What's THC Doing in There?

How the brain works has always been a particular source of wonder to me. I was fascinated in how the dynamics of literal brain chemistry can change the entire computational process.

Recently I have been wondering more and more about what exactly "being high" means. What is happening on a biomolecular level when we ingest cannabis? What changes in neurons that causes things to be perceived so differently?

This video wound up requiring the most reading I've ever done on a topic. The exact biomolecular mechanisms are nuanced and still not completely fleshed out. Especially with regards to processes beyond the dopaminergic pathways.

But this should be a pretty comprehensive overview of getting you up to speed on what's happening.

Used Sources:

[ButWhySci]

At @2:30 I say we will focus on Anadamide today.

Initially I had read significantly more papers and wanted to discuss the role of endocannabinoids in depression, anxiety, and stress. However, after writing and recording the sections on cellular mechanisms. I realized to adequately discuss what I wanted to, the video would be significantly longer. Since my schedule has been giving me less time to work on videos I removed that section.

This line is a missed remnant from the original scope of the script.

[ImpossibleEvan]

So this is why bro hasn't uploaded in a while

[PBnFlash]

My cells are filled with ribbons, blobs and little acronyms.

[freeridin]

i got stoned and watched this and i thought i could feel the shift from tonic firing to phasic firing in my brain.

[MIKAEL]

Biology has to be some of the craziest, most time consuming complicated stuff to research. I literally can't even imagine how you even begin to approach researching something like a complex interconnected chain of reactions and biological processes. With physics I can at least understand the big picture of "better telescope to see things further away" or "faster accelerator to see smaller particles" but I can't even imagine how they would've researched this and isolated the biological system enough to understand it.

[charlestaylor]

You have the most comprehensive graphics, the best I've ever seen.

[existencegaming]

This one of my favorite channels for information. You go into way more detail than anyone else and i love it.

[abavariannormiepleb]

A bit sad: 16 years ago I was assigned a talk in biochemistry class at university about this exact topic and it seems only very little new knowledge has been discovered since then :(

[nachocheese]

I love this level of detail on the mechanism of action. Keep it up man!

[johnathancorgan]

What an outstanding video! It goes beyond the surface level "summary" and explains the details involved, without oversimplifying or condescending. The GPCR activation cascade in particular was nice to see. It would be great in a future video to look at the feedback loop from GPCR activation via beta-arrestin that results in tolerance and dependence.

[Idrizze]

I got more questions than I started with😭 What happens when THC is saturated in the receptors? Do the receptors become somewhat resistant or it’s something else entirely? Why do some people have tolerances more than others? Adversely, why do some people always get high every single time every day after many years without fail? What does weight and height have to do with it? What’s its or does it have an interaction with our adipose tissue? Why do some people have bad trips but others have great times smoking the same spliff? Why is it that some people, including myself, lack the ability to digest and feel the effects of THC in all formats, purity, and different time? Why does smoking and working out or working out and then smoking work so well together???? or is that a lie we all collectively believe or want to believe at least? What are the effects of the other phytocannabinoids in the human body in greater detail? What are the effects of the phytocannabinoids in the human body at different concentrations and with different consumption methods? Are there any benefits to them? if yes, what and how? Although it’s nearly impossible to OD on weed, what would be the negative effects (beyond lacing) of phytoc’s over the period of one’s life? With that same question in mind, how does this interact with one’s physical activity levels and cardiovascular and vagus health? Why does weed in all its glory work so well with people with ADHD and other neurological conditions that self medicate with it? How exactly do cannabinoids help people with conditions like ASL? Or completely unrelated conditions like anxiety and depression but also not helpful at the same time for people with schizophrenic symptoms?

Last one might be unrelated but idk and a stretch. I got ALLLL the questions, i hope i can finally get answers for some of these questions. Outside my realm of answering but within my grasp of inquiry. And I wouldn’t even know how to test it. Can’t even ask my friends cuz I want science!! There’s so many more questions but the best answer is without it ✨✨✨

[mastershooter]

I love this channel because you actually read the papers of the field and go into some detail about the physical/biological processes behind the topic you're exploring! Never stop doing that!

[TheKiwijord]

These attention to detail and accuracy of the animations and explanations are top notch!

[tekjess_]

Not the video I was expecting, but still really cool information! Great stuff.

[jdave]

I’m so sad that this video is very likely gonna get less views than your typical stuff due to delving into biology instead of physics! This is just as good as (if not better than, for such a great explanation you give here!) everything else you make!

A seriously great video, I learnt so much! Never knew that there were endocannibinoids, let alone the slightest bit about all the neuro-stuff!

I’m glad you touched on the lack/presence of CB1 receptors on dopamine, I was wondering why the GABA producers were getting suppressed but not the dopamine producers! I find it interesting how when they removed the CB1 receptors on dopamine the effects of cannabis lessened, I would’ve assumed removing the inhibitor’s receptors would’ve made the dopamine production/effect skyrocket, not the inverse! Maybe I misinterpreted things though, haha.

Genuinely mind boggling how complex biology is when you get real deep into it like this, it’s awesome to get a guided tour into a tiny part of it! Thanks for the video, I’m sure there was a *lot* of research put into this, especially since it isn’t your usual affair! (Unless medical stuff was your “day job” prior to making physics YouTube videos, haha; even in that case though, I’m sure a lot of research went into it regardless!)

[mathew]

best video I've seen expalinign this mechanisms with detail.

[FranBunnyFFXII]

Further question, why does THC make some people "trip" like they took a smaller dose of Acid? This is a rare but recognized phenomenon that happens to only certain people. Some people experience it only after using another psychedelic like Psilocybin, or LSD. For others causing a trip is the only thing THC does for them. Why does this happen in some people but not all people?
What interaction causes a psychedelic experience when THC is involved?

[onkkke]

watching while high really hits differently....also, finally, a video that explains the questions I have in good detail.

[FabioMarziali]

Yes a new video! And yes cannabis!!!! ❤

[anthonynicoli]

Great explanation. It is very complicated.