What is LSD, what does it do to your brain and the reason it’s not lethal even at large doses?
In: Biology
LSD is a drug that has hallucinogenic properties– in other words, it can trigger you to see or hear things that aren’t really there. We actually don’t know much about LSD, since most scientists are more interested in studying drugs with a greater adverse societal impact, like nicotine, cocaine, or heroin.
However, we do know that LSD has a molecular structure very similar to that of another neurotransmitter called serotonin. This similarity led a lot of scientists to think that LSD must somehow affect serotonin transmission.
There is a cluster of neurons in your brain stem called the raphe nucleus, and almost all of the neurons that produce serotonin in your brain originate in the raphe nucleus. The raphe nuclei neurons then project to basically every other structure in your forebrain.
Studies in cats show that blocking serotonin receptors will block the behavioral effects of LSD. In humans, released serotonin is broken down by a molecule called monoamine oxidase. A class of antidepressants called monoamine oxidase inhibitors (MAOIs) will turn off monoamine oxidase, which will result in more serotonin in the brain. The way the brain works is that if you flood it with a neurotransmitter, it will try to adapt by reducing the amount of receptors for that neurotransmitter. So for people who have taken MAOIs for a long time, they will have lower amounts of serotonin receptors, in order to compensate for more serotonin in their brain. These individuals are also less susceptible to the effects of LSD. Furthermore, when attempting to synthetically create hallucinogens like LSD, it turns out that the better the drug binds to the serotonin receptor, the more potent its effects. These three lines of evidence lead to the idea that LSD works by binding to serotonin receptors somewhere in the brain.
But where? Well, let’s take a step back. Besides inducing hallucinations, what else does LSD do? Well, individuals who take LSD report symptoms of “oceanic boundlessness,” or this feeling of dissociation with the self, and feeling “at one” with the universe. They also report feelings of “anxious ego-disintegration,” where they feel completely removed from the self and feel like they have no control over their actions.
One idea is that it affects a network of neurons throughout the brain called the default mode network, or DMN. The DMN is composed of neurons that are MORE active when people are daydreaming, relaxed, or reflecting about the self. They also turn on when people are reminiscing about the past, or thinking about the future. In other words, the DMN looks like it activates when you’re engaged in personal, introspective sorts of thinking– activities of the “self”. On the other hand, if you’re actively looking for something or doing something, the DMN will turn off.
So maybe the DMN represents the “core self?” What will happen if the DMN is permanently turns off? One really interesting thing is looking at individuals with Cotard’s delusion. Individuals suffering from Cotard’s delusion wholeheartedly believe that they either dead, or do not exist. It turns out that individuals with Cotard’s delusion show significantly reduced activation of the DMN– in other words, it looks like that in order to have a sense that you exist as an entity, your DMN needs to be active.
Very interestingly, then, studies have shown that LSD actually turns off our DMN. The amount that an individual’s DMN is turned off by LSD correlates strongly with how much they experience its effects. Together, these results suggest that the DMN being active is at the core of having a sense of self. It looks like LSD binds to serotonin receptors in the DMN to suppress the sense of self, which can lead to people who take it feel disassociated with the self, or one with the universe.
Edit: The target audience of this response obviously isn’t literal 5 year olds. One of my pet peeves is that people who write on ELI5 often have no idea what they are talking about, and simplify their answers to the point of uselessness. My goal was to write a response that took a bit of effort to read, but would be as complete and accessible as I could make it. This is by no means the complex version of this answer, and if you’re confused by anything, I’m happy to elaborate. If you don’t think this is accessible **let me know and I will be happy to edit my post and make things more accessible**
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