Dear Burners: a treatise on drugs and addiction

Burning Man: it’s less than a week away! Because of Who I Am, I am already packed and wandering around our neatly organized piles in the dining room, finding tiny adjustments to make, futzing with this and that. Re-organizing the freezer. That sort of thing. I’m ready.

So, because I am a scientist, I thought I would take the time to talk to you all about drugs. They are bad, k?

That said, they are also fascinating. Once you dive into learning about neurochemistry, you realize that the brain is basically a giant Rube Goldberg machine. When a neuron fires, tiny gates open all along its membrane to let positively and negatively charged ions in and out. The current this generates means your brain is quite literally electric. It’s also chemical–neurons release neurotransmitters the way M&M’s release chocolate into your mouth.  Neurotransmitters are like keys that fit only certain locks, and when they find the lock that fits, more chain reactions are triggered. In the end, talking about drugs gets kind of boring, because they’re just like any other chemical in the brain. It’s the dynamics that are interesting, not the substances that trigger them.

One dynamic in particular involves everyone’s favorite good-time chemical, dopamine. Dopamine is released in the brain when things feel good. But that’s not all. Dopamine is also crucial for movement–in fact, Parkinson’s Disease arises when dopamine-producing neurons start to die off. Tremor sets in, and you more or less watch the brain run out of gas. Dopamine circuitry gets weird: it is the key to multiple types of receptor, which happen to have opposing gas/brake type actions. And when you learn something new, dopamine is there, sculpting your behavior.

Dopamine release triggered by various substances in the brain.

Dopamine release triggered by various substances in the brain. Slide lifted from Jon Wallis’s lecture slides–ditto for all of these figures.

We, like our brethren in the animal kingdom, do much of our learning by trial and error. When we try something that feels good, or produces a sense of reward, we get a squirt of dopamine. That squirt not tells some parts of our brain that it feels good, and it tells other parts–the parts that work our muscles–to do it again. This works great for, say, learning which turn a rat should take in a maze. Turn left and you’ll get a pellet, dopamine reminds rats.

When we learn that something is good, the dopamine starts to be released as soon as the first sign of it appears. Like Pavlov’s dogs, we salivate at the sound of a bell, and our dopamine rush comes as soon as the reward is predicted.  If the reward is then withheld, we actually see a dip in the amount of dopamine at the moment the reward was expected. As far as your motor system is concerned (and remember, they’re the ones controlling the hands that reach for the things), dopamine teaches you when to expect a reward, instead of telling you “oh shit this feels awesome.”

I hope the internet forgives this lifting of textbook material without permission--it's for a good cause!

Dopamine neurons start firing in response to the “conditioned stimulus (CS),” or the thing that tells you a reward is coming, instead of to the reward itself (R). If a reward is omitted, dopamine neurons grow surly, retreating into an indignant silence.

The trouble begins when it’s not a pellet (or even a piece of chocolate) we seek, but a substance which itself grabs hold of dopamine and drives it itself. Because your brain makes changes to accommodate new information that challenges its previous beliefs, it cares a lot when it sees its predictions violated. Once the reward is predictable, it stops learning. You know that food is good, or TV is good, or that lying motionless staring at the ceiling is good, and yet you have not triggered an uncontrollable downward spiral by learning this. Not necessarily, anyway. There is a difference between chemical and psychological dependence. You can form strong habits towards these things, but you cannot, strictly speaking, be “addicted” to them (this is a point I emphasize over and over with my Altered States and the Brain students). That is because when a drug comes in, you get the little predictive burst of dopamine that says, “Look, drugs!” but then something else happens. The drug itself pumps more dopamine out. This is much like the dopamine that happens early in learning, before you know how good something is going to be. Except the difference is, you already knew that. You didn’t need to learn it MORE. And yet, your brain is getting TAUGHT by that extra dopamine. Your want ratchets infinitely skyward, as you embark upon a neverending journey of learning to love the drug. You want it more each day than you did the last.

This idea comes from David Redish, now at the University of Minnesota, who refers to addiction as a computational process gone awry.

At this point I should say that I’m playing pretty fast and loose with the most standout memories of several classes I’ve either taken or taught. These were the mindblowing take-homes. I doubt I’d misremember the most important details, but it’s certainly possible. 

Anyway. The bitch of it is, different brain systems drive your wanting a drug and your liking it. This is why drugs of addiction have people reaching for them long after it’s stopped being fun. Dopamine keeps you wanting a drug long after your increasing tolerance has outgrown the opioid system’s pleasure response. In rats, they can measure how habitual something is by “devaluing” a reward. Rats, like humans, both eat and drink. They love their pellets, and they love love love sugar water. So say they’ve learned to press a bar for pellets. If you let them have all the pellets they want the day before your experiment, and the day of, they still press that bar even though they are so full of pellets, then you, my friend, have instilled a habit. Say, though, the rat loses interest, until it becomes clear that today you’re giving out sugar water, at which point he starts hitting the bar again. This behavior is not a habit, but goal-directed. The rat is doing it because he wants something you are giving.

Habits are scary because they erode our sense of control. And now, I would like to talk to you about cocaine and why it is the scariest drug. Below is a slide lifted/modified from this 2004 paper by Linda Porrino and colleagues.

The blue shows the increase in a certain kind of dopamine receptors in a part of the brain called the striatum. Your brain is popping out new locks for the key that is cocaine, and that scares the hell out of me. The blue spreads from the bottom to the top, starting in regions that are related to motivation and emotion, and spreading into regions responsible for sensory and motor function, decision-making, and other “smart” stuff we do.

Another finding comes from Linda Wilbrecht’s lab here at Berkeley: cocaine causes things to happen in another part of your brain, the part where sensory information meets up with stored information from memory to do things like rule following, decision making, etc. The neurons there grow new connections within a few hours, these connections are more iron-clad than most connections, and the amount of new connections in different rats is correlated with how much the rat prefers a cocaine chamber over a boring chamber.

Admittedly, both of these findings freak me out for totally visceral reasons. Granted, I don’t like to see studies where things change the brain and we don’t know why–the one where birth control thickened its users’ cortex was disquieting to me, in spite of the fact that (or especially because) they didn’t know what effects this had. I think it freaks me out, honestly, for the same reasons some images might (DO NOT CLICK THIS NEXT LINK UNLESS YOU KNOW WHAT IT IS OR ARE NOT SQUEAMISH AT ALL). Heard of trypophobia, fear of holes? Well, I have it bad. I think the fear has to do with like, if there were all of these little things emerging from your skin, it would mean that you had become like a sack of maggots or something. No wonder we fear it. BUT I DIGRESS.

I don’t like the idea of creepy little changes happening under my skin, and I don’t like the idea of them happening in my brain, especially when those changes mean my brain is circumventing my control, growing new little buggers that seek something desperately without my permission. So, take that for what you will.

But I would like to leave you with one closing thought (I’ve saved the best for last here–a list! Of drugs! IN ORDER! Get Buzzfeed on the phone, stat). Scientists can use bar-pressing as a measure of a substance’s addictive potential. The easier it is to get an animal to press a bar to receive a substance, the more addictive we figure it is. As it turns out, cocaine is at the very top of this scale. It goes like this:

The scale of addictiveness.

The scale of addictiveness.

And there you have it. I know many a burner for whom this chart is good news, and also many for whom their drug of choice, popular or obscure, is left out. Sorry. This is just what I got out of my Berkeley education, and you didn’t even have to grade papers or anything to receive this wisdom, so, practice gratitude, ya hippies. Anyway, I want to point out once again, drugs are bad. But what we’re talking about today is addiction, and as it turns out, that’s not really what you have to worry about with crazy psychonaut fuel. Anecdotally, I have heard it through the grapevine that lab animals just stone cold DO NOT LIKE psychedelics like LSD and mushrooms. Which, if you think about it, makes a lot of sense.

I hope this post has at least given you some food for thought, at least as far as your own burner-y spirit journey of self-discovery and freedom and whatever is concerned. Addiction is not cute, kids. Have a safe burn. See you out there.

This entry was posted in Science, Uncategorized. Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s