant relationship between 2-AG levels, hunger and metabolism. Researchers have found that 2-AG levels in certain parts of the brain are increased during fasting, where it is responsible for mediating the feeling of hunger and the compulsion to eat. Once fed, the 2-AG levels in parts of the brain decrease back to normal.4

It’s not hard to see how a dysregulated ECS could lead to problems with appetite and metabolism. 2-AG is an important part of a balanced ECS, and when it is pushed out of balance, there can be significant consequences. In the case of food intake, too much 2-AG could lead to excessive hunger, and too little could lead to a lack of appetite.

Some scientists speculate that 2-AG is a contributing factor to the global obesity problem. Overconsumption of omega-6 fats, like those from corn or canola oil, may be leading to an ECS imbalance for much of the modern world. Because 2-AG is made from omega-6 fats, overconsuming them may be leading to increases in appetite via the ECS, contributing to a vicious cycle of gaining weight and overeating.5 These speculations, like much of our knowledge of cannabis, are based primarily on rodent studies and have yet to be confirmed by human clinical investigations.

Scientists have found in recent years that diseases of the nervous system often have an inflammatory component, which means treatments may have therapeutic benefits. Cannabinoids have been shown to have anti-inflammatory properties6 and may be helpful in treating some neurodegenerative diseases. Furthermore, scientists are very interested in how the ECS, and 2-AG specifically, is involved in the development of certain neurologic diseases.

Neurodegenerative diseases like Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease are very burdensome, and finding an effective treatment for these diseases is a priority for scientists. Animal models have shown that by manipulating the levels of 2-AG and turning on or off the enzymes responsible for its production and degradation, scientists may be able to improve clinical outcomes.7

It’s true that 2-AG itself has anti-inflammatory actions within the brain, especially by interacting with CB1 and CB2 receptors. However, that isn’t the only role it plays in the inflammatory pathway. 2-AG has now been found to serve as a reserve of an important fatty acid in the body called arachidonic acid (AA). Common anti-inflammatory medications like ibuprofen(Advil), naproxen(Aleve), and acetaminophen(Tylenol) all target parts of the AA cascade.

The problem is that AA serves as the precursor for both pro-inflammatory and anti-inflammatory signaling in the body. In other words, 2-AG serves as one mediator in a complex system and its role is not one dimensional–it can be both pro-inflammatory and anti-inflammatory.8

Everyone experiences anxiety from time to time, but when that feeling becomes too intense or too frequent, it may become intrusive and develop into generalized anxiety disorder. It is not yet clear what exactly the role of 2-AG in anxiety is, but there is no doubt that it is involved.

Generally speaking, 2-AG appears to reduce anxiety. However, the ECS is not that simple of a system. If 2-AG levels remain elevated for an extended period of time, down-regulation of CB1 and CB2 receptors could occur, which could induce changes to baseline mood and anxiety.9 This is likely due to the CB1 receptor playing a major role in regulating anxious and depressive behaviors.

2-AG also plays a major role in mediating the stress hormone known as cortisol. When under stress, be it physical, mental or emotional stress, the body releases hormones to help protect itself. Scientists have figured out that 2-AG levels follow closely behind rising cortisol levels during times of stress.10 It’s not entirely clear why the body releases 2-AG along with cortisol, but a leading theory is that while stress signalling is important, too much of it is a bad thing. The body releases 2-AG at the same time as cortisol to help create balance, sending the signal back to the brain to turn off the cortisol.

Stress is one of the main causes of depression, and 2-AG is intimately and complexly involved with the stress response. Therefore 2-AG and depression have a relationship that is connected through the stress response. As per usual, the ECS plays a homeostatic role, helping to regulate the release of stress hormones like cortisol.11

There are numerous animal models showing abnormal 2-AG levels associated with depression. It is not yet clear if these abnormalities are the cause or symptom of the depression. In either case, animal studies have also found that numerous antidepressants can alter 2-AG levels in certain parts of the brain, suggesting that actions within ECS may be responsible for their antidepressant effects.12

Leveraging the endocannabinoid system for the treatment of depression makes sense, because the ECS has a well-established role in neuroplasticity and neurogenesis. 2-AG, through complex cellular mechanisms, can mediate the adaptability of the brain and body. In other words, the ECS helps humans respond to the world around them, helping them master a new skill, and new language, or a new movement. The nervous system is a dynamic system and the ECS helps to keep it agile and able to adjust to the changes of life. Modifying 2-AG levels could be helpful to those having difficulty adjusting to stress, thereby reducing symptoms of depression.

Given 2-AG’s broad actions in the brain noted above and AEA’s involvement in pleasure and reward processes, it comes as little surprise that this endocannabinoid plays a critical role in mediating reward and addiction. In the case of ethanol, drinking appears to cause a release of 2-AG which eventually leads to a release of dopamine, the reward chemical in the brain. Early rodent studies suggest that in the brain, reducing the amount of 2-AG that is produced reduces alcohol consumption.13 It isn’t just alcohol, though. Endocannabinoid levels (both 2-AG and anandamide) have been found to be altered by numerous addictive substances including nicotine, THC, ethanol, and opioids.14 Modifying levels of 2-AG may be beneficial to those who struggle with substance use disorders.

Similar to anandamide, 2-AG is a pain mediator. Numerous studies manipulating 2-AG levels have shown it plays an important role in all types of pain, especially inflammatory pain. It has been shown that local administration of 2-AG causes pain-relieving effects. In all the studies that found 2-AG benefited pain, it was a diminishing effect. 2-AG plays an important role in pain signaling and pain desensitization, and it does so by interacting directly or indirectly with receptors CB1, CB2, and/or TRPV1 in numerous parts of the body.15 Through this two-fold mechanism, 2-AG is a critical regulator of both inflammatory and neuropathic pain.

When you look at the full name of the endocannabinoids, you can see they are quite similar: N-

But those small name changes correlate to significant molecular changes and different functions within the body. That’s what really sets 2-AG apart from anandamide; the actions at the receptor site in the body. You see, each endocannabinoid is a unique key that opens the lock (aka the receptor) in a specific way.

In the case of anandamide and THC, they act remarkably similar in the body and open the lock similarly—they are both known as partial agonists (activators) at CB1 and CB2 receptors. If you think of activating the receptor like turning on a light bulb, THC and AEA both act similar to a dimmer switch, where the light is only partially turned on. This is different from 2-AG, which is considered a full agonist at both of these receptors which would be the equivalent of turning the light fully on.16 This means 2-AG produces a more robust biological response than partial agonists like anandamide.

This type of agonist can be useful, but regular exposure to full agonists can increase the risk of adverse effects and can also lead to tolerance development. This difference in agonism is very important pharmacologically and is one of the biggest distinguishing factors between 2-AG and anandamide.

There are numerous other nuances between these endocannabinoids, with one of the most important being affinity. Anandamide is very strongly attracted to the CB1 receptors, whereas 2-AG is not nearly as compelled to engage with CB1. Another primary difference is general abundance in the body. 2-AG can be found at significantly higher levels than anandamide within most tissues throughout the body.

The difference in affinity means that, despite being much more abundant throughout the body, anandamide can out-compete 2-AG at the CB1 receptor site. This type of endocannabinoid competition could help to explain the complex and dynamic actions of the ECS.

If 2-AG is so important, why haven’t you heard of it? Well, it’s unclear why 2-AG has not been talked about as much about anandamide. Perhaps it’s because anandamide was discovered first. Perhaps it’s the name—2-AG can’t compete with a name like “bliss molecule.” It is also possible that because anandamide functions almost exactly like THC in the body, people feel drawn towards it. In any case, 2-AG plays a crucial role throughout the body and brain and it shouldn’t be overlooked.

How can you increase/decrease 2-AG levels?

Some food can contain 2-AG; in particular, milk may contain significant amounts.17 But chugging a bunch of milk would not be a good way to directly increase your 2-AG levels, as most of it would be broken by the body before it can be absorbed. It is also unclear how pasteurization, a mandatory process for most milk sold in stores, would affect the endocannabinoids present in milk.

Some natural products may also contain molecules that can modify endocannabinoid breakdown. In fact, there are probably numerous plant molecules that interact with the ECS without even realizing it because they haven’t been studied from this perspective.

Flavonoids like kaempferol from fruits and vegetables may be able to inhibit an enzyme in the body known as FAAH18, which could reduce breakdown of anandamide, and therefore provide a mood enhancing effect. And while not yet studied at any length, there are other plants and herbs that produce molecules that interfere with the breakdown of 2-AG, by inhibiting an enzyme known as MAGL.19

Long before cannabis was being sold in legal dispensaries, in 1999 Israeli scientists looked at how certain lipids produced in the body may help to prevent the breakdown of 2-AG. These co-produced endocannabinoid-like lipids help to protect the endocannabinoid from enzymes that would attempt to metabolize them; somewhat similar to how an entourage would surround and protect their celebrity from swarming fans. This was the original description of the entourage effect before the term was later applied to whole plant cannabis.

An interesting fact about 2-AG is that it was one of the first molecules to be associated with the “entourage effect”. Those Israli scientists, in that same paper in 1999, made one of the earliest mentions of the modern definition of entourage effect that has been ascribed to cannabis saying that plant synergy “may play a role in the widely held (but not experimentally based) view that in some cases plants are better drugs than the natural products isolated from them.”20

This article was originally published on The Cannigma, and shared here with permission.

The Importance of 2 Arachidonoylglycerol (2-AG)

Stones being balanced together

If you’ve been paying attention to cannabis science, you may have heard about the endocannabinoid system (ECS) and the important role of cannabinoids for homeostasis in the human body. While often mentioned, this function is rarely explained. Still, understanding how the endocannabinoid system works to maintain balance in our body can be a big help in understanding the therapeutic potential of cannabinoids and how cannabinoid medicines might help (or in some cases worsen) different medical conditions.So, in this article, we’ll cover the science of homeostasis, how using cannabis might affect this important function and ECS functions.<h2 id="what-is-homeostasis">What is homeostasis?</h2>The word <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.omicsonline.org/open-access/role-of-homeostasis-in-human-physiology-a-review.php?aid=87462">‘homeostasis’</a>&nbsp;comes from the Greek words homeo which means “similar” or “same,” and stasis, which means “stable.” Essentially, it refers to a state of stability, equilibrium, or balance in the body — although the term can also be applied to the internal balance of cells or other systems. In humans, maintaining homeostasis is the way our natural systems keep conditions in the body optimal for our health and wellbeing. As conditions shift, either internally or externally, mechanisms kick into action to make sure that our body doesn’t suffer from the change. Specifically, the stimuli trigger hormones which are released into the bloodstream and then cause bodily responses which maintain this delicate balance. This is called feedback regulation and it is the basic way that homeostasis is maintained. It is interesting to note that ECS functions have been closely tied to feedback regulation, showing the success of cannabinoids for homeostasis, but we’ll get into that in a bit.&nbsp;Take, for example, the way we <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.scientificamerican.com/article/what-is-homeostasis/">adjust to changes in the temperature.</a>&nbsp;The ideal for the human body is to stay around 98.6°F on average. When our body begins to heat up beyond normal temperatures, we have an automatic response — sweating to moisten our skin and bring our temperature down. Or on the other side of the spectrum, when we get cold, our bodies sweat less and less blood is circulated to the skin. The stress response of CBD oil could potentially help with these changes.&nbsp;These responses are what is called negative feedback. Here negative doesn’t mean that the feedback is bad or problematic — but rather that it is an opposing response. When conditions are non-ideal, our body responds in part via the endocannabinoid system with some kind of negative feedback to bring conditions back to normal. In this case, we have a natural negative feedback loop. When temperatures get too high, they are naturally lowered, and when they get too low, they are increased. Whether reducing temperature or increasing it, negative feedback pushes the body’s temperature back towards the ideal, maintaining homeostasis.Positive feedback regulation is another way that the body maintains homeostasis, although it is less common. With positive feedback, the direction of change is sped up, rather than reversed. For example, in lactation, the stimulation from a baby suckling causes prolactin (the hormone responsible for milk production) to be released into the bloodstream. As the baby continues to suckle, the prolactin is released proportionally.There is a large variety of different ways in which the body maintains balance similarly to how it regulates temperature. These homeostatic actions are performed by various systems in the body such as the respiratory system, endocrine system, reproductive system, urinary system, endocannabinoid system and nervous system.<h2 id="the-endocannabinoid-system-and-homeostasis">The endocannabinoid system and homeostasis</h2>The endocannabinoid system is an <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.fundacion-canna.es/en/endocannabinoid-system">important system in the human body</a>&nbsp;for regulating the homeostatic activity. While it is, perhaps, best known for its ability to be stimulated by phyto-cannabinoids (the active chemicals in cannabis) to produce the therapeutic potential of cannabinoids, it plays a key role in the body without any help from cannabis. Researchers have found that ECS functions naturally modulate a variety of things, such as:<ul class="list-disc mx-5"><li>Sleep</li><li>Pain</li><li>Memory</li><li>Learning</li><li>Inflammation</li><li>Hunger</li><li>Energy</li><li>Muscle control</li><li>Temperature</li><li>Mood</li></ul>These ECS functions occur when cannabinoids (chemicals produced naturally in our body) bind with endocannabinoid receptors (such as CB1, CB2 or TRPV-1), setting off a chain reaction that triggers these effects, like therapeutic potential of cannabinoids or the stress response of CBD. Activation of the endocannabinoid system in different ways can make us sleepy or energized, hungry or without appetite, anxious or relaxed, and so much more. Then, enzymes break down our endocannabinoids and clear them from the body.Interestingly, this system and its effects can also be activated by the cannabinoids in cannabis. These chemicals are strikingly similar to our endocannabinoids in structure and are thus able to bind with our endocannabinoid receptors to trigger the same effects. This is why ingesting cannabinoids can lead to so many noticeable effects, such as sedation, hunger, pain relief.While there are many different ways in which homeostasis is modulated and maintained by the endocannabinoid system, scientists have studied a few areas more closely for the stress response of CBD.<h2 id="energy-homeostasis">Energy homeostasis</h2>One area of homeostasis that the endocannabinoid system has been tied to is <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.omicsonline.org/open-access/role-of-homeostasis-in-human-physiology-a-review.php?aid=87462">energy homeostasis</a> —the way our body regulates energy levels through food intake, metabolism, and energy expenditures. As regulators of metabolism, endocannabinoids and cannabinoids for homeostasis are generally anabolic, meaning that they increase caloric intake, promote storage, and decrease expenditures of energy.One way that endocannabinoids (and phyto-cannabinoids) affect energy metabolism is through influencing the appetite. Stimulating CB1 receptors with endocannabinoids like anandamide or phyto-cannabinoids like THC produces increased appetite. This should be no surprise to those who use cannabis and have enjoyed the therapeutic potential of cannabinoids. It’s long been known that consuming cannabis can result in an increase in appetite, sometimes referred to as “the munchies.”I&nbsp;addition, blocking CB1 in the endocannabinoid system can produce a lack of appetite. For example, in clinical trials, CB1 was blocked by the drug rimonabant, and the result was <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136184/">reduced food intake and decreases in weight.</a> The drug was eventually pulled from the market, however, due to its causing serious mood disorders.Still, appetite regulation or the stress response of CBD isn’t the only way that the endocannabinoid system regulates energy. In addition to affecting appetite, it also seems to alter our metabolism. For example, in one study, healthy volunteers smoked cannabis and had a three-day increase in caloric intake, presumably in response to increased appetite. However, after three days, the increases subsided. Despite this, subjects gained weight throughout the three-week study period — suggesting that cannabis has an effect on metabolism that goes beyond boosting appetite.Similarly, in studies where CB1 is blocked in rodents, they are able to rapidly adjust to the appetite-suppressing effects of the treatment but continued to see weight-reducing effects. Mice naturally deficient in CB1 also tend to be leaner than their normal counterparts, highlighting how ECS functions can affect various outcomes.Interestingly, there is also <a target="_blank" rel="noopener noreferrer nofollow" href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144270">research suggesting</a> that&nbsp;CB1 can lead to weight reductions. For one thing, obesity rates are lower in cannabis users than non-users, possibly as a stress response of CBD or THC. One study found that mice given THC gained less weight on a high-fat diet than control groups. In fact, the THC seemed to alter the gut biome of the mice — transforming it from a profile consistent with obesity to one found in healthy mice.The endocannabinoid system also seems to <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S0002934306013623">modulate important metabolic functions</a>&nbsp;related to glucose intolerance, insulin resistance, and triglyceride and cholesterol levels. Understanding exactly how could lead to big breakthroughs for people with diabetes, obesity, and metabolic syndrome, but more research is needed to understand the complex situation of cannabinoids for homeostasis.Still, one thing is clear — the therapeutic potential of cannabinoids and the endocannabinoid system plays a big role in our energy homeostasis.<h2 id="immune-response">Immune response</h2>The endocannabinoid system and the stress response of CBD and other cannabinoids have also been studied for its role in&nbsp;<a target="_blank" rel="noopener noreferrer nofollow" href="https://www.pnas.org/content/114/19/5005">maintaining immune homeostasis</a>.&nbsp;Further stressing on the importance of cannabinoids for homeostasis. Specifically, scientists have looked at the role the endocannabinoid anandamide plays in maintaining immune health in the gut. The gut’s immune system needs to be able to tolerate foreign antigens (substances that would usually stimulate an immune response) to allow for digestion, but this process is only partially understood.Still, scientists have recently noted that anandamide contributes to this process. When anandamide is produced by the body and binds with the CB2 receptor, it causes an increase in the number of CX3CR1hi macrophages, an immunosuppressive white blood cell. By promoting immunosuppressive white blood cells like these, anandamide is able to help maintain homeostasis in the gut and pancreas — even when antigens are present. While we have a long way to go towards understanding the endocannabinoid system’s role in immune health, this demonstrates that ECS functions are at least somewhat involved in maintaining immune homeostasis.<h2 id="emotional-homeostasis">Emotional homeostasis</h2>Scientists have also noted that the endocannabinoid system is critical for <a target="_blank" rel="noopener noreferrer nofollow" href="https://europepmc.org/abstract/med/19929814">the regulation of emotion and stress responses</a>.&nbsp;For example, consider the way that the therapeutic potential of cannabinoids can affect anxiety and panic responses. At low doses, the stress response of CBD and other cannabinoids usually induces relaxation, while at high doses it can cause anxiety, paranoia or panic. These effects are called biphasic, which means that the same substance can produce opposite effects in different conditions. Biphasic effects are common with cannabinoids for homeostasis (such as we saw with weight loss and weight gain), often in dose-dependent ways.While CB1 stimulation in the endocannabinoid system can produce either relaxation or anxiety, blocking CB1 has been shown to produce severe anxiety. As we saw above in the clinical study of rimonabant, CB1 was blocked in order to suppress appetite, but doing so led to severe mood disorders like anxiety and depression.So, importantly, in states where we see an excess of endocannabinoid signaling (such as when patients use high amounts of THC) or a deficiency of endocannabinoid signaling (such as when CB1 is blocked) our emotional homeostasis is thrown off,&nbsp;show how a moderate use of cannabinoids for homeostasis is ideal.&nbsp;Thus <a target="_blank" rel="noopener noreferrer nofollow" href="https://europepmc.org/abstract/med/19929814">maintaining a good balance of endocannabinoid signaling</a> may be key to psychological health and stability.These are just a few examples of the ways that the endocannabinoid system and ECS functions help maintain homeostasis in the body, and there are many ways we haven’t covered. In addition, we have only begun to study the therapeutic potential of cannabinoids in regard to this important topic, and as we continue to investigate it we will likely find more ways that homeostasis relies on this key system.<h2 id="cannabis-effect-on-homeostasis">Cannabis’ effect on homeostasis</h2><h2></h2>Now that we know that the endocannabinoid system helps support our internal homeostasis, it’s important to question what effect cannabis consumption and cannabinoids for homeostasis might have on this process. After all, the cannabinoids in cannabis activate this important system in many of the same ways that natural endocannabinoids do, so are likely to cause some changes.And indeed, the many effects of cannabis, both medicinal and adverse, show that cannabis can affect us in so many ways, calling to attention both the detrimental and the therapeutic potential of cannabinoids. In relation to maintaining homeostasis, cannabis could be a help but it could also potentially do harm.In healthy individuals, the endocannabinoid system is already working to maintain homeostasis, not calling for cannabinoids for homeostasis from cannabis. So adding cannabinoids to this situation may throw off your body’s internal balance — as we saw with anxiety and weight gain in the examples above. This may be in part because excessive cannabinoid levels or the stress response of CBD or other cannabinoids can also lead to&nbsp;a <a target="_blank" rel="noopener noreferrer nofollow" href="https://europepmc.org/abstract/MED/20952498">desensitization of your endocannabinoid receptors</a> which may reduce natural endocannabinoid functioning, especially over time.In addition, disrupting your homeostasis with cannabis can have effects you might not feel immediately, but could have big impacts on ECS functions. Researchers have noted that cannabis use during pregnancy can impact the homeostasis of the placenta by disrupting natural anandamide levels and related enzymes. This could lead to alterations in normal placental development and fetal growth.It’s important to remember when dealing with the endocannabinoid system, that it is all about balance, and too much can be as bad as too little to make the most of the therapeutic potential of cannabinoids.Endocannabinoid system, ECS functions, Stress response of CBD, Cannabinoids for Homeostasis, Therapeutic potential of CannabinoidsOf course, too little is also a problem. When endocannabinoid systems are deficient, and there isn’t enough endocannabinoid signaling, this also throws our system out of balance, perhaps calling for cannabinoids for homeostasis. A number of health conditions have recently been tied to impaired endocannabinoid functioning. According to the researchers who’ve studied this phenomenon, using cannabis could be beneficial in many of these cases — restoring endocannabinoid receptor signaling to healthy levels with the stress response of CBD and other cannabinoids. In this case, cannabis use could actually help to restore balance.If you are considering using cannabis for your own medical needs or cannabinoids for homeostasis, it’s best to check with a cannabinoid-specializing doctor. They can help you to decide whether cannabis is right for your particular situation.Explore cannabis<a target="_blank" rel="noopener noreferrer nofollow" href="https://savikalpa.com/collections/shunyata"> based medicine here</a>.This article was originally published on The Cannigma, and shared here with permission.

If you’ve been paying attention to cannabis science, you may have heard about the endocannabinoid system (ECS) and the important role of cannabinoids for homeostasis in the human body. While often mentioned, this function is rarely explained. Still, understanding how the endocannabinoid system works to maintain balance in our body can be a big help in understanding the therapeutic potential of cannabinoids and how cannabinoid medicines might help (or in some cases worsen) different medical conditions.

So, in this article, we’ll cover the science of homeostasis, how using cannabis might affect this important function and ECS functions.

 comes from the Greek words homeo which means “similar” or “same,” and stasis, which means “stable.” Essentially, it refers to a state of stability, equilibrium, or balance in the body — although the term can also be applied to the internal balance of cells or other systems. In humans, maintaining homeostasis is the way our natural systems keep conditions in the body optimal for our health and wellbeing. As conditions shift, either internally or externally, mechanisms kick into action to make sure that our body doesn’t suffer from the change. Specifically, the stimuli trigger hormones which are released into the bloodstream and then cause bodily responses which maintain this delicate balance. This is called feedback regulation and it is the basic way that homeostasis is maintained. It is interesting to note that ECS functions have been closely tied to feedback regulation, showing the success of cannabinoids for homeostasis, but we’ll get into that in a bit. 

 The ideal for the human body is to stay around 98.6°F on average. When our body begins to heat up beyond normal temperatures, we have an automatic response — sweating to moisten our skin and bring our temperature down. Or on the other side of the spectrum, when we get cold, our bodies sweat less and less blood is circulated to the skin. The stress response of CBD oil could potentially help with these changes. 

These responses are what is called negative feedback. Here negative doesn’t mean that the feedback is bad or problematic — but rather that it is an opposing response. When conditions are non-ideal, our body responds in part via the endocannabinoid system with some kind of negative feedback to bring conditions back to normal. In this case, we have a natural negative feedback loop. When temperatures get too high, they are naturally lowered, and when they get too low, they are increased. Whether reducing temperature or increasing it, negative feedback pushes the body’s temperature back towards the ideal, maintaining homeostasis.

Positive feedback regulation is another way that the body maintains homeostasis, although it is less common. With positive feedback, the direction of change is sped up, rather than reversed. For example, in lactation, the stimulation from a baby suckling causes prolactin (the hormone responsible for milk production) to be released into the bloodstream. As the baby continues to suckle, the prolactin is released proportionally.

There is a large variety of different ways in which the body maintains balance similarly to how it regulates temperature. These homeostatic actions are performed by various systems in the body such as the respiratory system, endocrine system, reproductive system, urinary system, endocannabinoid system and nervous system.

The endocannabinoid system and homeostasis

 for regulating the homeostatic activity. While it is, perhaps, best known for its ability to be stimulated by phyto-cannabinoids (the active chemicals in cannabis) to produce the therapeutic potential of cannabinoids, it plays a key role in the body without any help from cannabis. Researchers have found that ECS functions naturally modulate a variety of things, such as:

These ECS functions occur when cannabinoids (chemicals produced naturally in our body) bind with endocannabinoid receptors (such as CB1, CB2 or TRPV-1), setting off a chain reaction that triggers these effects, like therapeutic potential of cannabinoids or the stress response of CBD. Activation of the endocannabinoid system in different ways can make us sleepy or energized, hungry or without appetite, anxious or relaxed, and so much more. Then, enzymes break down our endocannabinoids and clear them from the body.

Interestingly, this system and its effects can also be activated by the cannabinoids in cannabis. These chemicals are strikingly similar to our endocannabinoids in structure and are thus able to bind with our endocannabinoid receptors to trigger the same effects. This is why ingesting cannabinoids can lead to so many noticeable effects, such as sedation, hunger, pain relief.

While there are many different ways in which homeostasis is modulated and maintained by the endocannabinoid system, scientists have studied a few areas more closely for the stress response of CBD.

One area of homeostasis that the endocannabinoid system has been tied to is 

 —the way our body regulates energy levels through food intake, metabolism, and energy expenditures. As regulators of metabolism, endocannabinoids and cannabinoids for homeostasis are generally anabolic, meaning that they increase caloric intake, promote storage, and decrease expenditures of energy.

One way that endocannabinoids (and phyto-cannabinoids) affect energy metabolism is through influencing the appetite. Stimulating CB1 receptors with endocannabinoids like anandamide or phyto-cannabinoids like THC produces increased appetite. This should be no surprise to those who use cannabis and have enjoyed the therapeutic potential of cannabinoids. It’s long been known that consuming cannabis can result in an increase in appetite, sometimes referred to as “the munchies.”

I addition, blocking CB1 in the endocannabinoid system can produce a lack of appetite. For example, in clinical trials, CB1 was blocked by the drug rimonabant, and the result was 

reduced food intake and decreases in weight.

 The drug was eventually pulled from the market, however, due to its causing serious mood disorders.

Still, appetite regulation or the stress response of CBD isn’t the only way that the endocannabinoid system regulates energy. In addition to affecting appetite, it also seems to alter our metabolism. For example, in one study, healthy volunteers smoked cannabis and had a three-day increase in caloric intake, presumably in response to increased appetite. However, after three days, the increases subsided. Despite this, subjects gained weight throughout the three-week study period — suggesting that cannabis has an effect on metabolism that goes beyond boosting appetite.

Similarly, in studies where CB1 is blocked in rodents, they are able to rapidly adjust to the appetite-suppressing effects of the treatment but continued to see weight-reducing effects. Mice naturally deficient in CB1 also tend to be leaner than their normal counterparts, highlighting how ECS functions can affect various outcomes.

 that CB1 can lead to weight reductions. For one thing, obesity rates are lower in cannabis users than non-users, possibly as a stress response of CBD or THC. One study found that mice given THC gained less weight on a high-fat diet than control groups. In fact, the THC seemed to alter the gut biome of the mice — transforming it from a profile consistent with obesity to one found in healthy mice.

The endocannabinoid system also seems to 

 related to glucose intolerance, insulin resistance, and triglyceride and cholesterol levels. Understanding exactly how could lead to big breakthroughs for people with diabetes, obesity, and metabolic syndrome, but more research is needed to understand the complex situation of cannabinoids for homeostasis.

Still, one thing is clear — the therapeutic potential of cannabinoids and the endocannabinoid system plays a big role in our energy homeostasis.

The endocannabinoid system and the stress response of CBD and other cannabinoids have also been studied for its role in 

. Further stressing on the importance of cannabinoids for homeostasis. Specifically, scientists have looked at the role the endocannabinoid anandamide plays in maintaining immune health in the gut. The gut’s immune system needs to be able to tolerate foreign antigens (substances that would usually stimulate an immune response) to allow for digestion, but this process is only partially understood.

Still, scientists have recently noted that anandamide contributes to this process. When anandamide is produced by the body and binds with the CB2 receptor, it causes an increase in the number of CX3CR1hi macrophages, an immunosuppressive white blood cell. By promoting immunosuppressive white blood cells like these, anandamide is able to help maintain homeostasis in the gut and pancreas — even when antigens are present. While we have a long way to go towards understanding the endocannabinoid system’s role in immune health, this demonstrates that ECS functions are at least somewhat involved in maintaining immune homeostasis.

Scientists have also noted that the endocannabinoid system is critical for 

the regulation of emotion and stress responses

. For example, consider the way that the therapeutic potential of cannabinoids can affect anxiety and panic responses. At low doses, the stress response of CBD and other cannabinoids usually induces relaxation, while at high doses it can cause anxiety, paranoia or panic. These effects are called biphasic, which means that the same substance can produce opposite effects in different conditions. Biphasic effects are common with cannabinoids for homeostasis (such as we saw with weight loss and weight gain), often in dose-dependent ways.

While CB1 stimulation in the endocannabinoid system can produce either relaxation or anxiety, blocking CB1 has been shown to produce severe anxiety. As we saw above in the clinical study of rimonabant, CB1 was blocked in order to suppress appetite, but doing so led to severe mood disorders like anxiety and depression.

So, importantly, in states where we see an excess of endocannabinoid signaling (such as when patients use high amounts of THC) or a deficiency of endocannabinoid signaling (such as when CB1 is blocked) our emotional homeostasis is thrown off, show how a moderate use of cannabinoids for homeostasis is ideal. Thus 

maintaining a good balance of endocannabinoid signaling

 may be key to psychological health and stability.

These are just a few examples of the ways that the endocannabinoid system and ECS functions help maintain homeostasis in the body, and there are many ways we haven’t covered. In addition, we have only begun to study the therapeutic potential of cannabinoids in regard to this important topic, and as we continue to investigate it we will likely find more ways that homeostasis relies on this key system.

Now that we know that the endocannabinoid system helps support our internal homeostasis, it’s important to question what effect cannabis consumption and cannabinoids for homeostasis might have on this process. After all, the cannabinoids in cannabis activate this important system in many of the same ways that natural endocannabinoids do, so are likely to cause some changes.

And indeed, the many effects of cannabis, both medicinal and adverse, show that cannabis can affect us in so many ways, calling to attention both the detrimental and the therapeutic potential of cannabinoids. In relation to maintaining homeostasis, cannabis could be a help but it could also potentially do harm.

In healthy individuals, the endocannabinoid system is already working to maintain homeostasis, not calling for cannabinoids for homeostasis from cannabis. So adding cannabinoids to this situation may throw off your body’s internal balance — as we saw with anxiety and weight gain in the examples above. This may be in part because excessive cannabinoid levels or the stress response of CBD or other cannabinoids can also lead to a 

desensitization of your endocannabinoid receptors

 which may reduce natural endocannabinoid functioning, especially over time.

In addition, disrupting your homeostasis with cannabis can have effects you might not feel immediately, but could have big impacts on ECS functions. Researchers have noted that cannabis use during pregnancy can impact the homeostasis of the placenta by disrupting natural anandamide levels and related enzymes. This could lead to alterations in normal placental development and fetal growth.

It’s important to remember when dealing with the endocannabinoid system, that it is all about balance, and too much can be as bad as too little to make the most of the therapeutic potential of cannabinoids.

Endocannabinoid system, ECS functions, Stress response of CBD, Cannabinoids for Homeostasis, Therapeutic potential of Cannabinoids

Of course, too little is also a problem. When endocannabinoid systems are deficient, and there isn’t enough endocannabinoid signaling, this also throws our system out of balance, perhaps calling for cannabinoids for homeostasis. A number of health conditions have recently been tied to impaired endocannabinoid functioning. According to the researchers who’ve studied this phenomenon, using cannabis could be beneficial in many of these cases — restoring endocannabinoid receptor signaling to healthy levels with the stress response of CBD and other cannabinoids. In this case, cannabis use could actually help to restore balance.

If you are considering using cannabis for your own medical needs or cannabinoids for homeostasis, it’s best to check with a cannabinoid-specializing doctor. They can help you to decide whether cannabis is right for your particular situation.

Homeostasis and the Endocannabinoid System

Cannabis plant image

Welcome back to our ongoing series on the introduction to the Endocannabinoid System. In our previous segment, we provided a basic introduction to the ECS (endocannabinoid system) functions. In this segment we will be discussing the different receptors of the ECS, including their locations, functions, and signalling that make the therapeutic potential of cannabinoids a possibility.&nbsp;<h2 id="cannabinoid-receptors">CANNABINOID RECEPTORS</h2>As mentioned in our previous segment the first cannabinoid receptor, aptly named the CB1 receptor, was first discovered in the late 1980s. Since then, researchers have learned a great deal about cannabinoid receptors, with the two most discussed and most abundantly found in the human body being the CB1 and CB2 receptors. These cannabinoid receptors fall under a classification of cell membrane receptors known as G protein coupled receptors and are responsible for the effects of cannabinoids, including CBD (cannabidiol) effects.Cannabinoid receptor activation occurs following the introduction of ligands from one or more of three groups.<ul class="list-disc mx-5"><li>Endocannabinoids – Cannabinoids produced and released within the body.</li><li>Phytocannabinoids – Plant based cannabinoids such as those found in cannabis.</li><li>Synthetic cannabinoids – Manufactured pharmaceutical synthetic THC and CBD.</li></ul><h2 id="receptor-signalling">RECEPTOR SIGNALLING</h2>What makes the process of cannabinoid receptor signalling unique is that it is presynaptic. This means that unlike in the case of neurotransmitters that travel from a neuron to a postsynaptic cell, cannabinoids attach to cannabinoid receptors located on the presynaptic neuron and effect ECS (endocannabinoid system) functions. Due to this presynaptic process, the therapeutic potential of cannabinoids can lead to a direct effect on neurotransmission.<img height="400" width="1200" class="" src="https://gglkfcubjshidhufqxdn.supabase.co/storage/v1/object/public/media/1740865670877_6_600x600.jpg?v=1632598253" alt="cm7qqh0s20095ulnwpcn2gvnz"><h2 id="locations-and-functions">LOCATIONS &amp; FUNCTIONS</h2>In a slight over-simplification, cannabinoids and cannabinoid receptors work similar to a lock and a key in that certain cannabinoids will ‘fit’ or bind with their matching receptors, creating CBD (cannabidiol) effects as well as other cannabinoids’ effects. The body’s ECS consists of a vast network of these cannabinoid receptors or ‘locks’. In fact, the CB1 receptor is one of the most abundant receptors found in the brain and in the central nervous system and plays a key role in ECS (endocannabinoid system) functions.Cannabinoid receptors can be found throughout the body, and are primarily concentrated in the brain, spinal cord, and the tissues of the immune system to help activate the therapeutic potention of cannabinoids.Much is still to be explored to fully understand ECS (endocannabinoid system) functions and its network of receptors. While there is still ongoing investigation and debate, research has shown that activation of the CB1 and CB2 receptors can influence many of the different systems and functions of the body. The popularity of CBD (cannabidiol) effects is on the rise for this reason.&nbsp;<h2 id="cb1-receptors">CB1 RECEPTORS</h2>PainInflammationMetabolism / AppetiteSleep CycleCardiovascular FunctionsMoodLearning &amp; MemoryNeurodegenerationAddictionMusculoskeletal DisordersRewardLiver FunctionNeuroinflammationBone MassReproductive Functions<h2 id="cb2-receptors">CB2 RECEPTORS</h2>Immune ResponsePainInflammationNeurological FunctionStress ResponsesMoodAddictionReproductive Function&nbsp;<img height="400" width="1200" class="" src="https://gglkfcubjshidhufqxdn.supabase.co/storage/v1/object/public/media/1740865672368_1_5_600x600.jpg?v=1632597620" alt="cm7qqh1vw0096ulnwpps835j6"><h2 id="secondary-cannabinoid-receptors">SECONDARY CANNABINOID RECEPTORS</h2>While research is limited on receptors of the ECS other than the CB1 and CB2 receptors, other receptors do exist that might contribute in the therapeutic potential of cannabinoids, with the two most notable being:<ul class="list-disc mx-5"><li>Transient Receptor Potential Channels (TRPV-1) – Membrane proteins involved in the modulation of ion entry.</li><li>Peroxisome Proliferator Activated Receptors (PPARS) – A group of nuclear hormone receptors.</li></ul>UP NEXT – In the next segment of our series covering the Endocannabinoid System, we will be discussing the endocannabinoids&nbsp;Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG).&nbsp;To begin your cannabis medicine journey today, book an appointment now with the <a target="_blank" rel="noopener noreferrer nofollow" href="https://eclinic.savikalpa.com/">Savikalpa Virtual Clinic</a> for an online doctor consultation, or request more information from a member of our highly trained clinic staff (eclinic@savikalpa.com).We pride ourselves on being one of India’s most qualified sources of fast, friendly, and professional access to <a target="_blank" rel="noopener noreferrer nofollow" href="https://savikalpa.com/collections/shunyata">cannabinoid medicine online</a>!Interested in learning more? Send us your questions (eclinic@savikalpa.com). It is our mission to educate patients in any way we can, and we would be delighted to hear from you.Research regarding the endocannabinoid system:<ul class="list-disc mx-5"><li>Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.liebertpub.com/doi/full/10.1089/can.2016.0009">https://www.liebertpub.com/doi/full/10.1089/can.2016.0009</a></li><li>CB1 and CB2 Receptor Pharmacology <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S1054358917300340?via%3Dihub">https://www.sciencedirect.com/science/article/abs/pii/S1054358917300340?via%3Dihub</a></li><li>Neurobiological Interactions Between Stress and the Endocannabinoid System <a target="_blank" rel="noopener noreferrer nofollow" href="https://pubmed.ncbi.nlm.nih.gov/26068727/">https://pubmed.ncbi.nlm.nih.gov/26068727/</a></li><li>The endocannabinoid system in guarding against fear, anxiety and stress <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871913/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871913/</a></li><li>Endocannabinoid system and stress and anxiety responses <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S0091305705001346">https://www.sciencedirect.com/science/article/abs/pii/S0091305705001346</a></li><li>Endocannabinoid system and pain: an introduction <a target="_blank" rel="noopener noreferrer nofollow" href="https://pubmed.ncbi.nlm.nih.gov/24148358/">https://pubmed.ncbi.nlm.nih.gov/24148358/</a></li><li>The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685274/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685274/</a></li><li>Endocannabinoid system in irritable bowel syndrome and cannabis as a therapy <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S0965229919310179">https://www.sciencedirect.com/science/article/abs/pii/S0965229919310179</a></li><li>CB2 receptors in reproduction <a target="_blank" rel="noopener noreferrer nofollow" href="https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0707444">https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0707444</a></li><li>Endocannabinoids in the regulation of appetite and body weight <a target="_blank" rel="noopener noreferrer nofollow" href="https://journals.lww.com/behaviouralpharm/Abstract/2005/09000/Endocannabinoids_in_the_regulation_of_appetite_and.4.aspx">https://journals.lww.com/behaviouralpharm/Abstract/2005/09000/Endocannabinoids_in_the_regulation_of_appetite_and.4.aspx</a></li><li>The endocannabinoid system: directing eating behavior and macronutrient metabolism <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.frontiersin.org/articles/10.3389/fpsyg.2014.01506/full">https://www.frontiersin.org/articles/10.3389/fpsyg.2014.01506/full</a></li><li>Endocannabinoids and immune regulation <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S104366180900108X?via%3Dihub">https://www.sciencedirect.com/science/article/abs/pii/S104366180900108X?via%3Dihub</a></li><li>Endocannabinoid Catabolic Enzymes Play Differential Roles in Thermal Homeostasis in Response to Environmental or Immune Challenge <a target="_blank" rel="noopener noreferrer nofollow" href="https://link.springer.com/article/10.1007%2Fs11481-015-9593-1">https://link.springer.com/article/10.1007%2Fs11481-015-9593-1</a></li><li>Antidepressants and Changes in Concentration of Endocannabinoids and N-Acylethanolamines in Rat Brain Structures <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067538/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067538/</a></li><li>Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/</a></li><li>Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.frontiersin.org/articles/10.3389/fncel.2016.00294/full">https://www.frontiersin.org/articles/10.3389/fncel.2016.00294/full</a></li><li>Endocannabinoid Binding to the Cannabinoid Receptors: What Is Known and What Remains Unknown <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120766/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120766/</a></li><li>Cannabinoid CB1 and CB2 Receptor Signaling and Bias <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.liebertpub.com/doi/10.1089/can.2016.0037">https://www.liebertpub.com/doi/10.1089/can.2016.0037</a></li></ul>DISCLAIMER – All individuals accessing this site undertake full responsibility for their own assessment of the accuracy/relevance of any and all content found herein. The content found on this site is not intended to serve as a substitute for medical advice/diagnosis/treatment from a qualified and licensed health care provider. This information should also in no way be misconstrued as professional legal advice regarding legislative, regulatory or any other matters. Individuals should always seek guidance of fully qualified professionals.

Welcome back to our ongoing series on the introduction to the Endocannabinoid System. In our previous segment, we provided a basic introduction to the ECS (endocannabinoid system) functions. In this segment we will be discussing the different receptors of the ECS, including their locations, functions, and signalling that make the therapeutic potential of cannabinoids a possibility.

As mentioned in our previous segment the first cannabinoid receptor, aptly named the CB1 receptor, was first discovered in the late 1980s. Since then, researchers have learned a great deal about cannabinoid receptors, with the two most discussed and most abundantly found in the human body being the CB1 and CB2 receptors. These cannabinoid receptors fall under a classification of cell membrane receptors known as G protein coupled receptors and are responsible for the effects of cannabinoids, including CBD (cannabidiol) effects.

Cannabinoid receptor activation occurs following the introduction of ligands from one or more of three groups.

What makes the process of cannabinoid receptor signalling unique is that it is presynaptic. This means that unlike in the case of neurotransmitters that travel from a neuron to a postsynaptic cell, cannabinoids attach to cannabinoid receptors located on the presynaptic neuron and effect ECS (endocannabinoid system) functions. Due to this presynaptic process, the therapeutic potential of cannabinoids can lead to a direct effect on neurotransmission.

In a slight over-simplification, cannabinoids and cannabinoid receptors work similar to a lock and a key in that certain cannabinoids will ‘fit’ or bind with their matching receptors, creating CBD (cannabidiol) effects as well as other cannabinoids’ effects. The body’s ECS consists of a vast network of these cannabinoid receptors or ‘locks’. In fact, the CB1 receptor is one of the most abundant receptors found in the brain and in the central nervous system and plays a key role in ECS (endocannabinoid system) functions.

Cannabinoid receptors can be found throughout the body, and are primarily concentrated in the brain, spinal cord, and the tissues of the immune system to help activate the therapeutic potention of cannabinoids.

Much is still to be explored to fully understand ECS (endocannabinoid system) functions and its network of receptors. While there is still ongoing investigation and debate, research has shown that activation of the CB1 and CB2 receptors can influence many of the different systems and functions of the body. The popularity of CBD (cannabidiol) effects is on the rise for this reason. 

While research is limited on receptors of the ECS other than the CB1 and CB2 receptors, other receptors do exist that might contribute in the therapeutic potential of cannabinoids, with the two most notable being:

UP NEXT – In the next segment of our series covering the Endocannabinoid System, we will be discussing the endocannabinoids Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG).

To begin your cannabis medicine journey today, book an appointment now with the 

 for an online doctor consultation, or request more information from a member of our highly trained clinic staff (eclinic@savikalpa.com).

We pride ourselves on being one of India’s most qualified sources of fast, friendly, and professional access to 

Interested in learning more? Send us your questions (eclinic@savikalpa.com). It is our mission to educate patients in any way we can, and we would be delighted to hear from you.

Research regarding the endocannabinoid system:

DISCLAIMER – All individuals accessing this site undertake full responsibility for their own assessment of the accuracy/relevance of any and all content found herein. The content found on this site is not intended to serve as a substitute for medical advice/diagnosis/treatment from a qualified and licensed health care provider. This information should also in no way be misconstrued as professional legal advice regarding legislative, regulatory or any other matters. Individuals should always seek guidance of fully qualified professionals.

Understanding Endocannabinoid Receptors

Two Green Leafs

Here we begin our ongoing series on the Endocannabinoid System&nbsp;or ECS introduction. In this series we will be exploring the many aspects of the ECS, including the ECS and our immune system, the ECS and inflammation, the ECS and mood regulation, the ECS and pain management and the critical role it plays in helping to regulate and maintain our overall health and wellbeing.<h2 id="the-endocannabinoid-system-what-is-it">THE ENDOCANNABINOID SYSTEM – What is it?</h2>Here is a brief ECS introduction: The Endocannabinoid System (ECS) helps in maintaining equilibrium amongst many of the different functions and systems within the human body. The ECS consists of a network of receptors that are activated by cannabinoids. What are cannabinoids? Cannabinoids that are created within the body are known as endocannabinoids. Cannabinoids created by plants are known as phytocannabinoids. The ECS is responsible for cannabinoids’ interactions with neurotransmitters.While many discoveries regarding this system have been made, including the biphasic relationship between the ECS and our immune system, the ECS and inflammation, the ECS and mood regulation and the ECS and pain management, there is still much research to be done to fully understand the ECS and its role in regulating homeostasis within the body. The first cannabinoid receptor and endocannabinoid were not discovered until the late 80s and early 90s respectively, thus our scientific research regarding how cannabinoids’ interact with neurotransmitters is a little understood aspect of human health and is still in the early stages. To date, there are over 120 known endocannabinoids being studied.<h2 id="primary-cannabinoids">Primary Cannabinoids</h2>PRIMARY ENDOCANNABINOIDSPRIMARY PHYTOCANNABINOIDSAnandamideTetrahydrocannabinol (THC)2-Arachidonoylglycerol (2-AG)Cannabidiol (CBD)<h2 id="functions-of-the-ecs">Functions of the ECS</h2>The ECS is responsible for regulating many of the body’s natural functions due to the relationship between the ECS and our immune system, the ECS and inflammation, the ECS and mood regulation and the ECS and pain management through activating endocannabinoid receptors found throughout the body, primarily concentrated in the brain, spinal cord, and immune system. Endocannabinoid receptors can also be found in the digestive tract, reproductive system, lungs, kidneys, liver, pituitary and thyroid glands, fat cells and muscle cells. Cannabinoids’ interactions with neurotransmitters throughout the body can be beneficial in various ways.&nbsp;The exact systems and mechanisms for regulation are still being explored, however the ECS plays a role in controlling the body’s immune system, appetite, pain, inflammation, mood, body temperature, memory, reproductive health, and sleep cycle regulation.REGULATORY FUNCTIONS &amp; EFFECTS OF THE ENDOCANNABINOID SYSTEMAPPETITECannabinoids can stimulate/increase appetite.NAUSEACannabinoids can block signals in the body that trigger nausea and vomiting.PAIN &amp; INFLAMMATIONCannabinoid receptors in the brain are capable of suppressing pain signalling.MOOD MANAGEMENTCannabinoids have the potential to produce feelings of relaxation and euphoria. They can also reduce feelings of anxiousness and worry.THERMOREGULATIONTHC can lower body temperature. The ECS also plays a role in the body’s immune response to ward off infection.MEMORY &amp; LEARNINGCannabinoid receptors are highly concentrated in areas of the brain responsible for regulating memory and learning.REPRODUCTIVE HEALTHPhytocannabinoids can potentially disrupt and lower the production of estrogen and progesterone in women.SLEEPSome cannabinoids can be sedating, specifically THC, which shares structural similarities to anandamide, an endocannabinoid that can affect sleep patterns.<h2 id="the-future-of-research-on-the-ecs">The Future of Research on the ECS</h2>While the initial research regarding the ECS began with the focus of studying the effects of cannabinoids from cannabis on the body, the discoveries that followed have exposed a need to better understand the natural functions of the ECS that occur independently from the introduction of phytocannabinoids like the relationship between the ECS and our immune system, the ECS and inflammation, the ECS and mood regulation and the ECS and pain management. Among the most interesting areas of current study is the research regarding endocannabinoid deficiency or dysfunction, and the potential implications this might have for a variety of common and difficult to treat chronic conditions.UP NEXT – In the next segment of our series covering the Endocannabinoid System, we will be discussing the endocannabinoid receptors of the ECS, including what are CB1 and CB2 receptors. We will take a closer look at these receptors, their locations, functions, and signalling processes.To begin your cannabis medicine journey today, book an appointment now with the <a target="_blank" rel="noopener noreferrer nofollow" href="https://eclinic.savikalpa.com/">Savikalpa Virtual Clinic</a> for an online doctor consultation, or request more information from a member of our highly trained clinic staff (eclinic@savikalpa.com).We pride ourselves on being one of India’s most qualified sources of fast, friendly, and professional access to ayurvedic medicine online!Interested in learning more? Send us your questions (eclinic@savikalpa.com). It is our mission to educate patients in any way we can, and we would be delighted to hear from you.Research regarding the endocannabinoid system:<ul class="list-disc mx-5"><li>Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.liebertpub.com/doi/full/10.1089/can.2016.0009">https://www.liebertpub.com/doi/full/10.1089/can.2016.0009</a></li><li>CB1 and CB2 Receptor Pharmacology <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S1054358917300340?via%3Dihub">https://www.sciencedirect.com/science/article/abs/pii/S1054358917300340?via%3Dihub</a></li><li>Neurobiological Interactions Between Stress and the Endocannabinoid System <a target="_blank" rel="noopener noreferrer nofollow" href="https://pubmed.ncbi.nlm.nih.gov/26068727/">https://pubmed.ncbi.nlm.nih.gov/26068727/</a></li><li>The endocannabinoid system in guarding against fear, anxiety and stress <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871913/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871913/</a></li><li>Endocannabinoid system and stress and anxiety responses <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S0091305705001346">https://www.sciencedirect.com/science/article/abs/pii/S0091305705001346</a></li><li>Endocannabinoid system and pain: an introduction <a target="_blank" rel="noopener noreferrer nofollow" href="https://pubmed.ncbi.nlm.nih.gov/24148358/">https://pubmed.ncbi.nlm.nih.gov/24148358/</a></li><li>The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685274/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685274/</a></li><li>Endocannabinoid system in irritable bowel syndrome and cannabis as a therapy <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S0965229919310179">https://www.sciencedirect.com/science/article/abs/pii/S0965229919310179</a></li><li>CB2 receptors in reproduction <a target="_blank" rel="noopener noreferrer nofollow" href="https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0707444">https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0707444</a></li><li>Endocannabinoids in the regulation of appetite and body weight <a target="_blank" rel="noopener noreferrer nofollow" href="https://journals.lww.com/behaviouralpharm/Abstract/2005/09000/Endocannabinoids_in_the_regulation_of_appetite_and.4.aspx">https://journals.lww.com/behaviouralpharm/Abstract/2005/09000/Endocannabinoids_in_the_regulation_of_appetite_and.4.aspx</a></li><li>The endocannabinoid system: directing eating behavior and macronutrient metabolism <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.frontiersin.org/articles/10.3389/fpsyg.2014.01506/full">https://www.frontiersin.org/articles/10.3389/fpsyg.2014.01506/full</a></li><li>Endocannabinoids and immune regulation <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.sciencedirect.com/science/article/abs/pii/S104366180900108X?via%3Dihub">https://www.sciencedirect.com/science/article/abs/pii/S104366180900108X?via%3Dihub</a></li><li>Endocannabinoid Catabolic Enzymes Play Differential Roles in Thermal Homeostasis in Response to Environmental or Immune Challenge <a target="_blank" rel="noopener noreferrer nofollow" href="https://link.springer.com/article/10.1007%2Fs11481-015-9593-1">https://link.springer.com/article/10.1007%2Fs11481-015-9593-1</a></li><li>Antidepressants and Changes in Concentration of Endocannabinoids and N-Acylethanolamines in Rat Brain Structures <a target="_blank" rel="noopener noreferrer nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067538/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067538/</a></li></ul>DISCLAIMER – All individuals accessing this site undertake full responsibility for their own assessment of the accuracy/relevance of any and all content found herein. The content found on this site is not intended to serve as a substitute for medical advice/diagnosis/treatment from a qualified and licensed health care provider. This information should also in no way be misconstrued as professional legal advice regarding legislative, regulatory or any other matters. Individuals should always seek guidance of fully qualified professionals.

Here we begin our ongoing series on the Endocannabinoid System or ECS introduction. In this series we will be exploring the many aspects of the ECS, including the ECS and our immune system, the ECS and inflammation, the ECS and mood regulation, the ECS and pain management and the critical role it plays in helping to regulate and maintain our overall health and wellbeing.

THE ENDOCANNABINOID SYSTEM – What is it?

Here is a brief ECS introduction: The Endocannabinoid System (ECS) helps in maintaining equilibrium amongst many of the different functions and systems within the human body. The ECS consists of a network of receptors that are activated by cannabinoids. What are cannabinoids? Cannabinoids that are created within the body are known as endocannabinoids. Cannabinoids created by plants are known as phytocannabinoids. The ECS is responsible for cannabinoids’ interactions with neurotransmitters.

While many discoveries regarding this system have been made, including the biphasic relationship between the ECS and our immune system, the ECS and inflammation, the ECS and mood regulation and the ECS and pain management, there is still much research to be done to fully understand the ECS and its role in regulating homeostasis within the body. The first cannabinoid receptor and endocannabinoid were not discovered until the late 80s and early 90s respectively, thus our scientific research regarding how cannabinoids’ interact with neurotransmitters is a little understood aspect of human health and is still in the early stages. To date, there are over 120 known endocannabinoids being studied.

The ECS is responsible for regulating many of the body’s natural functions due to the relationship between the ECS and our immune system, the ECS and inflammation, the ECS and mood regulation and the ECS and pain management through activating endocannabinoid receptors found throughout the body, primarily concentrated in the brain, spinal cord, and immune system. Endocannabinoid receptors can also be found in the digestive tract, reproductive system, lungs, kidneys, liver, pituitary and thyroid glands, fat cells and muscle cells. Cannabinoids’ interactions with neurotransmitters throughout the body can be beneficial in various ways. 

The exact systems and mechanisms for regulation are still being explored, however the ECS plays a role in controlling the body’s immune system, appetite, pain, inflammation, mood, body temperature, memory, reproductive health, and sleep cycle regulation.

REGULATORY FUNCTIONS & EFFECTS OF THE ENDOCANNABINOID SYSTEM

Cannabinoids can stimulate/increase appetite.

Cannabinoids can block signals in the body that trigger nausea and vomiting.

Cannabinoid receptors in the brain are capable of suppressing pain signalling.

Cannabinoids have the potential to produce feelings of relaxation and euphoria. They can also reduce feelings of anxiousness and worry.

THC can lower body temperature. The ECS also plays a role in the body’s immune response to ward off infection.

Cannabinoid receptors are highly concentrated in areas of the brain responsible for regulating memory and learning.

Phytocannabinoids can potentially disrupt and lower the production of estrogen and progesterone in women.

Some cannabinoids can be sedating, specifically THC, which shares structural similarities to anandamide, an endocannabinoid that can affect sleep patterns.

While the initial research regarding the ECS began with the focus of studying the effects of cannabinoids from cannabis on the body, the discoveries that followed have exposed a need to better understand the natural functions of the ECS that occur independently from the introduction of phytocannabinoids like the relationship between the ECS and our immune system, the ECS and inflammation, the ECS and mood regulation and the ECS and pain management. Among the most interesting areas of current study is the research regarding endocannabinoid deficiency or dysfunction, and the potential implications this might have for a variety of common and difficult to treat chronic conditions.

UP NEXT – In the next segment of our series covering the Endocannabinoid System, we will be discussing the endocannabinoid receptors of the ECS, including what are CB1 and CB2 receptors. We will take a closer look at these receptors, their locations, functions, and signalling processes.

We pride ourselves on being one of India’s most qualified sources of fast, friendly, and professional access to ayurvedic medicine online!

The Savikalpa Journal

The Importance of 2 Arachidonoylglycerol (2-AG)

Homeostasis and the Endocannabinoid System

Understanding Endocannabinoid Receptors

An Introduction to the Endocannabinoid System