播客 1006：大麻素药理学

这里是由CarePoint和HCA HealthONE赞助的急救医疗小贴士。

This is the Emergency Medical Minute sponsored by CarePoint and HCA HealthONE.

我想做个关于药物的医疗小贴士，本来打算讲大麻素和大麻素受体，因为在这儿科罗拉多州，我们平时很少接触到这方面的内容，觉得你们应该了解一下。

I wanted to do a medical minute on drugs And first was gonna be on cannabinoids and on the cannabinoid receptors because, you know, we just don't see it that often here in Colorado and thought that it'd be something that you guys should hear about.

说起来挺有意思的是，我们人体其实本身就拥有大麻素受体，对吧？

So anyway, it's kind of interesting if you think about it that we actually have cannabinoid receptors, right?

我们体内有两类受体，叫CB1和CB2，它们的名字其实是根据与之结合的物质命名的。

We have these receptors called CB1 and CB2 And in the the receptors were named after what we found bound to them.

并不是说这些受体生来就是为了和大麻发生作用的。

It wasn't like they were meant to bind to cannabis in the world.

事实上，我们身体自己会产生一些物质，能和这些受体结合，对吧？

It was that we actually have these endogenous compounds that we produce that bind to them, right?

这些物质被称为内源性大麻素。

And they're called endocannabinoids.

我们发现，身体组织会生成两种物质，叫2-AG和内源性大麻胺，它们在大脑和神经元里产生，也在免疫细胞和其他组织中合成，能调节神经系统的某些功能，比如缓解疼痛、压力和焦虑，同时也能控制炎症。

We found that our tissues produce these compounds called 2AG and anandamide which are produced in the brain and neurons and they're produced in immune cells and other tissues and they help regulate some neuronal effects so they regulate pain and stress and anxiety and they also regulate inflammation.

后来我们发现，大麻里有一种叫THC的物质，它也能结合这些受体，产生同样的效果。

We then discover that there is this compound that is in cannabis called THC which also binds these receptors and does the same things.

所以THC结合大脑中的CB1受体，就会引发人们大剂量吸食时常见的那一连串反应，对吧？

And so THC binding to CB1 in the brain causes all the litany of effects that we see when someone comes in super high, right?

它会让人产生偏执、焦虑、欣快感，也有镇痛作用，同时在身体其他部位也有影响。

So it causes paranoia, it causes anxiety, euphoria, analgesia but then also in the periphery.

另外，THC作用于下丘脑还会增加食欲。

Also not to mention increasing appetite with binding to the hypothalamus.

而在身体外周，我们也能看到它对免疫细胞的影响。

But then also in the periphery, we can see its effects on the immune cells.

实际上，THC还有抗炎的作用。

So there is anti inflammatory effects actually with THC.

你有没有注意到，吃大麻食品的人，体验跟抽烟的人不太一样？

Have you ever noticed that when someone takes edibles that they have like a different experience than someone who's smoking weed?

因为当你口服大麻时，THC会先经过肝脏，发生转化。

Because when you ingest marijuana, that THC goes to your liver and it changes.

它经过肝脏首过代谢，转化成一种叫11-羟基的化合物，也就是11-羟基THC，和Delta-9-THC不一样。

It goes through first pass metabolism and becomes this 11 hydroxy compound, this eleven THC, which is different than delta nine THC.

它的精神作用强得多。

It's way more psychoactive.

更容易穿过血脑屏障，对大脑里的CB1受体结合得也更紧密。

It crosses the blood brain barrier more and binds to the CB1 receptors in the brain with a much higher affinity.

所以效果更强，持续时间也比吸大麻长得多。

And so you get a way higher psychoactive effect and it's longer lasting than if someone is just smoking weed.

有人觉得吃大麻食品和吸大麻的感觉不一样，确实不一样，因为进入大脑的其实是两种不同的物质。

When people come in saying that it feels different when they you take edibles than when they are smoking weed, it is different because it is a different drug that's hitting their brain.

这其实是个挺有意思的现象，临床上经常遇到。

I think that's one just kind of interesting and something that we commonly see.

那除了这个，还有哪些和大麻相关的常见现象呢？

What's the other common thing that we see associated with cannabis?

高致吐反应。

Hyperemesis.

就是这个呕吐综合征，对吧？

The hyperemesis, right?

我们经常遇到这种情况。

It's like we see it all the time.

这很可能是因为长期激活大脑里的这些CB1受体。

And that is through probably chronic activation of these CB1 receptors in the brain.

他们逐渐产生耐受性，还会上瘾。

You know, they build up a tolerance and they build up a dependence.

同时，这也跟其他受体的激活有关，比如香草醛受体——这种受体和辣椒素结合，而辣椒素本身也会被高温激活，所以患者常常特别想洗热水澡，用辣椒素治疗时也能缓解症状。

It's also through activation of these other receptors, the vanilloid receptors and the vanilloid receptor binds to capsaicin which is activated also through heat which is why they often have these cravings for hot showers and why they get some relief when you give them capsaicin to help treat it.

我只是想深入聊聊一些和大麻相关的常见表现。

Anyway, just wanted to do a little deep dive on some of the things that we see related to cannabis and some of its common presentations.

哦，还有一件事。

Oh, one other thing.

现在还有一大类人工合成的大麻素。

There's all this whole realm of these synthetic cannabinoids.

目前已经出现了两百多种不同的化合物，它们在技术上是合法的，因为只要改一下分子结构，就变成了另一种新药。

There's over 200 different compounds which have been created that are, they're technically legal because when you create a different compound, that's now a different drug.

所以FDA也没法管，因为这根本不算同一种东西。

And so then the FDA cannot regulate it cause it's a different thing.

于是市面上就冒出了一大堆合成大麻素。

So there's a whole slew of different synthetic cannabinoids.

K2、Spice、Black Mamba、Mojo，各种名字都有，每种的效果都不一样，而且比普通的天然THC危险得多。

K2, spice, black mamba, mojo, all these different ones and they all have a whole litany of different effects and they're far more dangerous than just standard naturally occurring THC.

它们更容易引发癫痫、呼吸问题、心率过快、脱水、横纹肌溶解、急性肾损伤，各种严重反应都有。

They have a way higher incidence of causing seizures, respiratory effects, tachycardia, dehydration, rhabdo, AKI, all kinds of things.

跟普通的THC完全不是一个量级。

So far different than just your standard THC.

对这些情况主要还是支持性治疗，对吧？

It's mainly supportive care for those conditions, right?

我们通常就是用苯二氮䓬类药物、补液、密切观察，就这么处理。

Our standards just can be benzos, fluids, monitoring, that kind of thing.

所以如果病人出现这种情况，通常就是这么处理的。

So if a patient comes in with that, that's kind of the standard treatment for that.

另外有个挺有意思的小知识：对乙酰氨基酚可能通过结合CB2受体发挥作用。

Also one little fun fact, Tylenol, we think might be acting through binding some of the CB2 receptors.

我们还不完全清楚对乙酰氨基酚的具体机制，但有一种假说认为它部分通过结合CB2受体起效。

So we don't really know exactly how acetaminophen works, but one of the hypothesized pathways is through partial binding of CB2.

挺有意思的。

Kind of cool.

大家对这些内容有什么问题或想法吗？

Does anyone have any questions or comments about any of this?

我们可以聊的东西很多，不过

It's a lot of different things we could talk about, but

只是想简单跟你们梳理一下

just wanted to give you

这个情况。

a quick little review of it.

这里是《急诊医学一分钟》。

This has been the Emergency Medical Minute.

感谢我们的赞助商CarePoint和HCA HealthONE。

Thank you to our sponsors CarePoint and HCA HealthONE.

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Support from them and listeners like you helps us to continue providing free medical education to the masses.

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