Tolerance Internalization and Downregulation

@cannabichem

molecular mechanisms of tolerance part 2 internalization and down regulation #ouid #ouidtok #420 #science #education #fyp #foryourpage

♬ Summer – Instrumental – Devinney

Welcome back to another Riley Dee and Arbor Vita8 crossover! Today, we delve back into the concept of tolerance. There are a number of things that happen when we consume cannabis. This depends on how much of it we consume, and what kind. The possible combinations are just about endless.

Below, we take a deeper look into how cannabis tolerance internalization works through Riley’s eyes. Before continuing, be sure to read out last article discussing tolerance desensitization. Then after you’ve finished this series, check out one of our many other articles on cannabis at large. Ready? Let’s get into it!

How Tolerance Works

Cannabis tolerance works much like building up a tolerance to anything else. In general, the more you use it, the higher your tolerance becomes. And once that line is crossed, it’s rare that you’ll make it back to the starting point. That doesn’t mean you can’t lower your tolerance at all, though.

In fact, there are options like T-breaks to help you accomplish this. This is when you take a long enough breather from THC that your tolerance begins to slowly decline again. As we said, it’s rare that it’ll ever be as low as the first time use. But, this is enough to keep you from feeling burned out by usage.

Hitting Your Tolerance With THC

Have you ever used cannabis or one of it’s properties before and felt as though you over-indulged. This can be a result of low tolerance paired with excessive use.

The effects of over-indulgence can include a disoriented feeling. It can also lead to a strong feeling of drowsiness. But here’s something that you may not have noticed before. Did you know that once you reach your tolerance, you can’t get more “high”!? It’s a fascinating concept that Riley breaks down even further in the above clip.

What Happens When You Overuse THC

As we covered before, interesting things happen when you introduce THC to the body. First, it binds with you CB1 receptor. This replaces the GDP in your G Protein with GTP. In Riley’s words, this is what’s known as a “conformational change.”

But in the case of cannabis tolerance internalization, something even more interesting occurs. “Your cells have the ability to take away receptors. THC is still on the outside of the cell where it would normally bind to the receptor. But your body has literally endocytosed that receptor into an endosome.” From there, the receptor is either kept there until later, or obliterated altogether. So what does this mean?!

Pretty much, this means that once you reach your tolerance peak, you can’t get any “higher”. The THC is still floating around. But due to the endocytosis, it can’t pair with any receptors, and thus takes no further effect. This means that once you reach that limit, taking any more does nothing but prove wasteful. This is also the explanation for why and how your tolerance builds to it. Riley does an even better job at going into all the great scientific detail. Watch this and more from her here!

Arbor Vita8

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Clip Transcript

Riley Dee:
All right, now this is going to blow your mind. Now we’re going to talk about receptor internalization and down regulation. All right, so say that you’re still exposing your brain to way too much THC. Your cells actually have the ability to take away receptors. So THC is still on the outside of the cell where it would normally bind to that receptor, but your body has literally endocytosed that receptor into an endosome, which you could think of as a little fat bubble, just kind of saving it.

Now it can either keep it here until it’s a better time to reintroduce it, or it can literally destroy that receptor, and this leaves less receptors to facilitate that response that makes you feel high. Then you’re just stuck waiting around for your body to transcribe more of the genes that correspond to those receptors. So you tell me, where the hell does vitamin C fit in in this picture?

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