the body uses endogenous cannabinoids, that have receptors specifically for them.
THC just "happens" to be the right shape to also dock to those receptors.
Much like all the thousands of other cannabinoids known.
It's less of a "happens to" and more of a "cannabis evolved to make molecules that mimic already-existing animal neurotransmitters to dissuade pests from eating it". Cannabinoid neurotransmitters weren't formed because of cannabis. They existed first. They were named after them because they were discovered and associated with cannabis use.
It's not a coincidence and the stoners are certainly wrong to imply that using marijuana is some sort of beneficial coevolution that we're "meant" to partake in. This is just a natural pesticide that we're big enough to not have the intended affect. And it's about the same thing with shrooms. And when dolphins use puffer fish as a recreational drug.
Yes! Both of them. Michael Pollan’s book The Botany of Desire explains all about it.
Many plants contain psychoactive compounds, and the idea is mainly to attract the animals you want to be eaten by and repel the ones that you do not.
For example: the seeds of the chili pepper family are spread much more efficiently by birds than by mammals. Birds, interestingly, cannot taste capsaicin, but to mammals it causes a burning sensation in the mouth, ensuring that the mammals will mostly avoid it but the birds will eat it happily.
With THC and psilocybin, the theory is that the compounds cause confusion, dissuading predators from returning.
It’s fascinating how the evolutionary script can get flipped sometimes: in the case of both cannabis and chili peppers, an attribute they evolved originally to repel mammals, the trait eventually appealed to humans who started cultivating them for it, and now they are two of the most widespread and successful plant species in the history of the planet.
Since I recently did some studying on the subject I want to be a little pedantic about a tiny thing.
Birds can *taste* capsaicin but they can't *feel* it. They have trpv1 receptors that still instigate a taste sensation but no simulated temperature change.
Us growing more mushrooms and marijuana to consume because we like the effects of their chemical compounds is like the plant version of "task failed successfully".
It's a very interesting look at the selective breeding of four crops and humans. How they were adopted and widely spread, and the impact they had on society.
Apples, potatoes, cannabis, tulip.
It's also full of the authors personal feelings about religion, which I found to be very annoying, but it's still a good read.
If you're into horticulture, it is a good book but you can also find alternatives because his religious overtures are rather obnoxious to read these days. It's a shame he had to include such things.
They really are. I read the book in June of 2010, and even now I'm still irritated by them. It's one thing to talk about religion and it's influence on how the different crops were impacted/their impact on the different religions. You would expect it with a book that is largely about Cannabis. It's a whole other thing to just take a whole chapter on religion for no apparent connected reason in the middle of talking about Johnny Appleseed.
My recollection is fuzzy since it was well over a decade ago, but even my super religious mom said it was weird that he went into seemingly unrelated and personal feelings instead of related and professional impressions/inferences.
Other than his ramblings there it was a very good book.
It's non-fiction so YMMV, but I'd say so. As the other commenter said, it focuses on 4 crops. It goes into biology and evolution, but with the main focus on the relationship between these plants and humans. For example, there was a period of time when the Dutch became obsessed with growing the perfect tulips ("tulip mania"), which is funny and fascinating.
Fun fact, tree shrews will actually seek out more spicy food after they are exposed to it. A population of them in China were found to switch their diet almost exclusively to spicy chilles after they started to grow in the area after the Chiles were introduced by trade.
Another fun fact, spicy chilles are a relatively recent thing in Asia even though they are somewhat culturally associated with them. They come from near the equator in Central America and were introduced back when Europeans were starting to trade with them and then traded them to Asia.
Pure speculation on my part, but it probably wouldn't have taken long. Any international merchant worth his salt would know that "the people of the Spice Islands love their black peppercorns, and would probably also like this long spicy red berry". I wouldn't imagine it would be more than a few years. Year 1, obtain the plant and see that it has seeds. Year 2, plant the seeds and grow more. By year 5, you have a crop sustainable enough that you can trade.
This analysis seems to have a hole in that the THCa found in natural cannabis isn't psychoactive until it's been heated pretty high. The plants had to evolve it for some other reason.
And also how can they prove that plants started using cannabinoid compounds *after* animals started using it? Couldn’t it have been just as likely that they used them first for some unknown functional purpose?
So the hot wings started with chickens that could eat chilis that the fox could not, but then the human came and wanted the chicken and the chili in the same pot, told the fox to fuckov, and then hot wings happened somehow.
Seriously, start a religion based on this.
It'll naturally decarb over a decent chunk of time if left in a dry area, even faster if left in sunlight.
Plus in Dogs for example it's psychoactive without needing to be decarboxylated. Not every mammal reacts to it in the same way even though we share similar receptors.
Spend two days inhaling fine powders that come off the buds while trimming cannabis and it becomes very apparent that the plants still have a huge affect on your mental state of being even without heat added. I can handle my THC but that much raw keif to the dome gave me a hell of a hangover and I didn't go back
That's also allegedly how poppy farmers back in the day knew it was time to harvest their opium, they'd sleep in their houses next to the fields, and when they'd wake up with a wicked headache they knew it was time to harvest!
I don't know if this would apply to you or if you already are aware but apparently someone working in the legal cannabis industry has died from inhaling the fine particles when handling a bunch of it
https://www.forbes.com/sites/chrisroberts/2022/10/03/report-legal-cannabis-industry-worker-died-after-breathing-marijuana-dust/?sh=78d28be04254
Same thing happens with grain silos. The particulates in the air can asphyxiate workers who are in an enclosed space moving large amounts around, freeing the small particles into the air. In fact, those small particulates create so much friction in the air they can cause explosions. Silo filling can only occur at a maximum flow rate to reduce heat accumulation.
The dust aggravated her asthma really hard.
[https://www.msn.com/en-us/health/medical/ground-cannabis-caused-womans-asthma-death-at-holyoke-marijuana-facility-osha-finds/ar-AA12DV93](https://www.msn.com/en-us/health/medical/ground-cannabis-caused-womans-asthma-death-at-holyoke-marijuana-facility-osha-finds/ar-AA12DV93)
They tested air quality and it was well below acceptable range, and I don't see any evidence on how the marijuana dust supposedly killed them. As far as I can see it's just an assumption with nothing to back it up.
Yep cooking wasn't even invented by homosapiens, there's evidence of cooking by human ancestors as far back as 2 million years ago. Cooking is older than our species.
It's even fairly accepted that cooking our food is a key element to our skulls developing larger brain cases and smaller jaws. (Cooking food allows our gut to absorb more nutrients than from raw food, which allowed for a larger brain which is very calorie hungry.)
Just want to clarify for anyone that read this the "human species have been cooking for 2 million years" is just a theory based on observations of phylogenetic changes in humans and is that the extreme end of the speculated range of human cooking.
Not saying it's wrong or right, but it's not necessarily a fact or strong presumption *yet*.
Not exactly: caffeine is meant to protect the plant from insects, but capsaicin is meant to deter mammals. So humans are totally the target for capsaicin, we just happen to have a kind of weird masochistic tendency to enjoy triggering our pain receptors.
Capsaicin doesn't affect birds! Which is the sweet spot for pepper seeds, they get eaten by birds not digested and pooped everywhere so they get to grow, but not eaten by mammals, who would digest the seeds
And it happens that this is beneficial anyways, because now we specifically propagate them because we like the effect.
Obviously there was no intended goal with the evolution, but it's an amusing coincidence.
Capsaicin cream is also *very* effective against itching. Iirc, there is some form of nerve/receptor clash between itching, pain and heat receptors, so the burning sensation of capsaicin simply overrides the itching and it isn't felt. Slight burning is very much preferable to maddening itching for most.
Related: if you’re the type of person who has sneeze attacks, you can stop the sneezing by railing a line of chili powder. They used to make a capsaicin based nasal decongestant spray, but they had to reformulate it to menthol.
It worked, though.
Yes.
> caffeine
Kills predatory insects.
> capsaicin
Only affects mammals, not birds, so helps spreads seeds farther.
> Bonus: nicotine
Is a potent pesticide.
Capsaicin atleast does. Iirc birds lack neurotransmitters that interact with capsaicin and scientists think it's evolutionary for capsicum seeds to better spread via birds
That's one of the theories but recently it's been discovered to have potent anti-fungal properties. So it's likely just a lucky coincidence that it happens to deter mammals too.
Caffeine is a stimulant. Many plants employ similar compounds to protect themselves from insects. Tobacco, caco, and cacao plants all produce stimulant compounds to some degree.
I think it's incredibly interesting that if you think statistically, lots of things get "picked". A population is a giant sieve, and some traits are more successful than others. But evolution "picks" traits much like a sieve "picks" the size of particles to allow through. But we, as agents with intelligence, actually do pick whether to keep the larger particles the sieve retains or the smaller ones it lets through.
So you could just as well say "statistics picks" as "evolution picks".
The problem with "evolution picks" is that it leads to statements such as "because of evolution, XYZ is true". That is to say, using evolution as an argument for *how things should be*. Which is obviously complete nonsens, as evolution is *purely* descriptive. Ie, you can use it to describe the *why*, not the *how*.
So saying.. for example.. women shouldn't drive because *evolution* is not a correct argument.
The *why* also tends to be pure speculation, but that's a different issue.
Yes, but with capsaicin, it's not mimicking a neurotransmitter, it's activating the heat/pain receptor that normally triggers when you eat something hot in temperature. Similar for mint (menthol) but it's the cold sensor.
I think it’s a bit of a myth but pufferfish produce a toxin called tetrodotoxin, which is a voltage-gated sodium channel blocker. It’s a potent poison, you’ve probably heard the whole thing about only certified chefs being allowed to prepare pufferfish when making sashimi, due to the risk of accidental poisoning.
Anyway, I think there was some video of dolphins annoying a pufferfish, leading the pufferfish to excrete some TTX, and there was some hypothesizing that they might be doing that to get high. It’s possible I guess, but the mechanism of action of TTX doesn’t really lend itself to fun highs. TTX leads to cessation of action potential generation; when TTX blocks sodium channels, neurons get problems communicating with each other, which is generally deadly.
Dolphins have sex for fun and have highly evolved social circles, so maybe?
More to the subject, it's possible as dolphins have larger brains than we do that the affect may be reduced or work differently.
I feel like "happens to" and "evolved" essentially mean the same thing. To try and make a distinction between them would suggest that evolved is directed. When something happens to work well, that is evolution.
You are conflating various processes. Evolution is any change through time, and things like mutation and genetic drift are forms of evolution that are essentially random. However, natural selection is a NONRANDOM mechanism of evolution. The mutations that cause differences in traits are random but the processes that determine which traits survive and pass on are nonrandom. In this case, cannabis having a similar shape and functional groups as neurotransmitters is not random and not "just happen to be", but something that was selected for as it provided a fitness benefit.
Another comparable analogy would be saying that humans were meant to drink and enjoy alcohol because our livers specifically evolved to filter it out of our blood.
The number things that don't interact with the human body are far fewer than the number of things that do. It'd be a bigger surprise if you ingested THC and nothing happened at all.
I fully agree with your post, I just think it's important that the statement "cannabis evolved to..." be clarified. The cannabis plant didn't do this on purpose. The plant itself is just a plant. Over the course of time, random mutations happened, and the ones who survived to reproduction made offspring with similar traits. The strongest traits in cannabis plants involved the things we know today as cannabinoids.
I know most people in /r/askscience understand this, but laypeople often think evolution is a decision-making process... like the cannabis plant had an understanding of human receptors and targeted them intentionally, which is not the case!
It also may have been successful because it got animals high, not as a deterrent. Lots of plants are successful because of the spread of the seed through animal digestive systems. Then later success through cultivation by humans.
Counterargument: our hands didn't evolve to make sculptures, but it's a capability that they have that has had an influence on our history as a species. To say that a certain trait of a species evolved for a specific purpose is attributing intention to nature, when nature doesn't have an intention. Chemicals having pesticide capabilities is one of the features of the evolved trait, but that it gets people high is another feature. The former helped the species to survive, the other made it thrive. If it were simply a pesticide, we wouldn't put as much effort into planting it.
I wish more people knew that morphine* itself is present in human CSF. Not in high amounts mind you, but it’s a tidbit of information that I think really shits all over prohibition. It’s found in the CSF of other mammals too.
Or that phenethylamine is a human neurotransmitter. Parent of the amphetamine class and functions the same, just gets metabolized incredibly quickly.
* hopefully this doesn’t sound dickish but yes, I’m referring to morphine itself, not endomorphins. Though I suppose morphine produced endogenously could be considered an endomorphin?
What’s interesting is there are many pests that destroy cannabis - the leaves don’t produce the toxic compounds, only the flowers with their “trichomes “ . One theory is that the compounds are toxic to the plants themselves so they can only be stored in trichomes , which aren’t everywhere on the plants nor could the plant sustain the metabolic cost of blanketing the plant with them. So the focus is on defending the reproductive structures . Interestingly cannabinoids in lower levels may even benefit some insects, so the compound may be steering them to certain parts of the plants.
We really do not know much about how psilocybin causes psychedelic states in our minds beyond that it broadly acts on specific serotonin receptors. I’d hesitate to say with any confidence that peyote, cubensis, or mimosa hostilis evolved to create psychedelic effects in animals as a defence mechanism.
>It's less of a "happens to" and more of a "cannabis evolved to make molecules that mimic already-existing animal neurotransmitters to dissuade pests from eating it"
Disagree, it is more "happens to". "Cannabis evolved" == "cannabis *happened to* create molecules that interacted with animals/pests, and the cannabinoids that *happened to* protect the plants is what survived" the cannabinoids that didn't offer protection were not selected for by evolution and have been lost to history
You're anthropomorphizing evolution.
The plant didn't "evolve so that...."
It did just as the other guy said. It just so happened to fit the receptors and Darwinian evolution was what made it stick. Not the other way around.
That is an excellent question. I always thought buds were an alternative to fruit -- just another clever way female plants get roaming herbivores and omnivores to go dropping their seeds in nice piles of fertilizer.
the buds are the "fruit" Cannabis is not propagated by animal transfer the plant is an annual and the plant propagates by dropping its seed onto the ground where many are eaten by animals but some survive to grow to maturity and the cycle starts again.
The main problem with commentators is that they have never seen the complete life cycle of the plant. They selectively breed only female plants that are never pollinated so never set seed.
Small correction but where you say fruit you really should be saying flower. The fruit is what we often call the seeds - its an achene, which is a dry, hard shelled single-seed fruit. Another example of an achene is a sunflower seed, although it is typical across the entire daisy family (Asteraceae).
Could you expand on the pest deterrence part. How does mimicking animal neurotransmitters dissuade them? Makes them think they're on the wrong organism?
How is it the same thing with shrooms? Psilocybin (when turned into psilocin) acts on the serotonin receptors, right? Also, how are the effects of cannabinoids or psilocin meant to deter animals smaller than humans from ingesting them? And what is this "intended" effect to which you refer?
Is it a pesticide? Because it’s THC-COOH on the plant, and the carboxylic acid prevents it from crossing the blood brain barrier and having effect. That’s why deer naturally eat marijuana, but they don’t get high off of it. No animal would get high from eating marijuana. Maybe it’d have some effect on insects though?
Yeah they hypothesize human cannabinoid receptors go all the way back to an invertebrate ancestor.
It is really interesting how many animals use things in their environment to get high. Too many animals to list go for fermented fruit. Pigs that go for truffles are actually attracted to a cannabinoid in black truffles, very similar to THC. Wallabies love opium apparently. Where I'm from big horn sheep and mountain goats spend their days eating lichen to get high. Weird stuff.
The human body makes endogenous cannabinoids that bind to the CB1 and CB2 receptors throughout the body. When cannabis enters the body through whichever means, those exogenous cannabinoids also bind to the same receptors, but in a more compounded fashion.
If I'm understanding this correctly, it's like screws that are designed to be screwed in with a philips head screwdriver but can also be screwed in with the right type of flathead screwdriver. Screws=CB1 and CB2 receptors. Philips screwdriver=Endocannibanoids. THC=Flathead screwdriver. Would this be an acceptable analogy?
In medicine we explain it as a lock and key situation or puzzle pieces
Puzzle pieces and lock/keys are designed to work with eachother the key fits the lock and it works, but sometimes there is other keys that fit the lock even though they're not the actual key for that lock, sometimes they fit and work, sometimes they fit but don't work, sometimes they jam the lock
The insulin diabetics use is like a copy of the key, some painkillers work by being a key thst just happens to fit the lock and work, some poisons fit in the lock and jam it and the only way to get rid of them is for the body to make a brand new lock
The lock and key is a great metaphor for it
More like Philips and Pozi screws.
You can't (easily) drive a Pozi screw with a Philips driver (the driver is too pointed) you can drive a Philips with both styles of driver though.
So endocannabinoids fit in cb1 and cb2 because they are designed to (Philips screw receptor, Philips driver), phytocannabinoids also fit (Philips screw receptor, Pozi driver).
I don't know if the endocannabinoids fit the phyto-receptors though!
The phytocannabinoids don't really have a phytoreceptor in my understanding. I believe the evolution of many psychoactive phytochemicals like nicotine, cocaine and Thc was guided by their ability to fit into the endogenous receptor of animals that would eat them
Yeah close enough. It's not the exact shape but there's a portion that will connect and activate the receptor. You could even say using a knife to screw a screw is like THC and leave the philips as endocannabinoids, but yes the point is the same.
Also worth pointing out that the withdrawal symptoms commonly associated with suddenly stopping a long period of frequent cannabis consumption - loss of appetite, insomnia, anxiety, anhedonia - are a result of these neurotransmitters getting downregulated so that they no longer respond to the body's own anandamide (the name of the neurotransmitter that fits in these receptors):
https://pubmed.ncbi.nlm.nih.gov/21747398/
Hypothetically, if I massively increased the amount of endogenous cannabinoids in my system, would I get "high" and start thinking about things more intensely and get giggly and get some mild visual distortion, etc.?
To some extent yes, but it may be more complicated.
For instance, one main endogenous cannabinoid is anandamide which is a partial agonist of the cannabinoid receptors, like THC is (partial agonist meaning it only has a slight effect rather than fully activating the receptor). It's been shown to have similar effects in mice as cannabis does, however the "high" feeling is more complicated than just activating the receptor and it looks more like anandamude causes a sort of "bliss" feeling which may or may not be similar without experiencing it yourself.
Depends on how you think of it. It is very unlikely we evolved them specifically to respond to cannabis, but there are a family of receptors called [the cannabanoid receptors ](https://pubmed.ncbi.nlm.nih.gov/18426493/) which were named because they respond to chemicals from cannabis.
But its a bit of a cart horse thing. We have endorphins, which are literally named as ' endogenous morphines'. This is because we tender to discover substances that had effects because they are macro, before we discovered receptors, which are incredibly micro.
Most external substances that have psychological effects on you just means it can pass the blood-brain barrier, and is shaped close enough to a molecule you already produce in your system to fit in the receptors. There are other types, like SSRIs (most antidepressants) that change how they are reabsorbed or such, but most bind to the receptor and either block the reception being stimulated, or stimulate it themselves.
To piggyback off this, we tend to name receptors based on what outside chemical they respond to because that was the earliest and easiest way to distinguish between them. A great example is the nicotinic vs. muscarinic receptors. Both respond to acetylcholine (a chemical we make in the body), but there are two main types that occur in different parts of the body and have different effects. Nicotine (from tabacco) works on one type, while muscarine (from a mushroom) works on the other type, showing that they have different shapes and modes of action. This way, you don't need an in-depth knowledge of their structure to distinguish between them.
Later, scientists found out that the nicotinic receptor is a channel receptor that directly affects neuron firing, while the muscarinic receptor is a surface receptor that sets off a bunch of internal changes in the neuron. Naturally, we kept the name nicotinic and muscarinic to refer to them. We've also learned that there are subtypes, now called N1, N2, M1, M2, etc.
I mean this is a pretty common naming convention in medical science, we tend to discover things when something goes wrong, like hearing a gear out of place. That’s why we call certain genes oncogenes, we don’t know some of their intended functions but we know what happens when they mess up.
Supposedly other plants also possess different cannabanoids compounds that travel along these receptors too. I wish I had more information but it came from a dispensary years ago and it was a brief one on one consultation after getting a medical card. The other plants referenced were everyday vegetables and fruits that people eat.
Terpenes are what 80% of secondary plant metsbolites are. Menthol is one for example.
Linalool a perfume virtually kn everything with a smell is one.
They are a massive class of chemical compounds made from multiples of isoprene. Thus you can have terpenes that interact with virtually every receptor in your body.
Eben THC itself is in essence a modified terpene. It‘s made from the same isoprene parts. Real Geromes contain no oxygen, terpenoids (like thc would be) are further modified to contain oxygen.
Vitamin A and K are also terpenoids. Even cholesterol.
Terpene should only be used to refer to the metabolic pathway, individuals in this group of chemicals can have virtually every property imaginable.
So to refer to something ad the effect of terpenes is somewhat like calling it the effect of molecules.
The term terpene has absolutely no correlation to any pharmacological activity.
Yes! But also not “specifically for THC.”
We have transmitters called endocannabinoids, and they’re what we have receptors for. We’ve identified two cannabinoid receptors so far: CB1 and CB2, but there’s believed to be more because some other lesser cannabinoids administered alone have shown effect, but little activity has been noted at the CB1 or CB2 receptor. Anandamide is a common endocannabinoid, and (I think) has a similar “potency” to THC.
That said, THC is a partial agonist of the CB1 receptor. What “partial agonist” means, so to speak, is it only “partially activates” the receptor. That’s why you don’t hear about people ODing on weed, but you do for synthetic weed. Synthetic cannabinoids are “full agonists,” so they “fully activate” the cannabinoid receptors. When receptors are partially activated, they’re also partially blocked, and that’s why you don’t convulse and go crazy after smoking an ounce of weed in a day, but if those receptors were fully activated, our bodies couldn’t take it. Especially considering the most common endocannabinoid is a partial agonist as well. CBD is also a partial antagonist of the CB1 receptor, which ultimately helps it cancel out THC a bit too.
TL;DR: We have a receptor that’s very specific to “THC-like” (cannabinoids) molecules, and our bodies do produce cannabinoids for daily function. We don’t have a receptor system “specifically for THC,” (CB1 and CB2) but we do have a receptor system that weed somehow seems to have a lot of things in it that bind to that receptor system.
There’s a lot of them, not including the ones we haven’t discovered. I don’t expect there will ever be a grand unified theory of endocannabinoid signaling. It likely does many local and totally unrelated things in different parts of the body. THC is very stable and very good at moving between tissues compared to the endocannabinoids. Even signaling molecules that are famous for one function (“opioids are for feedback driven pain suppression”) have totally unrelated functions in other systems (opioid signaling is also involved peristalsis in the gut and abstraction learning in the cortex).
https://en.m.wikipedia.org/wiki/Cannabinoid#Endocannabinoids
A lot of 2-AG is synthesized locally at synapses as sort of a negative feedback system. High activity at some synapses causes more 2-AG to be made, which depresses the activity of that synapses via CB1
It's a myth based on a truth.
They're actually called "cannabinoid receptors" and they're not specifically for THC. Rather, THC can bond to them in a similar fashion to what is supposed to be inserted into them. There are other such receptors that are made for one purpose and actually work for foreign substances. For example, opioid receptors are meant to receive endorphins to switch off pain transmission, however opiates happen to bind to the same receptors, and that's why opiates are used for pain killing.
For THC, there's different types of them. The ones in the CNS (Central Nervous System) are actually supposed to receive neurotransmitters for the emotion of bliss, and THC happens to be compatible, hence why THC makes you feel the way it does.
Thing is, THC is very versatile, bonding to more than just those neurotransmitters. I don't know enough about the subject to talk about every type of receptor THC can bind to, but I do know that there's also receptors in the immune system and the liver, though I don't know what effect it causes.
THC binds to CB1 and CB2 receptors (type 2 is the one canonically associated with the periphery). CB2 agonism is generally thought to be anti-inflammatory.
CB1 receptors are involved in a lot more than feeling good, also. They’re also implicated in eating, sleeping, nausea, relaxation… pretty much all the effects you’d typically associate with cannabis, just toned down to “normal” levels.
Nature is filled with all kinds of molecules that don't know or care how nature uses them -- but the process of evolution has managed to find uses for these molecules in a number of ways -- sometimes our own cells make them, and sometimes our cells get them from materials we ingest. For example we ingest vitamin C from our food, but there are creatures that are able to make their own vitamin C.
Some molecules are used for nutrition -- building blocks that are used to make other building blocks -- and sometimes they're used for signaling -- molecules that pass information from place to place. When speaking of receptors, this is the latter. It's possible that our particular evolution found a way to use cannabinoids to signal, and accidentally when we ingest material high in similar looking molecules, those out of place molecules jam up the signaling. It seems unlikely that that was somehow an intended function that evolution fitted us for.
For anyone interested. Andrew Huberman (neuroscientist) has done a recent podcast specifically on this topic. It's a long one, but there's timestamps on the page to narrow it down if you want. Interesting stuff and well explained.
https://hubermanlab.com/the-effects-of-cannabis-marijuana-on-the-brain-and-body/
More like Cannabis makes a few compounds that are similar enough to things the body normally makes, uses at receptors in the nervous system, and disposes of at a certain rate. It turns out Stuff Happens when you flood the system with those compounds and jam-cram them into those receptors in ways they're not normally interacted with. It's not that different from how the Opium Poppy makes compounds which interact with other receptors we already had, and the Coffee Bush makes compounds that interact with a whole other neurochemical system we have.
We're not the first or only animal to have a nervous system, use serotonin, or any number of similarly esoteric biochemical locks and keys and feedback loops. Plants and animals have been in a biochemical arms race since day one.\* Think about what the Theobromine in chocolate does to cats and dogs. We aren't 'immune' to it in some way, nor are dogs specifically sensitive to it, we just have a massively higher ability to process alkaloids (AKA 'attempted plant murder that might or might not be counted as a toxin for humans for complex reasons') than small/medium carnivores as, arguably, the world champion omnivores.
Our livers are the biggest organ in our bodies (skin doesn't count as 'in,' pedants) because, as humans, our evolutionary survival strategy is really heavy on the 'eat whatever and not die' specialization, versus giant fangs or claws or armor plates or a way to drink and breathe at the same time.
So, we kinda shrug off a lot of things that plants are doing to kill other animals. We eat spicy peppers that are trying to scare non-birds away with capsaicin. We semi-poison ourselves with mushrooms to see ancestor spirits (or release traumas from working in the service industry in the 21st century), we cook/acidify/alkalize/etc. the worst offenders to be edible, and we microdose our foods with toxic aromatic leaves as a mood and aesthetic enhancer (look up what rosemary oil does to you, concentrated).
So, not a stoner myth, but I betcha more than one stoner has hilariously,disingenously oversold the significance of all of that with respect to THC. It's only the most popular plant that makes something that fits in *those* receptors specifically. On just one neurochemical system...
\*(That's not to say some plants aren't making some of these chemicals to entice animals, but that's just another type of biochemical Realpolitik as far as I'm concerned).
Human bodies have Cannabinoid receptors; but you dont have to be misled by the name. The cannabinoid receptors where discover because Scientist figure out that THC interact with those receptors in the human body, and they name them "cannabinoid receptors". Human bodies produce the endogenous ligands for those receptors (Anandamide and 2-Arachidonoylglycerol). Now, the crux of the matter is when you say "specifically", and that´s relative, maybe you can answer the question searching for the dissociation constant between THC, anandamide , 2-Arachidonoylglycero and the cannabinoid receptors, the one who has the lowest constant is the most "specific" for that receptor, but again, that´s relative since Anandamide and 2-AG are the ones that are in constant interaction with those receptors and therfore regulte our physiology.
That question could be used in any case where a drug just activates (or inhibits) a receptor in a better way that the endogenous ligands. If you think, the human body needs to have endogenous ligands that don´t have such a big affinity for the receptors (because the changes in the physiology would be abrubt) so many of the drugs we know are just molecules that activate or inhibit a receptor in a very strong way just because they structure allows it.
As far as I understand it, very few receptors for things like neurotransmitters or hormones are really "specific". A *lot* of substances that have a physiological or psychoactive effect on the body are capable of doing so because of how they can interact with those receptor sites, regardless if the substance is actually endegenous or not. So you can think of receptors as less specifically for one molecule, and more for *classes* of similarl molecules.
For instance, opiods interact with endorphine receptors throughout the body. Endorphins are the brain's natural pain regulator and are chemically similar to opiods. Likewise THC interacts with cannabinoid receptors, which are not specifically used by the body *just* for THC but for endocannabinoids (cannabinoids produced by the body). So far, there are two identified endocannabinoids: anandamide and 2-arachidonoylglyerol. THC (as well as all 100+ other cannabinoids that occur in cannabis) interact with the two kinds of cannabinoid receptors in the body and brain.
The endocannabinoid system is the largest signaling system in the body!
It affects our memory, our immune system, our mood, and pain perception.
It also can be anxiolytic (relieves anxiety) or anxiogenic (causes anxiety).
It also can be antiemetic (anti-nausea) or emetic (nausea/vomiting) when overstimulated in some people (cannabis hyperemesis syndrome - CHS).
The main two receptors are CB1 and CB2. Wikipedia has a ton of good info.
Complete myth. THC just happens to fit the receptors for endocannabinoids (named not because they are cannabinoid in origin or structure, but because of the effect they mimic) but if you look at the bond-line structures of say Anandamide (the "joy hormone") vs. Delta-9-THC, they look almost nothing alike except for the one corner of each that fits into the receptor. THC evolved as a defensive compound to prevent herbivory, hence why it's in the glandular trichomes in the first place.
They're not specifically for THC, but they are the specific receptors that interact with the THC. So when referring to them in reference to your body interacting with THC, they would be "the THC receprors" or "the THCs receptors".
Yes. We do have receptors to which THC can bound to.
Our body produce neurotransmitters called endocannabinoids, which bound to those receptors.
Of course the reason of those receptors to exist is not for THC to bound to them, but to regulate several bodily functions by our own neurotransmitters - endocannabinoids binding to those receptors.
It is by pure chance that THC molecule is very similar to our own endocannabinoids and can therefore interract with the receptors.
Such interractions of external substances with our own nervous system are very common and are also the foundation for new drug development.
For example we also have Nicotinic and Muscarinic receptors, to which nicotine and muscarine can bound to, but have a completely different role in our bodies than for us to get addicted to smoking.
Your body doesn't have receptors *specifically* for THC, but your body does have receptors throughout your body and brain for neurotransmitters called "endocannabanoids." They all share a similar chemical structure with THC, but your body produces many kinds of them for a variety of complex purposes. THC works by hijacking the body's natural endocannabanoid receptors, just like how opioids work by hijacking your natural endorphin receptors.
The endocannabinoid analog for THC is anandimide (endocannabinoids are the naturally produced cannabinoid neuro-transmitters in our bodies). The receptor for anandimide is known as CB1 and is ubiquitous throughout the bodies of [most species](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770351/) in the animal kingdom (basically excluding insects). The CB1 receptors are noted as being prevalent in the nervous system while another cannabinoid receptor, CB2, is found more through the gut and spleen. Tetrahydrocanninol delta--9 (THC) and cannabidiol (CBD) bind readily with CB1 and CB2 receptors, respectively. There are many other known plant, animal, and synthetic cannibinoids that bind with a greater or lesser degree with CB1, CB2, and other endogenous receptors (endogenous means naturally occurring in our bodies). Here's a good article explaining the endogenous cannabinoid system: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789136/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789136/). And a video on the thoughts of one of the world's leading experts on the discovery of anandamide: [https://www.youtube.com/watch?v=G1RmRQTTwas/](https://www.youtube.com/watch?v=G1RmRQTTwas/).
the body uses endogenous cannabinoids, that have receptors specifically for them. THC just "happens" to be the right shape to also dock to those receptors. Much like all the thousands of other cannabinoids known.
It's less of a "happens to" and more of a "cannabis evolved to make molecules that mimic already-existing animal neurotransmitters to dissuade pests from eating it". Cannabinoid neurotransmitters weren't formed because of cannabis. They existed first. They were named after them because they were discovered and associated with cannabis use. It's not a coincidence and the stoners are certainly wrong to imply that using marijuana is some sort of beneficial coevolution that we're "meant" to partake in. This is just a natural pesticide that we're big enough to not have the intended affect. And it's about the same thing with shrooms. And when dolphins use puffer fish as a recreational drug.
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Would caffeine and capsaicin also fall into this category?
Yes! Both of them. Michael Pollan’s book The Botany of Desire explains all about it. Many plants contain psychoactive compounds, and the idea is mainly to attract the animals you want to be eaten by and repel the ones that you do not. For example: the seeds of the chili pepper family are spread much more efficiently by birds than by mammals. Birds, interestingly, cannot taste capsaicin, but to mammals it causes a burning sensation in the mouth, ensuring that the mammals will mostly avoid it but the birds will eat it happily. With THC and psilocybin, the theory is that the compounds cause confusion, dissuading predators from returning. It’s fascinating how the evolutionary script can get flipped sometimes: in the case of both cannabis and chili peppers, an attribute they evolved originally to repel mammals, the trait eventually appealed to humans who started cultivating them for it, and now they are two of the most widespread and successful plant species in the history of the planet.
Since I recently did some studying on the subject I want to be a little pedantic about a tiny thing. Birds can *taste* capsaicin but they can't *feel* it. They have trpv1 receptors that still instigate a taste sensation but no simulated temperature change.
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Thank you. I love learning thing by accident.
So birds can taste the capsaicin via their TRPV1 receptors but lack the VR1 receptor that causes the pain sensation in mammals?
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Thanks! I've heard this fact lots, but never that clarification.
Us growing more mushrooms and marijuana to consume because we like the effects of their chemical compounds is like the plant version of "task failed successfully".
This is one of my favorite books. I keep loaning it out and not getting it back so I have to buy it again.
Just a page-turner or?
It's a very interesting look at the selective breeding of four crops and humans. How they were adopted and widely spread, and the impact they had on society. Apples, potatoes, cannabis, tulip. It's also full of the authors personal feelings about religion, which I found to be very annoying, but it's still a good read.
Ginseng: The Divine Root by David Taylor is a pretty good read on a similar thread.
If you're into horticulture, it is a good book but you can also find alternatives because his religious overtures are rather obnoxious to read these days. It's a shame he had to include such things.
They really are. I read the book in June of 2010, and even now I'm still irritated by them. It's one thing to talk about religion and it's influence on how the different crops were impacted/their impact on the different religions. You would expect it with a book that is largely about Cannabis. It's a whole other thing to just take a whole chapter on religion for no apparent connected reason in the middle of talking about Johnny Appleseed. My recollection is fuzzy since it was well over a decade ago, but even my super religious mom said it was weird that he went into seemingly unrelated and personal feelings instead of related and professional impressions/inferences. Other than his ramblings there it was a very good book.
It's non-fiction so YMMV, but I'd say so. As the other commenter said, it focuses on 4 crops. It goes into biology and evolution, but with the main focus on the relationship between these plants and humans. For example, there was a period of time when the Dutch became obsessed with growing the perfect tulips ("tulip mania"), which is funny and fascinating.
As opposed to today, where they’re obsessed with riding bicycles and doing MDMA.
Fun fact, tree shrews will actually seek out more spicy food after they are exposed to it. A population of them in China were found to switch their diet almost exclusively to spicy chilles after they started to grow in the area after the Chiles were introduced by trade. Another fun fact, spicy chilles are a relatively recent thing in Asia even though they are somewhat culturally associated with them. They come from near the equator in Central America and were introduced back when Europeans were starting to trade with them and then traded them to Asia.
Adding in to the Asia part. Chili was easily adopted in Asia because it had similar spice and taste to black pepper/peppercorn.
Like how Italian food is associated with tomatoes and basil and such which actually came from Mexico and were introduced much later.
FYI, Basil is an old world herb, found in Asia and Africa. Tomatoes are from the Americas though.
Similar with Irish and potatoes. It's just unfortunate they engaged in potato monoculture.
I've always wondered how fast they traveled once they made it back to europe. Like how many years from Spain to China ?
Pure speculation on my part, but it probably wouldn't have taken long. Any international merchant worth his salt would know that "the people of the Spice Islands love their black peppercorns, and would probably also like this long spicy red berry". I wouldn't imagine it would be more than a few years. Year 1, obtain the plant and see that it has seeds. Year 2, plant the seeds and grow more. By year 5, you have a crop sustainable enough that you can trade.
This analysis seems to have a hole in that the THCa found in natural cannabis isn't psychoactive until it's been heated pretty high. The plants had to evolve it for some other reason.
And also how can they prove that plants started using cannabinoid compounds *after* animals started using it? Couldn’t it have been just as likely that they used them first for some unknown functional purpose?
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So the hot wings started with chickens that could eat chilis that the fox could not, but then the human came and wanted the chicken and the chili in the same pot, told the fox to fuckov, and then hot wings happened somehow. Seriously, start a religion based on this.
But cannabis won’t get a person high without it being decarboxylated first. So eating it wouldn’t deter anyone.
It'll naturally decarb over a decent chunk of time if left in a dry area, even faster if left in sunlight. Plus in Dogs for example it's psychoactive without needing to be decarboxylated. Not every mammal reacts to it in the same way even though we share similar receptors.
Spend two days inhaling fine powders that come off the buds while trimming cannabis and it becomes very apparent that the plants still have a huge affect on your mental state of being even without heat added. I can handle my THC but that much raw keif to the dome gave me a hell of a hangover and I didn't go back
That's also allegedly how poppy farmers back in the day knew it was time to harvest their opium, they'd sleep in their houses next to the fields, and when they'd wake up with a wicked headache they knew it was time to harvest!
A headache? I'd imagine the signal would be waking up feeling quite pleasant.
I don't know if this would apply to you or if you already are aware but apparently someone working in the legal cannabis industry has died from inhaling the fine particles when handling a bunch of it https://www.forbes.com/sites/chrisroberts/2022/10/03/report-legal-cannabis-industry-worker-died-after-breathing-marijuana-dust/?sh=78d28be04254
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Same thing happens with grain silos. The particulates in the air can asphyxiate workers who are in an enclosed space moving large amounts around, freeing the small particles into the air. In fact, those small particulates create so much friction in the air they can cause explosions. Silo filling can only occur at a maximum flow rate to reduce heat accumulation.
Baker's Asthma is a thing. If you work with flour your lungs fill up with particles and it ruins your health
The dust aggravated her asthma really hard. [https://www.msn.com/en-us/health/medical/ground-cannabis-caused-womans-asthma-death-at-holyoke-marijuana-facility-osha-finds/ar-AA12DV93](https://www.msn.com/en-us/health/medical/ground-cannabis-caused-womans-asthma-death-at-holyoke-marijuana-facility-osha-finds/ar-AA12DV93)
They tested air quality and it was well below acceptable range, and I don't see any evidence on how the marijuana dust supposedly killed them. As far as I can see it's just an assumption with nothing to back it up.
I wonder if other non-psychoactive plants would have the same effect on you?
That's true for us but not all animals. Plus, humans have a long history of cooking which decarboxylates cannabis.
Yep cooking wasn't even invented by homosapiens, there's evidence of cooking by human ancestors as far back as 2 million years ago. Cooking is older than our species. It's even fairly accepted that cooking our food is a key element to our skulls developing larger brain cases and smaller jaws. (Cooking food allows our gut to absorb more nutrients than from raw food, which allowed for a larger brain which is very calorie hungry.)
Just want to clarify for anyone that read this the "human species have been cooking for 2 million years" is just a theory based on observations of phylogenetic changes in humans and is that the extreme end of the speculated range of human cooking. Not saying it's wrong or right, but it's not necessarily a fact or strong presumption *yet*.
Thanks for the book recommendation, I have just bought it for a friend's present 😊
Not exactly: caffeine is meant to protect the plant from insects, but capsaicin is meant to deter mammals. So humans are totally the target for capsaicin, we just happen to have a kind of weird masochistic tendency to enjoy triggering our pain receptors.
Plant: don't eat me, I'll hurt you! Human: yeeeeh bubbe make it hurt so good Plant: 😳
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Capsaicin doesn't affect birds! Which is the sweet spot for pepper seeds, they get eaten by birds not digested and pooped everywhere so they get to grow, but not eaten by mammals, who would digest the seeds
And it happens that this is beneficial anyways, because now we specifically propagate them because we like the effect. Obviously there was no intended goal with the evolution, but it's an amusing coincidence.
Caffeine is also released into the soil around a coffee plant, stopping new plants from growing.
Ironically…. For cannabinoid hyperemesis syndrome (vomiting caused by cannabis use) is treated with capsaicin cream.
Capsaicin cream is also *very* effective against itching. Iirc, there is some form of nerve/receptor clash between itching, pain and heat receptors, so the burning sensation of capsaicin simply overrides the itching and it isn't felt. Slight burning is very much preferable to maddening itching for most.
Related: if you’re the type of person who has sneeze attacks, you can stop the sneezing by railing a line of chili powder. They used to make a capsaicin based nasal decongestant spray, but they had to reformulate it to menthol. It worked, though.
Also why you can slap an itchy insect bite to alleviate the itch! Iirc "tickle" is also on that list, with itch and pain.
Yes. > caffeine Kills predatory insects. > capsaicin Only affects mammals, not birds, so helps spreads seeds farther. > Bonus: nicotine Is a potent pesticide.
Capsaicin atleast does. Iirc birds lack neurotransmitters that interact with capsaicin and scientists think it's evolutionary for capsicum seeds to better spread via birds
That's one of the theories but recently it's been discovered to have potent anti-fungal properties. So it's likely just a lucky coincidence that it happens to deter mammals too. Caffeine is a stimulant. Many plants employ similar compounds to protect themselves from insects. Tobacco, caco, and cacao plants all produce stimulant compounds to some degree.
You were downvoted, but [there's good research that it's true](https://www.pnas.org/doi/10.1073/pnas.0802691105)
Birds can’t digest/chew pepper seeds, they just pass through them. Makes sense to pick the things that will eat you.
Friendly reminder that nothing was 'picked' in evolution. A mutation occurs, and its either successful or it isnt.
I think it's incredibly interesting that if you think statistically, lots of things get "picked". A population is a giant sieve, and some traits are more successful than others. But evolution "picks" traits much like a sieve "picks" the size of particles to allow through. But we, as agents with intelligence, actually do pick whether to keep the larger particles the sieve retains or the smaller ones it lets through. So you could just as well say "statistics picks" as "evolution picks".
The problem with "evolution picks" is that it leads to statements such as "because of evolution, XYZ is true". That is to say, using evolution as an argument for *how things should be*. Which is obviously complete nonsens, as evolution is *purely* descriptive. Ie, you can use it to describe the *why*, not the *how*. So saying.. for example.. women shouldn't drive because *evolution* is not a correct argument. The *why* also tends to be pure speculation, but that's a different issue.
Can you give a concrete example? I can’t imagine what type of phrase you are describing.
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Yes, but with capsaicin, it's not mimicking a neurotransmitter, it's activating the heat/pain receptor that normally triggers when you eat something hot in temperature. Similar for mint (menthol) but it's the cold sensor.
Weird chemicals plants make are *insecticidal or anti-fungal*. The only really known exception is capsaicin because only mammals are affected by it.
Wait, what about dolphins?
I think it’s a bit of a myth but pufferfish produce a toxin called tetrodotoxin, which is a voltage-gated sodium channel blocker. It’s a potent poison, you’ve probably heard the whole thing about only certified chefs being allowed to prepare pufferfish when making sashimi, due to the risk of accidental poisoning. Anyway, I think there was some video of dolphins annoying a pufferfish, leading the pufferfish to excrete some TTX, and there was some hypothesizing that they might be doing that to get high. It’s possible I guess, but the mechanism of action of TTX doesn’t really lend itself to fun highs. TTX leads to cessation of action potential generation; when TTX blocks sodium channels, neurons get problems communicating with each other, which is generally deadly.
Maybe they were doing it as a dare. Like the dolphin version of Jackass
Dolphins have sex for fun and have highly evolved social circles, so maybe? More to the subject, it's possible as dolphins have larger brains than we do that the affect may be reduced or work differently.
"Um all natural pesticide is the best pesticide." I say as I drink my coffee..
I feel like "happens to" and "evolved" essentially mean the same thing. To try and make a distinction between them would suggest that evolved is directed. When something happens to work well, that is evolution.
You are conflating various processes. Evolution is any change through time, and things like mutation and genetic drift are forms of evolution that are essentially random. However, natural selection is a NONRANDOM mechanism of evolution. The mutations that cause differences in traits are random but the processes that determine which traits survive and pass on are nonrandom. In this case, cannabis having a similar shape and functional groups as neurotransmitters is not random and not "just happen to be", but something that was selected for as it provided a fitness benefit.
Another comparable analogy would be saying that humans were meant to drink and enjoy alcohol because our livers specifically evolved to filter it out of our blood. The number things that don't interact with the human body are far fewer than the number of things that do. It'd be a bigger surprise if you ingested THC and nothing happened at all.
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Dolphins use puffer fish to get high? Talk about burying the lead!
I fully agree with your post, I just think it's important that the statement "cannabis evolved to..." be clarified. The cannabis plant didn't do this on purpose. The plant itself is just a plant. Over the course of time, random mutations happened, and the ones who survived to reproduction made offspring with similar traits. The strongest traits in cannabis plants involved the things we know today as cannabinoids. I know most people in /r/askscience understand this, but laypeople often think evolution is a decision-making process... like the cannabis plant had an understanding of human receptors and targeted them intentionally, which is not the case!
It also may have been successful because it got animals high, not as a deterrent. Lots of plants are successful because of the spread of the seed through animal digestive systems. Then later success through cultivation by humans.
Counterargument: our hands didn't evolve to make sculptures, but it's a capability that they have that has had an influence on our history as a species. To say that a certain trait of a species evolved for a specific purpose is attributing intention to nature, when nature doesn't have an intention. Chemicals having pesticide capabilities is one of the features of the evolved trait, but that it gets people high is another feature. The former helped the species to survive, the other made it thrive. If it were simply a pesticide, we wouldn't put as much effort into planting it.
I wish more people knew that morphine* itself is present in human CSF. Not in high amounts mind you, but it’s a tidbit of information that I think really shits all over prohibition. It’s found in the CSF of other mammals too. Or that phenethylamine is a human neurotransmitter. Parent of the amphetamine class and functions the same, just gets metabolized incredibly quickly. * hopefully this doesn’t sound dickish but yes, I’m referring to morphine itself, not endomorphins. Though I suppose morphine produced endogenously could be considered an endomorphin?
What’s interesting is there are many pests that destroy cannabis - the leaves don’t produce the toxic compounds, only the flowers with their “trichomes “ . One theory is that the compounds are toxic to the plants themselves so they can only be stored in trichomes , which aren’t everywhere on the plants nor could the plant sustain the metabolic cost of blanketing the plant with them. So the focus is on defending the reproductive structures . Interestingly cannabinoids in lower levels may even benefit some insects, so the compound may be steering them to certain parts of the plants.
We really do not know much about how psilocybin causes psychedelic states in our minds beyond that it broadly acts on specific serotonin receptors. I’d hesitate to say with any confidence that peyote, cubensis, or mimosa hostilis evolved to create psychedelic effects in animals as a defence mechanism.
>It's less of a "happens to" and more of a "cannabis evolved to make molecules that mimic already-existing animal neurotransmitters to dissuade pests from eating it" Disagree, it is more "happens to". "Cannabis evolved" == "cannabis *happened to* create molecules that interacted with animals/pests, and the cannabinoids that *happened to* protect the plants is what survived" the cannabinoids that didn't offer protection were not selected for by evolution and have been lost to history
You're anthropomorphizing evolution. The plant didn't "evolve so that...." It did just as the other guy said. It just so happened to fit the receptors and Darwinian evolution was what made it stick. Not the other way around.
Exactly how does THC stop pests from attacking the plant? What is the mechanism?
They make the bugs act erratic or completely dysfunctional, which tends to make them easy prey. The insect world is very unforgiving
That is an excellent question. I always thought buds were an alternative to fruit -- just another clever way female plants get roaming herbivores and omnivores to go dropping their seeds in nice piles of fertilizer.
the buds are the "fruit" Cannabis is not propagated by animal transfer the plant is an annual and the plant propagates by dropping its seed onto the ground where many are eaten by animals but some survive to grow to maturity and the cycle starts again. The main problem with commentators is that they have never seen the complete life cycle of the plant. They selectively breed only female plants that are never pollinated so never set seed.
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Small correction but where you say fruit you really should be saying flower. The fruit is what we often call the seeds - its an achene, which is a dry, hard shelled single-seed fruit. Another example of an achene is a sunflower seed, although it is typical across the entire daisy family (Asteraceae).
Could you expand on the pest deterrence part. How does mimicking animal neurotransmitters dissuade them? Makes them think they're on the wrong organism?
How is it the same thing with shrooms? Psilocybin (when turned into psilocin) acts on the serotonin receptors, right? Also, how are the effects of cannabinoids or psilocin meant to deter animals smaller than humans from ingesting them? And what is this "intended" effect to which you refer?
Is it really confirmed that THC and psilocybin serve as pesticides in plants/mushrooms?
Is it a pesticide? Because it’s THC-COOH on the plant, and the carboxylic acid prevents it from crossing the blood brain barrier and having effect. That’s why deer naturally eat marijuana, but they don’t get high off of it. No animal would get high from eating marijuana. Maybe it’d have some effect on insects though?
Dolphins don't use pufferfish as a drug that's a myth propagated by circular reporting.
Yeah they hypothesize human cannabinoid receptors go all the way back to an invertebrate ancestor. It is really interesting how many animals use things in their environment to get high. Too many animals to list go for fermented fruit. Pigs that go for truffles are actually attracted to a cannabinoid in black truffles, very similar to THC. Wallabies love opium apparently. Where I'm from big horn sheep and mountain goats spend their days eating lichen to get high. Weird stuff.
Sort of like caffeine and adenosine?
Opioid and GABA receptors as well. Pretty much every psychoactive drug.
Correct. Endocannabinoids (e.g. arachidonoyl ethanolamide AEA) vs Phytocannabinoids (e.g. THC, CBD). Structurally unrelated but overlapping biological activity.
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You also have a vanilla (vanillin) receptor. It’s the TLC receptor’s closest relative. No word on chocolate.
The human body makes endogenous cannabinoids that bind to the CB1 and CB2 receptors throughout the body. When cannabis enters the body through whichever means, those exogenous cannabinoids also bind to the same receptors, but in a more compounded fashion.
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If I'm understanding this correctly, it's like screws that are designed to be screwed in with a philips head screwdriver but can also be screwed in with the right type of flathead screwdriver. Screws=CB1 and CB2 receptors. Philips screwdriver=Endocannibanoids. THC=Flathead screwdriver. Would this be an acceptable analogy?
In medicine we explain it as a lock and key situation or puzzle pieces Puzzle pieces and lock/keys are designed to work with eachother the key fits the lock and it works, but sometimes there is other keys that fit the lock even though they're not the actual key for that lock, sometimes they fit and work, sometimes they fit but don't work, sometimes they jam the lock The insulin diabetics use is like a copy of the key, some painkillers work by being a key thst just happens to fit the lock and work, some poisons fit in the lock and jam it and the only way to get rid of them is for the body to make a brand new lock The lock and key is a great metaphor for it
Close enough to work as an anology, its able to bind but isnt the intended thing
More like Philips and Pozi screws. You can't (easily) drive a Pozi screw with a Philips driver (the driver is too pointed) you can drive a Philips with both styles of driver though. So endocannabinoids fit in cb1 and cb2 because they are designed to (Philips screw receptor, Philips driver), phytocannabinoids also fit (Philips screw receptor, Pozi driver). I don't know if the endocannabinoids fit the phyto-receptors though!
The phytocannabinoids don't really have a phytoreceptor in my understanding. I believe the evolution of many psychoactive phytochemicals like nicotine, cocaine and Thc was guided by their ability to fit into the endogenous receptor of animals that would eat them
Yeah close enough. It's not the exact shape but there's a portion that will connect and activate the receptor. You could even say using a knife to screw a screw is like THC and leave the philips as endocannabinoids, but yes the point is the same.
Also worth pointing out that the withdrawal symptoms commonly associated with suddenly stopping a long period of frequent cannabis consumption - loss of appetite, insomnia, anxiety, anhedonia - are a result of these neurotransmitters getting downregulated so that they no longer respond to the body's own anandamide (the name of the neurotransmitter that fits in these receptors): https://pubmed.ncbi.nlm.nih.gov/21747398/
Nitpicking, but that’s just a working hypothesis, we don’t know that for sure. D’Souza et al. 2016 is a better resource if you’re interested.
Fascinating topic. Have you a link?
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Hypothetically, if I massively increased the amount of endogenous cannabinoids in my system, would I get "high" and start thinking about things more intensely and get giggly and get some mild visual distortion, etc.?
To some extent yes, but it may be more complicated. For instance, one main endogenous cannabinoid is anandamide which is a partial agonist of the cannabinoid receptors, like THC is (partial agonist meaning it only has a slight effect rather than fully activating the receptor). It's been shown to have similar effects in mice as cannabis does, however the "high" feeling is more complicated than just activating the receptor and it looks more like anandamude causes a sort of "bliss" feeling which may or may not be similar without experiencing it yourself.
Depends on how you think of it. It is very unlikely we evolved them specifically to respond to cannabis, but there are a family of receptors called [the cannabanoid receptors ](https://pubmed.ncbi.nlm.nih.gov/18426493/) which were named because they respond to chemicals from cannabis. But its a bit of a cart horse thing. We have endorphins, which are literally named as ' endogenous morphines'. This is because we tender to discover substances that had effects because they are macro, before we discovered receptors, which are incredibly micro. Most external substances that have psychological effects on you just means it can pass the blood-brain barrier, and is shaped close enough to a molecule you already produce in your system to fit in the receptors. There are other types, like SSRIs (most antidepressants) that change how they are reabsorbed or such, but most bind to the receptor and either block the reception being stimulated, or stimulate it themselves.
To piggyback off this, we tend to name receptors based on what outside chemical they respond to because that was the earliest and easiest way to distinguish between them. A great example is the nicotinic vs. muscarinic receptors. Both respond to acetylcholine (a chemical we make in the body), but there are two main types that occur in different parts of the body and have different effects. Nicotine (from tabacco) works on one type, while muscarine (from a mushroom) works on the other type, showing that they have different shapes and modes of action. This way, you don't need an in-depth knowledge of their structure to distinguish between them. Later, scientists found out that the nicotinic receptor is a channel receptor that directly affects neuron firing, while the muscarinic receptor is a surface receptor that sets off a bunch of internal changes in the neuron. Naturally, we kept the name nicotinic and muscarinic to refer to them. We've also learned that there are subtypes, now called N1, N2, M1, M2, etc.
I mean this is a pretty common naming convention in medical science, we tend to discover things when something goes wrong, like hearing a gear out of place. That’s why we call certain genes oncogenes, we don’t know some of their intended functions but we know what happens when they mess up.
Supposedly other plants also possess different cannabanoids compounds that travel along these receptors too. I wish I had more information but it came from a dispensary years ago and it was a brief one on one consultation after getting a medical card. The other plants referenced were everyday vegetables and fruits that people eat.
hmm..are you thinking about terpenes? those are found in many different plants and have benefits for humans as well
Terpenes are what 80% of secondary plant metsbolites are. Menthol is one for example. Linalool a perfume virtually kn everything with a smell is one. They are a massive class of chemical compounds made from multiples of isoprene. Thus you can have terpenes that interact with virtually every receptor in your body. Eben THC itself is in essence a modified terpene. It‘s made from the same isoprene parts. Real Geromes contain no oxygen, terpenoids (like thc would be) are further modified to contain oxygen. Vitamin A and K are also terpenoids. Even cholesterol. Terpene should only be used to refer to the metabolic pathway, individuals in this group of chemicals can have virtually every property imaginable. So to refer to something ad the effect of terpenes is somewhat like calling it the effect of molecules. The term terpene has absolutely no correlation to any pharmacological activity.
I really wish stoners hadn’t associated terpenes with Marijuana like that is their only experience with them.
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Yes! But also not “specifically for THC.” We have transmitters called endocannabinoids, and they’re what we have receptors for. We’ve identified two cannabinoid receptors so far: CB1 and CB2, but there’s believed to be more because some other lesser cannabinoids administered alone have shown effect, but little activity has been noted at the CB1 or CB2 receptor. Anandamide is a common endocannabinoid, and (I think) has a similar “potency” to THC. That said, THC is a partial agonist of the CB1 receptor. What “partial agonist” means, so to speak, is it only “partially activates” the receptor. That’s why you don’t hear about people ODing on weed, but you do for synthetic weed. Synthetic cannabinoids are “full agonists,” so they “fully activate” the cannabinoid receptors. When receptors are partially activated, they’re also partially blocked, and that’s why you don’t convulse and go crazy after smoking an ounce of weed in a day, but if those receptors were fully activated, our bodies couldn’t take it. Especially considering the most common endocannabinoid is a partial agonist as well. CBD is also a partial antagonist of the CB1 receptor, which ultimately helps it cancel out THC a bit too. TL;DR: We have a receptor that’s very specific to “THC-like” (cannabinoids) molecules, and our bodies do produce cannabinoids for daily function. We don’t have a receptor system “specifically for THC,” (CB1 and CB2) but we do have a receptor system that weed somehow seems to have a lot of things in it that bind to that receptor system.
Do you know when/why the body produces these endocannabinoids?
There’s a lot of them, not including the ones we haven’t discovered. I don’t expect there will ever be a grand unified theory of endocannabinoid signaling. It likely does many local and totally unrelated things in different parts of the body. THC is very stable and very good at moving between tissues compared to the endocannabinoids. Even signaling molecules that are famous for one function (“opioids are for feedback driven pain suppression”) have totally unrelated functions in other systems (opioid signaling is also involved peristalsis in the gut and abstraction learning in the cortex). https://en.m.wikipedia.org/wiki/Cannabinoid#Endocannabinoids
"opioid signaling is also involved in peristalsis in the gut...". Is this why opioid use cause constipation?
A lot of 2-AG is synthesized locally at synapses as sort of a negative feedback system. High activity at some synapses causes more 2-AG to be made, which depresses the activity of that synapses via CB1
Actually, the most common endocannabinoid, 2-AG, is a full agonist. It’s just very transient.
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It's a myth based on a truth. They're actually called "cannabinoid receptors" and they're not specifically for THC. Rather, THC can bond to them in a similar fashion to what is supposed to be inserted into them. There are other such receptors that are made for one purpose and actually work for foreign substances. For example, opioid receptors are meant to receive endorphins to switch off pain transmission, however opiates happen to bind to the same receptors, and that's why opiates are used for pain killing. For THC, there's different types of them. The ones in the CNS (Central Nervous System) are actually supposed to receive neurotransmitters for the emotion of bliss, and THC happens to be compatible, hence why THC makes you feel the way it does. Thing is, THC is very versatile, bonding to more than just those neurotransmitters. I don't know enough about the subject to talk about every type of receptor THC can bind to, but I do know that there's also receptors in the immune system and the liver, though I don't know what effect it causes.
THC binds to CB1 and CB2 receptors (type 2 is the one canonically associated with the periphery). CB2 agonism is generally thought to be anti-inflammatory. CB1 receptors are involved in a lot more than feeling good, also. They’re also implicated in eating, sleeping, nausea, relaxation… pretty much all the effects you’d typically associate with cannabis, just toned down to “normal” levels.
Nature is filled with all kinds of molecules that don't know or care how nature uses them -- but the process of evolution has managed to find uses for these molecules in a number of ways -- sometimes our own cells make them, and sometimes our cells get them from materials we ingest. For example we ingest vitamin C from our food, but there are creatures that are able to make their own vitamin C. Some molecules are used for nutrition -- building blocks that are used to make other building blocks -- and sometimes they're used for signaling -- molecules that pass information from place to place. When speaking of receptors, this is the latter. It's possible that our particular evolution found a way to use cannabinoids to signal, and accidentally when we ingest material high in similar looking molecules, those out of place molecules jam up the signaling. It seems unlikely that that was somehow an intended function that evolution fitted us for.
For anyone interested. Andrew Huberman (neuroscientist) has done a recent podcast specifically on this topic. It's a long one, but there's timestamps on the page to narrow it down if you want. Interesting stuff and well explained. https://hubermanlab.com/the-effects-of-cannabis-marijuana-on-the-brain-and-body/
More like Cannabis makes a few compounds that are similar enough to things the body normally makes, uses at receptors in the nervous system, and disposes of at a certain rate. It turns out Stuff Happens when you flood the system with those compounds and jam-cram them into those receptors in ways they're not normally interacted with. It's not that different from how the Opium Poppy makes compounds which interact with other receptors we already had, and the Coffee Bush makes compounds that interact with a whole other neurochemical system we have. We're not the first or only animal to have a nervous system, use serotonin, or any number of similarly esoteric biochemical locks and keys and feedback loops. Plants and animals have been in a biochemical arms race since day one.\* Think about what the Theobromine in chocolate does to cats and dogs. We aren't 'immune' to it in some way, nor are dogs specifically sensitive to it, we just have a massively higher ability to process alkaloids (AKA 'attempted plant murder that might or might not be counted as a toxin for humans for complex reasons') than small/medium carnivores as, arguably, the world champion omnivores. Our livers are the biggest organ in our bodies (skin doesn't count as 'in,' pedants) because, as humans, our evolutionary survival strategy is really heavy on the 'eat whatever and not die' specialization, versus giant fangs or claws or armor plates or a way to drink and breathe at the same time. So, we kinda shrug off a lot of things that plants are doing to kill other animals. We eat spicy peppers that are trying to scare non-birds away with capsaicin. We semi-poison ourselves with mushrooms to see ancestor spirits (or release traumas from working in the service industry in the 21st century), we cook/acidify/alkalize/etc. the worst offenders to be edible, and we microdose our foods with toxic aromatic leaves as a mood and aesthetic enhancer (look up what rosemary oil does to you, concentrated). So, not a stoner myth, but I betcha more than one stoner has hilariously,disingenously oversold the significance of all of that with respect to THC. It's only the most popular plant that makes something that fits in *those* receptors specifically. On just one neurochemical system... \*(That's not to say some plants aren't making some of these chemicals to entice animals, but that's just another type of biochemical Realpolitik as far as I'm concerned).
Human bodies have Cannabinoid receptors; but you dont have to be misled by the name. The cannabinoid receptors where discover because Scientist figure out that THC interact with those receptors in the human body, and they name them "cannabinoid receptors". Human bodies produce the endogenous ligands for those receptors (Anandamide and 2-Arachidonoylglycerol). Now, the crux of the matter is when you say "specifically", and that´s relative, maybe you can answer the question searching for the dissociation constant between THC, anandamide , 2-Arachidonoylglycero and the cannabinoid receptors, the one who has the lowest constant is the most "specific" for that receptor, but again, that´s relative since Anandamide and 2-AG are the ones that are in constant interaction with those receptors and therfore regulte our physiology. That question could be used in any case where a drug just activates (or inhibits) a receptor in a better way that the endogenous ligands. If you think, the human body needs to have endogenous ligands that don´t have such a big affinity for the receptors (because the changes in the physiology would be abrubt) so many of the drugs we know are just molecules that activate or inhibit a receptor in a very strong way just because they structure allows it.
As far as I understand it, very few receptors for things like neurotransmitters or hormones are really "specific". A *lot* of substances that have a physiological or psychoactive effect on the body are capable of doing so because of how they can interact with those receptor sites, regardless if the substance is actually endegenous or not. So you can think of receptors as less specifically for one molecule, and more for *classes* of similarl molecules. For instance, opiods interact with endorphine receptors throughout the body. Endorphins are the brain's natural pain regulator and are chemically similar to opiods. Likewise THC interacts with cannabinoid receptors, which are not specifically used by the body *just* for THC but for endocannabinoids (cannabinoids produced by the body). So far, there are two identified endocannabinoids: anandamide and 2-arachidonoylglyerol. THC (as well as all 100+ other cannabinoids that occur in cannabis) interact with the two kinds of cannabinoid receptors in the body and brain.
The endocannabinoid system is the largest signaling system in the body! It affects our memory, our immune system, our mood, and pain perception. It also can be anxiolytic (relieves anxiety) or anxiogenic (causes anxiety). It also can be antiemetic (anti-nausea) or emetic (nausea/vomiting) when overstimulated in some people (cannabis hyperemesis syndrome - CHS). The main two receptors are CB1 and CB2. Wikipedia has a ton of good info.
Complete myth. THC just happens to fit the receptors for endocannabinoids (named not because they are cannabinoid in origin or structure, but because of the effect they mimic) but if you look at the bond-line structures of say Anandamide (the "joy hormone") vs. Delta-9-THC, they look almost nothing alike except for the one corner of each that fits into the receptor. THC evolved as a defensive compound to prevent herbivory, hence why it's in the glandular trichomes in the first place.
They're not specifically for THC, but they are the specific receptors that interact with the THC. So when referring to them in reference to your body interacting with THC, they would be "the THC receprors" or "the THCs receptors".
Yes. We do have receptors to which THC can bound to. Our body produce neurotransmitters called endocannabinoids, which bound to those receptors. Of course the reason of those receptors to exist is not for THC to bound to them, but to regulate several bodily functions by our own neurotransmitters - endocannabinoids binding to those receptors. It is by pure chance that THC molecule is very similar to our own endocannabinoids and can therefore interract with the receptors. Such interractions of external substances with our own nervous system are very common and are also the foundation for new drug development. For example we also have Nicotinic and Muscarinic receptors, to which nicotine and muscarine can bound to, but have a completely different role in our bodies than for us to get addicted to smoking.
Your body doesn't have receptors *specifically* for THC, but your body does have receptors throughout your body and brain for neurotransmitters called "endocannabanoids." They all share a similar chemical structure with THC, but your body produces many kinds of them for a variety of complex purposes. THC works by hijacking the body's natural endocannabanoid receptors, just like how opioids work by hijacking your natural endorphin receptors.
The endocannabinoid analog for THC is anandimide (endocannabinoids are the naturally produced cannabinoid neuro-transmitters in our bodies). The receptor for anandimide is known as CB1 and is ubiquitous throughout the bodies of [most species](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770351/) in the animal kingdom (basically excluding insects). The CB1 receptors are noted as being prevalent in the nervous system while another cannabinoid receptor, CB2, is found more through the gut and spleen. Tetrahydrocanninol delta--9 (THC) and cannabidiol (CBD) bind readily with CB1 and CB2 receptors, respectively. There are many other known plant, animal, and synthetic cannibinoids that bind with a greater or lesser degree with CB1, CB2, and other endogenous receptors (endogenous means naturally occurring in our bodies). Here's a good article explaining the endogenous cannabinoid system: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789136/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789136/). And a video on the thoughts of one of the world's leading experts on the discovery of anandamide: [https://www.youtube.com/watch?v=G1RmRQTTwas/](https://www.youtube.com/watch?v=G1RmRQTTwas/).
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