What is microdosing cannabis and why do it

What is microdosing cannabis and why do it

The medical benefits of cannabis (and its active ingredients like THC and CBD) are hard to deny. So if cannabis is working well for your medical conditions, you might think that the more cannabis you take the better it will work at relieving your symptoms. But is this true? In the midst of a cannabis market with increasingly potent cannabis options, some are choosing a different route. Instead of increasing their cannabis intake they are scaling it back with something called “microdosing.” What is Microdosing?  Microdosing is the practice of taking a much smaller dose of a medication than is normally used. It’s a practice used with all kinds of compounds, but most often discussed with psychoactive substances such as LSD. Recently people have started to apply the practice to cannabis and its popular ingredients, THC and CBD. View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy) One recent clinical trial found that microdosing just 1 mg of THC, and even 0.5 mg, was effective at relieving chronic pain. One reason for microdosing cannabis is that taking a small amount may help to access it’s helpful effects without engaging negative side effects like a psychoactive high. But microdosing cannabis is also helpful for those who are trying to avoid triggering the wrong side of something called a biphasic effect.  To explain this simply, when a substance (like THC) has a biphasic effect, it means that it can produce two opposing effects — depending on the dose of the substance taken. Consider, for example, alcohol, which at low doses might make someone feel a bit energized, happy and chatty — but at high doses might leave them sedated, depressed and antisocial.  For many substances, these biphasic effects are important because the dose taken can drastically impact the effect it has on the human body. And with cannabis, multiple biphasic effects have been noted.  Cannabis’ Biphasic Effects Cannabis’ two most common and popular ingredients, THC and CBD, have been noted to have a variety of biphasic effects. One of the most commonly reported biphasic effects from cannabis is THC’s effect on anxiety. While many report cannabis can help ease their anxiety, others say that it makes them more anxious and paranoid. The science supports these claims, showing that dosing can make a big impact on how cannabis and its components affect anxiety. Studies on both animals and humans have found that while lower doses of THC tend to relieve anxiety, higher doses can spike it.  For example, in one animal study, mice given low doses of THC spent more time in open areas than controls (an indication of reduced anxiety), while those given high doses of THC spent less time in these stressful spaces (suggesting increased anxiety).  In one human study, a group of 42 patients were given a placebo, a low dose of THC (7.5mg), or a high dose of THC (12.5mg). Then they were subjected to various stress inducing tests and asked to rate their stress. Those in the low THC group showed reduced stress during these tests, but those who had the higher dose were more likely to have increased stress.   In another human study, a group of incarcerated patients with PTSD were given even lower doses (4mg) of the synthetic cannabinoid Nabilone, which mimics THC’s effects. Researchers found this low dose resulted in significant improvement in PTSD associated insomnia, nightmares, general symptoms, and even chronic pain. Still despite success treating anxiety conditions at these lower doses, the average dosing for cannabis products is around 10mg — which might be too high for some. And it’s not just anxiety that can benefit from microdosing. Biphasic effects from THC have been noted for pain, temperature regulation, motivational processing, appetite, novelty seeking, and locomotion and exploration. Biphasic responses have also been found for CBD with effects like pain, sedation, nausea and vomiting relief, and immune responses.  For many of cannabis’ effects — a lower dose might be the most effective option.  How to Microdose Cannabis Microdosing can be very helpful for some, and the research on biphasic effects suggests it could be particularly helpful for patients dealing with pain, appetite, energy or mood related issues like anxiety and depression. As we’ve seen above, all of these issues are common reasons for cannabis use that have strong dose-dependant biphasic reactions. So microdosing can be a great way to hone in on an optimal dose.  With microdosing, patients are advised to use the smallest dose that they can, which might be a small puff with an inhaled method like smoking or vaping, or a dose around 2.5mg for edibles or sublingual options.  There are few downsides to microdosing cannabis (when compared to taking larger doses) in terms of risk factors, but for some microdosing might not be the best option. Some patients actually do need a larger dose to effectively manage their condition. Take for example, studies on migraines, which show that relief is usually achieved only after high doses (around 20mg). Still, in the process of finding the optimal dose, starting with microdosing can be helpful. By starting low, patients can slowly increase their dosing to find an optimal dose. As they go up, they may find that the symptoms they are treating improve. But at a certain point, if they continue to increase, they are likely to hit a dose where the cannabis is actually causing negative symptoms. If this happens, they can return to the last dose that relieved their symptoms. For some, a microdose may actually be the most effective option. This is important because there can be big differences in how individuals respond to cannabis. In addition to condition related differences in the cannabis needed, there are also differences in how sensitive individuals are to the effects of cannabis because of genetic differences and differences in previous cannabis experience (which can make you tolerant to its effects). So an optimal dose for one patient might be 2mg while for another patient it might be more like 20mg. Either way, if you aren’t sure what your optimal dose is, starting low and slowly increasing is the best way to find out.  If you think microdosing cannabis might be right for you, talk with a practitioner who specializes in cannabinoid medicine. They can help make sure you are on the right track before you begin or change any cannabis regimen.    This article was originally published on The Cannigma, and shared here with permission.

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What is CBG?

What is CBG?

CBG (cannabigerol) is by far one of the most important cannabinoids in the cannabis plant. It is often called “the mother of all cannabinoids,” and it holds potential as a treatment for conditions such as diabetes, ALS, and Huntington’s disease, although human studies are seriously lacking. In addition to its potential medical applications, much like CBD, CBG is not considered intoxicating and will not get you high.  Many of the more popular and well-known effects of THC and CBD are derived from their interaction with the endocannabinoid system. CBG, however, mainly works through other mechanisms, which explains why it has such different effects. It is currently being researched as a treatment for a long list of conditions, such as dementia, PTSD, ADHD, Huntington’s disease, ALS, Parkinson’s disease, multiple sclerosis, diabetes, colitis, and of course, pain.  But it’s important to note that when it comes to CBG the word “potential” is of essence. Most of the evidence scientists have found regarding the efficacy of CBG is based on animal models, so it’s too early to say whether they are relevant for humans. And unlike THC and CBD, there’s practically no scientific information about the safety or dosing of CBG-dominant products.  Why is CBG so popular?  First isolated by Rephael Mechulam and Yehiel Gaoni in 1964, CBG is often referred to as “the mother of all cannabinoids,” suggesting that it is superior to other cannabinoids.  One of the reasons marketers often refer to CBG as “the mother of all cannabinoids” is to make it seem as if it is responsible for the benefits of the other cannabinoids, but at this time there is little science to suggest that.  What the “mother of all cannabinoids” really means is that CBGA is produced first by the plant, then is converted to other cannabinoid acids. So really, CBGA is responsible for the creation of THCA, CBDA, and CBCA because the plant needs CBGA to make them. This is important for scientists researching the plant, but does not mean it is superior therapeutically.  In fact, CBG usually occurs in much lower concentrations than other cannabinoids like THC and CBD — typically around 0-1% in a cannabis flower. With the hype surrounding CBG in the past few years, however, breeders have been developing CBG-dominant varieties, and companies are producing a multitude of products such as CBG oils and flowers.  It is important to note that research on the safety of CBG dominant products is remarkably scarce. It is possible that much of the hype about CBG is the result of a regulatory loophole that makes hemp-derived products accessible and legal. CBD has been a huge success in the wellness market, and though CBG is often proposed as its heir, there isn’t much to it yet from a scientific perspective. CBG vs CBD  Which is better, CBG or CBD? The answer depends on what you’re trying to achieve. CBG binds to different receptors that can produce a variety of effects in the body. For some conditions, like hypertension, CBG shows potential benefits that CBD doesn’t. In other cases, like controlling seizures, CBD is helpful while CBG isn’t. Still for other symptoms, like inflammation and pain, both CBD and CBG work on the same targets and can have similar effects. It really depends on what you’re trying to achieve. Unlike CBD, however, research on the safety and efficacy of CBG is practically non-existent. CBD products are often sold as dietary supplements due to a regulatory loophole, but CBD — albeit far from being fully understood — has been heavily studied for its safety and efficacy in a variety of symptoms and conditions. CBG products are accessible through the same regulatory loophole, but there’s not enough research to assess the safety and efficacy of CBG dominant products, especially when it comes to drug interactions.  How does CBG work? Unlike THC, which primarily interacts with the receptors of the endocannabinoid system, CBG produces most of its effects by binding to other families of receptors such as TRPs and the PPARs. This is important because it is one of the reasons CBG can produce such different effects than THC. Some of the receptors CBG interacts with are of interest for treating neurodegenerative and metabolic conditions, but others could actually cause drug interactions with medications that treat conditions like depression. The research on how CBG works is still ongoing and is fairly complex, but here’s a simplified review of what science knows.  CBG and the PPARs The PPARs (short for Peroxisome Proliferator-Activated Receptors) are a group of receptors with three main types  — PPAR alpha, gamma, and delta. PPAR-gamma plays a crucial role in the functioning of the nervous system and is also involved in the mechanisms of conditions such as diabetes and obesity. In fact, pharmaceutical companies have produced medications designed to treat diabetes (type II) that work on this receptor, but the drugs have been associated with serious side effects. CBG is suggested to be an agonist (activator) of PPAR-gamma, which may explain its potential role in treating neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and its potential for treating metabolic diseases like diabetes and high cholesterol.  CBG and the alpha-2 adrenoceptor  CBG is a potent agonist (activator) of alpha-2-adrenoceptor, which means it could potentially have utility as an anti-hypertensive, sedative, and analgesic. It could also play a potential role in improving impaired prefrontal cortex functioning, which is relevant for conditions such as ADHD, tic disorders, PTSD, and dementia. While all of this is exciting, it’s important to note that researchers’ understanding of this mechanism is still very limited, and CBG has not formally been tested for any of these conditions. All existing research on CBG is preliminary and based exclusively on animal models or lab studies done in test tubes. It is not yet clear to scientists exactly how CBG interacts with the three different types alpha-2 adrenoceptors, known as subtypes. As a consequence, the effectiveness of CBG for these conditions remains unknown. In addition, it is not known if CBG produces adverse effects related to the alpha-2 receptors such as changes in blood pressure, sedation, or interactions with other cardiovascular medications. How CBG works with TRP receptors  The TRPs (Transient Receptor Potential) are a large and diverse family of receptors that are usually involved in sensing and feeling changes in temperature. TRPs can interact with phytocannabinoids like THC and CBD, and other plant chemicals like capsaicin and menthol. The importance of these receptors are still being studied, but CBG can activate some of them to various degrees (TRPV1, 2, 3, and 4 and TRPA1) and block others (TRPM8). Some of the activities are similar to the way CBD interacts with these receptors, and may explain how CBG could potentially help with chronic pain, inflammation, and skin health.  CBG’s interaction with serotonin You may have heard of serotonin, an important neurotransmitter that plays a role in regulating functions such as mood, happiness, sleep, and hunger. Serotonin is particularly well known for the role it plays in conditions like depression and the group of SSRI (selective serotonin reuptake inhibitor) medications that influence it. One of many receptors serotonin binds to is 5-HT1a, with which many endocannabinoids and phytocannabinoids like CBD and CBG also interact. CBG is a potent antagonist (blocker) of 5-HT1a, which means it could easily alter the effects of other psychiatric medications.  However, the way CBG influences serotonin hasn’t been properly studied. Some researchers fear the potential dangerous consequences of high-CBG products being available to the public before its drug interactions and effects are better understood. How CBG works on cannabinoid receptors CBG can bind to the two main cannabinoid receptors (CB1 and CB2), but this interaction seems to be somewhat weak and produce complex pharmacological effects. GPR-55, a receptor that is increasingly being called a “potential CB3 receptor,” but currently there’s no knowledge about the activity of CBG on that receptor. The benefits of CBG CBG presents a rich pharmacological profile that could potentially have a lot of benefits for neurodegenerative conditions like Huntigton’s disease, ALS, Parkinson’s disease, and MS. It may also be of great benefit in inflammatory conditions like colitis, and also for metabolic conditions like diabetes and obesity. Once again, it’s extremely important to note that CBG research is still in its infancy and is very limited. Scientific evidence of its efficacy and safety in humans is practically non-existent. The best way to use the following information is when trying to find the right strain for you. If CBG shows potential for the condition you’re treating, it may make sense to prioritize cannabis products with some CBG. However, unless prescribed by a health care professional that specializes in cannabis therapy, you should avoid using CBG-dominant products such as CBG oil in order to avoid potential contraindications and drug interactions.  The potential of CBG as a neuroprotector CBG is currently being studied as a potential treatment for neurodegenerative conditions such as Huntington’s disease, ALS, Parkinson’s disease and multiple sclerosis. Scientists believe the neuroprotective properties of CBG (but also CBD) are mediated mainly through their interaction with the PPARγ receptor (which is not technically part of the endocannabinoid system). CBG and Huntington’s diseaseResearch on CBG as a treatment for Huntington’s disease shows it could be beneficial in preventing striatal neuron death (one of the main symptoms of Huntington’s disease), reducing inflammation, and improving motor activity. Some studies were more promising than others, and even more important — the studies were done in cell cultures or in animal models and have yet to be examined on humans. CBG and ALSIn a 2018 study, a derivative of CBG (called VCE-003.2) was able to improve neuropathological symptoms, and delay the progression of ALS in mice. Applicability in humans is still unclear, but PPAR-gamma and antioxidant effects were thought to be responsible. CBG and Parkinson’s diseaseUsing the same CBG derivative, the authors of another 2018 study were able to reduce three types of inflammation associated with Parkinson disease in mice. Again, this study was in mice and it’s unclear if this translates to humans. CBG and MS (multiple sclerosis)A 2012 study that looked at the potential of a CBG derivative in the treatment of Multiple Sclerosis concluded that it could potentially treat MS related inflammation in the central nervous system and help restore motor function impairment. Once again it is thought that CBG does this by reducing inflammation and preventing cellular damage as an antioxidant, but for now we only know that it’s effective in mice. CBG could help with gastrointestinal disease CBG and colitisA 2013 study on CBG for inflammatory bowel diseases concluded that “CBG may represent a new therapeutic opportunity in IBD.” The researchers suggested that CBG could be effective in preventing and treating colitis. A 2020 study examined the efficacy of CBG vs CBD for treating colitis in mice, finding that CBG was effective but CBD was not. The scientists then compared CBG and fish oil, CBD and fish oil, or all three together, and found that CBG combined with fish oil was more effective than CBD and fish oil, and that all three together were the most effective.  CBG and chemotherapy associated weight loss and loss of appetiteThere are studies showing CBG can increase appetite and reduce weight loss associated with chemotherapy, although in an earlier study CBG didn’t demonstrate any impact on appetite. So the jury is still out when it comes to appetite and CBG. One of the reasons this is an interesting research direction is because unlike THC, which is being looked at as a therapy to help with weight loss, CBG won’t get you high. CBG for diabetes and hypertension Diabetes and hypertension play a leading role in metabolic syndrome, a condition that affects up to one-third of adult Americans. Metabolic syndrome is described as a combination of elevated glucose, obesity, hypertension, and high cholesterol, and CBG shows signs as a potential treatment for both insulin resistance and hypertension. Although the evidence is preliminary, it seems to be very promising.  HypertensionCBG is currently the only cannabinoid known to activate alpha-2 receptors, which could mean that it has a role in treating high blood pressure.   Insulin resistanceA 2020 study showed that CBG, and the combination of CBG and CBD, could potentially increase insulin sensitivity. This makes sense given that CBG is an activator PPAR-gamma and there are already FDA approved drugs with this same mechanism for treating diabetes. How to use CBG There is great potential for CBG’s therapeutic uses, but science has a long way to go before we’ll have reliable information on how and when to use CBG products. Whether it is CBG oil, CBG cannabis flower, or any other CBG-dominant product, you should be cautious. Particular caution should be used if you take prescription medications, as CBG’s potential drug interactions, dosing recommendations, and contraindications are still being investigated.  Many marijuana chemovars on the market today have varying levels of CBG. If you already have a cannabis regimen for one of the conditions that could be helped by CBG (Huntington’s disease, ALS, Parkinson’s disease, MS, etc ) it would make sense to seek out products or strains that have at least some CBG. However, unless you’ve consulted a healthcare professional with cannabis expertise, you should probably avoid products in which CBG is the primary active ingredient. With the potential to treat a lot of incurable and burdensome conditions, cannabigerol is indeed one of the most interesting cannabinoids out there. However, for now the research is still too limited for good guidance surrounding its use. Until its safety and efficacy are more properly understood, you may want to wait before jumping on the CBG bandwagon.   This article was originally published on The Cannigma, and shared here with permission.

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Is 2-AG the most important endocannabinoid?

Is 2-AG the most important endocannabinoid?

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: regulating hunger mediating inflammation moderating mood reducing pain 2-AG and food intake 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. 2-AG and nervous system inflammation 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, by 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 2-AG and anxiety  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. 2-AG and depression 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. 2-AG and addiction 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. 2-AG vs AEA vs THC 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. 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 2-AG and the entourage effect 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 Sources: 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 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 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 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 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 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 Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17 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 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 Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17 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 Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17 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 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 Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17 Ueda N, Tsuboi K. Discrimination between Two Endocannabinoids. Chemistry & Biology. 2012;19(5):545-547. doi:10.1016/j.chembiol.2012.05.001 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 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 Yang, R., Lu, Y., & 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. 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     This article was originally published on The Cannigma, and shared here with permission.

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How to fit CBD products into your alternative health regimen

How to fit CBD products into your alternative health regimen

Hemp and cannabis-derived medications may not be quite as mainstream as apple pie or multivitamins, but the days in which it was an almost completely illegal plant with little if any recognized medical benefits seem like a distant memory. Countless people now use CBD and other hemp-derived products as part of a prescribed medical regimen, as a daily health supplement, or just a go-to panacea to make the stress of daily life a little bit easier to manage.  Part of a natural, alternative lifestyle While many health conditions can be treated with more traditional pharmaceuticals, plant-based products may be a safer and healthier option – or at least a safe health supplement. For instance when it comes to pain relief, THC and CBD have shown to be safer than opioids; and for anti-anxiety and sleep aids, CBD does not appear to be habit-forming like benzodiazepines. These natural alternatives may also be effective as part of a daily “microdosing” regiment. This can mean taking a small amount of THC each day — for instance in the form of an edible — just to take the edge off and not to get intoxicated.  That doesn’t mean that CBD or other cannabis products should be seen as a cure all on their own. Rather, they should be considered part of a wider, holistic approach to healthy living, and the perfect accompaniment to other wellness steps, such as:  Getting a good night’s sleep  Staying up late and binging Netflix once you finally have some time to yourself is great fun, but it can come at a cost. Getting a good night’s sleep is a crucial step in leading a healthier lifestyle, and the benefits can be felt throughout the day.  The problem is, things often get in the way, and not just Netflix. Anxiety can make you restless, and before you know it you have to get up for work in three hours and you haven’t slept a wink.  With or without the potential anti-anxiety effects of CBD, making sure that you find a way to tune out the background noise and hit the sack at a reasonable hour can pay huge dividends when it comes to your health.  Meditation and mindfulness  Research has found that meditation can potentially have a variety of health benefits, including lowering blood pressure, reducing anxiety and depression, and may even provide some relief from conditions like irritable bowel syndrome and ulcerative colitis. Meditation can also help people focus themselves on the here and now, away from anxieties about the present and regrets of the past.  Many turn to cannabis for relaxation, alongside this natural therapy, though some people find that if they have consumed THC, the intoxicating effects can be too distracting when trying to meditate.  A healthy diet  What we put into our bodies is of crucial importance for our health. And this doesn’t mean just trying to steer away from tobacco or alcohol. It’s more about making sure you have a balanced diet that includes a wide range of fruits, vegetables, and grains, and doesn’t lean too heavily on carbs, sugar, and anything that’s deep fried and/or dusted in sugar.  That doesn’t mean you can’t cheat at times (or often, even), but making sure you eat right can make a huge difference in how you feel – even if you aren’t taking any supplements whatsoever.  Less screen time couldn’t hurt It’s nearly impossible to completely unplug these days, but if you spend every evening glued to your smartphone in bed, you’re going to have a harder time getting a good night’s sleep. The constant distractions, notifications, and social media outrages of the day can also boost your anxiety and stress, and make it much harder to just live in the moment. Reducing your screen time and finding a way to spend more time offline is a natural, drug-free way to boost your mental health. How CBD and cannabis products can help In recent years, cannabis has been the subject of a tremendous amount of scientific research, and in 2020 there was a record number of scientific studies published on cannabis.  While more human clinical trials are needed, the current evidence suggests there may be potential therapeutic benefits for the following ailments: Chronic pain —  the most common reason people turn to medical cannabis in the United States today. Both THC and CBD rich products may help those suffering from pain lasting several months.  Nausea and vomiting — cannabis has long been seen as a potential supportive treatment option for cancer patients undergoing chemotherapy. Cannabinoids may ease nausea and vomiting. Pharma has successfully isolated and recreated THC for chemotherapy-induced nausea and vomiting called Marinol, an FDA-approved drug available as a prescription.  Loss of sleep or insomnia — THC-rich cannabis products may help people fall asleep by addressing some of the underlying conditions, while the potential anti-anxiety effects of CBD helps people to shut out the noise and get some shut eye.  Inflammation — both THC and CBD have been shown to help reduce inflammation in conditions like multiple sclerosis, rheumatoid arthritis, and irritable bowel disease. It’s worth noting that folks may experience pain relief simply by taking the inflammation away. For people who are recommended to use cannabis by a medical professional, the regimen may likely include a stepwise approach in figuring out your sweet spot, or the lowest effective dose.  If you’re navigating this on your own, the best rule of thumb is to start low with the THC amount (around 2.5mg) and work your way up slowly until you find the dose that works best for you.  And it should go without saying that cannabis should not be used to replace prescription medication or potentially life-saving medication, and consumers should contact a healthcare  professional before making any decisions about their medication. How CBD and cannabis products work  It was only in the 1990s that researchers discovered the endocannabinoid system (ECS), a communication system which affects all types of functions in the body, from sleep to hunger to pain, to name just a few. The receptors of the system can be influenced by chemicals in cannabis known as cannabinoids — the two most well-known being THC and CBD.  By interacting with the receptors of the ECS, cannabis modulates the bodily functions that cause or exacerbate health conditions. Furthermore, some researchers believe that health conditions like migraines or fibromyalgia, among others, may actually be the result of endocannabinoid deficiencies.  Types of cannabis products  There is a truly bewildering variety of cannabis products today, but many of them fall under three categories: inhalation, oral, and topical.  Inhalation includes cannabis flowers that are smoked or vaped, or concentrated like shatter, wax, or oils that are vaporized and inhaled. This method is the most popular, and is very simple and straightforward, with an almost immediate onset.  Oral includes edibles like gummies or chocolates, as well as tinctures, beverages, or capsules. This method is preferred by those who don’t want to or can’t smoke or vape, but it is also an easy way to microdose or to stick to a set dosing regimen. The onset depends on the type of edible (typical gummies can take up to an hour, while nano emulsified beverages can work much quicker), but it can take more than an hour. In addition, edibles produce a very different sensation than other intake methods, which many consumers prefer.  Edibles like Dimer illustrate how this works. Dimer is a hemp-derived, full-spectrum edible that provides a generous serving of 75mg CBD, 6mg of THC, 1mg of CBG, and 5mg of CBC in every “calming caramel.”  Each individually wrapped piece can easily be portioned up for microdosing or times when you don’t want a whole piece. Keep in mind that this is not your average CBD product; 6mg of hemp-derived Delta-9 THC per serving can be a high dose for new consumers, or people that are usually sensitive to cannabis. Depending on your tolerance to THC, this can be a good accompaniment if you’d like to relax during your daily routine. Topicals include balms, savles, lotions, and patches, which are applied directly to the skin. Used to help with skin conditions like psoriasis or eczema, topicals can also help ease muscle aches and soreness, and may be a therapeutic alternative for relief  without the use of prescription medication. That said, because topicals don’t penetrate the skin deep enough to enter the bloodstream, they are best used for localized areas and can be a great add-on to the other form factors for that dose layering effect.  Why CBD and THC can work so well together  Edibles like Dimer that have a high CBD content along with the THC may actually enhance the effectiveness of both cannabinoids. The cannabis plant is thought to have  more than 140 cannabinoids, along with 150 plus terpenes that provide the aroma and flavor of plants. Isolated on their own, each of these cannabinoids and terpenes may have unique, therapeutic effects. But when taken together, these chemicals are thought to work greater in concert.  Scientists have dubbed this synergistic relationship “the entourage effect,” and this hypothesis is behind the drive for products that are full spectrum or whole spectrum. The rationale being that if these various chemicals work better together, then it makes more sense not to develop isolates for specific cannabinoids or terpenes, rather, products that include a whole symphony of natural compounds working together. Take for instance how CBD and THC interact. THC has shown to provide great relief for pain or nausea, but many people may find that THC by itself can be dysphoric. CBD counters the unpleasant  “high” caused by THC, and may even help people “come down” when they get too high. In addition, CBD may  potentially alleviate some of the adverse effects associated with  THC, such as paranoia or anxiety.   CBD is generally well-tolerated, but it is not without side effects. Some people may experience nausea, drowsiness, dizziness, or changes in appetite. Similar to the effects of CBD on the intoxication of THC, THC may even help counter some of the side-effects with CBD – suggesting that a whole plant product with multiple chemical constituents is better than the constituent alone. Tips on how to dose with hemp products  When trying out hemp products, seek out products that include a full list of the ingredients, as well as a certificate of authenticity and lab results that indicate the full makeup of the cannabinoids, terpenes, and the presence of any contaminants.  Furthermore, when starting any wellness regimen, it’s best to take things slow, especially if you are not under the guidance of a healthcare professional.  If you’re using edibles, find products that include a clear quantifier of CBD and/or THC (and other cannabinoids) per serving, and which can easily be parcelled up for smaller or larger doses. This will help you make sure you get a consistent dose each time, and should help stave off any surprises.  And while CBD hemp-derived products are generally considered safe (depending on the production methods), always err on the side of caution, especially if other medications or supplements are involved. If you are taking  prescription medications, be sure to talk to a healthcare professional to ensure there are no adverse interactions in combination.. Check that they don’t contain any allergens or other components that you cannot consume. Perhaps most importantly, listen to your body. While these products seem to work great for many people, if you are feeling any discomfort, dysphoria, or other adverse side effects like nausea, vomiting, or diarrhea, immediately consult with a healthcare professional who can advise you further.  View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)   This article was originally published on The Cannigma, and shared here with permission.

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How cannabis can treat inflammation

How cannabis can treat inflammation

Overview There is scientific evidence suggesting that cannabis can reduce inflammation and may be able to help treat conditions that are either caused by inflammation or have it as a key symptom, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and hepatitis. Still, some research suggests cannabis can also increase inflammation in certain circumstances.  The body’s endocannabinoid system plays a role in regulating inflammation responses — which is how cannabis is able to have inflammation modulating effects. Unfortunately, current research is lacking information on how to best utilize cannabis as a treatment for inflammation. Research on inflammation and cannabis Cannabis has been used for inflammation throughout the ages. As far back as the 1st century, Roman philosopher and commander Pliny the Elder recommended using cannabis for the inflammatory condition gout. In modern times, we know from animal studies that cannabis has strong anti-inflammatory properties, and many humans use cannabis to relieve symptoms of inflammatory conditions like rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and hepatitis. In experimental models of rheumatoid arthritis (RA), cannabis’ anti-inflammatory effects have been shown to protect patients from the progression of the disease by reducing inflammation in the body. In one double-blind study on cannabis for RA patients, researchers found that cannabis not only relieved pain for these patients, it could also suppress the inflammatory activity of the disease.  Studies also show cannabis can help with multiple sclerosis (MS), in part by reducing inflammatory chemicals like cytokines produced in the body. In eight separate clinical studies, MS patients given cannabis reported improvement in symptoms and did better on objective measures like handwriting and bladder control tests.  Studies on inflammatory bowel diseases (IBD) like Crohn’s disease and colitis, have also shown some potential for treatment with cannabis. Animal studies show that cannabis’ active ingredients are capable of modulating the kind of inflammation in the GI tract that we see in IBD. Survey based studies on IBD have also found that cannabis can relieve its symptoms. Indeed, marijuana is an approved therapy for IBD in most jurisdictions where it is medically legal.  In human studies, including one placebo-controlled study, researchers have found that cannabis use was associated with improvement of disease activity in Crohn’s disease and reduction of other medications. Unfortunately, one study also found that cannabis use is associated with greater risk of requiring surgery for Crohn’s disease — which complicates our understanding of cannabis’ impact on this condition.  Cannabis may also help reduce viral infection related inflammation — in some cases also reducing the overall death rate. In animal studies, cannabis’ active chemical THC was able to protect mice from hepatitis, by reducing inflammatory responses. Some studies also showed it could help reduce risk of sepsis (a dangerous inflammatory response that can occur with infection) and even improved recovery rates for infections like malaria. But importantly, in other animal experiments, cannabis use decreased survival rates for influenza.  Other studies show cannabis’ inflammatory reductions may help reduce the growth of certain cancers that are triggered by chronic inflammation. CBD and inflammation Inflammatory relieving properties have also been found for CBD, a medicinal chemical found in cannabis which doesn’t cause the kind of psychotropic high we see with THC. For example, in animal models of rheumatoid arthritis, CBD stopped the progression of arthritis, while also relieving symptoms like pain.  There is also animal research suggesting that CBD can reduce inflammation in the gut Still, in one study, low dose CBD (unlike THC) did not show any impact on the progression or symptoms of Crohn’s disease.  That said, one review of the literature found that CBD could be a helpful treatment for inflammatory conditions, because it can stop or slow inflammatory factors like the production of cytokines.  Other studies looking at CBD’s effects on inflammation suggest that it may be particularly helpful for certain cardiovascular disorders, inflammatory bowel diseases, rheumatoid arthritis, types 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain. How cannabis works on inflammation  The endocannabinoid system (ECS) exists in all vertebrates and helps regulate crucial functions such as sleep, pain, and appetite. The human body produces its own cannabinoids, which modulate and activate its various functions, but as its name suggests, the endocannabinoid system can also be modulated and activated by cannabinoids found in the cannabis plant. Because the entire system was only discovered in the past 30 years, scientists still have much to learn about the myriad ways cannabis affects the human body. When it comes to modulating inflammation, cannabinoids mainly work by stimulating the ECS’ primary receptors, CB1 and CB2, along with lesser known receptors associated with the system. Our bodies’ natural cannabinoids, like anandamide and 2-AG, play an important role in these inflammatory effects, signaling increases and decreases in inflammation via these receptors, but external cannabinoids from cannabis can also stimulate these functions. When cannabinoids stimulate the ECS receptors, they cause a number of anti-inflammatory effects, such as reducing cytokine and chemokine production (which are markers of inflammation), increasing T-regulatory cell activity (which suppress inflammatory responses).  Still it’s notable that while cannabinoids can reduce certain inflammatory factors, they can increase others, in some cases worsening inflammation. For example, in one study, levels of an anti-inflammatory cytokine decreased and a pro-inflammatory cytokine increased in response to THC. Some researchers say this suggests different types of cells may respond differently to cannabinoids when it comes to inflammation.  In addition, some research has indicated cannabinoids may impact inflammation through routes other than receptor stimulation as well. But more research is needed to fully understand these alternative mechanisms. Using cannabis for inflammation If you are using cannabis for the treatment of inflammation, the best first step is to talk to a doctor who specializes in cannabinoid medicine. Because inflammation is a symptom present in a variety of conditions that have different factors to consider, the best way to utilize cannabis for inflammation may differ with each condition. Your treatment should be tailored to your specific condition — rather than inflammation in general.  Still, the research is fairly limited when it comes to specifying how to best utilize cannabis for inflammation with any of these conditions. The research above includes studies using a few different methods for taking cannabis, including inhalation, oral ingestion, and rectal suppositories. Studies also show that cannabis can reduce inflammation when used topically. But there have yet to be comparisons on whether any methods outperform the others in terms of treating inflammation. Similarly, the studies above show cannabis’ main compounds, THC and CBD, are both able to reduce inflammation — separately or in combination with each other — but don’t tell us whether one or the other might be superior in creating these effects. Potential side effects of cannabis use Cannabis can also have side effects — particularly high-THC cannabis. These may include temporary psychoactive effects such as mental confusion, lightheadedness, euphoria, anxiety, and slower cognitive skills; or uncomfortable physiological changes like, coughing, allergies, dry mouth and eyes, increased appetite, heart palpitations, and drowsiness.  For inflammation treatment, it’s also important to note that while cannabis often reduces inflammation, some research has shown its ability to increase inflammation as well. In addition, there is a worry from some researchers that cannabis’ pain relieving properties might mask ongoing inflammation.   View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)     This article was originally published on The Cannigma, and shared here with permission.

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How cannabis affects your memory

How cannabis affects your memory

The main active chemical in cannabis, tetrahydrocannabinol (THC), may have a negative impact on short-term memory. Some research even points to memory issues and changes to the brain for longer-term cannabis users. Still, the data also suggests that using cannabidiol (CBD) can reverse or prevent these issues — and that both CBD and THC may have big potential benefits for those suffering from Alzheimer’s disease.  Cannabis has a wide range of medicinal and wellness-enhancing benefits, but many worry about its possible impact on memory. These worries are not unfounded, the research suggests, but the picture isn’t entirely negative either. How cannabis interacts with memory To understand how cannabis interacts with memory, we first need to understand how cannabis interacts with the body as a whole — through the endocannabinoid system. This system, found in humans as well as all other vertebrates, is always at work in the body but also interacts with cannabinoids found in the cannabis plant. The endocannabinoid system as a whole is tasked with maintaining homeostasis or balance in the human body. To do this, it regulates a number of bodily functions such as sleep, hunger, energy, temperature, pain, and immune function. Importantly, it also helps to regulate our processes surrounding memory and learning.  There is strong evidence that the endocannabinoid system is involved in regulating memory, and in particular, that the cannabinoid receptor CB1 is important to this process. Both animal and human studies have found that activating CB1 with the endocannabinoid anandamide — as well as THC and synthetic versions of THC — can cause deficits in short-term memory.  In animal studies, both rodents and squirrel monkeys performed worse on spatial learning tasks when CB1 was activated. Researchers were able to reverse this effect with the drug rimonabant, which deactivates CB1 activity, adding further evidence that CB1 is involved. Some researchers have hypothesized that this effect is due to the high density of CB1 receptors in the hippocampus, which is also involved in memory tasks.  The benefits of marijuana for memory When it comes to cannabis’s effect on memory, the evidence suggests it may be detrimental or beneficial depending on a number of factors. On the beneficial side, there is a growing body of evidence pointing towards cannabis as a potential treatment for Alzheimer’s Disease.   In the study of Alzheimer’s, one of the primary hallmarks of the disease is the accumulation of toxic beta-amyloid plaques, which build up in the brain outside of neurons. This kills off neurons, leading to severe cognitive impairment and problems with memory. But research suggests that cannabis, particularly its active cannabinoids THC and CBD, may be able to help slow the progression of Alzheimer’s Disease by reducing the levels of beta-amyloid in the brain, as well as improving other important factors related to the disease.  In one study, for example, researchers found that THC is able to lower levels of beta-amyloid in the brain and prevent it from accumulating in the brain, by interacting with beta-amyloid peptides. It was also able to reduce GSK-3 (another important marker for Alzheimer’s Disease), and enhance mitochondria function, which is dysfunctional in Alzheimer’s Disease.  A small human study on 11 patients using THC to treat the symptoms of Alzheimer’s disease found that it was safe and well tolerated. Patients who used it for four weeks had significant reductions in delusions related to the condition, as well as improvement in aggression, irritability, apathy, sleep, and caregiver distress.  Synthetic THC hasn’t been shown to perform as well, however. Two trials using synthetic THC found that while it was safe and well-tolerated, it did not offer patients any significant therapeutic effect.  Studies looking at CBD have also found positive results. A review of existing research including human, animal, and lab studies found that CBD protected cells from beta-amyloid toxicity, increased cell survival, and encouraged new neuron growth in the hippocampus — as well as improving other factors involved with Alzheimer’s Disease. The researchers also found that when THC and CBD are used together, the effect is even more substantial, suggesting this combined cannabinoid treatment should be investigated further.  But marijuana is more than just THC and CBD. Other molecules found in cannabis, such as terpenes, also show potential as treatment for dementia. Most notably, pinene, limonene, and beta-caryophyllene (BCP) all seem to interact with beta-amyloids, although all of the research has been conducted either in labs or on animals. Pinene has also been shown to reduce some of the negative effects THC has on memory. One study suggested a “possible neuroprotective potential of alpha pinene for the management of dementia with learning and memory loss.” The authors of another study wrote that “high levels of limonene in food or medication are expected to help treat or prevent Alzheimer’s disease.” Beta-caryophyllene, given orally in a study on mice, was shown to prevent cognitive impairment. The evidence is preliminary and based entirely on animal models, yet terpenes may explain the varying cognitive effects of different cannabis varieties.   Is marijuana bad for memory? While cannabis may have benefits for those with Alzheimer’s, other research points to potential detrimental effects of cannabis on memory. For one thing, cannabis is known to produce mild, short-term memory impairment for some who are actively high on the drug. Still, it’s not entirely clear that these effects occur in all cannabis users. For example, in a survey of 1,333 British cannabis users, only a small subset (6.1%) reported impaired memory.  These changes are usually reversed sometime after the cannabis high subsides, although there is some disagreement as to how long. Some report that these effects subside after the high is gone, while others say it may linger. A small study on cannabis-dependent adolescents found that the cannabis-using subjects had short-term memory deficits that lasted for six weeks after the last use of cannabis. Still, with such a smaller sample size, more research is needed to confirm these results. A much larger review of 69 studies found no evidence for cognitive deficits after 72 hours of cannabis abstinence.  Still, other studies have found that long-term or heavy cannabis use may also lead to problems with working memory and verbal episodic memory, with impairments in encoding, storing and retrieving memories. And some alterations have been found in brain structure and function for cannabis users, specifically in the areas of the brain that support memory processing.  Some studies have found that cannabis users had higher activation in spatial memory related areas of the brain. Researchers hypothesized that they were ‘working harder’ to compensate for the changes to the brain caused by cannabis.  Interestingly, some research suggests that CBD may alleviate the memory problems induced by the THC in cannabis. Comparing cannabis users who used high-THC cannabis to those who used the same amount of THC alongside high amounts of CBD, one study found that the second group did not have memory impairment. This suggests CBD may have a protective effect for memory — essentially shielding it from the impacts of THC. For those who are concerned about cannabis’ negative effects on memory, one might consider utilizing whole plant extracts with a balanced THC:CBD profile and other cannabinoids and terpenes like cannabichromene (CBC), cannabigerol (CBG), limonene, pinene, and beta-caryophyllene.   This article was originally published on The Cannigma, and shared here with permission.

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How cannabis affects your blood pressure

How cannabis affects your blood pressure

Research suggests that marijuana can impact blood pressure in humans. Some studies even indicate that cannabis use could be a helpful way to lower blood pressure and treat conditions like hypertension. Still, other research shows conflicting results — that it could be a risk factor for increased blood pressure. While we don’t yet have enough evidence, scientists continue to study whether and how it could be effective.  How cannabis impacts blood pressure View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)   Cannabis works primarily by modulating a system in the human body known as the endocannabinoid system. This system includes chemicals naturally produced by the human body called endocannabinoids, cannabinoid receptors, which are activated by endocannabinoids, and enzymes which clear the endocannabinoids from the body. This system is believed to be responsible for maintaining homeostasis or balance in a wide range of bodily functions, including mood, sleep, energy, hunger, and pain response.  The chemicals in cannabis, called cannabinoids, are also able to trigger these cannabinoid receptors, and thus modulate many of the functions that the endocannabinoid system is involved in regulating.  Studies have revealed that the endocannabinoid system plays a key role in cardiovascular activity. In animal studies looking at these cardiac factors, researchers have noted that activation of this system can cause significant changes in heart rate, blood vessel constriction, inflammation, oxidation, and blood pressure — both increasing and decreasing blood pressure in different contexts.  In cardiovascular disease states we generally see an upregulation of the endocannabinoid system, so researchers believe that the body’s endocannabinoids play a role in the progression of cardiovascular disease.  In particular, there are studies that show an association between an overactive endocannabinoid system and maladies like arterial, pulmonary and portal hypertension.  Still, researchers aren’t sure whether these elevated endocannabinoid levels are causing these problems with heart health, or if they are being deployed by the body as a counteractive measure to balance out the problems.  When tested in animal studies, endocannabinoids have shown both the potential to widen blood vessels, thereby lowering blood pressure, and to contract blood vessels, thus raising blood pressure.  The evidence cannabis lowers blood pressure Given what we know about how the endocannabinoid system and how it impacts blood pressure, it’s likely that the cannabinoids present in cannabis will also have some effects. Because of this, there is great interest in the therapeutic potential of cannabis for modulating blood pressure.  Anecdotally, many medical cannabis users report that cannabis has increased their cardiovascular health and well-being. Unfortunately, the actual research on this is somewhat limited and conflicted.  Some studies suggest that cannabis use can lower blood pressure and reduce risk of hypertension. For example, animal studies on rodents with high blood pressure found that activating the endocannabinoid system by adding cannabinoids reduced blood pressure, while blocking cannabinoid receptors increased blood pressure.   In one review of the literature, researchers reported that cannabis doesn’t have an immediate impact, but can lead to longer term lowering of blood pressure. In these studies, while they found increased heart rate with use, they didn’t see immediate changes in blood pressure. Still, this review found that chronic cannabis use was tied to lower blood pressure and heart rate overall.  In another study, researchers found that cannabis withdrawal could lead to spikes in blood pressure. Researchers observed and monitored heavy cannabis users before and after a period of cannabis abstinence. While the cannabis users had normal blood pressure before going cold turkey, abruptly stopping caused some participants’ blood pressure to spike — actually hitting hypertensive ranges.  Since this only impacted 31% of the participants, researchers on this study hypothesised that cannabis might be offering protection from high blood pressure and, when that protection was removed, these patients stopped benefiting from cannabis’ blood pressure lowering effects. For those with heart problems who are already using cannabis, the authors of this study suggest that stopping should only be done under doctor supervision to ensure that blood pressure levels stay in a safe range. While we might assume that these studies reflect impacts from THC, the primary cannabinoid in cannabis, it’s also important to note that cannabis contains many different compounds. It’s possible some of the research is conflicted because different types of cannabis may have different effects.  For example, research looking at the cannabinoid CBD, while limited, suggests that it can both lower blood pressure directly and reduce stress that can cause increases in blood pressure. Some researchers even suggest CBD may be helpful for treating hypertension. Another study found that blocking endocannabinoid receptor activity reduced blood pressure for obese patients with hypertension. Still this research is in early phases and more needs to be investigated before we can make any firm conclusions.  The evidence cannabis raises blood pressure The studies above indicate that cannabis may be a helpful treatment for those suffering from high blood pressure. Still, other research suggests the opposite, with findings suggesting that cannabis can actually increase blood pressure. For example, one study on six individuals found that recent cannabis use temporarily increased blood pressure within an hour of taking the medicine.  A review of the literature on cannabis and heart health didn’t find any links between cannabis use and hypertension, but it did find some evidence that suggested cannabis use leads to an increased risk of ischemic stroke — another condition associated with high blood pressure.  Survey based studies have added to this confusing state of affairs. One study looked at the correlation between blood pressure and cannabis and reported that those who had ever used cannabis (even just once) were more than three times more likely to die from high blood pressure. Still, this survey was limited because it did not look at dosing, frequency of use, or chemical profile, and it is unclear whether those surveyed may have used other illicit drugs, and if so, whether those were a factor.  In a later survey study, researchers found no relationship between ongoing cannabis use and high blood pressure. They did find that recent cannabis use led to increased systolic blood pressure, but chronic cannabis use did not seem to impact blood pressure in any way. Even for those who regularly used cannabis throughout their life, there was no association with increased blood pressure.  These studies on cannabis and blood pressure certainly present a confusing picture. And researchers continue to investigate to try to find a way to clarify the role these cannabinoids play.  Risk factors for cannabis and blood pressure  Cannabis and its effects on the cardiovascular system remain unclear. Findings support both an increasing as well as a lowering effect on blood pressure. Randomized prospective trials are needed to answer many questions surrounding the therapeutic use of cannabis. Those who are already using cannabis should also exercise caution in stopping the medication, as a sudden withdrawal from cannabis use could trigger increased blood pressure in some.  Because of these serious risk factors, anyone considering cannabis — particularly anyone who already has issues with pre-existing cardiovascular conditions — should be cautious and always check with their doctor before starting any cannabis regimen.   This article was originally published on The Cannigma, and shared here with permission.

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How cannabis affects your liver

How cannabis affects your liver

There isn’t a great deal of research on how cannabis affects the human liver. From the research that does exist, we know the relationship between the two is somewhat complicated and varies depending on condition.  For most healthy individuals, cannabis use shouldn’t cause liver complications. It may even potentially play a protective role against developing alcoholic liver disease and nonalcoholic fatty liver disease.  Anyone with a severe liver condition or taking other medications should ensure they are helping and not hurting the liver.  Although medicine still has many questions on medical marijuana and the liver, here is what science can tell us. How marijuana interacts with the liver View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)   To understand the effects of cannabis on the liver, let’s start with an explanation of how the endocannabinoid system (ECS) affects the liver. The ECS modulates many of the human body’s most crucial functions — like sleep, energy, memory, hunger, inflammation, and mood, to name just a few — and helps keep them in homeostasis or internal balance. Common cannabinoids found in the cannabis plant — like THC and CBD — can activate the endocannabinoid system. Our body also produces its own cannabinoids (endocannabinoids) — and they also activate the ECS.  Studies show that activation of certain endocannabinoid receptors may worsen cirrhosis, enhancing factors like fibrogenesis, fibrosis, ascites, and steatosis. Activating a different endocannabinoid receptor seems to have the opposite effect. It can counteract fibrosis, steatosis, collagen deposition, and inflammation — promoting a healthy liver.  Endocannabinoids have also been shown to impact cirrhosis of the liver. Some can even act against fibrogenesis, improving liver health. So researchers are looking to further explore endocannabinoids as a potential target for the treatment of liver disease.  The benefits of cannabis for liver health  Existing research shows that activating ECS receptors with endocannabinoids may have a big impact on the liver — either helping or harming. So how does cannabis, a plant that activates these same receptors, impact the liver?  The effects of cannabis on the liver have mostly been studied in populations with liver disease — not healthy livers. That said, one small study did look at the influence of chronic cannabis use on liver function in general.  In this study, researchers found no significant differences in liver function for those with higher levels of THC markers in their blood. But they did find slightly better liver function for those with higher THC-OH levels. This research was limited due to a small sample size but suggests that chronic medical marijuana use doesn’t negatively impact liver health for healthy individuals.  Other research looks at cannabis and liver health relative to specific conditions or symptoms. For example, researchers investigated cannabis’s effects on alcoholic liver disease (ALD). Heavy, long term alcohol use causes ALD and cannabis may serve a protective role for this disease.  One very broad study found that those with the highest levels of medical marijuana use had significantly lower levels of ALD at all stages of the disease. These heavy cannabis users saw a 45% reduction in steatosis, or alcoholic fatty liver disease, a 40% reduction in steatohepatitis, or alcoholic hepatitis, a 55% reduction in alcoholic cirrhosis and fibrosis, and an impressive 75% reduction in hepatocellular carcinoma, or liver cancer.  Another study, which tied lower levels of ALD to CBD use, seems to suggest that cannabis use (or even just CBD) may actually be protective against the deadly long term effects of alcohol use.   Cannabis may help more than just alcohol-induced liver disease. Marijuana may also protect against non-alcoholic fatty liver disease. One study tied cannabis use to lower levels of this condition, in addition to ALD. So medical marijuana may be protective for our livers in general, not just as a protection against drinking.  Cannabis may also play a protective role in other specific conditions.  One study found that cannabis can protect the livers of patients suffering from psychosis — lowering the risk of steatosis.  Animal models also show evidence that cannabis use can improve symptoms of hepatic encephalopathy, likely via the anti-inflammatory properties of cannabis. Unfortunately, there have been no human studies on this condition to confirm the results.   CBD oil and the liver These days, many cannabis users never smoke weed or eat THC edible, instead choosing to consume CBD oil. So how can CBD oil affect the liver?  In a 2019 study on mice, a high dosage of CBD led to fatalities for some of the mice subjects. Researchers noted elevated liver enzymes and increased liver size in the mice who died and concluded they died from liver issues.  They concluded that “CBD has the potential to cause liver injury,” based on how the highest CBD dose given to the rodents (2460mg/kg) “exhibited clear evidence of hepatotoxicity.” They added that lower doses of (246 mg/kg and 738 mg/kg) increased liver-to-body weight ratios.  Or in plain English, the researchers found that when given very high doses of CBD, the mice showed signs of liver toxicity, while in lower doses the researchers found liver swelling.  The researchers found that CBD doses above the 50 mg/kg minimum effective dose (MED) “were toxic when repetitively delivered,” and that the general toxicity observed included “pan-hepatic cytoplasmic swelling, increases in liver-to-body weight ratios, and elevated ALT, AST, and total bilirubin.”  They also cited animal studies that have show increased liver size in monkeys “and elevated liver enzymes in dogs when CBD was administered at doses as low as 2mg/kg of body weight,” as well as recent clinical trials in which 5-20% of human patients treated with CBD exhibited elevated liver enzymes at doses of 20 mg/kg.  The researchers concluded that CBD “poses a risk for liver injury,” and that additional studies are needed.  Other researchers, however, have pointed out some methodological problematic issues in the study.  For one thing, the dose of CBD administered was extremely high — a dose 100 times higher than the maximum recommended dose for Epidiolex, the only FDA approved CBD-based medicine for humans. But more importantly, the CBD was extracted using hexane — a solvent with known neurotoxic properties. It’s unclear whether the hexane was a factor in the mice’s death.  Beyond this, the sample size was only six mice, which is too small to have much statistical significance. Researchers on the study reported that 75% of the mice died — which would mean 4.5 mice died. Since this is an impossibility, one might ask what other errors the authors or researchers made. Confirming or discrediting these findings will require more research.  Also in 2019, the FDA issued a revised consumer update on CBD and products containing CBD, which stated simply that “CBD can cause liver injury.” Can weed be bad for your liver? Risk factors For liver related conditions other than hepatic encephalopathy, cannabis use may have more complicated interactions. Cannabis use may worsen chronic hepatitis C virus, for example. Animal studies show cannabis can actually worsen liver fibrosis and steatosis in hepatitis C. Human studies show that marijuana use can lead to suppression of anti-viral immunity in hepatitis C patients. In addition, studies on hepatitis C patients found that steatosis risk was predicted by daily cannabis smoking.  On the other hand, other studies have reported positive effects for hepatitis C patients using cannabis. One 2018 study found hepatitis C patients who use cannabis had lower levels of cirrhosis and lower total health costs. Another study found hepatitis C patients who used cannabis better adhered to their antiviral treatments and had better virologic outcomes. So for patients with this condition, cannabis could be helpful or harmful. Another important area of risk management related to cannabis and the liver is drug interactions. Cannabis can interact with drug metabolizing enzymes in the liver. If taken with certain medications, this can cause them to become more or less potent and efficacious. In addition, certain drugs may make cannabis more or less potent.  While there has been little research on these drug interactions, we can deduce from what we know about pharmacology that certain drugs are more likely to have these interactions. For example, fluoxetine, fluvoxamine, fluconazole, clarithromycin, verapamil, itraconazole, voriconazole, and ketoconazole are all more likely to increase the concentration of THC and CBD in the blood by inhibiting its elimination from the body. In the other direction, rifampin has been reported to reduce THC blood levels by 20-40% and CBD levels by 50-60%.  While there is still only a limited amount of research, there are some interesting studies showing both risks and benefits of cannabis use on the liver. For healthy individuals, cannabis should not have a significant impact on liver function. It may even serve a protective role against developing alcoholic liver disease and nonalcoholic fatty liver disease. Still, for those with hepatitis C, or those using certain medications, cannabis use can cause complications.  If you do have a liver condition, it’s advisable to work with a cannabinoid specializing physician.    This article was originally published on The Cannigma, and shared here with permission.

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How cannabis affects women and men differently

How cannabis affects women and men differently

The cannabis experience is significantly influenced by mindset (intention/expectation) and setting (environments of consumption and post drug onset). One’s male or female biological sex can also affect the mind and body reaction to cannabis, alongside and in concert with a number of other factors, including an individual’s endocannabinoid system and the cannabis chemovar(s) being used.  Biological sex-associated differences can range from how strongly the effects are felt, side effects like anxiety, changes in heart rate, effectiveness at relieving pain, and sexual arousal. Researchers have even found that the risks of cannabis abuse and driving under the influence differ for men and women.   How does that work? The differences in how the body reacts to drugs, how drugs act on the body, and dose, all play a role in the ways that some medications can have a different — and potentially more dangerous — reaction for women than men.  A Swedish study from 2008 said that “many but not all, such gender related differences can be explained by the effects of sex hormones,” and added that while sex differences in drug response can be seen on the receptor level, there is a paucity of research on the matter.  The overall lack of an explanation into the “why” of gender differences in drug reactions and efficacy is a recurring theme in the research, but a number of studies have already asserted that there are at least some clear differences in how men and women use cannabis.  Why cannabis affects men and women differently Scientists are not all in agreement about how and why sex differences lead to different effects of cannabinoids and cannabis. The theories include hormonal differences, muscle mass and fat ratios, volume of cannabinoid drug distribution, and cannabinoid metabolism in the liver. One review of existing research found that sex differences in cannabinoid effects might be from different pharmacodynamics (how drugs affect an organism), and pharmacokinetics (how the organism affects drugs), both of which influence dosing, benefits, and adverse effects. Sex differences with cannabis are also due at least in part to the ways males and females experience emotions as well as “differences in muscle mass at fat tissue distribution between males and females.” The researchers were careful to add though, that “investigation of such differences is still at an early stage.”  They did stipulate that some of the differences they found in their review included that, among non-marijuana smokers, “men are more sensitive to the subjective effects of delta-9-THC alone than women,” and that women “report significantly more dizziness than men.” They clarified though that they did not find any gender differences in regard to how THC affects impulsivity (disinhibition).  The review also found that preclinical studies show that men may be more receptive to the hunger-inducing effects of cannabis (the munchies).  However, females are still underrepresented in clinical research and if these studies “routinely included subjects of both sexes, greater progress in the field would be reached in a shorter time. Clinical studies should also report all findings, whether positive or negative, in order to quantitatively define the issues related to the gender differences in cannabis consumption,” the researchers added. Yet another theory holds that sex can actually impact how sensitive one is to cannabinoids. The authors of the study that produced that theory wrote that there is growing evidence to show the endocannabinoid system is sexually dimorphic (it has two different forms) and that hormone differences could seemingly be the basis for the different ways men and women react to cannabinoids like those in cannabis. The ways weed affects men and women differently Stronger effects for women While feeling stronger effects of cannabis might be a good thing in some situations, it can also have its down-side.  A study published in 2020 found that females exhibited greater peak blood concentrations of an important cannabis metabolite and greater subjective ratings of “drug effect,” even when controlling for body weight. These drug effects included ratings of “anxious/nervous,” “heart racing,” and “restless,” which were significantly higher among the female respondents.  The researchers concluded that starting doses for females should be lower, and that public health officials should issue warnings about the higher risk of acute anxiety related reactions among female cannabis users. More effective at reducing pain for men There is evidence that cannabis has a stronger pain-reducing effect on male users than it does for women. Researchers, who published a 2016 study on the matter, had 42 people put their hands in ice water — some given cannabis with THC and others cannabis without THC — and found that the men in the group were able to keep their hands in the cold water longer than the women.  It should be noted, however, that the cannabis used in the experiment had relatively low levels of THC (3.56-5.60%), and cannabis with levels closer to what is available in the medical and recreational markets could have led to different results. More sexually arousing for women Numerous studies over the years have found that women who use cannabis have more sexual satisfaction — and the more they use the greater the satisfaction.  A survey-based study published in 2020 found that “Increased frequency of marijuana use is associated with improved sexual function among female users, whereas chemovar type, method of consumption, and reason for use does not impact outcomes.” For men, it’s a little bit of a different story. One study suggested “some experienced (male) smokers have derived an enhancement of sexual pleasure while they were using marijuana.”  The question of erectile dysfunction, however, still hangs undecided. Some subjects in studies have reported superior erectile function, while others the opposite. Those studies, however, aren’t the final word — in 2010, researchers found that the influence of cannabis on sexual behavior appeared “to be dose-dependent in both men and women.” This article’s medical editor points out, the presence of pesticides or other contaminants could also adversely impact sexual function, memory impairment, and in other ways reduce the quality  of the cannabis experience. How men and women use cannabis differently Gender differences in risk perception, stigma, intake method, the role of peer pressure, and propensity to develop a dependency (Cannabis Use Disorder) have all been asserted in published research in recent years.  Females “[are] nearly two times more likely to perceive risk in regular marijuana use compared with males,” a study from 2015 found, though it added that the perceived risk among women dropped from 59% in 2002 to 47% in 2012.  A comprehensive review of existing research published in March 2020 found that when women use cannabis, they “transition more quickly to cannabis use dependence compared to males.” This doesn’t mean that women are more prone to develop Cannabis Use Disorder, rather those that do, develop it on average 4.7 years after they first use marijuana, as opposed to 5.8 years for men. The study found there was no difference between men and women in terms of how old they were when they first started using cannabis.  Gender-based stigmas and quality of life effects Among other differences, the review found that “the negative effect of cannabis use on mental quality of life scores was more pronounced for women.” Part of this may be social in nature, in that women may face greater stigma and discrimination for using substances like cannabis, according to the researchers. Another reason could be greater sensitivity to contaminants. In other words, those women who do develop Cannabis Use Disorder not only do so quicker than men on average, but they feel it more intensely, in part because of the greater stigma attached towards women who consume cannabis.  The stigma might be partly because men are more likely to use marijuana, and thus it’s more expected of them, if not more accepted. A 2019 National Cannabis Survey in Canada found that 18.4% of male respondents had smoked cannabis in the three months prior, as opposed to only 15.1% of women.  Doctors less likely to support medical cannabis for women Furthermore, there may also be differences in how medical professionals consider cannabis use by female patients. A survey of 361 medical cannabis users in Illinois, for instance, found that women reported “lower levels of support from physicians for [medical cannabis] use.” The study also found that women were more likely to decrease their use of other prescription medications after receiving a medical marijuana license — particularly from a physician supportive of their cannabis use. Women eat more edibles, men smoke more flower But what about when men and women actually get high? Is there a gender difference in the consumption methods used? That same National Cannabis Survey found that men are more likely to smoke marijuana flower and women are more likely than men to use edibles, while a separate Canadian study from 2019 found that men were more likely to prefer vaping cannabis (15.8% vs 10.8% of women), and surmised that this could be because taking edibles is more discrete and allows women to easier avoid scrutiny for using cannabis.  Women don’t drive while high as often as men Perhaps the most glaring difference could be in terms of driving while under the influence of cannabis. A 2018 report compiled in the US found that while 43.9% of male reported driving after using cannabis, only 8.7% of female respondents had.  In summary, common sense, anecdotal evidence, and scientific studies tell us that each person’s experiences with cannabis may be influenced by dose, route of administration, frequency of use, assessment of risk, their biological sex, hormonal environment, expectations (set), and context of use (setting).   This article was originally published on The Cannigma, and shared here with permission.

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How cannabis affects the immune system

How cannabis affects the immune system

Cannabis interacts directly with a system in our body that helps regulate our immune responses and we know that it can be helpful in treating auto-immune diseases. It is not necessarily as helpful when it comes to fending off viruses and other pathogens, however. What cannabis does to the body Chemicals in the cannabis plant like THC and CBD, called, cannabinoids, interact directly with the body’s endocannabinoid system. These chemicals mimic natural chemicals the body produces, all of which can trigger a wide variety of effects on functions like sleep, hunger, pain and mood. Part of the endocannabinoid system’s role is to maintain homeostasis or balance of the immune system. While the literature contains some contradictions on how exactly that works, it is generally considered a “gate-keeper” of the immune system — preventing it from causing overwhelming inflammatory responses. Suppressing the immune system may make cannabinoids helpful in conditions where immune responses turn against the patient’s own body. Indeed, many autoimmune conditions, such as rheumatoid arthritis, multiple sclerosis, and diabetes, have already been tied to dysregulation in the endocannabinoid system. Still, in cases of infection from pathogens, researchers warn that these immunosuppressive effects could be problematic — suppressing the body’s natural and needed immune responses.  Research on cannabis for immune health View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)   While our theoretical understanding of the endocannabinoid system suggests that cannabis could suppress important immune responses, thereby increasing our susceptibility to infectious diseases, the research actually presents a more complex picture. Beyond treating autoimmune conditions, suppressing immune responses can in some other situations be desirable when dealing with certain infections. When under attack from an infection our bodies sometimes go into sepsis — producing a systemic inflammatory response that can lead to death. Reducing this response could be live-saving. Research on animals shows that stimulating endocannabinoid receptors with cannabinoids like those in cannabis can reduce infection-related inflammation, in some cases also reducing the overall death rate. Some studies also showed it improved recovery for infections like malaria. In other animal experiments, reducing stimulation of these same receptors led to increased survival from infection. And in some experiments stimulating these receptors decreased immune response against infections like candida, legionella pneumophila, and influenza. These animal studies present a somewhat conflicted picture, and human studies have been extremely limited.  Potential benefits and harms Interestingly, in spite of the data from animal studies, early double-blind, placebo-controlled human studies found no immunological alterations observed with THC use. Later though, some immunosuppressive effects were found in the human research. Notably though, in the same study, this effect reversed in two patients who had long term exposure to cannabis. So it’s possible that the long term effects of cannabis may differ from acute use when it comes to immune response. Still, while researchers have found immune differences in humans from cannabis use, they haven’t confirmed that these alterations make cannabis users more susceptible to infection. So, while in some ways cannabinoids show promise for treating viral infections (such as reducing sepsis), they can also pose risks like suppressing needed immune responses. Researchers report that cannabinoids do have potential as treatments for infectious disease but say we need much more research to learn exactly how to use them in a way that ensures they are helping and not hurting our chances against an infection. Until more research is done, we really can’t say for sure.   This article was originally published on The Cannigma, and shared here with permission.

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Homeostasis and the endocannabinoid system

Homeostasis and the endocannabinoid system

If you’ve been paying attention to cannabis science, you may have heard about the endocannabinoid system and its important role in maintaining 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 how cannabinoid medicines might help (or in some cases worsen) different medical conditions.  So, in this article, we’ll cover the science of homeostasis and how using cannabis might affect this important function.  What is homeostasis? The word ‘homeostasis’ 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 well being. 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.  Take, for example, the way we adjust to changes in the temperature. 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.  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 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, and nervous system. The endocannabinoid system and homeostasis The endocannabinoid system is an important system in the human body 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), it plays a key role in the body without any help from cannabis. Researchers have found that it naturally modulates a variety of different functions, such as: Sleep Pain Memory Learning Inflammation Hunger Energy Muscle control Temperature Mood These 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. Activation of this 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, or 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. Energy homeostasis  One area of homeostasis that the endocannabinoid system has been tied to is energy homeostasis — the way our body regulates energy levels through food intake, metabolism, and energy expenditures. As regulators of metabolism, endocannabinoids 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. It’s long been known that consuming cannabis can result in an increase in appetite, sometimes referred to as “the munchies.” In addition, blocking CB1 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 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.  Interestingly, there is also research suggesting that stimulating CB1 can lead to weight reductions. For one thing, obesity rates are lower in cannabis users than non-users. 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 modulate important metabolic functions 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.  Still, one thing is clear — the endocannabinoid system plays a big role in our energy homeostasis.  Immune response  The endocannabinoid system has also been studied for its role in maintaining immune 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 it is at least somewhat involved in maintaining immune homeostasis.  Emotional 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 cannabis use can affect anxiety and panic responses. At low doses cannabis 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 cannabis (such as we saw with weight loss and weight gain), often in dose-dependent ways.  While CB1 stimulation 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. 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 helps maintain homeostasis in the body, and there are many ways we haven’t covered. In addition, we have only begun to study this important topic, and as we continue to investigate it we will likely find more ways that homeostasis relies on this key system.  Cannabis’ effect on homeostasis View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)   Now that we know that the endocannabinoid system helps support our internal homeostasis, it’s important to question what effect cannabis consumption 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. 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. 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 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. 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.  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. 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. In this case, cannabis use could actually help to restore balance.  If you are considering using cannabis for your own medical needs, it’s best to check with a cannabinoid-specializing doctor. They can help you to decide whether cannabis is right for your particular situation.    This article was originally published on The Cannigma, and shared here with permission.

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Good news for migraine sufferers: more evidence cannabis can help

Good news for migraine sufferers: more evidence cannabis can help

More than 60% of migraine sufferers using medical cannabis found a long-term reduction of migraine frequency in a recent study. The research, which joins a fair number of previous studies affirming the efficacy of cannabis for treating migraines, also found an association with less disability and lower intake of other medications. The cross-sectional questionnaire-based study, published in “Brain Sciences” earlier this month, polled medical marijuana patients over the age of 18 in Israel who are using cannabis to treat migraines. They looked at a total of 145 respondents (97 females and 48 men) who had been using medical marijuana for between 1-12 years. Of the respondents, 61% noted that they had lower current migraine disability and negative impact from migraines, and used opioids and triptans at lower rates.  The study also found that medical cannabis related adverse effects were reported by 37% of the respondents, with what they described as adverse central nervous system and psychological effects being the most common.  In explaining the potential effectiveness of cannabis, the researchers cite “both clinical and preclinical data suggest an abnormal endocannabinoid system function in migraine,” something that has been described as endocannabinoid deficiency. The endocannabinoid system is an important biological system involved in maintaining homeostasis — a healthy state of balance in the body. The system consists of cannabinoid receptors, endocannabinoids, and the enzymes that synthesize and break down endocannabinoids. It helps regulate many critical processes in the body, including cognitive function, mood, immunity, and pain, to name a few. Plant-derived cannabinoids, such as THC and CBD, are able to interact with the cannabinoid receptors inside the body and may be able to affect migraines.  The authors of the study also call for further research into how other minor cannabinoids — in addition to THC and CBD — can work together and produce a multi-compound effect, what is known as the “entourage effect.” The participants in the study used a wide variety of cannabis cultivars and the researchers found that patients who used cultivars with higher levels of specific phytocannabinoids reported better success relieving migraines with medical cannabis.  According to the researchers “the most novel finding of this study was the identification that higher rates of patients that reported significant migraine frequency reduction following [medical cannabis] treatment also consumed higher monthly doses of [the phytocannabinoid] ms_373_15c and lower monthly doses of [phytocannabinoid] ms_331_18d.”  Although there is not enough evidence to attribute the anti-migraine effect of medical cannabis specifically to these phytocannabinoids, the researchers still suggested using the presence of those cannabinoids to help in choosing specific cannabis chemovars for further research.   Previous studies have also shown the potential benefits of cannabis for people dealing with migraines. One University of Colorado study from 2016 found that “migraine headache frequency decreased from 10.4 to 4.6 headaches per month with the use of medical marijuana,” and that positive effects were reported in 39.7% of the migraine patients in the study. The study also noted that cannabis could be effective not only in reducing the number of migraines, but also alleviating them in real time if taken while a migraine was taking place.   Meanwhile, a 2019 study published in Neurology found that out of 316 patients with chronic migraines, 88.3% reported improvement of migraines after using medical marijuana. Medical marijuana can also help alleviate the two main symptoms of migraines: pain and nausea, and dozens of studies have demonstrated as such.   This article was originally published on The Cannigma, and shared here with permission.

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