Your Brain on Drugs Ep 2 – Overdose, Heart Attacks, and Blackouts

Lollie: Alright, we’re sitting here today with Dr. Benedetto Romoli. Or, as we’ll probably call him henceforth, Ben, if that’s alright with you?

Ben: “Ben” is perfect.

Seymoore: Meow.

Lollie: And Seymoore the cat. And we’re going to talk to Ben today (and Seymoore) about how drugs work in the brain, and particular classes- how particular classes of drugs affect the brain. So, Dr. Ben, can you give us a quick recap of how drugs work in the brain?

Ben: So drugs can work in the brain because they interfere with the action of the chemicals, of the molecules neurons use to communicate with each other. Molecules called neurotransmitters. They can either increase the release of a particular neurotransmitter, a particular molecule; they can prolong its effect- they can prevent the re-absorption of these molecules; or, they are very similar in shape and charge to a neurotransmitter- so they can mimic the effect of these neurotransmitters.

Lollie: Okay, so to kind of circle back to the metaphors that we were using in the last episode, drugs can get into the brain and they can either lock the floodgates open (I think that was the metaphor we used) where the releasing neuron gets basically locked open so that they’re releasing heavy amounts of neurotransmitters. Drugs can go in and imitate these neurotransmitters. So they can basically act like a substitute for a key, the neurotransmitter being the key, the drug being a copy of that key that’s just slightly different but similar enough to activate the next neuron.

Ben: Exactly.

Lollie: And they can prevent the releasing cell from re-absorbing. So they basically block off that re-absorption from happening so that all the neurotransmitter that was released just stays in the gap there, the synapse, so that the subsequent neuron gets chronically activated.

Lollie: Okay, so I think one of the most pertinent concerns in today’s world is really surrounding opioids. Opioids are their own class of drugs from my understanding, is that correct?

Ben: Yes, they are.

Lollie: Okay, and we’re facing right now, especially in the United States, an opioid epidemic of sorts, where people are overdosing on these medications, these things that are prescribed by doctors, and getting addicted to them, and facing serious life repercussions including potential overdose death. So, what are opioids and why are we facing such a problem with them in the U.S. right now?

Ben: Opioids are a particular class of drugs that can alter specifically pain perceptions, so they are also considered pain killers, right? So if you think about morphine, for example, it’s the most powerful painkiller*. Also, like any other drug, they are able to increase the release of a neurotransmitter called dopamine in the reward system. They activate this reward system in our brain that gives us this sense of pleasure. So the combined effect of this painkiller action and the increased effect on the reward system creates one of the most powerful combinations that we can achieve in the brain by a drug.

*I would like to clarify really quick what Ben means by saying that morphine is the most powerful painkiller we know. What he means is that we use morphine as the comparison for the strength of other opioids. Some are stronger than morphine, such as Fentanyl or methadone, while others are weaker than morphine, such as codeine or tramadol.

Lollie: So would you say that opioid drugs mimic neurotransmitters, then?

Ben: That’s exactly what they do. For example, we talked about morphine- it’s really funny because the molecule morphine does not exist in our body. It was actually discovered before the opioid system of the brain was discovered. So they discovered this molecule called morphine and then they found that the brain has a system of receptors, called opiate receptors, that respond to an endogenous molecule that was never discovered before, which is funny because then they called it “endorphin,” which means that it’s a substance in our body that is similar to morphine. So, morphine can mimic the endorphin effect.

Lollie: Okay so we’re born with receptors for these endorphins, these endogenous, or self-made, self-produced, painkillers.

Ben: Exactly, so endorphins are normally produced in situations of extreme stress or extreme pain, so the body can actually reduce the level of pain it feels, and it’s called a central pain killer because it decreases the feeling of pain at the level of your brain, at the brain level. So, it’s not like an anti-inflammatory drug like, for example, ibuprofen, that reduces the pain, the inflammation, at the site, at the injury. Endorphins reduce the sensation of pain at the brain level.

Lollie: Okay, opioids have a clear role in pain reduction- opioids and endorphins. The endorphins are basically our self-produced opioids, in a way. Well, opioids are the fake versions of our endorphins, but they have a clear role in pain reduction in sort of emergency situations like childbirth or after you run a marathon.

Ben: Exactly, extreme exercise.

Lollie: What other roles do they have?

Ben: Their role ranges from pain reduction to giving us a sense a pleasure. Endorphins are released, for example, during an orgasm. So we feel pleasure in all our body because of the effect of the endorphins released during an orgasm. Drugs like heroin, or morphine, are so powerful because they mimic the effects of these endorphins, but they amplify it ten times, a hundred times. Imagine being in a state where you don’t feel any discomfort in your body and also this sense of pleasure that, for example, could come from an orgasm, is actually given by this drug. Ten times, a hundred times more.

Lollie: Wow! So, extreme euphoria. So, there’s pain reduction as well as these very, very good feelings.

Ben: Definitely.

Lollie: What kind of physiological effects does it have? What effects could it have on your body? Why is it that overdose on an opioid is so deadly?

Ben: So, morphine gets its name from Morpheus, the Greek god of sleep, right? So morphine, and endorphins, and opioids can induce a very deep sleep. They slow down your heart beat, they slow down your breathing, your respiration rate. These can be extremely dangerous. If you take too much, your heartbeat can slow down too much, your breathing rate can slow down too much, and you go into shock and you die.

Seymoore: Meow.

Lollie: So essentially when somebody overdoses on opioids, they take too high of a dose for their body to handle, they get this intense rush of euphoria and of pain reduction and everything, but because opioids also depress breathing, or slow down breathing and heart rate, if they take too much it essentially makes them just stop breathing and/or stop beating blood through their body.

Ben: Exactly.

Lollie: So you die by this deep sleep, this Morpheus… wait, not Morpheus.

Ben: Morpheus, yeah.

Lollie: It is Morpheus! Getting some Matrix things up in here.

Ben: Oh yeah, Matrix too, yeah. Morpheus- it kind of makes sense.

Lollie: Okay, the next class of drugs that I would like you to tell me about is stimulants. So crack (crack cocaine), cocaine, crystal meth, methamphetamine, Adderall, all these kinds of drugs work in a similar way?

Ben: Not really, actually. So, stimulants usually, in general, mimic, or increase the release, or block the re-absorption, as we said before, of a neurotransmitter called dopamine. Dopamine is the most important neurotransmitter of the reward system of the brain. So, dopamine is released whenever something important, something good, happens that the brain needs to focus on. Dopamine is involved, for example, in motor coordination, it’s involved in arousal.

Lollie: Like, the state of being awake, or alert.

Ben: Yeah, exactly. Being focused, being in a euphoric or high state. And it’s also involved, as I said, in motivation and reward. So, whenever we take one of these stimulants that increase the activity of this dopamine, we feel this rush. We feel like we are able to focus for hours and hours on one task. We are able to dance forever. We are able to… we’re invincible. So, this all comes from a not normal, a huge, release of this dopamine.

Lollie: So how are stimulants, which release a lot of dopamine, different from opioids, which also release dopamine.

Ben: Opioids have an activity on these opiate receptors that stimulants do not have. So, whenever we take cocaine, for example, we don’t feel a sense of pleasure itself. We feel a rush, we feel a high. But, they’re different. The feeling is actually very different. With opioids, for every drug that can cause addiction, somehow dopamine is always involved because in this state of pleasure that opiates give you, the brain registers it as an important state, as I said, so it releases dopamine. But, opiates don’t have a direct effect on the release of dopamine.

Lollie: Oh, I see, so the opioids affect endorphin receptors, which in turn affect dopamine, but only in particular regions of the brain.

Ben: Yeah, exactly. But, it’s more of an indirect effect on dopamine. Instead, stimulants have a direct effect on the release and action of dopamine.

Lollie: So, because of this rush that people get when they use stimulants, stimulants tend to be used in more of a binge pattern. When they’re being abused they’re used in sort of a binge pattern, taking high amounts, crashing, needing more in order to just kind of feel normal. Because of this, a lot of people end up neglecting food, neglecting sleep, and end up in sort of a manic state.

Ben: Exactly, because the only… the brain… what happens with drugs, or with stimulants, the brain gets so used to having these not normal, these huge rushes of dopamine, that nothing, now, for the brain, is more important than the drug itself.

Lollie: Okay, so taking all of this into account: that stimulants cause this massive release of dopamine, this intense rush, this kind of sense of, “I can do anything for as long as I want to do it” – what are the dangers of taking a lot of stimulants?

Ben: So, the dangers can be direct and indirect. The indirect effect is that if you’re on coke and you think you can drive on a highway at 200 mph you will do it and you will kill yourself and possibly other people. But, the more direct effect of cocaine, for example, is that cocaine skyrockets your heartbeat, skyrockets your blood pressure, and you can go into hyperthermia, so your body gets overheated. It can cause strokes.

Lollie: And heart attacks?

Ben: Heart attacks, yeah. It can increase your heart beat so much that you get a heart attack and die.

Lollie: Wow, so basically the dopamine release stimulates your body so much that it’s in hyperactive mode, whereas with opioids you are basically inhibited so much, or slowed down so much, that you kind of stop breathing, your heart rate stops. This is the opposite. With stimulants, you run the risk of too high of a heartbeat, too high blood pressure, and having a heart attack, or stroke, or whatever have you- overheating, even, is one of the big dangers.

Ben: Yep, exactly.

Lollie: Interesting, very interesting.

Lollie: Okay, Dr. Ben (and Seymoore), the third class of drugs that I want to talk to you about are depressants, so alcohol, benzodiazepines, barbiturates, non-benzo sedatives like Ambien. What do these drugs do, how do they work?

Ben: So these drugs have actually a wide range of mechanisms, but they ultimately affect a neurotransmitter called GABA. So GABA, or gamma-aminobutyric acid, is the main inhibitory neurotransmitter in the brain.

Lollie: Inhibitory meaning it slows activity. So GABA slows activity.

Ben: Yes, it reduces activity of the neurons. So, for example, alcohol has a direct effect on the GABA receptor.

Lollie: So it acts like the lock and key.

Ben: Exactly. It mimics GABA itself.

Lollie: And benzos work in a similar way or they vary?

Ben: They vary between themselves, yeah.

Lollie: Okay, so once it binds, once these drugs bind to the GABA receptor on the receiving cell, which subsequently basically tricks that cell into thinking that GABA is present, it slows the firing. So it sort of stops firing in many regions of the brain, which is how we get the effects of all these drugs. Alcohol reduces inhibitions, kind of makes you lose a little bit of motor control at a certain point…

Ben: Like many other depressants, alcohol, taken in small quantities, reduces, for example, anxiety. So it kind of makes you feel less anxious, makes you feel happier, reduces your inhibitions- this is due to a reduction of the inhibitions of your neurons, of the firing of your neurons. But when taken in a large quantity, the activity of your brain gets slowed down, gets reduced, so much that you cannot talk anymore, you cannot put words together, or your coordination, your motor coordination is completely impaired so you can’t even walk and sometimes you just pass out or are incapable of forming memories.

Lollie: Like a blackout?

Ben: Yeah. A blackout actually is not the loss of memory, but it’s the inability to form new memories because the activity of the brain is too low due to alcohol.

Lollie: Hm, interesting. Which is I guess why some people can appear semi-normal, but be…

Ben: Yeah, exactly.

Lollie: So, with benzos, benzodiazepine medications, these are medications that are prescribed to reduce anxiety and it is precisely because they affect GABA that they actually work. One thing that is really important to note about benzodiazepines (like Valium, like Xanax, like Ativan)- these are all extremely dangerous to withdraw from. Alcohol included, all sedatives pretty much. The withdrawal period can be deadly, and that is because when the brain gets so used to these inhibitory signals, to this activity-reducing chemical being present, it kind of adjusts to this lower level of activity. So, your new baseline, your new normal, is now adjusted down to this lower level of activity overall. And this also happens, I think I said, with alcoholics and everything. But when you stop using these drugs, you cannot go cold turkey on these, first of all, unless you have close medical supervision. When you stop using, when you start to increase activity in the brain because you’re taking away this drug that stops you from signaling, you can suffer seizures which can turn deadly. So, it’s extremely important if you’re going to try to withdraw from any of these sedatives (alcohol, barbiturates, benzos), get medical help because they’re some of the few drugs that withdrawal can be lethal, directly. And it’s precisely because of the way that they exert their effects that they can be deadly. So, kind of circling back around to GABA, there are certain disorders where inefficient levels of GABA can cause restlessness, or insomnia, anxiety, and, again, seizures because there’s no signaling in your brain. We need GABA to kind of help reduce these signals.

Ben: Totally.

Lollie: People turn to a lot of these sedative drugs to help with any of these kinds of symptoms. A lot of these kinds of drugs are being used to…

Ben: To kind of like tame a hyperactive, or hyper-excited brain, if you want to put it this way.

Lollie: Yeah, to kind of self-medicate.

Ben: Exactly, if your brain is constantly taken by something, constantly working, you’re constantly worried about things, this is one of the reasons you might start drinking, because alcohol mimicking GABA reduces the activity of the brain so it calms down these thoughts.

Lollie: These drugs also affect the reward pathway, is that correct?

Ben: Yes, like any other drug. This is more of an indirect effect than a direct effect. Every drug, every event that is relevant to the brain, that produces either pleasure or takes away something negative like anxiety, gets registered in the brain as a positive thing, as an important thing. So, this is why the reward system is affected.

Lollie: Interesting. And what is the risk of taking too high of a dose of any of these?

Ben: It’s similar to the opiates effect. So, your brain function gets slowed down that much. Your brain is what controls, indirectly, your breathing rate, as we said before, so if it slows down too much, you may stop breathing, or your heart beat goes down too much and you go into shock.

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