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What’s going with the biochemistry of weed and exercise?

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Leafly’s Dr. Nick Jikomes explains your body’s own weed molecule signaling system and what happens when you get your blood pumping.

The endocannabinoid system is crucial for maintaining homeostasis (balance). As a result, cannabinoids influence everything from emotion and pain perception to metabolism, prenatal development, and the gut microbiome. The plant cannabinoid THC exerts its psychoactive effects through cannabinoid receptors in the brain. These receptors (CB1 receptors) are widespread in organs and tissues beyond the brain, including the lungs and cardiovascular system. As a result, we would expect that cannabinoids have some kind of relationship to physical activity and therefore a potential influence on exercise performance.

What is known about cannabinoids and physical activity? Let’s explore the following questions across three articles:

  • Part I: How & Why the Endocannabinoid System Responds to Physical Activity
  • Part II: How THC Influences Exercise Performance & Recovery
  • Part III: How Body Fat & Exercise Influences THC levels in the Body.

How physical activity affects the endocannabinoid system

… it was generally found that anandamide levels acutely increase following exercise.

The two major endogenous cannabinoids are anandamide and 2-AG. A number of clinical (human) and preclinical (animal) studies conducted since the 2010s looked at how acute (short-term) exercise affects endocannabinoid levels in the body. A 2022 meta-analysis looked at these to identify trends in the results. 

There was a lot of variability in the results and design of studies, but it was generally found that anandamide levels acutely increase following exercise. This tendency was seen for different forms of exercise (e.g. running, cycling, resistance training), in both animals and humans, as well as human patients with and without preexisting conditions (e.g. PTSD, depression). The effects of acute exercise on 2-AG were much less consistent across studies, and there wasn’t enough data to assess the effects of chronic (long-term) exercise on endocannabinoid levels. 

In animal studies, where biological mechanisms can be studied in detail, both voluntary exercise and palatable food consumption have similar effects on the endocannabinoid system. CB1 receptors in the brain are important for reward processing generally, and specific CB1 receptor-containing neurons are crucial for the rewarding effects of everything from drugs (including THC) to the motivation to engage in exercise. In the case of mice, exercise means wheel running–they love it. They also love sugar water.

If given the opportunity, mice spend quite a bit of time running on wheels and sipping sucrose–it’s rewarding to them. It has been shown that engaging in either behavior increases the sensitivity of CB1 receptors on specific neurons in the brain. After wheel running or sugar consumption, these receptors are more sensitive to cannabinoids–both exogenous cannabinoids (pharmaceutical drugs) and endogenous cannabinoids found naturally in the brain. This means that both an animal’s physical activity and dietary patterns can alter its sensitivity to cannabinoids.

Similar to what’s generally been observed in humans and other animals, mice experience an acute elevation in blood endocannabinoid levels following running wheel exercise. Human long-distance runners sometimes describe a “runner’s high,” a feeling of euphoria, lower anxiety, and analgesia (pain relief) from running. Something akin to this is also seen in mice. Behavioral analysis indicates that they experience anxiety- and pain-relief from wheel running. This “runner’s high” effect depends on CB1 receptors in specific neurons in the brain, and further illustrates the endocannabinoid system’s involvement in coordinated changes across the brain and body in response to physical activity.

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To learn more detail about the relationship between exercise and the endocannabinoid system, listen to my conversation with neuroscientist Dr. Matthew Hill:

Why would an animal’s lifestyle–the pattern of behaviors it engages in–result in changes to its endocannabinoid system that influence everything from the inclination to engage in certain behaviors (exercise) to metabolic shifts (hunger, fat accumulation) and experiential changes (anxiety levels, pain perception, etc.)? How might we think about why animals are wired up this way?

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Why the endocannabinoid system may have evolved to coordinate changes in the brain & body

Consider what we’ve previously explored–how increased endocannabinoid levels affect hunger and metabolism on the one hand, and anxiety, fear, and pain perception the other. The metabolic effects of activating CB1 receptors are generally aimed at motivating animals to find food (short-term hunger) and store the energy for later (fat accumulation). An overactive endocannabinoid system is associated with metabolic states like obesity and diabetes. This may be a consequence of what some scientists think the general, evolved function of the CB1 receptor may be: to motivate behavior and coordinate physiological changes in favor of energy accumulation (e.g. food acquisition, fat storage).

For most wild animals, it can be adaptive to binge on plentiful food sources when they’re present, as food often becomes scarce in the future. Feast to prepare for famine.

For anxiety, pain perception, and fear memory, an overactive endocannabinoid system is associated with lower anxiety, lessened pain perception, and weaker fear memories. While lower levels of anxiety, pain, and fear may sound like a good thing, it can be deadly for wild animals. Imagine a mouse that doesn’t get anxious when it smells a nearby cat, or remember where it was last attacked by one. It’s life may be less stressful moment-to-moment, but it’s probably not going to live long. 

Why would excessively high endocannabinoid levels, leading to an overactive endocannabinoid system, tend to drive this pattern of biological effects–metabolic changes that promote energy accumulation together with various experiential changes (lower anxiety, etc.)? It can seem weird until you think about it in terms of the ecological contexts in which animals must survive.

After a physically demanding hunt, you will naturally want a good meal. 

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Again, imagine you’re a wild mouse. You’re well-fed and plump, with food stocked up in your den. Times are good. What’s your best bet for survival? Stay home, groom yourself, and nap? Or venture outside the safety of the nest, risking death by predation? The answer is clear: rest and digest. 

Now imagine a time of famine. You’re out of food and have burned through your fat stores. The only way to survive is to venture out and find more to eat. Will you be motivated to do that if you’re extremely anxious and gripped by fear of predators? Of course not. A risky foraging adventure is a much better survival bet than starving from the comfort of home. Animals are wired up to be more exploratory, less fearful, and more willing to take risks in times of energy scarcity. 

So why would levels of an endogenous cannabinoid like anandamide generally be higher following exercise? Perhaps the body is sensing a depletion of its energy stores–you’re burning through calories and may soon need more. For most of human prehistory this would have meant, much like a wild mouse, being motivated to move outside the safety of home. This can only be done if you’re not gripped by fear and anxiety. 

For most of human evolution, we basically had to exercise in order to eat–engage in physical exertion (hunting, foraging) to acquire calories. It makes sense that humans and other animals would have evolved biological mechanisms that prepare their bodies for energy utilization and storage after they engage in the physical activities required for food acquisition. After a physically demanding hunt, you will naturally want a good meal. 

This perspective also starts to make sense of modern health problems that have become common for humans who never face the threat of starvation.

Ancient Biology, Modern Health Problems

Thinking about biology in an ecological-evolutionary context can help make sense of modern, “civilizational” problems. For example, humans today are simultaneously becoming more metabolic dysfunctional (e.g. obese, diabetic) and seeing a rise in mental health issues like anxiety. Could these things be connected?

Today, a near-infinite supply of calories is readily available. Those calories feed bodies with the evolved tendency to store up fat reserves, preparing us for the next famine–a famine that no longer arrives. We’re in perpetual rest-and-digest mode. On an evolutionary timescale, we created civilization yesterday. But our behavior is influenced by biological systems millions of years in the making. Our biology hasn’t had time to fully adapt to the hyper-novel, rapidly changing environment we’ve invented. 

Because life-threatening food deprivation never motivates us to venture back into a dangerous wilderness, we’re primed to dream up new fears and anxieties. Many of our mental health issues may stem, at least in part, from the very comfort of modern existence. There’s more room for fresh anxieties when you don’t face the threat of imminent starvation.

Our modern environment has also given us the ability to alter our endocannabinoid system in new ways, through the intentional use of exogenous cannabinoids like THC. If the endocannabinoid system helps regulate our biology in response to physical activity, can plant cannabinoids like THC influence things like exercise performance? That will be the subject of the next article in this series.


Read the other two articles in this content series:

  • Part II: How THC Influences the Lungs, Cardiovascular System & Exercise Performance
  • Part III: How Exercise & Body Fat Influence Blood THC Levels



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Cannabinoids

Making Cannabis Oil In A Slow Cooker I Easy

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What about combining the magic of the slow cooker with the benefits of cannabis!  A match made in chill heaven

Marijuana has become mainstream popular, but not as popular as the slow cooker. Over 70% of homes has one and the last major statistics reported in 2019 say approximately 11.6 million slow cookers were sold in the US and Canada.  The slow cooker, originally known as the crock pot, was introduced in the 40s and has become a staple for meals ever since.  But what about a different use? Making cannabis oil in a slow cooker is easy!

Cannabis oil has a ton of uses, from massage candles to pizza sauce, and the benefits from incorporating a little CBD into your diet are just as endless as its uses in cooking and salves.

Luckily, making cannabis-infused oil at home is super simple, especially if you have a slow cooker. The recipe is easy to remember: You’ll need two cups of an oil of your choosing for every ounce or ounce-and-a-half of weed. Adjust the marijuana amount to your liking, and choose whichever oil you enjoy the flavor of—coconut and olive oil work best, for their high fat content which absorbs all those good cannabinoids.

RELATED: Smoking Marijuana For The First Time: A Beginner’s Guide

Next, grab your slow cooker and throw the oil in there. In goes the weed next! Don’t panic over throwing an ounce of good bud in there, it’ll be great. Gently mix it up, cover, and cook on the lowest setting for three hours. Allow it to cool, then repeat the heating process again for a more potent infusing.

It’ll smell up the place, so make sure you’re in a friendly environment (or be ready to light a few non-infused candles).

When you’re satisfied with the potency, strain out the oil from the leaves. Now you’re ready to try any one of our oil-infused recipes!



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Going Blind: The Debate on Cannabis Use for Glaucoma

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Since the late 1900’s, a popular reason for medical marijuana use, is to treat glaucoma. Today, however, debate exists as to whether this is beneficial. Here’s the lowdown on cannabis for glaucoma.

What is glaucoma?

According to the American Academy of Ophthalmology, “Glaucoma is a disease that damages your eye’s optic nerve. It usually happens when fluid builds up in the front part of your eye. That extra fluid increases the pressure in your eye, damaging the optic nerve.”

It goes on to explain, “Your eye constantly makes aqueous humor. As new aqueous flows into your eye, the same amount should drain out. The fluid drains out through an area called the drainage angle. This process keeps pressure in the eye (called intraocular pressure or IOP) stable. But if the drainage angle is not working properly, fluid builds up. Pressure inside the eye rises, damaging the optic nerve.”

There are two types of glaucoma: open-angle, and narrow-angle. The more common version, open-angle, causes no vision changes at first. However, over time, an inability to properly drain this fluid in the eye, causes damage to accrue over time. Those who have this glaucoma, do not experience any pain.

Eye pressure test
Eye pressure test

The second version, narrow angle (or closed-angle), occurs in people whose iris is closer than it should be to the drainage angle. In this case, the iris can actually act as a block to proper drainage. If the iris blocks it completely (or mostly), pressure can build very fast, called an acute attack; and this can cause blindness very quickly. This kind of glaucoma often comes with eye pain, and feelings of sickness and headache. This kind of glaucoma can also build slowly, and often sufferers don’t know they have a problem, until the damage is done.

Glaucoma is a leading cause of blindness for those 60 and above, and the second most prevalent cause of blindness worldwide; with about 60 million approximated cases. According to glaucoma.org, more than three million Americans have it, but only about half know. Roughly 9-12% of these result in blindness, accounting for about 120,000 cases. This is a subject where African Americans sure don’t win out; as they are 6-8 times more likely than Caucasians to get glaucoma, and 15 times more likely to have vision impairment because of it.

Glaucoma damage cannot be reversed, and there is no medicine to cure it. Anyone can get it, including babies, but its more prevalent in older populations. It’s also very much genetic, and having family members who have it, means a greater probability of getting it. Diabetes, extreme nearsightedness, and being African American are other risk factors.

Cannabis and glaucoma

Long before cannabis re-entered the medical world as a possible treatment for a myriad of issues, it was still very much suppressed in terms of popular culture and medicine. However, in the early 1970’s, research started coming out indicating that cannabis could greatly help glaucoma sufferers from losing more vision.

The main reason for this connection, is that cannabis lowers intraocular pressures. Remember in the explanation of glaucoma, that the reason for damage is from rising intraocular pressures due to liquid not draining correctly, and building in the eye? Well, using cannabis keeps that from happening, or at least, decreases the amount of pressure. Now, before going on, to be clear, no one is contradicting this information. As in, it’s generally medically understood, that cannabis has this ability.

In 1978, the National Eye Institute began its own studies into the topic. This research produced results that indicated marijuana derivatives are able to briefly lower intraocular pressure; whether the plant is smoked, taken orally, or given intravenously. The organization did not find a benefit to topically applying it to the eye.

Can cannabis help with vision issues like glaucoma?
Can cannabis help with vision issues like glaucoma?

According to the article Marijuana and Glaucoma, published in Glaucoma Today, marijuana can lower intraocular pressure by 60-65%, but that this lasts for about 3-4 hours only. It also explains a dose-response relationship, whereby the amount consumed, is relational to the amount of pressure-reduction. However, greater amounts did not elongate the time frame of effectiveness.

One of the main reasons this caught on early, is because glaucoma medication have unwanted side-effects; then and now. These include (depending on medication): stinging, bleeding, burning, and itching of the eyes; fatigue; upset stomach; tingling hands and feet; memory problems; depression; lowered sex drive; shortness of breath; eye, and skin, color changes; drowsiness; frequent urination; droopy eyelids; and *lowered blood pressure – we’ll get to the importance of this one soon.

Why the debate over cannabis for glaucoma?

For as much as there is a known connection between cannabis and lowering eye pressures, its not an open and shut case. Perhaps this simply represents another example of official health platforms pushing people toward the pharmaceutical option; and maybe there is some value in the opposition. You can decide for yourself.

There are a couple issues with the use of cannabis for glaucoma. The first one is that it only works very temporarily. This could mean using it 6-10 times a day to keep pressure down. That’s a lot of getting stoned, and for people not interested in getting stoned, this is very problematic. It also means that if a person cannot take the weed frequently or regularly enough, then their pressures will go up and down; and there will be no consistency.

Along with this, there’s another issue. Glaucoma causes damage to the optic nerve from fluid building up. But other things, like low blood pressure, can also damage the nerve. Unfortunately, cannabis is often associated with lowering blood pressure. So it is possible that cannabis use can lower blood pressure enough to actually weaken the optic nerve more. However, remember that list of side effects? Pharmaceutical medications can lower blood pressure too, and they’re still used. Which makes it silly to point out cannabis for this.

What’s the uncomfortable problem here? There are no long-term studies. In fact, when you look up information on cannabis for glaucoma, while NO ONE argues that cannabis brings down pressures; somehow in all this time, no long-term or cohort studies were done. In fact, one paper which references progress into this topic, reported that as of 2006, despite constant complaints of having no long-term study, none were done. Now, nearly 20 years after that, and over 50 years after the first findings of cannabis lowering intraocular pressures, this still doesn’t exist.

Glaucoma is 2nd leading cause of worldwide blindness
Glaucoma is 2nd leading cause of worldwide blindness

Instead, you’ll find article after article positing ideas as to why it might or might not be okay for long-term use, but nothing more substantial. And that means that all these official health platforms are using the idea of blood pressure or being high, to rule it out; even though there’s no confirming information as to whether this possible dip in blood pressure, ever causes further issue.

So, let’s break it down. If a person doesn’t mind being high 24-hours a day, then using marijuana for glaucoma isn’t an issue in terms of getting high, so long as no tolerance to pressure-reducing effects is noted (and this can happen). Now, it could be an issue in terms of blood pressure reduction, but right now, that’s the part of this that’s unverified.

We simply don’t know if a reduction in blood pressure from cannabis can damage the optic nerve. In fact, one study referenced here, indicates that its higher blood pressure patients that see the biggest drop. Some of the studies in that review found a negligible effect on blood pressure altogether. If a specific patient doesn’t have a problem here, then it’s a moot point anyway; and if the FDA sees fit to use drugs like beta blockers (which also lower blood pressure) for treatment of the condition; then it seems this might not be the issue its made to sound like in the press.

For all the commentary out there, not one study exists that gives any insight as to whether the change in blood pressure from cannabis, can make glaucoma worse. And once again, this is now over 50 years after the introduction of cannabis to treat the condition; and an argument that takes place while pharmaceutical medications are prescribed, that are known to drop blood pressure.

Conclusion

If you’ve got glaucoma, you’re probably doing whatever you have to, to not go blind. For now, cannabis does provide a way to reduce pressures; however, there are certain factors which still after all this time, have not been appropriately examined at all.

As a side note, there is a new investigation into using DMT to treat glaucoma by way of a device that can apply the medicine directly to the eye. Those with the disorder should keep an eye on this story. All pun intended.

Welcome to the site! We appreciate you making your way to Cannadelics.com, a publication in the wellness space, here to bring you the best stories of today. Visit us regularly to keep up with the Joneses; and check out the Cannadelics Weekly Newsletter, for top-level product promos as well.



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Where’s the Money in the Weed Industry?

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We’ve had legal recreational weed in the US to some degree since 2012; but the industry is quite unstable, with many going broke. So, where is all the money in the weed industry?

Is the weed industry working?

There are dispensaries pretty much everywhere in legal states. And a ridiculous amount of new products constantly coming out, which introduce new ways of using weed. None of us were using oil vapes a few years ago, for example, but its hard to bypass them now. This is the same for other products like shatter, or gummies, or pills. They didn’t exist, or only did in tiny amounts before dispensaries came around. Now they’re commonplace.

Plus, we know everyone is using weed. How do we know that? Because weed as an industry didn’t just pop up. It’s been around as a black market since the drug was first made illegal back in the early-mid 1900’s. It’s been the most popular illicit drug for decades. There was never a chance that legalizing it would diminish use, either. It hasn’t shown to increase it, but whatever status quo for use there was, still exists. Now we just have more ways to get it in us, and a variety of products we never dreamed of.

And we know that there’s tax money coming in. It’s hard to know when reading a headline, however, if the amount is a high amount per expectation, or low amount. Those ideas are not based off the actual amount, but in what the initial prediction for sales would be. So though the titles exist, the articles rarely give an indication as to whether the amount spoken of, is considered good by regulators. If its not, they don’t tend to want to say it.

Cannabis taxation
Cannabis taxation

Yes, the weed industry is working. But then, it also was before any recreational legalization took place. Perhaps ‘working’ is not the way to look at it. Perhaps its more about if its working as well as predicted? And, of course, this question only refers to legal markets. If you’re paying attention, you already know many companies are having problems – from dispensary owners, to cultivators, to product producers.

So if its working, and the product is available, and we’re all using it, why are there problems? And where does all the money go? Aren’t we all collectively smoking enough that weed should be a massively big industry, bringing in ungodly amounts of money? Well, it is… The real question is: ‘where is the money in the weed industry’? Far as I can tell, two places. And really in the end, it comes down to the second.

Corporate weed

A general reality of legal business is that those who cannot afford to be in operation, won’t be. While this goes for all businesses, legal or not; in legal industries it means a company having to comply with regulation measures. In the case of weed, this has been a constant issue, and caused many small business owners (and larger ones) to go under.

In terms of legal cannabis markets, the only operations to fundamentally do well, are the corporate ones. Big corporate companies like Trulieve, Curaleaf, and Tilray; which can pay the necessary fees, and which can even influence government practices and legalization efforts. Trulieve is behind Florida’s efforts to put recreational cannabis on 2024’s ballot. Trulieve knows it needs the sales, and this is a good way to get them.

Think of Walmart vs a mom-and-pop brand. Nearly all the time, Walmart wins out; even to the point of reducing an industry to just corporate players. And considering most states have regulatory measures that ensure a certain number of licenses (sometimes a majority) go to social equity applicants, (who are disadvantaged people from locations most affected negatively by drug wars); much of the competition for these big firms, are people with no money to begin with. In fact, such requirements have repeatedly been stifling industries, leaving only big players.

It often takes money to earn money, and the cannabis industry is a great example of how that happens. Essentially, only those that went into it with money in the first place, are reaping any rewards. Although even they often have problems. And this can be seen in company closures/sales, downsizing, and restructuring activities; which many big companies have had to do since getting involved in the industry.

Corporations are where much of the money in the weed industry is
Corporations are where much of the money in the weed industry is

While a few smaller brands like Cookies have been able to make it, there are very few stories like this. It’s very much a one-of-a-kind situation. Perhaps its not shocking that Cookies is often targeted, and no less for things like corruption; even as large companies seem to avoid such issues. This isn’t to say Cookies never did anything corrupt – I can’t speak to that. But whatever a smaller company like that did, will almost never compare to the corruption of bigger companies. Think Curaleaf and tainted products.

Cookies recently closed an LA store because of issues with a landlord, and it’s hard to know if anything more was behind this than standard landlord complaints. If anything, it seems the company takes a lot of flack; and my guess is that its because it’s a small player that got big enough to be competitive with big companies.

The black market weed industry

Corporations beat out the little guy, but they’re not the real answer. The most relevant answer to all of this, is that the black market is the biggest money-maker in the weed industry. In fact, when you look at any data about number of dispensaries, it becomes quite clear that the legal market can barely compete with the black market, anywhere in the US. And this doesn’t even account for cannabinoid products sold online, or in other non-dispensary locations.

A great example of this is California, which according to Forbes in early 2023, had all of 1,000 legalmdispensaries for a state of 40 million people. Yet, there are dispensaries all over the place. New York has the same issue. It’s a huge city, with all of 60 licenses for legal dispensaries given out as of September 2023; which was the same amount given out when first reported in the spring of last year. These are only licenses, and don’t mean there are 60 dispensaries yet. However, it was estimated the city has about 1,400+ illegal dispensaries. So less than 60 vs 1,400 plus.

Automatically this indicates a huge divide in terms of earnings between legal and illegal markets. If an illegal market has 23X the stores of a legal market, it can be generally assumed that the illegal market brings in 23X more. That’s just basic math; although it doesn’t account for size of stores or number of sales. Still says a lot, though. There might be tons of headlines about cannabis taxes rolling in, but logically, those taxes come from only a small percentage of sales. In no state do legal dispensary numbers come close to the number of illegal ones.

Perhaps this could’ve been different if every place to legalize, didn’t feel the need to adopt insane tax policies, and institute expensive and unnecessary regulation measures. But they did, and they still continue to despite these issues having such an obvious effect. I mean, really, we’re years in. And yet every new state to legalize, does the exact same thing by applying high taxes; along with laws that make opening dispensaries difficult.

Most dispensaries are black market
Most dispensaries are black market

So, where’s the money in the weed industry? It’s where it has been since cannabis was first made illegal: with the black market. And the only other companies to do well, are big corporate enterprises that can compete…and let’s be honest, they have so many problems that their futures aren’t much more stable than the little guys who keep going under.

The black market doesn’t have to worry about expensive regulatory and tax measures. While this can lead to some problems, like rising THC levels in products; it also means products are priced lower; and the prices can quickly change to stay competitive. There is no lack of dispensaries, or inability to get them up; and while this market keeps exploding out, states like New York and California, can’t manage to get dispensaries open. Beyond this, the entirety of the cannabinoids market (sold in dispensaries and beyond), is solely illicit – and its huge! No wonder the black market is where all the money is.

Conclusion

When recreational weed markets first opened, it was spoken about like it would be a gold rush. In reality, its mainly still a black market, with a small amount diverted to legal sales. And should legal systems keep instituting insane regulation policies; the legal segment is likely to get smaller and smaller in comparison to its black market counterpart.

Hello weed fans! We welcome you to Cannadelics.com, where we report on the most interesting cannabis and wellness stories of today. Keep us company by coming by frequently for updates; and head over to the Cannadelics Weekly Newsletter, for news and product promos, all in the same place.



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